Practical Veterinarian Veterinary Oncology

Copyright © 2002 by Butterworth–Heinemann

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Library of Congress Cataloging-in-Publication Data

Hahn, Kevin A.Veterinary oncology / Kevin A. Hahn.

p. ; cm. — (The practical veterinarian)Includes bibliographical references and index.ISBN 0-7506-7296-X (alk. paper)1. Veterinary oncology. I. Title. II. Series[DNLM: 1. Neoplasms—veterinary. SF 910.T8 H148v 2002]

SF910.T8 H35 2002636.089'6992—dc21 2001043874

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Series Preface

The Practical Veterinarian series was developed to helpveterinary students, veterinarians, and veterinary techni-cians quickly find answers to common questions. Unlikelarger textbooks, which are filled with detailed informa-tion and meant to serve as reference books, all the booksin The Practical Veterinarian series are designed to cut tothe heart of the subject matter. Not meant to replace thereference texts, the guides in this series complement thelarger books by serving as an introduction to each topicfor those learning the subject matter for the first time oras a quick review for those who have already masteredthe basics of each subject.

The titles for the books in our series are selected toprovide information for the most common subjects onewould encounter in veterinary school and veterinarypractice. The authors are experienced and establishedclinicians who can present the subject matter in an easy-to-understand format. This helps both the first-time stu-dent of the subject and the seasoned practitioner toassess information often difficult to comprehend.

The editor and authors hope that the books in ThePractical Veterinarian series will meet the needs ofreaders and serve as a constant source of practical andimportant information. We welcome comments and

vii

suggestions that will help us improve future editions ofthe books in this series.

Shawn P. Messonnier, D.V.M.

viii Series Preface

Preface

Veterinary Oncology represents a brief review of the practi-cal aspects of veterinary medical oncology. As many of myclose friends know, I hate cancer but I love oncology. Ihope you find the information within this text as helpfulin your practice as I have found it in mine. The informa-tion presented comes from a collection of lecture notes,handouts, and seminars that I presented or attended overthe past 15 years. During this short career, I have learnedtwo principles that should be passed on to every medicaloncologist or veterinarian practicing medical oncology.The first is “when in doubt, check it out.” This means geta diagnosis and avoid the wait-and-watch-it approach—this is a wait-and-watch-it-get-worse approach. The secondprinciple is “measure twice, cut once.” There are so manyplaces for making math errors when prescribing chemo-therapy. As I tell my sons, “you can never unpeel abanana” (my residents hate my quotes). I hope you findthe following information helpful in your practice of vet-erinary medical oncology.

K.A.H.

ix

Acknowledgments

Thanks to all the folks at Butterworth–Heinemann. Iwish The Practical Veterinarian series continued success,and I know it will become a continued resource for vet-erinary students and veterinarians alike. I would like tothank the doctors and staff of Gulf Coast Veterinary Spe-cialists for their encouragement and teamwork; it’s agreat place to practice veterinary medicine.

I would like to thank the many pet owners and theirpets that I’ve come to know over the years. The love theyshare with me and my staff means so very much. I wouldlike to thank the support of my wife Lisa, who, as a for-mer oncology technician, is very understanding of theemotional burden we carry with us every day as we carefor the family who has a pet with cancer. Finally, I wouldlike to thank my sons Evan, Erick, and Bryan who keepme young at heart and light as a feather. They are thereason I wear a smile on my face every day (and whistleDisney tunes).

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1Three Rules for Managing

the Cancer Patient

RULE 1: Get a DiagnosisBiopsy, biopsy, biopsy. A veterinarian can never give anaccurate assessment (prognosis) or develop an appropri-ate treatment plan for the tumor-bearing pet without acomplete diagnosis. Knowing the histologic type oftumor gives the veterinarian a sense of the natural behav-ior of the tumor (how it will grow, where it will go).

RULE 2: Evaluate the Entire PatientRemember, there is a pet attached to the tumor. Manytimes we forget the big picture. A thorough evaluation of

1

the pet includes obtaining appropriate laboratory infor-mation (blood counts, blood chemistry, urinalysis) andsurveying radiographic images of the thorax, abdomen,and the tumor site. Additional information may berequired, depending on the known natural behavior ofthe tumor (remember that biopsy you took in rule 1—itis extremely important). These tests may include a bonemarrow aspirate, electrophoresis of serum or urine,buffy coat smears, more biopsies, ultrasound of a bodyarea, nuclear imaging, serology, virology, or many otherprocedures. A thorough knowledge of the entire patientis necessary before an appropriate therapeutic plan can bepresented. The goal is to identify or rule out the pres-ence of concurrent illnesses and tumor metastases toregional lymph nodes or other body tissues (lungs, liver,skin, bone, for example). This information is essentialnot only for treatment planning but also to determinetreatment success or failure.

RULE 3: Develop an Appropriate Treatment Plan

Determine your goal. Is curing possible or should moreemphasis be placed on quality of life or can both beachieved? In general, three choices face every family witha tumor-bearing pet.

2 Three Rules for Managing the Cancer Patient

Choice 1: What Is Best for the Cancer?

In today’s world there are basically two ways to treat can-cer: remove the tumor with surgery and getting cancer-free edges all around the tumor or destroy the tumor’sability to grow, using radiation, chemotherapy, or both,maybe in combination with surgery. A number of otherinnovative strategies are under development, such asimmune stimulants, nutriceuticals, and tumor vesselgrowth inhibitors, but their true ability to control canceris not yet known or proven, nor the best way to use themin managing cancer patients, human or animal.

Veterinarians cure a large majority of cancers withsurgery. Those that cannot be completely removed andhave not yet spread to other body sites can be cured withadditional measures—radiation, chemotherapy, and thelike—no differently than in people. Common concernsare how a pet will look without a leg, a lower jaw, or a rib,how much radiation therapy costs, and what the sideeffects are. Every pet owner whose loved one has cancerfaces these and other questions. There are no easyanswers. However, if the objective of the planned treat-ment is to attempt to cure the cancer, surgery, with orwithout radiation, has to be strongly considered. Talk toa veterinary oncologist!

Three Rules for Managing the Cancer Patient 3

Choice 2: What Is Best for the Pet?

Remember, for most families, the quality of life for theirpet is more important than the pet’s remaining quantityof life. Remember, cancer is uncontrolled growth. If theabnormal growth cannot be removed from the body orcontrolled with localized radiation therapy, it is entirelyappropriate to use medications, such as anticancerdrugs, nutritional supplements, pain control medica-tions, anticough or antinausea medications, to maximizethe quality of life of the cancer-bearing pet. To controlthe uncontrolled growth of cancer, anticancer drugs(chemotherapy) are used. The goal of chemotherapy isnot to cure the cancer but to slow down the growingphase of the cancer. Yes, many cancer cells are killed withchemotherapy and tumor shrinkage can be observed;however, it is impractical in most situations to expect thatevery cancer cell will be killed by any chemotherapy pro-tocol or strategy. With chemotherapy, the more drugsused and the more often they are given, the more cancercells are killed. Therefore, to significantly decrease theburden of cancer and increase the lifespan of the pet,combination chemotherapy protocols that prescribedrugs every 2, 3, or 4 weeks throughout the remaininglifespan of the pet should prolong the pet’s survival.Obviously, most chemotherapy drugs do not know a nor-mal cell from a cancer cell; therefore, more drugs givenoften results in the possibility of more side effects. If thegoal is to provide better quality of life than more quan-


tity of life, a fewer number of drugs at lesser doses givenless often will still slow down cancer, just not as much.

Choice 3: What Is Best for the Family?

It is entirely appropriate not to treat cancer in pets. Infact, in some situations, we should not recommend can-cer therapy. However, just because we are not controllingthe cancer does not mean we cannot provide the pet acomfortable life. When this cannot be accomplished, weshould strongly urge pet owners to consider the choiceof euthanasia. It is important to have a support groupduring this process. Please rely on the good advice offamily and friends during this difficult time. In addition,many pet owners are willing to share their positive andnegative experiences. It is essential to provide adequatenutritional support, pain control, and other measuresthat ensure the pet’s good quality of life. Quality of life isvery subjective. Everyone has an opinion. Ask for opin-ions and listen to them. Then, make your best choice.Hindsight is 20:20, but if you follow the precedingrules—get a diagnosis and evaluate the whole patient—you should have plenty of information to make the bestchoice available at that time.

I hope this book provides some insights toward myapproach in managing the veterinary cancer patient.Always consult with a board-certified veterinary oncolo-gist. Use a team approach and allow the pet owners toparticipate in the team. Cancer is a battle that can be

Three Rules for Managing the Cancer Patient 5

won—engage in the fight but realize when it is time toretreat.


2Getting a Diagnosis

Fine-needle AspirationFine-needle biopsy is a powerful diagnostic tool that hasvery good client (and patient) acceptance because it isminimally invasive. A good biopsy technique widens theapplications and increases diagnostic yield.

Technique

STANDARD ASPIRATION TECHNIQUE Attach a 22-gaugeneedle (length variable depending on depth of lesionaspirated) to a 12-cc syringe. Localize and immobilizethe lesion by manual palpation or with ultrasound guid-ance. Introduce the needle into the lesion and applynegative pressure by repeatedly (three to five times)

7

pulling back on the plunger of the syringe. If the lesionis large enough, redirect the needle, without withdraw-ing it, into various areas of the lesion. Release all nega-tive pressure, and then withdraw the needle from thelesion. Quickly remove the needle from the syringe, fillthe syringe with 8–10 cc of air, reattach the needle to thesyringe, and expel the material within the needle onto aclean glass slide by rapidly depressing the syringeplunger. Quickly prepare smears as described later.

CAPILLARY ACTION (NONASPIRATION) TECHNIQUEThis technique is easier to perform and yields resultsequally diagnostic to the standard aspiration technique.It may provide samples with less blood contamination,especially in more vascular lesions or lesions that do nottypically exfoliate cells readily (mesenchymal tumors).Attach a 22-gauge needle (length variable depending ondepth of lesion aspirated) to a 12-cc syringe that hasbeen prefilled with 10 cc of air. Localize and immobilizethe lesion by manual palpation or with ultrasound guid-ance. Move the needle through various areas of thelesion repeatedly (five to eight times, do not aspirate).Withdraw the needle from the lesion and expel thematerial within the needle onto a clean glass slide by rap-idly depressing the syringe plunger. Quickly preparesmears as described later.

TRU-CUT BIOPSIES To perform Tru-cut biopsies, make asmall puncture in the skin overlying the lesion with an 11

8 Getting a Diagnosis

blade. Semiautomated and fully automated instrumentsshould be spring-loaded prior to introducing the needleinto the lesion. Introduce the needle, specimen notchclosed, into the lesion, leaving enough room for the nee-dle to travel 1.5–2.0 cm forward, depending on penetra-tion length of needle, and still remain in the lesion.Then, obtain the biopsy specimen as follows:

• Manual Tru-cut. Advance the caudal portion of thehandle of the needle forward to open the specimennotch, then advance the cranial portion of the nee-dle handle forward to close the specimen notch andobtain the biopsy. Always move in a forward direc-tion. Remove the needle and specimen.

• Semiautomated. Advance the caudal portion of thehandle of the needle forward to open the specimennotch, then firmly depress caudal portion of the han-dle of the needle farther forward to complete biopsyprocedure. Remove the needle and specimen.

• Fully automated. While holding the apparatus still,depress firing button to obtain the biopsy. Removethe needle and specimen.

Sample Preparation and Handling

GENERAL COMMENTS Always obtain several samplesfrom various sites within each lesion. This optimizes thechance of achieving a diagnosis. Single aspirates or biop-sies may be nondiagnostic for various reasons, such as

Getting a Diagnosis 9

missing the lesion, sampling a nonrepresentative ornecrotic area of the lesion, or blood contamination dur-ing sampling. Make several slides to examine, especiallyif slides are to be submitted to an outside lab for evalua-tion, because labs charge by the lesion not by the num-ber of slides submitted. Keep slides for cytologicalevaluation away from formalin fumes and formalin-fixedtissues. Formalin partially fixes cells on microscopeslides, which results in poor slide staining and nondiag-nostic samples. This occurs during both slide prepara-tion and shipping; do not mail unstained slides andformalin-fixed tissues in the same package. When send-ing slides to an outside lab, use Styrofoam or plastic mail-ers (flat cardboard mailers often result in broken slides),provide a thorough history (including drug therapy)and problem list, and call the lab to discuss results if theyare unusual or unexpected.

FLUID FOR ANALYSIS All fluid for analysis should be col-lected in EDTA to prevent coagulation and help pre-serve cells. Non-EDTA specimens usually cannot beinterpreted. A portion of the fluid can be retained in asterile tube if culture and sensitivity are desired. If usingan outside lab, it is helpful to prepare a few slides to shipalong with the EDTA fluid sample, in case cells degener-ate or microbial overgrowth occurs in the sample priorto it arriving at the lab. Again, do not fix cells withethanol (or formalin) unless the laboratory with which


you deal uses a trichrome or other Papanicolaou-typestain; most do not.

SLIDE PREPARATION Use only clean, new slides whenmaking smears or imprints. Reused slides, even if thor-oughly cleaned, usually have surface changes andresidues that result in uneven spreading and alteredstaining characteristics. The two most common tech-niques for preparing specimens are obtained by fine-needle aspiration of fluid or tissue. Tissues obtained bysurgery or from biopsy instruments can be squashed ifvery small or gently blotted on several areas of or rolledacross a slide. Blotting a biopsy sample to remove bloodprior to making imprints enhances the diagnostic qualityof the slide. Whatever technique is used, rapid drying ofslides by waving them in the air or using a hair dryer seton low helps fix the cells to the slide and preserves cellmorphology.

Cytologic Criteria for Malignancy Cytologically, neoplasia is characterized by the presence ofa monomorphic population of cells that appears to havecome from the same tissue of origin. This is best appreci-ated by the presence of cells with the same cytoplasmiccharacteristics. If a neoplasm is diagnosed, two importantdeterminations must be attempted: whether the lesion isbenign or malignant and what is the tissue of origin.


Benign versus Malignant

Benign neoplasia or hyperplasia is characterized by auniform population of cells. There should be a uniformcytoplasmic and nuclear size and shape, uniform nuclearto cytoplasmic (N:C) ratio, and if nucleoli are present,they are of consistent size, shape, and number amongindividual cells. Malignant neoplasms have nuclear fea-tures considered abnormal and indicate a cell popula-tion that is growing rapidly and uncontrollably. Thefollowing are nuclear characteristics considered to beabnormal: anisokaryosis, pleomorphism, high or vari-able N:C ratio, increased mitotic activity, nucleoli thatvary in size, shape, and number (angular, irregularlyshaped nucleoli), coarse chromatin or uneven margina-tion of chromatin at the nuclear membrane, nuclearmolding, multinucleation. If many of the cells showthree or more of the criteria of malignancy, the tumor ismalignant. In the vast majority of the cases, the cytologiccriteria of malignancy are accurate predictors of thepotential biological behavior of the tumor. However, insome circumstances, and these are the exception to therule, the cytologic appearance may not accurately pre-dict the biological behavior. A practicing cytologist mustbe aware of the exceptions to the rule if we are to rely oncytology to provide us with meaningful, accurate infor-mation regarding the prognosis of a patient.


Inflammation and Malignancy

The criteria for malignancy are more meaningful ifinflammation is not present. Inflammation may causereactive changes in epithelial or mesenchymal cells thatmimic malignancy. Therefore, the criteria of malignancymust be interpreted with caution if the cell population ofa lesion contains a mixed cell population of both inflam-matory (neutrophils, eosinophils, lymphocytes,macrophages) and noninflammatory cells (epithelial,mesenchymal, round cells, or neuroendocrine cells). Inmost mixed cell populations, neoplasia may be sus-pected; however, the diagnosis must be made from a tis-sue biopsy and histologic evaluation of the lesion.

Specific Tumor Types and Locations

In addition to the presence of inflammation, there arespecific instances where the cytologic appearance of theneoplasm does not correlate well with the biologicalbehavior of the lesion. The location of some tumors andoccasionally the specific tumor type must be consideredwhen using cytology to determine the malignant poten-tial of certain neoplasms.

MESENCHYMAL NEOPLASMS Mesenchymal tumors arecomposed of small to medium cells. Aspirates are usuallyless cellular than with epithelial tumors and the cellsarranged more individually. Cytoplasm is wispy and oftenspindle shaped, with tags of cytoplasm trailing off in one


or two directions from the nucleus. Cytoplasmic bordersare usually indistinct. The nuclei are typically oval topolygonal. Malignancies of mesenchymal origin aretermed sarcomas. The nuclear features of malignancy areusually reliable indicators of the malignant potential ofmesenchymal tumors.

Leiomyosarcoma and myxosarcoma are exceptions.Leiomyosarcomas and the myxosarcomas are uncommontumors of smooth muscle and fibroblast origin, respec-tively. These tumors are difficult to differentiate fromtheir benign counterparts (leiomyoma and myxoma)based on cytologic or even histologic features alone.Since some leiomyosarcomas and myxosarcomas haveno bizarre nuclear features, histologists often must relyon invasion into surrounding tissues to determine themalignant potential of these tumors. However, if thenuclear criteria of malignancy are met, the lesion is con-sidered malignant. Leiomyomas and leiomyosarcomastypically occur in the GI (gastrointestinal) tract or uri-nary bladder. The nuclei of these smooth muscle cellshave an elongated, cigar-shaped appearance. The cyto-plasm is very fragile, and free nuclei are abundant oncytologic preparations. Myxomas and myxosarcomasmay occur anywhere in the subcutaneous tissues. Thecharacteristic cytologic feature is an abundant mucinousbackground that appears cytologically as an amorphouseosinophilic material, similar to synovial fluid. Low tomoderate numbers of mesenchymal cells are mixedwithin the mucin.


The differentiation between sarcoma and reactivefibroplasia associated with inflammation is the primaryconcern when evaluating mesenchymal tissue. Inflam-mation can stimulate the production of a reactivepopulation of fibroblasts that are cytologically indistin-guishable from sarcoma cells. Therefore, in the presenceof inflammation and mesenchymal cells (mixed cell pop-ulation), the cytologic criteria used to diagnose malig-nancy are not reliable. Histologic confirmation isrequired, because in most cases, if inflammation is pres-ent, the population of fibroblasts is likely reactive.

EPITHELIAL NEOPLASMS Epithelial tumors are usuallycomposed of large cells. Aspirates are usually very cellu-lar and the cells characteristically exfoliate in clumps orsheets. The cells are round to polygonal with very dis-tinct cytoplasmic borders. They are often tightly adher-ent to each other with extensive contact betweenadjacent cells and clear zones between areas of cell junc-tions. Prominent cytoplasmic vacuolation, signet ring, oracinar formation may be seen if the tumor originatesfrom glandular epithelium. Malignancies of epithelialorigin are termed carcinomas or adenocarcinomas. Unlessinflammation is present, the nuclear criteria for malig-nancy are reliable indicators for the vast majority ofepithelial neoplasms. Two notable exceptions, which areactually quite common tumors, are basal cell tumors andperianal or anal gland tumors.


Basal cell tumors are common cutaneous tumors ofthe dog and cat. They have a site predilection for headand neck. They are the most commonly reported cuta-neous tumors of the feline. They have also been calledbasal cell carcinomas, but since they are usually benign, thisterm does not accurately describe their biological behav-ior in domestic animals. Cytologically, these tumors con-tain tight clumps of epithelium with deep bluecytoplasm. They have some nuclear features of malig-nancy, such as a high N:C ratio, anisokaryosis, and occa-sional nucleoli. Mitotic figures may be observedoccasionally. However, most of these tumors are benignand can be successfully removed surgically. These lesionsmust be identified as basal cell tumors so they are notmistaken for a malignancy based on the cytologic appear-ance. The deep basophilic, tightly adherent balls ofepithelium with a high N:C ratio in a cutaneous tumor isvery characteristic. In addition, low numbers of maturesebaceous gland epithelium may be mixed within theclumps of basal cells. Sebaceous differentiation is associ-ated with some basal cell tumors. This can also aid in thediagnosis. Some basal cell tumors, especially in the cat,contain variable amounts of melanin pigment and mustbe distinguished from true melanocytic tumors. Thecohesiveness of basal cells is a predominant differen-tiating feature. These tumors grow slowly and rarelymetastasize. Surgical excision is usually curative, butrecurrence may occur after incomplete excision.


Perianal gland adenomas are benign tumors of the cir-cumanal glands, commonly seen in intact, male dogs >8years of age. Perianal gland adenocarcinomas do occur,but they are much less common and may be seen ineither intact or neutered male dogs. They are seen lessfrequently in neutered female dogs and rarely in intactfemales. Perianal gland adenomas are composed prima-rily of large, polyhedral, hepatoid-like cells, occurring inclumps or clusters. They contain abundant basophiliccytoplasm, often with a pink hue. The N:C ratio is lowand nuclei are typically round to oval with clumped chro-matin and one or two large nucleoli. This gives the cell aremarkable resemblance to hepatocytes. Most perianalgland adenomas usually contain variable numbers of asecond population of smaller epithelial cells with a muchhigher N:C ratio. These cells are called reserve cells. Thedistinctive population of cells allows easy identificationof the tumor; however, the variability of the cell popula-tion, along with the prominent nucleoli and clumpedchromatin may mimic a malignancy, even with adeno-mas. In reality, perianal gland adenomas and perianalgland adenocarcinomas are often cytologically indistin-guishable. In these tumors, the signalment of the patientplays a major role in determining how to interpret cyto-logic findings. The vast majority of perianal glandtumors occur in intact males and most of these are ade-nomas. Some investigators believe there may be a pro-gression of these lesions to adenocarcinomas if not


surgically removed. However, in intact males, most peri-anal adenocarcinomas do not metastasize, so local recur-rence with incomplete excision is about all that happens.In contrast, about half the perianal gland tumors inneutered males and females are adenocarcinomas, andthese may metastasize. If a perianal gland tumor is foundon a neutered male or female dog or if there is tumorregrowth following surgical removal of a previously diag-nosed adenoma on an intact dog, an adenocarcinomashould be suspected. Histology is required.

Anal sac apocrine gland adenocarcinomas are epithelialtumors of the anal sac apocrine glands of the dog.Unlike perianal gland tumors, these tumors are oftenseen in older, female dogs. Most affected animals havean associated hypercalcemia. This tumor appears asclumps of epithelium with very few distinct cytoplasmicborders. The appearance of free nuclei embedded in amass of cytoplasm gives this lesion a neuroendocrine-likeappearance. This allows easy identification by finding aneuroendocrine-like appearance of cells from a masslocated around the anus. The cells have a high N:C ratio(lots of nuclei), but the cells are fairly uniform withround nuclei. Occasionally a mild anisokaryosis andsometimes small, indistinct nucleoli can be seen. How-ever, there are usually not enough abnormalities to fulfillthe cytologic criteria of malignancy. Cytologically, thistumor usually appears benign; however, the cytologicalappearance of this tumor does not accurately predict thebiological behavior. The N:C ratio is often high but


nuclei are fairly uniform and nucleoli, when present, areindistinct. Even so, it is a malignant apocrine glandtumor. In female dogs, there is a 50% rate of metastasisto regional lymph nodes at time of presentation, 13% inmales. In addition, most patients with this tumor haveassociated paraneoplastic hypercalcemia, which also aidsin identification.

ROUND CELL NEOPLASMS Round cell tumors, as a group,share the common cytologic characteristics of being com-posed of individually arranged, round cells, which usuallyexfoliate in moderate to large numbers. The cells containdiscrete cytoplasmic borders but are not very adherent toeach other and contain no junctions between cells. Thecytologic criteria of malignancy are not reliable indica-tors of the biological behavior of round cell tumors. For-tunately, this group of tumors can usually be definitivelyidentified cytologically. The biological behavior then canbe considered, based on the tumor type, location, andsometimes cellular differentiation. The six specificround cell tumors are histiocytic tumor, lymphoma, mastcell tumor, transmissible venereal tumor, plasma celltumor, and melanoma.

Histiocytomas are benign cutaneous tumors of youngdogs (usually <3 years of age). The cells contain moder-ate amounts of pale to lightly basophilic cytoplasm.Nuclei are round to pleomorphic with fine chromatinand indistinct nucleoli. Because these lesions are com-posed of histiocytes, cells typically display a variable N:C


ratio, pleomorphic nuclei, and anisokaryosis. Thetumors frequently become infiltrated with lymphocytes,adding to the heterogeneity of the population. Thesefeatures may be confused for malignant criteria; how-ever, once identified as a histiocytoma, the diagnosis of abenign neoplasia can be made. Many of these lesionsspontaneously regress and surgical removal is curative.

Malignant histiocytosis is the malignant counterpart ofthe histiocytoma. These tumors may occur anywhere onthe body and often invade internal organs. They havesignificant nuclear features of malignancy and usuallyshow some differentiation toward the macrophage cellline, such as vacuolated cytoplasm, phagocytic activity,pleomorphic nuclei, or multinucleation. The criteria ofmalignancy are accurate predictors of the biologicalbehavior of this tumor. There appears to be a breedpredilection for this tumor in golden retrievers, rotweil-ers, and Bernese mountain dogs.

Lymphoma, by definition, is a malignancy of lympho-cytic origin. Lymphomas are round cell tumors contain-ing individually arranged cells with distinct cell borders.The cells contain scant amounts of deeply basophiliccytoplasm, a very high N:C ratio, and round to polygonalnuclei. The slide preparation often contains small tags of cytoplasmic fragments called lymphoglandular bodies.Other cytologic characteristics vary dramatically,depending on the type of lymphoma and the maturity ofthe neoplastic population. In the dog, most lymphomasare a high-grade malignancy composed of a predomi-


nant population of immature lymphoblasts with nucleithat are 1.5 or more times the size of erythrocytes andone or more nucleoli. However, in the cat, some lym-phomas, particularly hepatic and intestinal lymphomas,are composed of small, well-differentiated lymphocytes.These cells have a small mature nucleus approximatelythe size of an erythrocyte with a small tag of cytoplasm.They are difficult to distinguish cytologically from a nor-mal or reactive population of lymphocytes. Likewise, theanatomic location(s) of the tumor and stage of the dis-ease, along with the cytologic appearance of the cells andany paraneoplastic conditions all affect the prognosis ofthe patient with regard to expected response tochemotherapy and survival time. Therefore, the cyto-logic criteria of malignancy play a small role in predict-ing the overall behavior of this tumor.

Mast cell tumors are composed of individuallyarranged, round cells with round to polygonal nucleiand variable numbers of purple-staining, small, cytoplas-mic granules. All these tumors are considered potentiallymalignant and, as the saying goes, never trust a mast celltumor. The potential for metastasis and invasiveness isevaluated using two criteria, the cytologic differentiationof the tumor cells and their anatomic location.

Cytologically, mast cell tumors can be classified aswell differentiated, moderately differentiated, or poorlydifferentiated. In general, moderately and poorly differ-entiated tumors have a much higher tendency to metas-tasize than well-differentiated tumors. However, some


well-differentiated tumors may be aggressive in their bio-logical behavior. Well-differentiated mast cell tumors havehigh numbers of cytoplasmic granules that often occludevisualization of the nucleus in intact cells. Nuclei are uni-form in size and round to oval in shape. Moderately differ-entiated tumors have low to moderate numbers ofcytoplasmic granules that usually do not occlude visuali-zation of the nucleus. Anisokaryosis is moderate andthere is a variable N:C ratio. Mitotic figures may be seenin low numbers. Poorly differentiated mast cell tumors havesparse to no cytoplasmic granules. Anisokaryosis and avariable N:C ratio are frequently observed and may bemarked. Nuclei are irregular in shape, and mitotic fig-ures are seen in moderate numbers. An associatedeosinophilic inflammatory response may be the key torecognition of an undifferentiated mast cell tumor. Theless differentiated the cells are, the greater the potentialfor invasion and metastasis, regardless of the anatomiclocation. However, even well-differentiated mast celltumors may metastasize, depending on the location ofthe lesion. In the dog, cutaneous mast cell tumorslocated in the perineal or inguinal regions frequentlymetastasize, usually to popliteal or abdominal lymphnodes. In addition, mast cell tumors located around themuzzle, in the oral or nasal cavity, or at mucocutaneousjunctions frequently metastasize to regional lymphnodes. In these locations, the biological behavior of thetumor cannot be accurately predicted by the cytologicdifferentiation of the mast cells.


Most cutaneous mast cell tumors in the cat arelocated on the head and neck (58%). Some cats candevelop multiple mast cell tumors. An uncommon, histi-ocytic form may occur in young cats, <4 years of age.Most cutaneous mast cell tumors in the cat are consid-ered benign. An exception would be the histologicallydiffuse (vs. compact) or poorly differentiated tumor.Siamese cats appear to have a breed predilection fordevelopment of cutaneous mast cell tumors. Systemicmastocytosis occurs in the cat causing mastocythemiaand severe splenomegaly with marked infiltration ofmast cells. Cutaneous mast cell tumors and systemic mas-tocytosis are not known to occur simultaneously. Anintestinal form of feline mast cell tumor may result in amilder mastocythemia. This disease carries a poorerprognosis than the splenic form.

Transmissible venereal tumors (TVTs) are composed oflarge numbers of round cells with variable amounts ofmoderately basophilic cytoplasm. The cytoplasm oftencontains small punctate vacuoles. Nuclei are round topolygonal with coarse chromatin and one or two largeprominent nucleoli. This is the only tumor known to benaturally transmissible. It is transmitted by direct contactand interestingly, does not represent normal dog cells that have become malignant. In TVT cells, thechromosome number is 59. In normal canine cells, thechromosome number is 78, thus TVT cells are cells thathave been transformed into cancer cells by passage fromdog to dog. It acts somewhat like a parasite, except that


a single tumor cell line causes it. This tumor is usuallylocated in the genital area or nasal cavity (dogs are“nosey”). TVTs can be locally very invasive but rarelymetastasize. They are highly sensitive to chemotherapywith vincristine (every 7 days) and gone usually withinfive or six weeks. The cytologic characteristics of thistumor are useful only in making a diagnosis and have lit-tle value in predicting behavior.

Plasma cell tumors, neoplasms of plasma cell origin,are classified as either extramedullary plasmacytomas ormultiple myelomas. Plasmacytomas are lymphoid neo-plasms with site predilections for the skin (76%) of thedigits and foreleg (32%) as well as the oral cavity (28%),ears, and gastrointestinal tract. This tumor more com-monly affects dogs; however, there are reported cases inthe cat. In the dog, there may be a breed predilection inairedale terriers (7.7%), boxers (9.4%), and cockerspaniels (11.1%). Plasmacytomas have the cytologicappearance of other round cell tumors with aspiratesyielding moderate to large numbers of individuallyarranged, round to oval cells with discrete cytoplasmicborders. These cells contain variable amounts of deeplybasophilic cytoplasm. Many of the cells have a character-istic plasmacytoid appearance with a round nucleus thatis often eccentrically located in the cell. This can varydepending on the maturity of the individual cells withinthe tumor. A perinuclear clear area “Golgi zone” is oftenseen in the cytoplasm. In the dog, extramedullary plas-macytomas are mostly benign. However, these tumors


often display criteria of malignancy, including markedanisokaryosis, pleomorphism, binucleation, multinucle-ation, variable N:C ratio, and clumped chromatin.Surgical removal is curative in most cases. Some plasma-cytomas in the dog can be locally invasive, resulting inregrowth following surgical removal; and rare reports ofmetastasis to regional lymph nodes, liver, and spleenhave occurred. Extramedullary plasmacytomas in thedog have also been associated with local amyloid pro-duction and rarely with amyloidosis, monoclonal spikes,or hypercalcemia. In the cat, these tumors appear to bemore aggressive, frequently resulting in monoclonalgammopathies and metastatic disease. However, the bio-logical behavior of this lesion cannot be accurately pre-dicted by the cytologic appearance. The cytologicappearance of plasmacytomas is identical to the appear-ance of the malignant plasma cell tumor, multiplemyeloma, which originates in the bone marrow of dogsand cats. These neoplasms are always malignant, diag-nosed by finding greater than 20% plasma cells in thebone marrow of an animal that has other clinical find-ings consistent with the disease. These include mono-clonal gammopathy, hypercalcemia, or lytic bone lesions,particularly in the vertebral column.

Melanomas can occur cutaneously anywhere on thebody. However, in the dog they appear to have a sitepredilection for the oral cavity and digits and are themost common canine oral neoplasm. They frequently arefound on the buccal mucosa. This neoplasm is sometimes


included in the group of round cell tumors. Melanomasare similar to mast cell tumors in that the differentiatedcells are composed of many cytoplasmic granules andthe biological behavior of the lesion depends heavily onthe anatomic location as well as cellular differentiation.Cytologic preparations of most differentiated mela-nomas contain cells that are individually arranged butmay cytologically appear to be spindle shaped, epithe-lioid, or a mixture of both. The cytoplasm often containsvariable amounts of fine, brown-black to green-black pig-ment granules. In contrast to melanocytes, mast cellscontain purple granules. Oral melanomas that lack cyto-plasmic pigment therefore are classified as amelanotic.However, cytologically small amounts of fine pigmentcan usually be found even in poorly differentiatedtumors. If cells from an aspirated lesion appear veryanaplastic and contain both mesenchymal and epithelialfeatures, a malignant melanoma should be suspected.With cutaneous melanomas, the more pigmentedtumors are more differentiated and less likely to behaveaggressively. Most cutaneous melanomas of the dog arebenign, and most well differentiated, cutaneous mela-nomas are considered benign. However, oral melanomasand melanomas involving the nail bed of the digits arevery aggressive. Even well-differentiated (highly pig-mented) tumors in these locations are aggressive andmetastasize early. The treatment of choice is wide surgi-cal excision or amputation. Melanomas are uncommontumors in the cat; however, a recent study identified five


types of cutaneous melanomas in the feline: epithelioid,spindle, mixed, signet ring, and balloon cell. Theepithelioid, spindle cell, and mixed tumors of the cat areusually pigmented and often found on the ears, fore-head, nose, and eyelids. Balloon cell and signet ringtypes are typically amelanotic. The balloon cell type alsousually is found on the head. Cells are large and swollenwith cytoplasm, which appears like a balloon. Nuclei dis-play many anaplastic features. The signet ring type is usu-ally found on the shoulder, thorax, and flank areas. Thecytoplasm is large and distended with the nucleuspushed off to one side, giving cells a signet ring appear-ance. Nuclei display many features of malignancy. Thesignet ring and balloon cell types are believed to be vari-ants of the epithelioid cell type, highly aggressive withmetastasis to lymph nodes and several organs. Mean sur-vival time from surgical removal was 4.5 months.

Note: Melanomas should not be confused with the morecommon pigmented cutaneous tumor in the cat, the basal celltumor. Basal cell tumors may contain melanin, but the cellsoccur in tight, cohesive clusters with a very high N:C ratio.

NEUROENDOCRINE NEOPLASMS Neuroendocrine tumorsare tumors of chemoreceptor or endocrine glands, suchas the thyroid, parathyroid, pancreas, or adrenal gland.These tumors share a characteristic cytologic feature.Slide preparations appear as free, round nuclei embed-ded in a background of cytoplasm, with few distinctcytoplasmic borders visualized. With the exception of


thyroid tumors, which are often bloody, most prepara-tions are very cellular. Knowledge of the malignantpotential for each tumor type is important because thecytologic criteria for malignancy are not easily inter-preted with these neoplasms. If criteria of malignancyare present, the tumors are likely to metastasize or locallyinvade surrounding structures. However, nuclei fromthese tumors often do not display sufficient criteria ofmalignancy, even when the potential for metastasis orinvasion is likely. The most frequently encountered neu-roendocrine neoplasm is the thyroid tumor.

Canine thyroid tumors are usually located on the neckor near the thoracic inlet, although some tumors havebeen identified within the thoracic cavity. There is abreed predilection for boxers, beagles, and goldenretrievers. More than 90% of the clinically apparent thy-roid tumors in the dog are malignant. Aspirates from thy-roid tumors, particularly carcinomas, may contain a largeamount of blood contamination. Clumps of epithelialcells may be seen scattered throughout the preparation.These clumps appear as free nuclei embedded in a back-ground of pale blue cytoplasm with infrequent visualiza-tion of cytoplasmic membranes or borders. Amorphouspink material (colloid) may be associated with someclumps. Dark, blue-black pigment (tyrosine granules) issometimes seen in the cytoplasm of epithelial cells. Thispigment along with the neuroendocrine appearance ofthe cells may be used to definitively identify the tissue as


thyroid in origin. Nuclei are round to oval; however,anaplastic features are minimal. Most thyroid tumors,even adenocarcinomas, are composed of a fairly uniformpopulation of cells, displaying few if any criteria of malig-nancy, even though in the dog most are malignant.Therefore, in the canine, anytime a tumor is identified asthyroid in origin, it must be assumed to be a carcinomauntil further confirmation by histopathology. In dogs,hypersecretion of thyroid hormones is uncommon; how-ever, some dogs with adenocarcinomas may be hypothy-roid. Adenomas are benign and the prognosis isexcellent with surgical excision. Adenocarcinomas areinvasive and metastasize if given sufficient time. Progno-sis and potential for metastasis depend on tumor size.Dogs with tumors <5 cm in diameter were metastasis freeafter seven months. Dogs with larger tumors have a 40%chance of metastatic disease at the time of diagnosis.

Note: Thyroid adenocarcinomas in the dog have been asso-ciated with the development of fragmentation hemolysis and dis-seminated intravascular coagulation (DIC).

Thyroid tumors in the cat are cytologically identicalto those seen in the dog. However, the vast majority oftumors in the cat are benign adenomas or adenoma-tous hyperplasia and may occur bilaterally. Cytologi-cally, thyroid adenomas, or adenomatous hyperplasia,appear as clumps of epithelial cells scattered through-out the preparation. These clumps contain free nucleiembedded in a background of pale blue cytoplasm with


infrequent visualization of cytoplasmic membranes orborders. Amorphous pink material (colloid) may beassociated with some clumps. Dark, blue-black pigmentis sometimes seen in the cytoplasm (tyrosine granules).This pigment, along with the neuroendocrine appear-ance of the cells may be used to definitively identify thetissue as thyroid in origin. Nuclei are round to oval andfairly uniform in size and shape. Adenocarcinomas areuncommon, but it is not possible to cytologically distin-guish between adenomas and adenocarcinomas. In thecat, most thyroid tumors are most likely to be benignuntil proven otherwise; however, histologic evaluation ofcapsular or lymphatic invasion is often required for adefinitive diagnosis. Unlike the canine, most thyroidtumors (adenomas and adenocarcinomas) in the catactively secrete thyroid hormones. Adenomas are usuallywell encapsulated and the prognosis is excellent withsurgical removal. If bilateral thyroidectomy is per-formed, the patient must be monitored for signs ofhypothyroidism or hypocalcemia, resulting fromremoval of the parathyroid glands. Adenocarcinomas arelocally invasive and metastasize to regional lymph nodes.Metastatic disease was reported in 40–71% of cats withadenocarcinomas.

Blood Smear EvaluationThe evaluation of a blood smear allows the veterinarianto gain rapid, valuable information regarding the health


of the patient when the evaluation is performed in a sys-tematic fashion. Estimating cell numbers and evaluatingthe morphologic changes in erythrocytes, leukocytes,and platelets can obtain the important clinical informa-tion needed for the hematologic evaluation of an ani-mal. The value of these findings, many of which are notrecognized by automated cell counters, cannot beoveremphasized.

Blood Collection and Slide Preparation

Vacutainer tubes containing EDTA should be filled tothe designated amount. Partial filling of vacutainer tubeswith blood may cause artifactual changes in cell mor-phology and numerical values. Blood smears should beprepared as quickly as possible to minimize artifactualchanges in erythrocytes and leukocytes, such as red cellcrenation, leukocyte vacuolation, and nuclear pyknosis.The coverslip technique for making smears is preferredover the glass slide technique. This technique minimizestraumatic injury to cells during slide preparation. Thistechnique produces more even distribution of cells,allowing more accurate estimation of leukocyte andplatelet numbers. Smears should be rapidly dried with ablow drier to eliminate artifacts of air-drying red bloodcells. This is particularly important when attempting toidentify red cell parasites, such as Haemobartonella felis, orevaluation of erythrocyte shape changes.


Systematic Evaluation of a Blood Smear

SCANNING THE SMEAR The first step in the evaluationof a blood smear is to scan the slide using a 10� or 20�objective. With regard to the red blood cells, observe thered cell density and look for the presence of rouleaux oragglutination. (Rouleaux may be differentiated fromagglutination by saline test where 1 drop of blood ismixed with 4 drops of saline and observed on wetmounts; rouleaux will disperse with saline dilution.)With regard to nucleated cells, confirm that the matureneutrophil is the predominant cell type. The presence ofany left-shifted neutrophils or large or atypical leuko-cytes, as well as the presence of any nucleated erythro-cytes, should be recorded. Platelet clumps should also beidentified at this magnification, because they affect howplatelet numbers are interpreted later in the evaluation.Leukocyte numbers may be estimated using the follow-ing formula:

Number of cells/μl = (average number of cells per field) � (objective power)2

The objective used to estimate leukocyte numbersshould be that through which approximately 5–10 leuko-cytes are seen per field. For example, if an average of 5cells were counted for each 50� field, the total leukocytecount would be (5) � (2,500) = 12,500 cells/μl.


ERYTHROCYTE EVALUATION Erythrocyte evaluationbegins with the search for agglutination or rouleaux for-mation using a scanning objective. Erythrocyte mor-phology should be evaluated using the 100X, oilimmersion lens in an area of the smear where red cellsare evenly spaced, usually slightly behind the featherededge. Red blood cells are evaluated for changes in size,shape, color, and inclusions. Erythrocytes are normallyvery uniform in size. Typically, minimal variation isfound in the size, shape, or color of the erythrocytes inthe blood smear of a normal cat or dog.

Nucleated red blood cells (NRBCs) are usually seenin regenerative anemias; however, they are not used toevaluate a regenerative response. A nucleated red bloodcell in the absence of polychromasia is a dysplasticchange and indicates a nonregenerative response. Thismay be observed in such conditions as lead poisoning,bone marrow damage due to septicemia, or myeloprolif-erative diseases (particularly erythroleukemia due toFeLV). When the number of nucleated erythrocytesexceeds 5–7/100 white blood cells (WBCs), the leuko-cyte count must be corrected for these cells. The formulafor this correction is

Corrected WBC = (100 � WBCs)/(100 + number of NRBCs)

The interested reader is directed to a hematology text forthe interpretation and significance of other erythrocyticabnormalities.


PLATELET EVALUATION Platelet evaluation begins withthe search for clumps using a scanning objective. An esti-mation of platelet numbers is done using the 100� oilemersion lens. The formulas for estimation of plateletnumbers are

Dog: Number of cells/μl = (number of cells per100� oil field) � 15,000

Cat: Number of cells/μl = (number of cells per100� oil field) � 20,000

The technique of platelet evaluation is particularly usefulin evaluating platelets in the cat, since automated cellcounts are often unreliable in assessing platelet numbersfor this species. Megaplatelets, platelets as large or largerthan erythrocytes, may indicate platelet regenerationdue to a peripheral destruction or consumption ofplatelets. Thrombocytopenia may result form a produc-tion problem in the marrow or a loss in the peripheralcirculation due to destruction or consumption ofplatelets. A bone marrow evaluation may be necessary tomake this distinction.

LEUKOCYTE EVALUATION Leukocyte evaluation beginsusing a scanning objective by observing the matureneutrophil as the predominant cell type and identifyingthe presence of immature neutrophils (bands) or reac-tive changes in monocytes and lymphocytes. Large,immature blast cells should also be identified at this time.


These pathological changes and other changes then areevaluated more closely using the 100�, oil immersionlens. One important change in neutrophils is the pres-ence of cytoplasmic toxicity. It is particularly important toevaluate toxicity of neutrophils in patients with a leuko-cytosis or a left shift. Toxicity is a cytoplasmic change usu-ally associated with the presence of bacterial infections ortoxins. A +1 toxicity is defined by the presence of Döhlebodies: small, basophilic aggregates of RNA in the cyto-plasm of cells. This condition may be normal, if they are seen in low numbers of neutrophils in cats. A +2 tox-icity shows Döhle bodies and diffuse cytoplasmic baso-philia. A +3 toxicity contains all of the preceding plusfoamy cytoplasmic vacuolation; and a +4 toxicity has allthe preceding plus giantism and nuclear lysis. Hyperseg-mentation, although not a toxic change, is another sig-nificant finding in the neutrophil population. This isdefined as the presence of a neutrophil with five or morelobes in the nucleus. Hypersegmentation is most com-monly associated with steroid administration but mayalso be seen in myeloproliferative diseases or bloodsmears made from blood left too long in the vacutainertube. Lymphocytes do not develop toxicity but maybecome reactive as a result of some antigenic stimulationfrom an infectious agent, neoplasm, or immune-medi-ated disease. The cytoplasm of reactive lymphocytesbecomes more intensely basophilic, almost a royal blue.Reactive monocytes may also be seen if the cytoplasmbecomes more intensely basophilic and vacuolated. This


usually indicates a chronic inflammatory process or maybe seen with hemobartonellosis in the cat.

NEOPLASTIC CELLS IN CIRCULATION Neoplastic cells, pri-marily those of hematopoietic origin, may also be identi-fied in the peripheral blood. These cells would alert theclinician to the possibility of a leukemia; however, thisdiagnosis technically must be made using a bone marrowaspirate. Hematopoietic blast cells may be of erythroid,granulocyte, monocyte, or rarely megakaryocyte origin(myeloproliferative disease), or lymphoid origin (lym-phoproliferative disease). In general, they are identifiedas large cells with nuclei often two or more times the sizeof erythrocytes. They may have an abnormal nuclearmorphology, including a high N:C ratio; a diffuse, alteredchromatin pattern; and prominent nucleoli. The cyto-plasm of these cells is often deeply basophilic.

Bone Marrow EvaluationThe evaluation of bone marrow is an important tool inthe diagnosis of hematologic disorders and the staging ofcertain neoplasms. Proper sample collection and slidepreparation may provide the basic information neededto assist in patient diagnosis or prognosis.

Indications

In most cases, indications for doing a bone marrow aspi-rate are determined by evaluation of a complete blood


count (CBC) on the peripheral blood. In fact, it is oftenimpossible to interpret findings in the marrow without arecent CBC. The following is a list of indications forevaluation of a bone marrow aspirate.

ANEMIA Bone marrow aspirates should be performedwhenever there is a nonregenerative or poorly regenera-tive anemia. It is not necessary to evaluate the bone mar-row in cases of regenerative anemia, since the marrow isshowing evidence of adequate red cell production.

LEUKOPENIA Reduced leukocyte numbers may resultfrom lymphopenia or neutropenia. Lymphopenia is usu-ally not an indication of decreased marrow productionand does not typically require marrow evaluation. Neu-tropenia, on the other hand, may result from decreasedproduction from the marrow or increased use ordestruction in the periphery. A persistent neutropenia isa good indication for bone marrow evaluation.

THROMBOCYTOPENIA A bone marrow aspirate isimportant in differentiating a production problemverses peripheral destruction or utilization of platelets inpatients with a peripheral thrombocytopenia.

UNEXPLAINED ELEVATION IN CELL NUMBERS Persistentpolycythemia, leukocytosis, or thrombocytosis with noevidence of a clinical disease that could account for thesefindings is an indication for bone marrow evaluation.


ABNORMAL CIRCULATING CELLS The presence ofabnormal cells in the peripheral blood may be an indi-cation of neoplasia in the bone marrow and is an impor-tant indication for marrow evaluation. These may be inthe form of hematopoietic blast cells, such as lym-phoblasts or myeloblasts, or dysplastic cells. Dysplasia isdefined as an abnormal maturation of cells, usually asso-ciated with a preleukemia or leukemia. Some examplesof dysplastic changes are nucleated red blood cells withno evidence of polychromasia, abnormally largemetarubricytes, hypersegmented neutrophils, giantmetamyelocytes, megaplatelets, and dwarf megakary-ocytes. Other clinical conditions may cause dysplasticchanges in circulating cells in addition to leukemia orpreleukemia. Lead poisoning may cause circulatingNRBCs without polychromasia, and steroid administra-tion is the most common cause of hypersegmentation ofneutrophils. Additionally, the presence of nonhema-topoietic cells in the peripheral circulation may be anindication for bone marrow evaluation. The presence ofcells not normally found in circulation may suggestmetastasis of a neoplasm to the marrow. The classic, andprobably most common, example is the presence of mastcells in the blood of an animal with a mast cell tumor.

CLINICAL STAGING OF MALIGNANCY The absence of cir-culating neoplastic cells does not ensure the bonemarrow is free of metastatic disease. This is particularlytrue of animals with lymphoma. Therefore, a marrow


evaluation is necessary for clinical staging and prog-nosticating.

UNEXPLAINED HYPERCALCEMIA In the dog, hypercal-cemia is most often the result of a paraneoplastic syn-drome associated with a lymphoid neoplasia or an analsac apocrine gland adenocarcinoma. In cases of hyper-calcemia with no lymph node or anal sac involvement, abone marrow evaluation is of paramount importance.The majority of these animals have a lymphoid leukemiawhere only the bone marrow is involved. Circulatingtumor cells may not be found in the peripheral blood.

MONOCLONAL GAMMOPATHY Monoclonal gammopathyis due to an increased production of a single immuno-globulin. This usually results from uncontrolled growthof a clonal population of B-lymphocytes. In small ani-mals, monoclonal gammopathy is most often associatedwith lymphoproliferative disorders. Immunoglobulin-producing tumors include multiple myeloma, chroniclymphocytic leukemia, primary macroglobulinemia(Waldenström’s syndrome), and lymphoma. A bonemarrow aspirate is often needed to identify the neoplas-tic lymphocyte population.

Materials Needed

Bone marrow aspirates are performed using a sterile, 15-to 18-gauge Illinois sternal/iliac bone marrow aspiration


needle (Pharmaseal Division of Baxter Healthcare Corp.,Valencia, CA). For core biopsies, a Jamshidi biopsy nee-dle (11 gauge, 4 inches) should be used. Prior to aspira-tion of a sample, approximately 0.2 cc of anticoagulant(5% EDTA or heparin sulfate) is aspirated into a sterile12-cc syringe. A 2% lidocaine solution is needed for localanesthetic to the periosteum in patients not undergoinggeneral anesthetic. The marrow is deposited in a petridish or other clear glass surface to allow the peripheralblood contamination to be tilted away from the marrowparticles aspirated. The marrow particles adhere to thesurface of the petri dish, where they can be removed bycapillary action with a hematocrit capillary tube andtransferred to microscope slides for smearing. Diff Quikor another, comparable stain can be used to fix and stainthe air-dried smears.

Sample Collection

The hair is clipped and the bone marrow aspiration siteis prepared with a surgical scrub. Preferred sites andpatient positioning include dorsocranial or lateral aspectsof iliac crest (patient is sternal), greater trochanter of thefemur (patient is in lateral recumbency), and greatertubercle of the proximal aspect of the head of thehumerus (patient is in lateral recumbency).

Using a 25-gauge needle, approximately 2–3 ml localanesthetic agent, lidocaine, is injected in and around thesite where the bone marrow needle is to be introduced.


Care is taken to deposit lidocaine in and around all thetissues that extend from the skin to the bone.

The biopsy area is scrubbed a final time after thelidocaine is injected. A surgical drape may be applied forsterility.

The bone marrow site is identified, the skin isstretched between the thumb and index finger, and asmall stab incision is made with a number 11 surgicalblade in the area blocked with lidocaine. The bone mar-row needle with the stylette in place is advanced throughthe stab incision in the skin, subcutaneous tissue, andmuscle down to the bone. It is crucial to keep the stylettein place because it has a tendency to back out during theprocedure. A 1- to 1.5-inch long, 16-gauge Illinois orRosenthal bone marrow needle is preferred for dogs,and a 1-inch long, 18-gauge Illinois or Rosenthal needleis preferred for the cat. After a sample is obtained forcytologic evaluation, if a biopsy is required, a Jamshidineedle is utilized.

With the stylette in place, the bone marrow needle isadvanced into the bone using a corkscrew motion. Theinstrument should not be allowed to wobble but shouldbe fixed firmly into bone like a nail that has beensecurely hammered into wood. When the needle isfirmly fixed in the bone, the stylette is removed and thesyringe is affixed. Many clinical pathologists suggestrinsing the syringe and bone marrow needle with EDTAbefore the procedure to reduce clotting of the bone


marrow sample. The bone marrow sample then is aspi-rated briskly into the 12-ml syringe; usually, 1 ml is ade-quate. The aspiration may be accompanied with a fewseconds of pain, but this cannot be prevented. If a sam-ple is not obtained, the stylette is replaced in the bonemarrow needle and the instrument is advanced fartherinto the bone for a second attempt at aspirating marrowcontents.

Once marrow has been obtained, smears are pre-pared. The particle is blown onto one edge of a cleanmicroscope slide and a second slide is laid parallel atopthe first. The weight of the slide causes the material todiffuse out, leaving the particle in the center. The slidesare gently slid apart making an even smear with marrowparticles in the center of the slide. The slides are thenstained with Diff Quik or a comparable stain.

Bone Marrow Evaluation

Valuable information can be obtained from marrow eval-uation without advanced clinical pathology training.Interpretation of the bone marrow depends critically onthe findings of a concurrent CBC. For example, if an ani-mal has a high M:E ratio (more myeloid cells than ery-throid), the CBC results may determine if it is due to anerythroid hypoplasia or a myeloid hyperplasia. Theinterpretation depends on whether the animal has aperipheral anemia or a leukocytosis.


CELLULARITY The cellularity of the marrow is deter-mined by examining the relative amounts of fat and cel-lular material present in the marrow particles. Normalcellularity has approximately 50% cells and 50% fat;slightly more in young growing animals, and slightly lessin geriatric patients. Increased cellularity or hyperplasticmarrow (>75% cells) is seen in marrows responding toperipheral cytopenias (e.g., regenerative anemia, leuko-penia, or thrombocytopenia). This also is noted inanimals with an increased demand for leukocyte pro-duction (e.g., leukocytosis). Increased cellularity is alsoseen when the marrow is occupied by neoplastic cells(myelophthisic disease). Decreased cellularity (hypoplas-tic or aplastic marrow; >75% fat) is observed followinginsult or injury to one or more of the hematopoietic celllines. This may result in an aplastic anemia, where all celllines are decreased, or a cytopenia of only one or two ofthe different cell lines. Many infectious agents, drugs,hazardous materials, and immune-mediated diseases cancause hypoplastic or aplastic marrows. Unless previousexposure to drugs or infectious agents can be identified,most etiologies are undetermined and the disease is clas-sified as idiopathic.

MARROW IRON OR HEMOSIDERIN The bone marrow is amajor site for storage iron to be used in hemoglobin syn-thesis. Iron or hemosiderin appears as blue or black inclu-sions of amorphous material either in the background of


the smear or within the cytoplasm of marrow macro-phages. The presence or absence of stainable iron mustbe evaluated within a unit particle. The evaluation ofiron content in a marrow is significant only in anemicanimals. The evaluation of iron stores in the marrow ofdogs is a judgment call. If abundant stainable iron is seenwithin a unit particle, it is assumed to be increased. Inthe cat, stainable iron is normally not detected, so anyamount of visible iron would be an indication ofincreased iron stores. Marrow iron stores are increasedin the anemia of chronic inflammatory disease,hemolytic anemias, and in cases of decreased red cellproduction, such as red cell aplasia or aplastic anemias.Marrow iron stores are also increased in animals thathave received recent blood transfusions. Decreased stor-age iron is seen in cases of iron deficiency. In small ani-mals, this is associated almost exclusively with chronicblood loss. It should be noted that the absence of stain-able iron in the marrow of cats cannot be used as an indi-cation of iron deficiency, since stainable iron is notusually present in normal cats.

MEGAKARYOCYTES Megakaryocytes are the largest cellsin the bone marrow, easily recognized with the 10� or20� objective. Mature megakaryocytes have abundantamounts of pale blue cytoplasm that often contains fineeosinophilic granules. The cells appear to be multinu-cleated but actually contain a single, large, lobulated


nucleus. Immature megakaryocytes are smaller cells butare still at least two times larger than other hematopoi-etic precursors. They contain scant, deep blue cytoplasmand a round to slightly lobulated nucleus (four lobes orless). In normal marrow, the majority of the megakary-ocytes should be mature. Increased numbers of imma-ture cells are seen in a regenerative response toperipheral thrombocytopenias. One of the most com-mon and most useful reasons for a veterinarian to evalu-ate a bone marrow is to assess a patient with a peripheralthrombocytopenia. Megakaryocyte numbers in the mar-row allow classification of the disease as a production ora destruction problem. In a normal animal, one to threemegakaryocytes should be seen while examining themarrow particles on a low power objective (10�). If thepatient is responding to peripheral destruction or con-sumption of platelets, increased numbers of megakaryo-cytes are seen (megakaryocytic hyperplasia), some ofwhich are immature. This patient has a much betterprognosis and is more likely to respond to appropriatetherapy than one with a production problem, where fewto no megakaryocytes are found (megakaryocytichypoplasia).

ERYTHROID SERIES Erythroid precursors are character-ized by a round nucleus with dark, dense chromatin. Theimmature erythroid precursors (rubriblasts) are largecells with deep blue cytoplasm. They have a round


nucleus with clumped chromatin and one or morenucleoli. As these cells mature into rubricytes andmetarubricytes, they become smaller, the nucleusbecomes dark and pyknotic, and the cytoplasm changesfrom deep blue to gray. In normal marrow, the majority(>90%) of the erythroid precursors are mature cells,rubricytes, and metarubricytes. In normal marrow, thered cell series must mature all the way to anucleated,polychromatophilic erythrocytes (reticulocytes). If abone marrow aspirate is performed to evaluate a periph-eral anemia, we want to determine if we have an ery-throid hyperplasia or erythroid hypoplasia. Erythroidhyperplasia has increased numbers of erythroid precur-sors (M:E ratio of <1), in the presence of a peripheralanemia. This indicates the bone marrow is responding to a peripheral loss or destruction of erythrocytes.Increased numbers of rubriblasts may be seen, but thesecells should not exceed more than 10% of the totalnucleated cell population. Phagocytosis of erythroidcells by marrow macrophages may indicate an immune-mediated destruction or be seen in patients who havehad a recent blood transfusion. Erythroid hypoplasia, ordecreased numbers of erythroid precursors (M:E ratio of>2) in the presence of peripheral anemia, indicates thebone marrow is not responding. This suggests the ane-mia is due to an erythrocyte production problem or animmune-mediated destruction of erythroid precursors.


MYELOID SERIES Immature myeloid cells (myeloblasts)have round to irregularly shaped nuclei with one ormore nucleoli and paler cytoplasm than erythroid cells.The cytoplasm of these cells often contains fineeosinophilic granules (primary granules). The nucleicontain chromatin that is less clumped and more diffusethan the nuclei of the erythroid cells. In normal mar-row, the majority (>90%) of the myeloid cells are mye-locytes, metamyelocytes, bands, and segmentedgranulocytes. The neutrophil line is the most abundantcell type in the myeloid series. As the neutrophilsmature to myelocytes, metamyelocytes, bands, and seg-mented neutrophils, the cytoplasm changes from lightblue to clear, and the nucleus develops from beanshaped to banded to segmented. If the bone marrow isevaluated because of abnormal leukocyte numbers inthe peripheral blood, we want to determine if there is amyeloid hyperplasia or a myeloid hypoplasia. Myeloidhyperplasia, or increased numbers of myeloid precur-sors (M:E ratio of >2), in the presence of a peripheralleukocytosis or leukopenia is most consistent withmarrow responding to a peripheral demand for neu-trophils. This may be seen in a number of immune-mediated and inflammatory diseases. Increasednumbers of immature myeloid cells may be present;however, myeloblasts should not exceed more than 10%of the nucleated cell population, even in a stronglyregenerative response. Myeloid hypoplasia, or decreased


numbers of myeloid precursors (M:E ratio of <1), in thepresence of a peripheral leukocytosis or leukopenia,indicates decreased production of neutrophils by themarrow. This is particularly significant if the patient hasa peripheral neutropenia. A number of chemotherapeu-tic agents, drugs, and infectious agents may damage thebone marrow, resulting in myeloid hypoplasia.

LEUKEMIAS Leukemia is a bone marrow neoplasm ofthe hematopoietic cells. Leukemia may be classified as amyeloproliferative disease (erythroid, myelogenous, ormonocytic leukemia) or a lymphoproliferative disease(lymphoid leukemia), depending on the cell line fromwhich the neoplastic population arises. Leukemia also isclassified as acute or chronic, depending on the imma-turity of the neoplastic cell. In all types of leukemia, thebone marrow is hypercellular. In acute leukemia, theneoplastic cell is the blast cell or immature precursor.Acute leukemia is diagnosed whenever the blast cell pop-ulation of the marrow exceeds 30% of the nucleatedhematopoietic cells. Acute leukemia may involve any oneof the hematopoietic cell lines (erythroid, myelogenous,monocytoid, or lymphoid). Myeloproliferative diseases(erythroid, myelogenous, or monocytoid) may occasion-ally have two neoplastic cell lines occurring simultane-ously (e.g., myelomonocytic). In cases of acute leukemia,it may be difficult to determine which type of leukemiais present without the use of special cytochemical stains.


Therefore, whenever acute leukemia is diagnosed, extramarrow slides should be air dried and mailed to a refer-ence laboratory for classification. It is important to rec-ognize that not all leukemia patients have blast cells inperipheral circulation. Some patients may have“aleukemic” leukemia. In chronic leukemia, the neo-plastic cell is the mature blood cell (erythrocyte, granu-locyte, lymphocyte, monocyte, or platelet). Patients withchronic leukemia have an unexplained, marked eleva-tion of the affected cell line in the peripheral blood.With the exception of the chronic lymphocytic leu-kemia, the diagnosis is sometimes difficult because theneoplastic cells are mature and blast cells do not exceed30% of the bone marrow population. Finding dysplasticchanges in the hematopoietic cells in the peripheralblood or bone marrow may aid diagnosis (see the previ-ous discussion of dysplastic changes). Patients withchronic leukemia have a better short-term prognosisthan those with acute leukemia. In general, patients withlymphoid leukemia have a better prognosis with regardto survival time and response to therapy than patientswith the comparable myeloproliferative disorder (e.g.,acute lymphocytic leukemia vs. acute myelogenousleukemia). In lymphoid leukemia, hematopoietic celllines other than lymphoid are not involved in the neo-plastic process. Therefore, severe peripheral cytopeniasare not usually encountered except in advanced cases,where myelophthisic disease has occurred.


Biopsy GuidelinesWhen Should You Obtain a Biopsy?

A preoperative biopsy should be obtained if it willchange your choice of therapeutic modality or alter thedegree or extent of therapy you choose. For example, itis very important to know the tumor type prior to sur-gery of the appendicular skeleton. Soft tissue sarcomasare locally invasive, aggressive tumors that usuallyrequire radical margin resection, whereas lipomas arebenign and require only marginal resection. Pretreat-ment biopsies are also important if the knowledge that apet has cancer will change the owner’s willingness totreat the pet. Some owners are more willing to have theirpet undergo a radical surgery, such as an amputation, ifthey know that there would be a good chance for cure,such as in the case of a fibrosarcoma.

Some masses, due to their location within a body cav-ity, are difficult to biopsy preoperatively. For example,obtaining a representative sample of a splenic or a soli-tary lung mass usually requires an exploratory laparo-tomy or thoracotomy, respectively. In these particularexamples, the surgical removal of the mass is both diag-nostic and therapeutic. The surgical treatment in boththese examples would not have changed, even if thetumor type had been known prior to surgery.

Delaying obtaining a biopsy specimen until excisionis also a possibility if retreatment is an option. For


example, if a small skin mass on the trunk is excised withdirty margins, plenty of tissue is left for a second opera-tion without jeopardizing a cure with surgery. However,this would not necessarily be the same case with the samemass on the appendicular skeleton, where tissue for skinclosure is at a premium.

Tumors are not homogeneous tissue masses. Theycontain areas of inflammation, necrosis, and reactive tis-sue. In general, the larger are the tissue samples, the bet-ter the diagnostic yield. Care should be taken not tocreate an excessive crush artifact with the surgicalinstruments when handling the biopsy sample. Cauteryshould be avoided on the biopsy specimen, as it alters thetissue architecture and cellular morphology. Adherenceto aseptic technique reduces the chance of wound infec-tion; however, all biopsy sites should be monitoredclosely for signs of infection and inflammation. Delayedhealing at a tumor site may indicate wound infection ortumor regrowth.

Cancer and coagulation abnormalities often gohand in hand. Thrombocytopenia, disseminated intra-vascular coagulation, and increased heparin productionare the most common coagulation abnormalities seenwith cancer. A coagulation panel and buccal mucosalbleeding time should be evaluated in all suspect cancerpatients prior to an invasive biopsy procedure.

Good preoperative biopsy technique allows for exci-sion and radiation of all biopsy tracts during definitive


therapy. Gentle manipulation of the mass and the use ofsmall gauge needles for aspiration minimize tumor seed-ing. Despite a short-lived increase in cancer cells docu-mented within the efferent vessels and lymphatics ontumor manipulation, there is no real risk of distant tumormetastasis. When performing a surgical biopsy, blunt dis-section of the surrounding soft tissues should be mini-mized and accurate hemostasis should be employed toprevent unnecessary local tumor seeding within thewound. In addition, biopsy sites should never be drained.

Biopsy Needles

CUTTING NEEDLES Various biopsy needles can be usedfor percutaneous biopsy. In general, newer automatedneedles are preferred. These spring-loaded needles aresimilar in style to manual Tru-cut needles. Automatedneedles can be completely automatic or semiautomatic.Completely automatic needles thrust the inner obtura-tor (containing the biopsy tray or specimen notch) fol-lowed by the outer cutting sheath into the organ in afraction of a second. These needles can easily be oper-ated with one hand. Since the action is so quick, there isminimal displacement of the organ, a shorter intra-parenchymal phase, and much more reliable yield of tis-sue. This allows the organ to be biopsied with minimalmanual mobilization and allows use of a smaller diame-ter needle and a lighter degree of sedation. In addition,


extremely soft tissues (such as lung) tend to be less frag-mented by the rapid cutting action.

SEMIAUTOMATIC NEEDLES Semiautomatic needlesrequire manual thrusting of the internal obturator (con-taining the biopsy tray or specimen notch) into theorgan, followed by an automatic thrusting of the outercutting sheath by the spring-loaded mechanism. Theseneedles have some of the advantages of the completelyautomatic needles and the additional advantages ofmore control over the final needle position, lighterweight with a smaller handle, and precise localization ofthe needle tip before the outer cutting sheath is “fired.”The older, manual cutting needles offer no advantagesover these newer needles.

ASPIRATION NEEDLES Aspiration needles are generallyused to obtain smaller samples that would be suitable forcytologic preparations (rather than histopathology).These needles are also well suited to obtain samples offluid, such as intraparenchymal cysts, loculated effusions,gall bladder puncture, etc. Usually these are smallergauge needles (20–22 gauge) and therefore tend to beless traumatic.

Biopsy Methods

PUNCH BIOPSY Biopsy punches are disposable and avail-able in diameters ranging from 2 to 6 mm. Generally,


larger biopsies are preferred so the pathologist has ade-quate tissue to make a histologic diagnosis. When possi-ble, the junction between normal and abnormal tissueshould be biopsied. Punch biopsies are usually inade-quate to obtain tissue below the dermis; subcutaneousfat is rarely obtained in the average punch biopsy of theskin.

The hair is clipped and the surgery site preparedwith a surgical scrub. Using a 25-gauge needle, approxi-mately 2–3 ml of the local anesthetic agent lidocaine isinjected around the lesion. It is important to not distortor disturb, with lidocaine, the normal architecture of thetissue to be biopsied. The biopsy area is scrubbed a finaltime after the lidocaine is injected. The skin is stretchedbetween the thumb and index finger. The biopsy punchis placed at right angles to the skin surface. The punch isrotated in one direction while at the same time firmdownward pressure is applied until the subcutis isreached. The punch is then angled almost parallel withthe skin while still applying pressure along the long axisof the biopsy punch. The punch is rotated to sever thebase of the biopsied material. The punch is removed.The core of tissue is gently elevated with the point of aneedle and the base severed with a scalpel or iris scissors.One or two sutures are placed to close the defect.

INCISIONAL BIOPSY In some cases, an incisional biopsyis preferred over a punch biopsy because larger sectionsof tissue can be obtained for histologic diagnosis. In


addition, if the lesion is biopsied at the junction of thenormal and abnormal tissue, a “wedge” of tissue isobtained that retains a larger section of the tissue’s archi-tecture. This allows the histopathologist to better seecharacteristics of malignancy, such as invasion of normaltissue.

The animal is placed under general anesthesia afterroutine screening tests have been performed to identifyproblems such as coagulopathies and metabolic disease.The hair is clipped and the surgery site prepared with asurgical scrub. After the region is draped, an elliptical orwedge incision is made at the margin of the normal andabnormal tissue. Care is taken to obtain adequate tissueand ensure that a subsequent definitive surgery can suc-cessfully remove the tumor and the incisional biopsyincision. Vessels going to and from the tissue to be biop-sied are carefully identified and ligated. The specimen islifted and severed at the base with either a scissors or ascalpel blade. The incision is sutured for closure.

EXCISIONAL BIOPSY An excisional biopsy should be per-formed when tissue is required for a histologic diagnosis,but the lesion must be small enough and in an anatomiclocation that allows wide surgical removal without com-promising the normal tissue around it. In general, anexcisional biopsy is preceded with, at least, fine-needleaspirate cytology to give the surgeon as much informa-tion as possible about the characteristics of the tumorprior to removal. For example, a mast cell tumor or a soft


tissue sarcoma requires wide surgical margins (2–3 cm),whereas a sebaceous cyst or sebaceous adenoma couldbe treated with smaller margins.

This biopsy is performed in the same manner as anincisional biopsy except the lesion is excised completely,with adequate margins.

NEEDLE CORE BIOPSY Needle core biopsy is generallysafe and quick and can be performed on an awake, coop-erative patient. The histopathologic results are generallymore accurate than fine-needle aspirate cytology but notas accurate as excisional biopsy.

The lymph node is grasped by an assistant and heldfirmly against the overlying skin, and the biopsy site isprepared as noted earlier. Approximately 2–3 ml 2%lidocaine is injected under the skin overlying theenlarged lymph node. Using a number 11 surgical blade,a stab incision is made in the skin to allow ease of entryof the needle core biopsy instrument. The needle corebiopsy instrument is advanced through the incision andinto the capsule of the enlarged lymph node for subse-quent biopsy. At least three to five biopsies are taken ofthe lymph node through the same stab incision. Theneedle biopsy specimens are fixed in 10% buffered for-malin as described already. A separate container shouldbe used for each lesion biopsied. The stab incision issutured only if indicated.


LYMPH NODE BIOPSY Lymph node biopsy is oftenimportant in the diagnosis, staging, and proper thera-peutic management of the pet with cancer. A biopsy isoften performed after fine-needle aspirate cytology sug-gests the presence of a disease. Despite the accuracy offine-needle aspirate cytology in determining certain dis-eases such as lymphoma, mast cell tumors, and the pres-ence of metastatic solid tumors, a histopathologicdiagnosis is always recommended prior to initiation oftherapy. In each case, adequate tissue must be obtainedfor histopathologic diagnosis and special stains, if indi-cated. When possible, the submandibular lymph nodesshould be avoided; they often are reactive in the normalanimal because they drain the oral cavity, where the bac-terial count is usually quite high. These reactive cells aresometimes misdiagnosed as neoplastic cells. If a carci-noma or a sarcoma is suspected, a biopsy should not beperformed unless an overall plan for definitive therapy ismade because the biopsy procedure can “seed” the oper-ative field with tumor cells if the principle of en bloc dis-section is violated. As with all biopsies, the surgeon whowill perform the definitive surgery should be consultedprior to the biopsy to ensure that incisions are properlyplaced for a subsequent definitive procedure.

Biopsy Specimen Handling Considerations

Punch biopsy specimens should be removed from theforceps with the utmost of care. These minute specimens


are readily subject to crush and squeeze artifact, particu-larly before fixation. Specimens should be teased fromthe forceps with a needle and gently placed on lenspaper or specially designed biopsy sponges presoaked informalin. Attempts to reorient specimens on the surfacesshould be avoided. After all specimens are placed on asuitable surface, the biopsies are immersed in formalinand submitted to the laboratory. Fixation in 10% neutralbuffered formalin is adequate for routine histologicexamination. Glutaraldehyde fixation is optimal forspecimens for electron microscopic examination. Freshfrozen tissue (e.g., via liquid nitrogen) may be requiredfor immunohistochemical studies of certain antigens.

Diagnostic Imaging As in human medicine, veterinary medicine has shownan increasing trend toward noninvasive procedures todiagnose many different types of the neoplasia, whetherprimary or metastatic. In response to this need andtechnologic advances, radiology has evolved to includemany different forms of imaging in nuclear medicine,color flow and power doppler ultrasonography, and mag-netic resonance imaging (MRI).

Plain Film Survey Radiography

Despite new advances, plain film radiographs remain thestandard. The radiograph is not intended to serve as a


shortcut diagnosis or take precedence over a thoroughphysical examination. It provides information about dis-ease location, type, and extent; supplements findingsfrom the database; and helps formulate and integratetreatment strategies. Radiographic interpretation mustbe consistent and thorough. Procedurally, the clinicianshould assess the radiographic technical quality, checkfor artifacts, evaluate extrathoracic structures (spine,ribs, soft tissue), analyze thoracic organs and structures(trachea, heart, lungs), assess breed-specific anatomicvariations, and correlate areas of concern or suspicionwith the database, including physical examination, ECG,clinical pathology, echocardiogram, and other imagingtechniques.

Nuclear Medicine

Nuclear medicine techniques have been used extensivelyin humans to diagnose various forms of cancer. In fact,nuclear oncology is one of the most promising fields, asnew, tumor-specific radiopharmaceuticals are introducedwith increasing frequency. Veterinary nuclear medicine isbeing used clinically to help diagnose the presence of pri-mary bony and soft tissue tumors as well as in the stagingof potential metastatic disease. The thyroid scan usingeither 99m TcO4 or 123I have been used to evaluate suspectthyroid adenocarcinomas in both dogs and cats.Although a thyroid scan cannot differentiate benign ver-sus malignant disease, it is helpful as a screening tool.


Benign hyperfunctional thyroid glands have round oroval shapes and homogeneous uptake with intense cen-ters and tapering margins. “Hot nodules” or dumbbell-shaped glands are common, as is benign ectopic thyroidtissue. Glands that have irregular shapes and heteroge-neous uptake with multiple photopenic areas and evi-dence of extension (invasion) into adjacent fascialplanes are suggestive of a malignant tumor. Thyroidscans can also be useful in diagnosing distant metastaticdisease to the lungs or bone. Thyroid scans have provento be useful in predicting the ease of which a tumor canbe surgically removed or debulked, by providing an esti-mate of peritumoral invasion.

Bone scans are used with increasing frequency toevaluate possible bony metastatic disease. Although thefrequency of skeletal metastasis from primary bonetumor is low, the presence of metastatic disease maygreatly alter the treatment plan or the owner’s decisionto treat at all. The incidence of metastatic disease tobone from other types of tumors has not been evaluatedextensively. It is known, however, that prostatic and mam-mary gland adenocarcinomas, as well as transitional cellcarcinomas, may metastasize to the bone. Bone scanningis the most sensitive and economical way to evaluate thispossibility.

Gallium (67 Ga) has been used in humans to detectlocal recurrences of primary soft tissue sarcomas as wellas define the presence of regional metastasis. Tumortypes evaluated in humans include leiomyosarcomas,


mesotheliomas, schwannoma, rhabdomyosarcoma,fibrosarcoma, liposarcoma, and synovial cell sarcoma.The 67 Ga appears to be specific for active malignant sar-comatous tissue and can differentiate benign fibrous(scar) tissue from active tumor tissue. In this regard, 67Ga appears to diagnose primary soft tissue fibrosarcomasand demonstrate regional metastatic “skip” lesions, guid-ing the surgeon for more complete surgical removal aswell as diagnose early recurrence. The uptake in thesetumors does not appear altered by previous radiation,chemotherapy, or soft tissue surgery. All sarcomatous tis-sue seen had marked, heterogeneous uptake and mostlypoorly defined margins.

Ultrasonography

Ultrasound is used extensively to evaluate intra-abdominal, intracardiac and heart base neoplasia. Simi-lar to many forms of nuclear scintigraphy, ultrasound isvery sensitive but in many cases rather nonspecific. Ultra-sound is especially sensitive when there is nodular ormultinodular disease, where the nodules have differentacoustic properties than the surrounding tissue paren-chyma. It is much less sensitive in diagnosing diffuse dis-eases, such as mast cell tumors or lymphosarcoma.Ultrasound-guided aspirates and Tru-cut biopsies havebecome the method of choice for obtaining tissue sam-ples for cytologic or histologic diagnosis. The advantagesof ultrasound-guided tissue sampling are many and


include minimal morbidity, the ability to sample specificnodules and normal tissue, and the ability to samplenodules located deep within an organ. The disadvan-tages include limited tissue sample volume.

Color flow doppler ultrasound has been investigatedin many types of tumors to evaluate increased blood flowand abnormal arteriovenous shunting. Recently, an alter-native to the display of frequency information with colorflow doppler imaging is to use a color map that displaysthe integrated power of the doppler signal instead of itsmean frequency shift. The result is an absence of alias-ing. The image gives no information regarding the direc-tion of flow or velocity and is much less angle dependentthan frequency-based color flow imaging, where noisefrom vessel wall movements may add to the displayedinformation. This form of doppler is referred to as powerdoppler. The resultant image permits higher effectivegain settings for flow detection and increased sensitivityfor flow detection and is especially useful for evaluatingslow flow.

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is commonly used todiagnose many forms of neoplasia that, due to location,are difficult to evaluate using other modalities. Examplesinclude brain and brain stem neoplasia, spinal cordtumors, and adrenal tumors. MRI has proven helpful indemonstrating the size, shape, and amount of local tis-


sue invasion. For nasal adenocarcinomas, it is muchmore sensitive than even high-quality radiographs inevaluating the extent of disease. It has been shown to besuperior to computed tomography (CT) in determininginvasion into the rostral brain. It is also felt to be superiorto CT in differentiating tumor tissue versus trapped fluidin the frontal sinus. CT, on the other hand, is consideredmore sensitive than MRI in evaluating bony lysis second-ary to tumor invasion. MRI cannot differentiate amongtypes of primary brain neoplasia; but based on thetumor’s location, amount of signal intensity on T1, T2,proton density, and contrast-enhanced T1 images, aneducated guess can often be made.


3Tumor Tidbits

Acute Lymphoid Leukemias in Dogs and Cats

Common Clinical Rapid onset of anorexia and Signs: weight loss; lymphadenopathy is

common.Common Lymphocytosis >20,000 Histologic Types: cells/μl whole blood; predomi-

nantly lymphoblasts; difficult todifferentiate from lymphoma.

Biological Behavior: May occur at any age; large breeddogs or young cats; most cats areFeLV antigenemic.

Prognostic Findings: None identified.

65

Treatment Supportive treatment—antibiotics Considerations: and transfusions of blood and

blood products.Chemotherapy—consider usingprednisone and Elspar to initiallydecrease malignant cell counts,then follow using a combinationdrug protocol (see protocols 6 and7; protocols are outlined in Chap-ter 7) and anticipate a 60–70%remission rate for a median dura-tion of 7–9 months.

Acute Nonlymphoid Leukemia in Dogs and Cats

Common Clinical Nonspecific; rapid onset of Signs: inappetence and lethargy; clinical

signs reflect cytopenias;hepatosplenomegaly.

Common Not clinically relevant to Histologic Types: distinguish because of poor prog-

nosis, but terminology includesacute myeloid (granulocytic),myelocytic, promyelocytic,monocytic, monoblastic,myelomonocytic, megakaryocytic,and erythroleukemic;

66 Tumor Tidbits

myelomonocytic is the most com-mon type.

Biological Behavior: May occur at any age; female dogsor young cats; FeLV antigenemiain 90% or more of cats; rapidlyprogressive; organ infiltration iscommon.

Prognostic Findings: None identified.Treatment Supportive treatment—antibiotics Considerations: and transfusions of blood and

blood products.Chemotherapy—no real efficacyof chemotherapy in this disease,aggressive chemotherapy oftencauses marrow ablation and death.

Anal Sac AdenocarcinomaCommon Clinical Dyschezia, perianal mass, and Signs: polyuria and polydipsia due to

hypercalcemia.Common Adenocarcinoma.Histologic Types:Biological Behavior: Old, female dogs; production of

parathyroid hormone-related pro-tein causes hypercalcemia; metas-tasis to regional lymph nodes iscommon.

Tumor Tidbits 67

Prognostic Findings: Dogs with hypercalcemia or withdetectable metastases have shortersurvival times.

Treatment Surgery—may require local Considerations: excision of tumor and sublumbar

lymph nodes; surgery usuallyresolves hypercalcemia.Radiation therapy—applied tolocal tumor site and sublumbarnodes to prevent tumor regrowth;may resolve hypercalcemia.Chemotherapy—may be useful asan adjunct to surgery or radiationtherapy; consider cisplatin,Adriamycin, or mitoxantrone (seeprotocols 1–4).

Bone Tumors in CatsCommon Clinical Lameness for appendicular tumorsSigns: (60% of tumors); palpable mass

for axial tumors, which most com-monly affect the head; primarilylytic lesions.

Common Osteosarcoma.Histologic Types:Biological Behavior: Old cats; no obvious gender

predilection; metastatic rate is low.

68 Tumor Tidbits

Prognostic Findings: None identified.Treatment Surgery—potential for cure if Considerations: surgery eliminates all tumor (e.g.,

amputation).Radiation therapy—seems toimprove local control of osteo-sarcoma.Chemotherapy—not reported.

Brain Tumors in CatsCommon Sudden-onset visual deficits and Clinical Signs: neurologic dysfunction.Common Meningioma.Histologic Types:Biological Behavior: Old cats (75% >9 years of age);

locally invasive, rare metastases.Prognostic Findings: None identified.Treatment Surgery—treatment of choice due Considerations: to slow regrowth of meningioma.

Radiation therapy—may be usefuladjunct to incomplete excision.

Brain Tumors in DogsCommon Seizures and temperament Clinical Signs: changes.

Tumor Tidbits 69

Common Meningioma.Histologic Types:Biological Behavior: Mixed breeds and boxers; old

dogs (10 years of age and older);slight male predilection; locallyinvasive, rare metastases.

Prognostic Findings: Worse prognosis with severe neu-rologic dysfunction, abnormalcerebrospinal fluid, or multipletumors.

Treatment Palliation—corticosteroids and Considerations: anticonvulsants.

Surgery—may be beneficial formeningiomas.Radiation therapy—treatment ofchoice for gliomas; useful alone oras an adjunct to surgery formeningiomas.Chemotherapy—hindered byblood-brain barrier; possible rolefor carmustine and lomustine.

Cardiac Hemangiosarcoma in DogsCommon Collapse and cardiac tamponade; Clinical Signs: hind limb paresis; and right atrial

mass.

70 Tumor Tidbits

Common Hemangiosarcoma.Histologic Types:Biological Behavior: Average age is 10 years; German

shepherds are predisposed; metas-tasis may be widespread, commonto lungs.

Prognostic Findings: None identified.Treatment Surgery—palliative in dogs with Considerations: resectable lesions.

Chemotherapy—considerAdriamycin-based protocols (seeprotocol 1).

Chronic Lymphocytic Leukemia in DogsCommon Nonspecific; often asymptomatic.Clinical Signs:Common Mature lymphocytosis; differenti-Histologic Types: ate from reactive lymphocytosis

and well-differentiated lymphoma.Biological Behavior: Old dogs; often slow to progress.Prognostic Findings: None identified.Treatment Supportive treatment—repeated Considerations: monitoring by blood counts may

be all that is required for asympto-matic animals.

Tumor Tidbits 71

Chemotherapy—combined use ofprednisone and an alkylatingagent (Cytoxan, melphalan, orLeukeran) provides long-termremissions in symptomatic dogs.

Cutaneous and Extramedullary Plasmacytomas in Dogs

Common Clinical Solitary cutaneous mass in trunkSigns: or limbs; may affect oral cavity,

ears, and head; less commonly,may occur in multiple or othersites, such as diffuse gastrointesti-nal (GI) tumors.

Common Mature plasma cells.Histologic Types:Biological Behavior: Old dogs; cutaneous tumors are

usually benign; plasmacytoma ofother sites (e.g., GI) may metasta-size.

Prognostic Findings: None identified.Treatment Surgery—surgery with wide surgi-Considerations: cal margins is curative in most

cases of cutaneous plasmacytoma.Radiation therapy—radiation-sensitive tumor.

72 Tumor Tidbits

Chemotherapy—melphalan, pred-nisone, and doxorubicin havecaused tumor responses, often fora long duration in dogs withextramedullary plasmacytoma.

Cutaneous Hemangiosarcoma in DogsCommon Raised, red lesion, often in skinClinical Signs: that is lightly pigmented.Common Hemangiosarcoma.Histologic Types:Biological Behavior: Average age is 10 years; whippets

and other dogs with glabrous skinare predisposed; metastasis isuncommon.

Prognostic Findings: Histopathologic evidence of solarelastosis adjacent to tumor is goodprognostic sign.

Treatment Surgery—curative for dermalConsiderations: origin tumors; approximately 30%

of subcutaneous origin tumorsmetastasize.Radiation therapy—radiation-sensitive tumor; excellent localcontrol for incompletely excisedtumors.

Tumor Tidbits 73

Chemotherapy—role undecideddue to low metastatic rate andresultant lack of need for adjuvanttherapy.

Cutaneous Melanoma in DogsCommon Darkly pigmented epidermalClinical Signs: lesion, usually raised but not

ulcerated.Common Most are well differentiatedHistologic Types: (benign); subungual tumors are

more aggressive.Biological Behavior: Adult to aged dogs.Prognostic Findings: Subungual melanoma, 50% metas-

tasize; other cutaneous sites,metastasis is rare.

Treatment Surgery—surgical excisionConsiderations: curative for most cutaneous lesions

Radiation therapy—radiation-sensitive tumor; >85% localcontrol rates observed for 2 yearsor longer.Chemotherapy—cisplatin orcarboplatin chemotherapy formetastatic lesions or possibly as an

74 Tumor Tidbits

adjunct to surgery in subungualmelanoma; see protocol 5.

Cutaneous Squamous Cell Carcinoma in Cats

Common Ulcerated cutaneous lesions, mostClinical Signs: often on head and neck.Common Most are well differentiated;Histologic Types: metastasis to regional lymph nodes

is rare.Biological Behavior: Cats lacking skin pigment are

prone to actinically inducedtumors; tumors are locally invasivewith a low metastatic rate.

Prognostic Findings: None identified.Treatment Early lesions—brachytherapy,Considerations: radiation therapy, local current-

field hyperthermia, photodynamictherapy, and cryotherapy if lesionsare <1 cm.Invasive lesions—external beamradiation therapy, surgery, photo-dynamic therapy, and intralesionalchemotherapy may be considered.Chemotherapy—anecdotal reportsof bleomycin have shown efficacy.

Tumor Tidbits 75

Cutaneous Squamous Cell Carcinoma in Dogs

Common Ulcerated cutaneous lesions, mostClinical Signs: often on limbs (digits); lesions

may be induced by sunlight ontrunk.

Common Most cutaneous squamous cellHistologic Types: carcinomas are well differentiated

and rarely metastasize.Biological Behavior: Large, black-breed dogs are prone

to subungual tumor, which maymetastasize; light-skinned dogs areprone to actinically inducedtumors.

Prognostic Findings: Nasal-plane tumors more aggres-sive; subungual and skin tumorsmay metastasize; lymphatic inva-sion for subungual lesion does notinfluence prognosis for survival.

Treatment Early lesions—surgical excision,Considerations: retinoids, topical 5-fluorouracil or

carmustine ointments, andcryotherapy if lesions are <1 cm.Invasive lesions—surgery, with orwithout radiation therapy andintralesional chemotherapy.

76 Tumor Tidbits

Metastatic lesions—cisplatin ormitoxantrone chemotherapy.

Erythrocytosis in Dogs and CatsCommon Polyuria, polydipsia, bleeding,Clinical Signs: seizures, and hyperemic mucous

membranes.Common Mature erythrocytosis; rule outHistologic Types: relative and secondary poly-

cythemia.Biological Behavior: Middle-aged animals; no breed

predilection; bleeding and seizuresdue to hyperviscosity; elevated redcell mass with no increase in ery-thropoietin.

Prognostic Findings: None identified.Treatment Phlebotomy—periodic removalConsiderations: eventually induces iron deficiency

and microcytic cells that may assistin palliation.Chemotherapy—hydroxyurea hasshown efficacy giving long remis-sion durations.

Tumor Tidbits 77

Pancreatic Tumors (Exocrine) in DogsCommon Nonspecific anorexia and weightClinical Signs: loss.Common Exocrine pancreatic carcinoma.Histologic Types:Biological Behavior: Old dogs (mean age is 9 years);

cocker spaniels may be predis-posed; high metastatic rate.

Prognostic Findings: None identified.Treatment Surgery—may not be beneficialConsiderations: due to high metastatic rate.

Chemotherapy—anecdotal reportsof Gemzar efficacy in dogs.

Hemangiosarcoma in CatsCommon Intraabdominal and cutaneousClinical Signs: tumors occur with similar fre-

quency as in dogs.Common Hemangiosarcoma.Histologic Types:Biological Behavior: Cutaneous hemangiosarcoma may

be sunlight induced in areas ofunpigmented skin.

Prognostic Findings: Hemangiosarcomas of spleen andmesentery are highly metastatic;

78 Tumor Tidbits

tumors of skin are highly recur-rent and >50% develop metastasis.

Treatment Surgery—excision of cutaneousConsiderations: tumors is reported to be curative

by some if margins are wide; sur-vival <6 months reported by othersregardless of surgical procedure.Radiation therapy—radiation-sensitive tumor; prognosis guardeddue to metastatic behavior.Chemotherapy—unproven butconsider protocol 7.

Hyperadrenocorticism in DogsCommon Hypercortisolism, polydipsia,Clinical Signs: polyuria, and cutaneous changes;

nervous system dysfunction withlarge pituitary tumors.

Common Pituitary adenomas of par distalisHistologic Types: in 80% of dogs; less commonly,

adrenal gland tumors (usuallycarcinoma).

Biological Behavior: Middle-aged to old dogs; poodles,dachshunds, and boxers are athigher risk; no gender predilec-tion; metastasis is rare for pituitary

Tumor Tidbits 79

tumors but common for adrenaltumors.

Prognostic Findings: None identified.Treatment Surgery—treatment of choice forConsiderations: adrenal tumors.

Medical management—for pitu-itary tumors, mitotane and keto-conazole offer good long-termpalliation by their effects of adre-nal cortical destruction and inter-ference with steroid synthesis,respectively; L-deprenyl may alsobe a useful agent; mitotane (o,p’-DDD) may be a useful agent athigh doses for adrenal tumors.Radiation therapy—provides goodpalliation for neurologic dysfunc-tion caused by large pituitarytumors and gives moderatecontrol of cortisol levels.

Hypereosinophilic Disease in CatsCommon Gastrointestinal signs due toClinical Signs: eosinophilic infiltration; often

chronic history.

80 Tumor Tidbits

Common Mature eosinophilia; rule outHistologic Types: allergic diseases and eosinophilic

granuloma complex.Biological Behavior: Adult cats (median age is 8 years);

females may be predisposed; catsmay have widespread organinfiltration.

Prognostic Findings: None identified.Treatment Prednisone and hydroxyurea mayConsiderations: be palliative, consider dietary modi-

fication using hypoallergenic diets.

Injection Site–Associated Sarcomas in CatsCommon Mass near site of previousClinical Signs: vaccination.Common Fibrosarcoma or other soft tissueHistologic Types: sarcoma; other histologic types

have been reported (malignantfibrous histiocytoma).

Biological Behavior: Tumor develops months to yearsafter vaccination; multiple vaccina-tions at the same site at one timeincrease risk of tumor develop-ment; locally aggressive; frequentrecurrence after surgery; rare dis-tant metastasis.

Tumor Tidbits 81

Prognostic Findings: None identified.Treatment Surgery—treatment of choice;Considerations: wide and deep surgical margins

are essential for all tumors.Radiation therapy—should be con-sider prior to surgical excision toreduce tumor burden and providegreater local control.Chemotherapy—unproven efficacyalone but should be consideredconcurrently with radiation ther-apy; consider Adriamycin ormitoxantrone (see protocols 4, 7,and 10).

Insulinoma in DogsCommon Hypoglycemia and hyperinsuline-Clinical Signs: mia; tachycardia and neurologic

signs may be intermittent; periph-eral polyneuropathy may causetetraparesis.

Common Carcinoma.Histologic Types:Biological Behavior: Old dogs with no gender predispo-

sition; large-breed dogs are morecommonly affected; most tumorsare highly metastatic.

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Prognostic Findings: Dogs with tumors confined to pan-creas have a longer symptom-freeperiod and survival after surgery;dogs that have only lymph nodemetastasis live longer than dogswith distant metastasis.

Treatment Surgery—treatment of choice forConsiderations: localized tumors.

Medical management—prednisone, diazoxide, Sando-statin, octreotide, and propranololmay control hypoglycemia.Chemotherapy—streptozotocinand alloxan may be effective; how-ever, both are extremely nephro-toxic and require diuresis.

Intestinal Tumors in CatsCommon Small intestine—vomiting, weightClinical Signs: loss, and anorexia.

Large intestine—hematochezia.Common Adenocarcinoma; other tumorsHistologic Types: are rare.Biological Behavior: Old cats; mean age is 11 years;

Siamese are predisposed; tumorsusually cause annular constriction;

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and metastasis to peritoneal sur-faces is common.

Prognostic Findings: None identified.Treatment Surgery—surgical resection resultsConsiderations: in 15-month average survival;

some cats live more than 2 years;lymph node metastasis at surgerydoes not always influence survival.Chemotherapy—unproven effecton survival but consider protocol10 as adjunctive to excision orprotocol 7 if surgery cannot beperformed.

Intestinal Tumors in DogsCommon Duodenum/jejunum—vomiting,Clinical Signs: melena.

Jejunum/ileum—weight loss anddiarrhea.Colon/rectum—tenemus andhematochezia.

Common Adenocarcinoma; less commonly,Histologic Types: leiomyosarcoma and lymphoma;

leiomyosarcoma common in thececum.

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Biological Behavior: Old, male dogs; most tumors areadenocarcinoma; adenocarcinomais more likely to metastasize thanleiomyosarcoma, usually toregional lymph nodes.

Prognostic Findings: Colorectal—dogs with annularlesions have poor chance of sur-vival; other types of lesions have abetter prognosis.

Treatment Surgery—little information forConsiderations: adenocarcinoma; average survival

of dogs with colorectal adenocarci-noma is 15 months after surgery;median survival is >1 year forleiomyosarcoma.Radiation therapy—rectal adeno-carcinoma may be controlled byhigh-dose fractions; median con-trol is >6 months.Cryotherapy—small, minimallyinvasive tumors of the rectum anddistal colon.Chemotherapy—consider adjunctto surgery or radiation therapy;consider protocol 1, 2, or 4.

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Liver Tumors in CatsCommon Nonspecific lethargy and anorexia;Clinical Signs: cats often have a palpable mass.Common Intrahepatic bile duct tumorsHistologic Types: (more than half are benign);

hepatocellular carcinoma is nextmost common type.

Biological Behavior: Most cats >10 years of age; intra-hepatic bile duct tumors mayprogress from benign to malig-nant; benign tumors usuallyinvolve a solitary lobe; carcinomasoften metastasize.

Prognostic Findings: None identified.Treatment Surgery—treatment of choice forConsiderations: benign tumors; however, carcino-

mas are usually diffuse and prog-nosis is poor.Chemotherapy—rarely considereddue to hepatic insufficiency tometabolize anticancer agents.

Liver Tumors in DogsCommon Nonspecific lethargy and weightClinical Signs: loss; dogs may be asymptomatic

and may have a palpable mass.

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Common Primary hepatocellular carcinoma.Histologic Types:Biological Behavior: Old dogs; large solitary lesions

have low metastatic rate, but themajority have multiple nodular ordiffuse involvement.

Prognostic Findings: None identified.Treatment Surgery—treatment of choice;Considerations: dogs with solitary hepatocellular

carcinoma, regardless of size, havea good prognosis after resection(median survival exceeds 1 year).Chemotherapy—palliative use ofalkylating agents (Cytoxan andLeukeran) have been beneficial indogs with diffuse or nodulardisease.

Lower Urinary Tract Tumors in CatsCommon Hematuria, mucoid vaginalClinical Signs: discharge, and other signs of blad-

der inflammation.Common Transitional cell carcinoma,Histologic Types: squamous cell carcinoma.Biological Behavior: Old cats, except lymphoma and

rhabdomyosarcoma.

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Prognostic Findings: None identified.Treatment Surgery—recurrence is commonConsiderations: unless surgery is aggressive; cats

are more amenable to surgerythan dogs, because tumors aremore cranioventral in location.Chemotherapy—may be helpful;consider protocol 4 for carcino-mas and protocol 6 or 7 forlymphoma.

Lower Urinary Tract Tumors in DogsCommon Mimic infection—hematuria,Clinical Signs: stranguria, and pollackiuria; dogs

often have secondary infections.Common Transitional cell carcinoma.Histologic Types:Biological Behavior: Old dogs, usually female; insectici-

dal dips and obesity may be associ-ated with development of bladdertumors.

Prognostic Findings: None identified.Treatment Surgery—palliative only; mostConsiderations: tumors involve trigone region of

the bladder.

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Radiation therapy—excellent localcontrol; however, fibrosis of blad-der may occur as a late effect.Chemotherapy—palliative at best,should be consider adjuvant tosurgery or radiation; best resultsare seen with mitoxantrone com-bined with piroxicam (protocol 4)followed by carboplatin orpiroxicam.

Lung Tumors in Dogs and CatsCommon Persistent cough, dyspnea,Clinical Signs: hemoptysis, lameness in cats

(metastasis to digits), hypertrophicosteopathy (in dogs), anorexia,lethargy, and malaise.

Common Adenocarcinoma (bronchogenic)Histologic Types: is most common.Biological Behavior: Disease of older aged animals;

tumors are likely to cause pleuraleffusion and respiratory stridor;metastases are common early inthe course of the disease.

Prognostic Findings: Normal appearing hilar regionallymph nodes are associated withsignificantly longer survival time

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following surgery than enlargednodes; effusion, increasing size,and presence of metastases arealso negative prognostic signs.

Treatment Surgery—lung lobectomy is theConsiderations: treatment of choice in dogs and

cats without effusive disease;median survival exceeds 1 year.Chemotherapy—unproven results,consider protocols 1–3 or 10 adju-vant to surgery due to the highmetastatic potential for lungtumors.

Lymphoma in CatsCommon Anterior mediastinal or alimentaryClinical Signs: involvement.Common Typically mixed B and T cell.Histologic Types:Biological Behavior: Often FeLV positive but depends

on anatomic location of lym-phoma; occurs in all breeds with abimodal age peak.

Prognostic Findings: Single nodal (mediastinal) orextranodal (nasal) location stagebetter than multiple locations.

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FeLV positive—worse survival rate,no effect on response to therapy.

Treatment Surgery—considered only forConsiderations: localized conditions (intestinal).

Radiation therapy—extremelyradiation-sensitive tumor; considerfor curative intent for nasallocations.Chemotherapy—consider proto-cols 6 and 7 as primary therapy oradjunct to surgery or radiationtherapy; median survival typicallyranges from 6–12 months (medi-astinal) to >18 months (nasal or ifradiation or surgery used).

Lymphoma in DogsCommon Generalized peripheralClinical Signs: lymphadenopathy.Common Diffuse large cell, immunoblastic,Histologic Types: and small lymphocytic.Biological Behavior: All breeds, middle-aged, systemic

disease.Prognostic Findings: Clinical stage—advancing stage

and dogs with clinical signs areassociated with a worse prognosis.

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Hypercalcemia—worse when asso-ciated with an anterior mediastinalmass.Sex—female dogs have a betterprognosis than male dogs.Body size—small dogs do betterthan large dogs.Pretreatment corticosteroids:worse (controversial findings).High grade: higher response rateand longer duration of remission.

Treatment Surgery—rarely considered unlessConsiderations: confined to a single node.

Radiation therapy—unproven effi-cacy; considered in the palliativecare of multidrug-resistant lym-phoma (4–6 months additionalremission).Chemotherapy, single agent—prednisone, cyclophosphamide,vincristine show 50% completeremission (CR) for a median of1–6 months; doxorubicin shows60–75% CR for a median of 6–8months.Chemotherapy, combinations—various usages of multiple drugsshow 70–80% CR for a median of

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9–18 months (see protocols 6 and 7).

Mammary Tumors in CatsCommon Presence of a mass in theClinical Signs: mammary chain.Common Mammary adenocarcinoma.Histologic Types:Biological Behavior: Siamese may be at increased risk;

most affected cats are 10–12 yearsof age; 70–90% of tumors aremalignant; >25% are ulcerated;>50% involve multiple glands;>80% have metastases at time ofeuthanasia.

Prognostic Findings: Increasing tumor size is associatedwith a poor prognosis.

Treatment Surgery—mastectomy of theConsiderations: affected side is superior to

regional resection; recurrence isunlikely to be reduced by ovario-hysterectomy; recurrence of tumorshould be treated with surgerywhenever possible.Radiation therapy—rarely consid-ered due to excessive local diseaseand metastatic behavior.

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Chemotherapy—doxorubicin andcyclophosphamide reported toreduce metastatic disease; mitox-antrone may be helpful in somecases (see protocols 2, 4, and 7).

Mammary Tumors in DogsCommon Presence of a mass in theClinical Signs: mammary chain.Common Approximately 50% are benignHistologic Types: (e.g., fibroadenomas, simple ade-

nomas, and benign mixed mam-mary tumors); approximately 50%are malignant (e.g., solid carcino-mas and tubular or papillaryadenocarcinomas).

Biological Behavior: Most common neoplasm infemales; average age is 10–11years; poodles, terriers, cockerspaniels, and German shepherdsare overrepresented; early ovario-hysterectomy protective; 50% oftumors are multiple; lungs andlymph nodes are most commonsites of metastasis.

Prognostic Findings: German shepherds have a poorprognosis; poor prognosis is

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associated with increasing tumorsize, ulceration, degree of inva-sion, increasing degree of malig-nancy, lymph node involvement,and lack of hormone receptors.

Treatment Surgery—regional resection ofConsiderations: tumor is as effective as mastectomy

for localized tumor(s); removal oflymph node may be of prognosticvalue; ovariohysterectomy may notbe of value for preventingrecurrence.Radiation therapy—unprovenefficacy; may be considered in thepalliation of inflammatorycarcinomas.Chemotherapy—doxorubicin- ormitoxantrone-based protocols maybe effective in some cases (seeprotocols 1, 2, 4, and 7).

Mast Cell Tumors in CatsCommon Cutaneous—single or multipleClinical Signs: raised hairless masses.

Lymphoreticular—splenomegalyand chronic vomiting.

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Intestinal—chronic vomiting ordiarrhea.

Common Cutaneous tumors are usually wellHistologic Types: differentiated; lymphoreticular

and intestinal tumors aremalignant.

Biological Behavior: Histiocytic cutaneous mast celltumors in Siamese may regressspontaneously; lymphoreticularand intestinal tumors are alwaysmalignant; cutaneous tumors areoften benign, even multipletumors; may occur in younganimals.

Prognostic Findings: None identified.Treatment Cutaneous—surgery, radiationConsiderations: therapy, with or without corticos-

teroids, for invasive lesions.Lymphoreticular—splenectomygives 12-month median rate ofsurvival.Intestinal: wide resection, with orwithout corticosteroids, but sur-vival is poorChemotherapy—unproven efficacybut may consider protocol 8.

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Mast Cell Tumors in DogsCommon Raised or ulcerated intracutaneousClinical Signs: mass; may be hairless or haired;

may be single or multiple. Mastcell tumors can look and feel likeanything.

Common Histologic grade influencesHistologic Types: surgical prognosis. Moderately dif-

ferentiated (grade II) tumors arethe most common.

Biological Behavior: Boxers, Boston terriers, andgolden retrievers are predisposedbut can occur in any breed, at anyage; metastasis is similar to otherhematopoietic tumors, to regionallymph nodes as well as liver,spleen, and bone marrow.

Prognostic Findings: Tumors on limbs have better prog-nosis than those on the trunk(especially perineum); slow growthand long duration of presencemay be favorable; most importantprognostic factor is histologicgrade.Recurrence rate 6 months afterincomplete-excision surgery—25%for well-differentiated tumors;

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44% for moderately differentiatedtumors; 76% for poorly differenti-ated tumors.

Treatment Well-differentiated to moderately-Considerations: differentiated tumors—wide surgi-

cal excision; adjunctive radiationtherapy (88% achieve 5-year con-trol for moderately differentiatedtumors); although efficacy isuncertain, recent use of CCNU orVelban have shown promise.Poorly differentiated tumors—surgery, with or without radiationtherapy, is palliative; H2 blockers,prednisone, and vincristinechemotherapy may be helpful (seeprotocol 8).

Mesothelioma in DogsCommon Effusion of body cavities causingClinical Signs: abdominal discomfort, tachypnea,

and respiratory distress; indecreasing order of incidence—affects pleural, peritoneal, or peri-cardial cavities.

Common Epithelial-type mesothelioma.Histologic Types:

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Biological Behavior: Old dogs; exposure to asbestosand pesticide powders may beassociated with development ofmesothelioma in dogs.

Prognostic Findings: None identified.Treatment Chemotherapy—intracavitaryConsiderations: cisplatin may provide palliation;

responses to intravenous doxoru-bicin and mitoxantrone have beennoted (see protocols 1–4).

Multiple Myeloma in CatsCommon Nonspecific clinical signs; mostClinical Signs: cats are anemic; lytic bone lesions

are rare.Common Mature plasma cells.Histologic Types:Biological Behavior: Old cats; mostly domestic short-

hair; no association with FeLV.Prognostic Findings: None identified.Treatment Surgery—rarely considered.Considerations: Radiation therapy—radiation-

sensitive tumor; excellent localpalliation of signs and completeremissions reported; guardedprognosis due to systemic natureof disease.

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Chemotherapy—remission rates of40% with a median survival of 170days reported in clinical casestreated with prednisone and analkylating agent (melphalan,Cytoxan, Leukeran); consider asadjunct to radiation therapy insome patients.

Multiple Myeloma in DogsCommon Anemia and secondary infectionsClinical Signs: due to myelophthisis; lameness

and pain from bone lytic lesions;polyuria and polydipsia fromhypercalcemia, renal disease, andparaproteinuria; hemorrhage dueto hyperviscosity.

Common Mature plasma cells.Histologic Types:Biological Behavior: Median age is 8–9 years; most

cases occur in purebred dogs; sys-temic disease.

Prognostic Findings: Dogs with hypercalcemia, exten-sive bone lysis, or light-chain(Bence Jones) proteinuria have aworse prognosis.

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Treatment Surgery—rarely considered; usedConsiderations: to palliate neurologic signs (paral-

ysis) due to vertebral disease. Radiation therapy—radiation-sen-sitive tumor; excellent local pallia-tion of signs and completeremissions reported; guardedprognosis due to systemic natureof disease.Chemotherapy—prednisone is pal-liative only; median survival is 220days; melphalan and prednisoneprovide complete remission in40% and partial remission in 50%of dogs for a median survival of540 days; other agents, such ascyclophosphamide or chlorambu-cil, may be effective; considerchemotherapy adjunct to radiationtherapy.

Myelodysplasia in Dogs and CatsCommon Reflects cytopenias, such as feverClinical Signs: and neutropenia or petechiation

and thrombocytopenia.

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Common Differentiated from leukemias byHistologic Types: <30% blasts in a dysplastic bone

marrow.Biological Behavior: No age, gender, or breed predilec-

tion; usually progresses to an acuteleukemia in cats (most are FeLVantigenemic).

Prognostic Findings: None identified.Treatment Supportive treatment—antibioticsConsiderations: and transfusions of blood, blood

products, or cytokines (Epogen,Neupogen).Chemotherapy—cytosine arabi-noside (ara-C) and retinoids areunder investigation as differentiat-ing agents.

Nasal Tumors in CatsCommon Epistaxis, sneezing, facialClinical Signs: deformity, and epiphora.Common Carcinoma and lymphoma.Histologic Types:Biological Behavior: Old males (8–10 years of age);

locally invasive and rarely metasta-sizes to distant sites until late inthe course of the disease.

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Prognostic Findings: None identified.Treatment Surgery—contraindicated.Considerations: Radiation therapy—treatment of

choice; survival time for non-hematopoietic malignancies is20–27 months; median survivaltime for cats with nasal lymphomaapproaches 16 months.Chemotherapy—recommendedfor nasal lymphoma due to sys-temic disease (see protocols 6, 7,and 10).

Nasal Tumors in DogsCommon Unilateral epistaxis, facialClinical Signs: deformity, and epiphora.Common Adenocarcinoma.Histologic Types:Biological Behavior: Most common in old dogs; no

breed or sex predilection; tumor islocally invasive and rarely metasta-sizes to distant sites until late inthe course of the disease.

Prognostic Findings: Brain involvement is a poor prog-nostic sign.

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Treatment Surgery—contraindicated unlessConsiderations: combined with radiation therapy.

Radiation therapy—with or with-out surgery, the treatment ofchoice; median survival rates varyfrom 8 to 23 months.Chemotherapy—cisplatin isreported to be effective in palliat-ing clinical signs; mitoxantrone isused concurrent with radiationtherapy to improve radiation effi-cacy (survival times exceeding 2 years).

Nonosteosarcoma Bone Tumors in DogsCommon More often affects axial skeletonClinical Signs: than appendicular skeleton; care is

required in interpreting incisionalbiopsy specimens.

Common Chondrosarcoma, fibrosarcoma,Histologic Types: and hemangiosarcoma.Biological Behavior: Old dogs, except oral fibrosar-

coma, in which younger dogs pre-dominate; metastases occur atlower rate than with osteosarcomaand may occur late in the courseof the disease.

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Prognostic Findings: None identified.Treatment Surgery—palliative; may beConsiderations: curative in some dogs, although

metastases may arise even monthsor years after surgery.Radiation therapy—may improvetumor control; palliative for bonepain.Chemotherapy—unproven efficacybut consider protocols similar forosteosarcoma to prevent or delaycomplications arising frommetastatic disease (see protocols1–4).

Ocular Tumors in CatsCommon Buphthalmos, poor vision, irisClinical Signs: pigment change, and glaucoma.Common Melanoma; less commonly, ocularHistologic Types: sarcoma.Biological Behavior: Melanomas are malignant and

have high metastatic potential; oldcats usually are affected; no associ-ation with breed, gender, or FeLVstatus; sarcomas (often precededby ocular trauma) are highlymalignant.

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Prognostic Findings: None identified.Treatment Surgery—enucleation should beConsiderations: performed early in course of dis-

ease for melanoma; increasingdegree of ocular involvement isassociated with poorer survival.Radiation therapy—may improvelocal control, but melanoma andocular sarcoma have high metasta-tic rates.Chemotherapy—unproven effi-cacy; low dosage weekly carbo-platin has significantly improvedsurvival in dogs with melanomaand may have efficacy in cats (seeprotocol 5).

Ocular Tumors in DogsCommon Glaucoma, uveitis, hyphema, orClinical Signs: visible mass.Common Melanoma; less commonly, epithe-Histologic Types: lial tumors of the ciliary body.Biological Behavior: Melanomas and epithelial tumors

have low potential for metastasis;old dogs are affected.

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Prognostic Findings: High mitotic index may indicatepotential for metastasis inmelanoma.

Treatment Surgery—enucleation is usuallyConsiderations: curative, even after failure of local

excision; other treatment modali-ties are generally not required.Chemotherapy—unproven effi-cacy, possibly consider piroxicamor tamoxifen as palliative therapy.

Oral Tumors in CatsCommon Halitosis, bleeding from mouth,Clinical Signs: and dysphagia.Common Squamous cell carcinoma is theHistologic Types: most common, followed by

fibrosarcoma and acanthomatousepulis.

Biological Behavior: Old cats; sublingual squamous cellcarcinoma is more common thangingival squamous cell carcinoma.

Prognostic Findings: None identified.Treatment The efficacy of multimodalityConsiderations: therapy (surgery, radiation ther-

apy, and chemotherapy) greatlyexceeds any single modality

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approach. Consider protocols 2and 4 adjunctive to radiation orsurgery.

Oral Tumors in DogsCommon Oral mass, bleeding from theClinical Signs: mouth, and dysphagia.Common Benign—fibromatous epulis;Histologic Types: acanthomatous epulis (may invade

bone).Malignant—melanoma, squamouscell carcinoma, and fibrosarcoma.

Biological Behavior: Melanoma—high metastatic rate;old dogs.Squamous cell carcinoma—mod-erately metastatic; lingual and ton-sillar types are highly metastatic;old dogs.Fibrosarcoma—low metastaticrate, young dogs.Epulides—do not metastasize; all ages.All tumor types—small tumors androstral location have a betterprognosis.

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Prognostic Findings: Melanoma—low mitotic index isassociated with a better prognosis.Squamous cell carcinoma—dogswith maxillary tumors and youngdogs have a better prognosis.

Treatment Surgery—mandibulectomy orConsiderations: maxillectomy for local control of

malignant tumors.Radiation therapy—curative foracanthomatous epulis; coarse frac-tionation may be useful formelanoma; adjunctive for squa-mous cell carcinoma and fibrosar-coma after surgery gives goodcontrol.Chemotherapy—platinum com-pounds are best for melanoma,50% report 1 year survival times;chemotherapy is not usuallyrequired for other tumor types;see protocols 2, 4, and 5.Biological response modifiers—piroxicam and tamoxifen haveanecdotal efficacy for dogs withmelanoma and squamous cellcarcinoma.

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Osteosarcoma of the AppendicularSkeleton in Dogs

Common Lameness and pain at metaphysealClinical Signs: sites, particularly distal radius,

proximal humerus, proximal tibia,and distal femur; lytic and produc-tive bone lesion on radiographs.

Common Osteoblastic osteosarcoma is mostHistologic Types: common; other diagnoses are

possible—chondroblastic, telangi-etic, and fibroblastic.

Biological Behavior: Large to giant breeds; no sexpredilection; usually middle-agedto old dogs; metastasis occurs earlybut may not be clinically evident.

Prognostic Findings: Survival is poor; prognosis isuncorrelated with gender, tumorsite, or whether a presurgicalbiopsy is performed.

Treatment Surgery—with amputation alone,Considerations: median survival is 162 days; 11%

of dogs are alive at 1 year; limbsparing provides good limb func-tion for distal radius tumors.Radiation therapy—radiation-sensitive tumor but curative intentprotocols rarely are considered

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due to poor prognosis; palliativeuse for pain control as an alterna-tive to amputation is consideredgood, median duration of paincontrol is 8 months.Chemotherapy—regardless oflimb removal, various chemother-apy protocols have shown efficacyin prolonging survival time. Cis-platin or carboplatin (protocol 3)shows 40–60% of dogs alive at 1year; doxorubicin (protocol 1)shows 50% of dogs alive at 1 year;combination (protocol 2) shows50% of dogs alive at 18 months.

Osteosarcoma of the Axial Skeleton in Dogs

Common Tumors of the appendicularClinical Signs: skeleton are four times more com-

mon than axial tumors. Common Multilobular osteochondroma andHistologic Types: osteosarcoma.Biological Behavior: Old dogs (except rib tumors,

which often affect young dogs); nobreed predilection; more femalesmay be affected; highly metastatic,

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but local recurrence is more of aproblem; mandibular osteosar-coma may have lower metastaticrate.

Prognostic Findings: None identified.Treatment Surgery—difficult due to locationConsiderations: of tumors; mandible and rib

tumors can be resected.Radiation therapy—may be usefuladjunct to surgery to reduce localrecurrence or for palliation ofpain.Chemotherapy—recommendedfor osteosarcoma of all sites (seeprotocols 1–3).

Ovarian Tumors in CatsCommon Irregular or prolonged estrus.Clinical Signs:Common Granulosa cell tumor.Histologic Types:Biological Behavior: Mainly domestic shorthairs; ovar-

ian tumors are rare tumors.Prognostic Findings: None identified.

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Treatment Surgery—rarely curative becauseConsiderations: of high metastatic rate of all tumor

types.Radiation therapy—unproven.Chemotherapy—unproven.

Ovarian Tumors in DogsCommon Abdominal mass or swelling;Clinical Signs: unexplained or abnormal estrus

or bleeding.Common Adenomas and adenocarcinomas.Histologic Types:Biological Behavior: Old dogs (median age is 10 years);

teratomas occur in young dogs.Prognostic Findings: None identified.Treatment Surgery—surgical excisionConsiderations: curative for most tumors.

Chemotherapy—consider proto-cols 1–4 adjuvant to surgical exci-sion if carcinomatosis observed.

Peripheral Nerve Sheath TumorsCommon Slowly progressive lameness.Clinical Signs:

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Common Dogs—neurofibrosarcoma.Histologic Types: Cats—lymphoma.Biological Behavior: Dogs—large-breed dogs; middle-

aged dogs (average age is 7 years);local disease, rare metastasis.Cats—systemic disease.

Prognostic Findings: None identified.Treatment Surgery—surgical resection ofConsiderations: tumor for small masses; amputa-

tion and resection for large massesor if severe neurologic deficits arepresent; complete excision is diffi-cult, recurrences are common.Radiation therapy—used forincompletely excised tumors, dis-ease-free times can exceed 2 years.Chemotherapy—most effective forlymphoma; not necessary for softtissue variants.

Prostatic Tumors in DogsCommon Tenesmus, constipation, dyschezia,Clinical Signs: and less commonly, dysuria and

hematuria.Common Adenocarcinoma.Histologic Types:

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Biological Behavior: Equal frequency in castrated andintact dogs regardless of age at cas-tration; old dogs (median age is 10years).

Prognostic Findings: May be more aggressive in cas-trated dogs but highly malignantin both castrated and intact dogs.

Treatment Surgery—difficult because ofConsiderations: anatomy of canine prostate.

Radiation therapy—palliative only,due to high metastatic rate.Chemotherapy—has no provenefficacy.Hormonal therapy—ineffectivebecause of hormone independ-ence of canine prostaticcarcinoma.

Renal Tumors in CatsCommon Nonspecific; hematuria rare.Clinical Signs:Common Lymphoma, then adenocarcinoma.Histologic Types:Biological Behavior: Old cats; no gender or breed pre-

disposition; nephroblastoma canoccur in young cats but is rare.

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Prognostic Findings: None identified.Treatment Surgery—rarely reported; carcino-Considerations: mas may have high metastatic rate.

Chemotherapy—renal lymphomamay respond to combinationchemotherapy (see protocols 6, 7,and 10).

Renal Tumors in DogsCommon Often no clinical signs; hematuriaClinical Signs: with transitional cell carcinoma.Common Carcinomas and adenocarcinomas.Histologic Types:Biological Behavior: Old dogs, usually males; nephro-

blastoma in young dogs; Germanshepherds may have cystadenocar-cinomas and nodular dermato-fibrosis on an inherited basis.

Prognostic Findings: None identified.Treatment Surgery—high metastatic rate forConsiderations: carcinomas makes cure unlikely;

early removal of nephroblastomamay be curative.Chemotherapy—reported only fornephroblastoma; vincristine, doxo-rubicin, and actinomycin D may

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be palliative (consider protocols1–4).

Retrobulbar Tumors in CatsCommon Exophthalmos or enophthalmos.Clinical Signs:Common Primary retrobulbar tumors areHistologic Types: rare; extension of oral squamous

cell carcinoma; nasal tumors andlymphoma.

Biological Behavior: Old cats; behavior varies withtumor type.

Prognostic Findings: None identified.Treatment Surgery—rarely useful as aConsiderations: primary modality, as most tumors

have grown by extension fromother sites; oral squamous cell car-cinoma is unresponsive to surgery.Radiation therapy—may be a use-ful adjunct for squamous cell carci-noma when used in combinationwith mitoxantrone chemotherapyor for nasal tumors (considerprotocol 4).Chemotherapy—may be useful forretrobulbar lymphoma, with or

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without radiation therapy (seeprotocols 6 and 7).

Retrobulbar Tumors in DogsCommon Exophthalmos, nicitansClinical Signs: protrusion, and deviation of globe.Common Multiple types; osteosarcoma,Histologic Types: fibrosarcoma, mast cell tumors,

and lymphoma are most common.Biological Behavior: Most tumors are locally aggressive;

metastatic rate varies with tumortype.

Prognostic Findings: None identified.Treatment Surgery—orbitectomy may beConsiderations: curative for small tumors.

Radiation therapy—should beuseful as an adjunct to surgery forall tumor types but is still underinvestigation.Chemotherapy—may be useful forlymphoma; consider protocols 1–4as adjunct to local modalities fortreatment of osteosarcoma andosteochondrosarcoma.

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Salivary Gland Tumors in Dogs and CatsCommon Cervical mass; anorexia orClinical Signs: dysphagia is possible.Common Adenocarcinoma.Histologic Types:Biological Behavior: May be diffuse oral tumor rather

than a mass; metastasis may bemore common in cats than dogs;old animals affected (median ageis 10 years); poodles and Siamesecats are predisposed.

Prognostic Findings: None identified.Treatment Surgery—high rate of localConsiderations: recurrence in cats and dogs.

Radiation therapy—when used asan adjunct to surgery, radiationtherapy seems to improve localcontrol in dogs; presumably thesame in cats.Chemotherapy—unproven efficacybut should be considered in catsdue to aggressive behavior; con-sider protocols 2–4.

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Soft Tissue Sarcoma in Dogs and CatsCommon Subcutaneous firm and irregularClinical Signs: mass appears (but is not) encapsu-

lated.Common Fibroma, fibrosarcoma,Histologic Types: hemangiopericytoma, neuro-

fibroma, neurofibrosarcoma,schwannoma, rhabdomyoma,rhabdomyosarcoma, leiomyoma,leiomyosarcoma, and malignantfibrous histiocytoma.

Biological Behavior: Young cats; may be related to FeSVand FeLV infection; possible corre-lation with vaccination site in cats;locally invasive with a low metasta-tic rate.

Prognostic Findings: Wide surgical excision at first sur-gery; metastasis is uncommon.

Treatment Surgery—wide surgical excisionConsiderations: with cancer-free margins rarely

results in cure.Radiation therapy—adjuvant exter-nal beam radiation therapy of >50 Gy gives control of 70–90% at1 year.

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Chemotherapy—doxorubicin-based protocols and intralesionalmethods are being investigated;consider protocols 2–4 as adjunctto surgery or concurrent with radi-ation therapy.

Spinal Tumors in DogsCommon Pain; slow onset of ataxia andClinical Signs: paresis.Common Extradural tumors; vertebral bodyHistologic Types: most common.Biological Behavior: Large-breed dogs, young to

middle-aged; locally invasive.Prognostic Findings: None identified.Treatment Surgery—treatment of choice forConsiderations: extradural and intradural-

extramedullary tumors;intramedullary tumors are notamenable to surgical excision.Radiation therapy—may be a use-ful adjunct to incomplete surgery.Chemotherapy—rarely consideredunless tumor is of lymphoidorigin.

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Spinal Tumors in CatsCommon Acute paresis.Clinical Signs:Common Lymphoma.Histologic Types:Biological Behavior: 70% of cats are FeLV positive and

85% have bone marrow that con-tains lymphoma; most tumors areextradural.

Prognostic Findings: None identified.Treatment Surgery—rarely indicated becauseConsiderations: of systemic disease.

Radiation therapy—may give localpalliation.Chemotherapy—in general, givesa poor response; best when usedin combination with radiationtherapy; consider protocol 6, 7, or 10.

Splenic Hemangiosarcoma in DogsCommon Palpable abdominal mass;Clinical Signs: hemoperitoneum; anemia; shock;

and possibly collapse.Common Hemangiosarcoma.Histologic Types:

122 Tumor Tidbits

Biological Behavior: Average age is 10 years; Germanshepherds are predisposed; metas-tasis may be confined to abdomi-nal cavity if no concurrent rightatrial lesion exists.

Prognostic Findings: Ruptured viscera, hemoperi-toneum, coagulopathy, signs attrib-utable to anemia are poorprognostic signs.

Treatment Surgery—palliative without grossConsiderations: metastases, but survival is short.

Radiation therapy—consideredpalliative for some lesions.Chemotherapy—prolongs survival;most protocols result in a mediansurvival time of 12–15 months;consider protocols 1–4 and 7.

Splenic Tumors in DogsCommon Abdominal swelling and weakness;Clinical Signs: palpable abdominal mass.Common Leiomyosarcoma, osteosarcoma,Histologic Types: and fibrosarcoma.Biological Behavior: Average age is 11 years; no breed

or gender predilection; metastasiscommonly occurs to abdominalsites.

Tumor Tidbits 123

Prognostic Findings: Ruptured viscera, hemoperi-toneum, coagulopathy, signs attrib-utable to anemia are poorprognostic signs.

Treatment Surgery—palliative without grossConsiderations: metastases, but survival is short.

Radiation therapy—consideredpalliative for some lesions.Chemotherapy—prolongs survival;most protocols result in a mediansurvival time of 12–15 months;consider protocols 1–4 and 7.

Stomach Tumors in DogsCommon Chronic vomiting, weight loss, andClinical Signs: inappetence.Common Adenocarcinoma; less commonly,Histologic Types: leiomyomas; most common in

lower two thirds of stomach.Biological Behavior: Old, male dogs; tumors cause

ulceration and commonly metasta-size to perigastric lymph nodes orviscera.

Prognostic Findings: None identified.Treatment Surgery—tumors are usuallyConsiderations: diffuse and have metastasized at

124 Tumor Tidbits

the time of diagnosis; therefore,aggressive surgery is rarely success-ful; recurrence is common.Radiation therapy—unproven.Chemotherapy—unproven.

Synovial Cell Sarcoma in DogsCommon Lameness and palpable mass.Clinical Signs:Common Fibroblastic cell type.Histologic Types:Biological Behavior: Middle-aged dogs; medium to

large breeds; predominately maledogs; predilection for the stifle.

Prognostic Findings: Mitotic index has prognostic value.Treatment Surgery—amputation, better thanConsiderations: 75% chance of 3-year survival.

Radiation therapy—anecdotalresponses reported in soft tissuetumors; provides pain palliation inthose with substantial bonyinvolvement.Chemotherapy—inadequatelystudied; cisplatin or combinationof doxorubicin and cyclophos-phamide may be helpful; consider

Tumor Tidbits 125

protocols 1–4 and 10 adjunctive tosurgery or radiation therapy.

Testicular Tumors in DogsCommon Palpable mass in normal orClinical Signs: atrophic testis; many are not pal-

pable; feminization changes withsome Sertoli cell tumors andseminomas.

Common Seminomas, Sertoli cell tumors,Histologic Types: and interstitial cell tumors.Biological Behavior: Seminomas and Sertoli cell tumors

have a high incidence in retainedtestes; old dogs; no breedpredilection.

Prognostic Findings: None identified.Treatment Surgery—usually curative asConsiderations: metastatic rate is low.

Radiation therapy—may achievelong-term control for metastaticseminoma to sublumbar lymphnodes.Chemotherapy—no reports ofchemotherapy for metastatictumors.

126 Tumor Tidbits

Thymoma in CatsCommon Dyspnea due to pleural effusion orClinical Signs: large mass.Common Malignant epithelial componentHistologic Types: with mature lymphocytes and mast

cells.Biological Behavior: Old cats; no association with FeLV;

tumors are usually encapsulated;paraneoplastic syndromes includemyasthenia gravis, but this is lesscommon than in dogs.

Prognostic Findings: None identified.Treatment Surgery—treatment of choice inConsiderations: cats, may be curative.

Radiation therapy—long-termremissions (>2 years) in nonsurgi-cal patients.Chemotherapy—palliativeresponses observed using weeklyvincristine therapy.

Thymoma in DogsCommon Cough; less commonly, dyspneaClinical Signs: and lethargy; may have aspiration

pneumonia secondary to myasthe-nia gravis and megaesophagus.

Tumor Tidbits 127

Common Epithelial malignant componentHistologic Types: associated with mature lympho-

cytes and mast cells.Biological Behavior: Old dogs; females possibly predis-

posed; usually large, invasive, slow-growing tumors with lowmetastatic rate.Paraneoplastic syndromes—myas-thenia gravis is most common;polymyositis, hypercalcemia, andsecond malignancies may occur.

Prognostic Findings: Dogs with megaesophagus have avery poor prognosis.

Treatment Surgery—may be curative forConsiderations: small or encapsulated tumors;

dogs with megaesophagus need to be monitored for aspirationpneumonia; most thymomas areunresectable.Radiation therapy—long-termremissions (>2 years) in nonsurgi-cal patients.Chemotherapy—palliativeresponses observed using weeklyvincristine therapy.

128 Tumor Tidbits

Thyroid Tumors in CatsCommon Hyperthyroidism with associatedClinical Signs: cardiac and hypermetabolic

changes; peritracheal mass may bepalpable.

Common Adenoma; carcinomas are rare.Histologic Types:Biological Behavior: Old cats; no gender or breed pre-

disposition.Prognostic Findings: None identified.Treatment Supportive treatment—for Considerations: example, propranolol and dilti-

azem, particularly for cardiacconditions.Medical management—methima-zole and carbimazole reduce circu-lating thyroid hormone levels, butlong-term use requires dosageincrease.Surgery—as tumors are often bilat-eral, both glands should beremoved; hypoparathyroidism orhypothyroidism may occur but isusually of short duration.Radiation therapy—radioactiveiodine (131I) gives good response

Tumor Tidbits 129

with prolonged remissions and fewside effects; may also palliateeffects of thyroid carcinoma.

Thyroid Tumors in DogsCommon Mass in ventral neck; rarely signsClinical Signs: of hyperthyroidism.Common Adenocarcinoma.Histologic Types:Biological Behavior: Old dogs; no gender predilection;

beagles, golden retrievers, andboxers are predisposed; local inva-sion is common; moderatemetastatic rate.

Prognostic Findings: Dogs with invasive tumors (“fixed”to underlying tissues) or largetumors predict worse survivalrates; not correlated with histo-logic type, age, breed, or gender.

Treatment Surgery—curative for adenomas;Considerations: may provide long-term control for

small, noninvasive carcinomas, butthese have potential to metastasize.Radiation therapy—external beamradiation may improve local con-trol or reduce size of mass before

130 Tumor Tidbits

surgery; radioactive iodine (131I)may cause regression in active hor-monal tumors, which are rarelyseen in dogs.Chemotherapy—significant con-trol of metastatic lesions observedwith platinum-based protocols;consider protocols 1–4.Hormonal therapy—anecdotalreports of long-term palliation ofmetastatic lesions (>1 year) seenwith thyroxine supplementation.

Transmissible Venereal Tumor in DogsCommon Bleeding mass on externalClinical Signs: genitalia.Common Transmissible venereal tumor.Histologic Types:Biological Behavior: Spread by coitus and canine social

behavior; females more susceptiblethan males; spontaneous regres-sion in most cases after months,but not in immunosuppressed ani-mals; rare metastasis.

Prognostic Findings: None identified.

Tumor Tidbits 131

Treatment Surgery—curative if wide excisionConsiderations: and localized tumor.

Radiation therapy—low doses (10 Gy); may be curative iflocalized.Chemotherapy—weekly vincristinefor 5–6 weeks may provide cure in90% of dogs.

Vaginal and Uterine Tumors in Dogs and Cats

Common Signs due to pelvic or urethralClinical Signs: obstruction.Common Leiomyoma and fibroma.Histologic Types:Biological Behavior: Rare tumors, usually benign; often

associated with ovarian cysts andendometrial hyperplasia.

Prognostic Findings: None identified.Treatment Surgery—may be curative forConsiderations: benign lesions.

Radiation therapy—radiation-sensitive tumor; excellentresponses observed.

132 Tumor Tidbits

4Principles of Chemotherapy

When Should Chemotherapy Be Considered?

When considering the use of chemotherapy in thetumor-bearing patient, the approach to therapy willdepend greatly on the therapeutic intent. Will the thera-peutic goal be a cure or palliation? It is important todetermine the goal clearly at the outset. A cure is theideal outcome but not necessarily realistic in most casesor likely to be achieved unless it is the initial intent. If acure is the intended outcome, aggressive therapy mayprovide substantial long-term benefit and a relativelyhigh level of short-term toxicity may be justified. Morecommonly, the accepted goal of cancer therapy in

133

veterinary medicine is palliation. Toxicity to chemother-apy is minimized in an attempt to prolong an acceptablequality of life.

Although localized primary tumors, which are atminimal risk for metastasis, are most commonly treatedwith surgery or radiation or both, chemotherapy mayoccasionally be used instead of or in addition to standardlocal therapy. Systemic chemotherapy is also indicatedfollowing local treatment for adjunctive therapy intumors that are commonly widespread or demonstrate ahigh rate of metastatic behavior (e.g., osteosarcoma ororal melanoma).

Tumor Growth and Response toChemotherapy

An understanding of cell growth, the biologic behaviorof tumors, and the metastatic pattern of specific tumortypes is essential prior to formulating a treatment plan.The phases of the cell cycle are S, in which new DNA issynthesized; gap G1, a period of RNA and protein syn-thesis; M, when the cell undergoes mitosis; and a secondgap, G2. The duration of each phase varies for differentcell types. Resting cells, G0, may retain the capacity todivide on proper stimulation. Normal and neoplastic cellpopulations are composed of both proliferating and rest-ing cells; the proportion and the rate of cell death varywith the tissue type. Growth fraction is the proportion of

134 Principles of Chemotherapy

a population of cells actively proliferating, in contrast tothose that are viable but quiescent. This concept must bedistinguished from growth rate, the increase in size ofthe tumor over time.

It is helpful to consider the rate of growth of a tumormore in terms of doubling time than in terms of size pertime. Doubling time refers to the time required for num-ber of cells to double, which is clinically evident asvolume. Some tumors are anatomically difficult to char-acterize; however, most can be assumed to be roughlyspherical for purposes of calculation.

The smallest clinically detectable tumor generallyhas a mass of 1 g, about 1 cm diameter, and containsapproximately 109 cells. If a tumor is assumed to haveoriginated from a single cell, then it has already under-gone 30 doublings by the time it is clinically detected. Toincrease in size to 1 kg theoretically takes only another10 doublings, assuming that all cells survive. Therefore,the majority of the lifespan of a tumor is probably spentin the subclinical phase.

Depending on the growth fraction and the rate ofcell death, normal cell growth is classically thought of asan exponential phenomenon in which the rate of dou-bling of the population remains fixed over time. Tumorcell populations, however, tend to adhere more closely toGompertzian kinetics, meaning that the doubling timetends to increase exponentially over time then reach aplateau phase. The plateau phase is most likely due to a

Principles of Chemotherapy 135

decrease in the growth fraction due to hypoxia, deple-tion of nutritional factors, and an increase in the rate ofcell death rather than an increase in the length of thecell cycle.

In general, the higher the growth fraction of a pop-ulation of cells, the more chemosensitive they areexpected to be. This explains why the most common sideeffects of chemotherapy are gastrointestinal distur-bances and bone marrow suppression, since these popu-lations are constantly proliferating. Likewise, a tumorreaching the plateau phase of the growth curve due tohypoxia and poor cell nutrition is more chemoresistantthan one in the exponential or linear phase.

Whether palliation or a cure is the therapeutic goal,the remission of tumors is desirable. Complete remissionis specified as an inability to detect clinical evidence oftumor. This does not mean that all tumor cells have beenremoved. The remaining cells are a source of potentialrelapse or recurrence of the gross tumor. When relapseoccurs during chemotherapy, it implies that the tumor isresistant to the agents being given.

Pharmacologic Principles of ChemotherapyTo induce remission without harming the patient, anti-cancer drugs must damage tumor cells to a greaterdegree than normal cells. Cytotoxicity is to thechemotherapeutic action of a drug. The mechanism ofcytotoxicity varies with each drug class. In general,


however, efficacy is greatest against actively cycling cells,and some agents act specifically on cells in certain phasesof the cell cycle. Knowledge of the mechanism of actionfor each drug allows the use of drug combinations thatmay act synergistically and avoidance of drugs that mayantagonize each other’s mechanism of action.

When a cytotoxic drug is administered to a popula-tion of cells, the number of cells killed will not beabsolute but a percentage of the total number. If a tumorcontaining 109 cells is exposed to a dose of drug that kills99% of the population, 9.9 � 108 cells will be killed and107 will remain, but the tumor now will be clinicallyundetectable. If the tumor starts at a mass of 100 g, or1011 cells, 9.9 � 1010 cells will be killed and 109 will sur-vive; the drug has been equally effective but the tumorremains clinically detectable.

The cytotoxic action of chemotherapeutic agentsdepends on concentration over time rather than peakplasma levels, whereas peak plasma level often deter-mines adverse effects on normal tissue. This makes theuse of slow infusion techniques desirable for intravenousdrugs.

Dose Response Curve

For all effective drugs, a sigmoid curve can be definedbetween the dose administered and the effect, such aspercentage of cells killed. This curve exists for normalcells as well as tumor cells. An ideal drug has a response


curve with a steep slope for tumor cells and a gradualslope for normal cells; furthermore, the therapeuticdose should fall on the linear portion of the curve fortumor cells and at the foot of the curve for normal cells.Thus, a small increase in dose brings about a largeincrease in tumor response and a small increase in toxi-city. The curve plateaus at a point of maximal effect,beyond which any further increase in dose will notincrease the response.

Therapeutic Index

As with other medications, the therapeutic index refersto the ratio of the toxic dose to the effective antitumordose. The therapeutic index of most chemotherapeuticagents is relatively low, necessitating careful dosing.Improvements in therapeutic index can be made byusing techniques that either make the drug more effec-tive or protect against toxic effects.

The optimum dose is at the point on the doseresponse curve where maximum antitumor effect andacceptable toxicity occur. It may be necessary to acceptsome toxicity or some risk of incomplete response orboth. In practice, the optimum dose in a given circum-stance depends on the goal of therapy. If the goal is acure, toxic risks are likely. If palliation is the goal, toxic-ity will be avoided, but an incomplete response is likely.

Toxicity from chemotherapeutic agents ranges frommild to life threatening. Tissues with high growth


fractions such as bone marrow and epithelial tissues,including the gastrointestinal tract, normally are mostsusceptible to toxic side effects. Some drugs have addi-tional toxic effects on other tissues, such as in the urinarytract, myocardium, or pancreas. These effects may beunrelated to the cytotoxic effects and idiosyncratic orspecies specific. Anaphylaxis is of concern in the use ofcertain drugs, as a reaction to either the drug itself or thecarrier.

Drug Classes

The major classes of chemotherapy agents are the alky-lating agents, antimetabolites, mitotic inhibitors such asplant alkaloids and podophyllotoxins, and antibiotics.Two additional important agents are the platinum com-pounds and the enzyme L-asparaginase. The alkylatingagents are the largest, oldest group and are not cell cyclespecific. The antibiotics have a variety of mechanisms ofaction; the most commonly used are the anthracyclines.

The toxic side effects of some chemotherapy agentscan be specifically antagonized or minimized by the useof special administration techniques, such as salinediuresis before administration of cisplatin to minimizerenal toxicity, or a second drug, which does not havedirect antitumor effect but does allow the use of higherdoses because of an increased therapeutic index. Anexample is the use of mesna to prevent hemorrhagic cys-titis caused by ifosfamide.


Resistance to Chemotherapy

Tumors may be intrinsically resistant to anticancer drugsor they may acquire resistance as a result of exposure. Atumor cell may be naturally unaffected by the mode ofaction of a chemotherapeutic agent; the cell may nothave receptors or activating enzymes for the drug or maynot be reliant on the biochemical process with which thedrug interferes. In addition, some anatomical locationsare difficult to treat with chemotherapy because of theinability of the drug to reach the site of the tumor (e.g.,blood-brain barrier). Furthermore, drugs may not reachall cells in a poorly vascularized tumor, and these cellsmay survive in a quiescent state to reemerge at a latertime.

Acquired resistance develops after tumor cells havebeen exposed to a drug or similar class of drugs. Spon-taneous mutation is assumed to be ongoing regardless ofthe presence of any drug and the occurrence of sponta-neously resistant cells in a population approximates therate of mutation. The rate of spontaneous genetic muta-tion in both normal and neoplastic cell populations isgenerally estimated at 10–7–10–5 per mitosis. If the popu-lation then is exposed to the drug, the resistant cell willhave a growth advantage. Many chemotherapy agents aremutagenic and may increase the risk of development ofclones resistant to one or more drugs. Therefore, thelarger the number of cells in a tumor, the more likely itis that spontaneous resistance will occur. If only a small


subset, or clone, has the resistant phenotype, it will even-tually become the dominant cell type in the tumorbecause of the growth advantage conferred by its abilityto grow in the presence of a given drug. Until the resist-ant clone reaches a certain size, this may not be clinicallyevident, if most of the tumor is sensitive. This is onemechanism of relapse.

Gene amplification is another source of acquireddrug resistance enhanced by the presence of graduallyincreasing concentrations of the drug. Drugs, such asmitotic inhibitors, that promote a delay in the cell cyclejust prior to the M phase are most likely to promote thisphenomenon. A good example of acquired drug resist-ance by gene amplification is the multiple drug resist-ance phenotype. Multiple drug resistance (MDR) is aphenomenon of cross-resistance of cells to a variety ofagents not structurally or functionally related. Theseinclude the antitumor antibiotics, podophyllotoxins, andthe plant alkaloids. MDR is mediated by p-glycoprotein,a cell membrane pump that is present normally on thesurface of some epithelial cells. The protein activelyremoves drug from the cell, making it resistant to anydrugs that are substrates for the pump.

Chemotherapy Protocols

COMBINATIONS AND SCHEDULING Using drugs incombination maximizes therapeutic potential. The mostimportant criterion for inclusion of a drug into a


combination protocol is efficacy as a single agent againstthe tumor in question. Using closely related drugs incombination usually does not improve efficacy signifi-cantly and may increase toxicity, whereas effective com-binations generally consist of drugs that target differentmetabolic pathways. Some drugs are synergistic whenused in combination, but often the effects are simplyadditive. Combinations allow the use of a higher totalcytotoxic dose when the toxic effects of the individualdrugs are different.

Scheduling of drug administration can be criticalsince giving it too late may markedly decrease the anti-tumor effect of a drug, either because the growth frac-tion of the tumor has decreased or a resistant clone hasdeveloped. Also, the scheduling of the various drugs inrelation to each other is important. Differences and sim-ilarities in mode of action, toxicity, and mode of resist-ance should be considered.

It is critical to avoid overlapping the toxicity of the drugs in combination chemotherapy protocols. Themost commonly encountered example of this is in theuse of multiple myelosuppressive agents. The onset ofthe neutrophil nadirs of various drugs must be takeninto account when planning the sequence and timing oftherapy; and since some alkylating agents cause delayedmyelosuppression, this may not be readily evident until asecond drug is administered.


MULTIMODAL THERAPY Chemotherapy is often usedsuccessfully in combination with other therapeuticmodalities, particularly surgery and radiation therapy. Ifmultimodal therapy is to be used, the combinationshould be planned in advance rather than using differ-ent modalities one after the other as each one fails. Pre-operative (neoadjuvant) chemotherapy is indicatedwhen a primary tumor is so large that it is inoperable orinvolves vital structures. Usually, however, chemotherapyis used postoperatively (adjuvant) after incomplete exci-sion or when micrometastases are expected to be pres-ent, based on a knowledge of the behavior of a particulartumor. In theory, adjuvant therapy should be particularlyeffective since the growth fraction of residual tumor islikely to be relatively large.

Dose Determination

Because the therapeutic index of chemotherapeuticagents is generally low, accurate dosing is imperative.Despite numerous examples in humans where clinicalpharmacokinetics have been successfully applied toimprove anticancer therapy, most veterinary anticancerdrug dosages and regimens are based on human doseextrapolation and empirical trial and error. It is impor-tant, therefore, to realize there are specific speciesdifferences in metabolic rates and pathways (e.g.,cisplatin-induced fatal pulmonary toxicity in cats but notin dogs).


Body surface area, an accurate reflection of meta-bolic rate, has been used to calculate drug dosage inhumans. Most anticancer drugs prescribed in veterinarymedicine are dosed on a per body surface area basisrather than a per weight basis for similar reasons. How-ever, in recent times many veterinary oncologists havebecome aware that, in doing so, smaller-sized patientsreceive a much higher mg/kg dose than larger-sizedpatients. For example, when dosing doxorubicin on aper body surface area basis (30 mg/m2, equivalent to 1 mg/kg), smaller-sized dogs (e.g., a 5-kg dog dosed at 30 mg/m2 is given a dose equivalent of 1.74 mg/kg) havehigher peak plasma concentrations, greater plasma drugconcentrations versus time curves, longer drug elimina-tion half-lives, greater volumes of distribution of the cen-tral compartment, more pronounced myelosuppression,and more clinical signs of toxicoses than larger-sizeddogs.

Although these findings do not imply a carteblanche revision of anticancer drug dosages in veteri-nary medicine, application of knowledge regardingspecies variability in drug pathways, coupled with limitedveterinary studies and phase I and II human pharmaco-kinetic studies should result in improved veterinary ther-apy compared to empiric trial and error.


Administration

Anticancer drugs have been given orally, intravenously,subcutaneously, topically, by an intracavitary or intraves-icular route, and intraarterially. Efficacy and toxicityoften vary based on the route of administration chosen.Care should be given to assure proper administration ofall chemotherapy drugs. Only a few chemotherapy drugsare available in an oral form, but they are widely used inveterinary oncology, where frequent office visits for ther-apy and a perception of the pet’s discomfort may deterthe client from pursuing other equally or more impor-tant forms of treatment. When chemotherapeutic agentsare dispensed for home use, the client must be madeaware of the hazards associated with handling the drugs.Appropriate precautions should be taken to preventhuman exposure, especially when children or adults ofchildbearing age are members of the household.

The intravenous route is readily accessible in mostveterinary patients and is most commonly used. A fewdrugs can be extremely irritating if administered perivas-cularly (e.g., vincristine, doxorubicin), so care must betaken in using these drugs in animals that are difficult torestrain.

Only a few chemotherapy agents are available forintramuscular or subcutaneous administration. The useof a subcutaneously implanted continuous infusion orabsorption devices holds great promise for drugs that arenot irritating. Some drugs are actually less toxic when


given by the subcutaneous or intramuscular route. L-asparaginase is associated with a much lower rate ofanaphylaxis when used intramuscularly than when givenintravenously.

A few drugs are available in topical form for use inhuman medicine; however, these generally are not usefulin veterinary medicine. Toxicity and poor efficacy havebeen encountered.

The use of intracavitary and intravesicular chemo-therapy has applications in special cases where the tumoris not bulky, since the drug will penetrate only a few mil-limeters from the drug-cell interface. Examples of suchtumors may include mesotheliomas, pleural or peri-toneal carcinomatosis, and noninvasive transitional cellcarcinomas. The drug used must be nonirritating. Sincesystemic absorption is likely, the dose should be withinthe safe systemic range.

If a major artery supplying a tumor can be identifiedand catheterized, some drugs may be given intraarteri-ally to deliver a high concentration of drug to the tumorwithout exposing the host to an excessively high totalbody dose.

Chemotherapy Safety Guidelines Concerns in the Workplace

Health concerns regarding occupational exposure todrugs used in cancer therapy are primarily associated


with those drugs referred to as cytotoxic. Beginning in theearly 1980s, a series of Technical Assistance Bulletinshave been developed by the American Society of Hospi-tal Pharmacists and recommendations from the FederalOccupational Safety and Health Administration, theNational Institutes of Health, the American MedicalAssociation, and others to address the potential healthhazards of low dose occupational exposure to cytotoxicanticancer drugs. Similar guidelines have been pub-lished in the veterinary literature. The potential dangerto health care professionals from handling a cytotoxicdrug stems from a combination of its inherent toxicity,individual susceptibility, concurrent exposure to knowncarcinogens, and the level and type of exposure. Expo-sure may occur through inadvertent ingestion of a drugin foodstuffs or cosmetics, inhalation of drug dusts ordroplets, or direct skin contact. Health risks from low-level occupational exposure must be addressed as a real-ity, but the word potential must be used, since noconclusive evidence establishes an association betweenoccupational exposure and disease. However, consider-able controversy stems primarily from retrospective stud-ies suggesting that nurses who handled cytotoxic drugsin an unprotected fashion had an increased risk of fetalloss. In addition, some cytotoxic drugs are mutagenic,teratogenic, or carcinogenic under laboratory or clinicalconditions. Given the current level of concern and theneed to protect veterinary professionals from potential


occupational health risks, many veterinary hospitals haveinstituted formal procedures for the safe handling ofcytotoxic drugs in the workplace. Correct preparationand handling techniques prevent dust particles and liq-uid droplets from escaping into the workplace whencytotoxic drugs are being manipulated. Workplace con-tamination can also occur through accidental spills andbreakage of drug containers. Although the need for cau-tion and common sense when handling cytotoxic drugsis real, there is no justification for hysteria. Safety equip-ment and safe handling methods relating to cytotoxicdrugs should be followed in the same way that safetyequipment and safe techniques are accepted when oper-ating X-ray equipment or handling infectious material.All hospital personnel who handle cytotoxic drugsshould have training in the procedures and access toinformation pertaining to their responsibilities. As withother conditions in the workplace, “right to know” poli-cies for health care professionals should be followed.

Drug Storage and Preparation

All chemotherapeutic drugs should be clearly identifiedas potentially hazardous.

Chemotherapeutic drugs requiring refrigerationshould be stored separately. Store chemotherapeuticdrugs in a properly marked zipper closure plastic bag orin a bin designed to contain accidental leaks. A goodlocation for drug preparation is a side room away from


ward traffic and food preparation areas. Windows, doors,and air vents should be closed to eliminate drafts. Noother activity should occur in the room during drugpreparation and administration. Read the package insertprior to admixing any chemotherapeutic drug. Have thefollowing materials and supplies readily available in theimmediate work area: plastic-backed diaper, gauze pads,cotton balls, alcohol, gown, gloves, face mask, glasses orgoggles, syringes, needles, venting pins, stopcocks, dilu-ent, drug, zipper bags, pen or marker, sharps container,and hazard labels. Wash hands thoroughly prior to drugpreparation.

Prepare drugs on a working surface at waist level.Use plastic-backed absorbent sheets to line the immedi-ate work surface. During preparation wear a lint free dis-posable gown made with low permeability fabric. Thegown should have a solid front, long sleeves, and snug fit-ting elastic cuffs. Wear two layers of talc-free latex gloves.Necropsy gloves are appropriate, since latex gloves maybe less permeable to chemotherapeutic drugs thangloves made from polyvinyl chloride. Torn or puncturedgloves should be discarded and not used. When wearingdouble gloves, one glove should be under the gown cuffand the other over it so no skin of the wrist or forearm isexposed. If clothes become contaminated do not washthem. This could expose others. Discard contaminatedclothes in a properly marked container for chemothera-peutic waste. Wear a disposable face mask. Wear a pair ofsafety glasses or splash goggles.


Once the proper diluent and the correct amounthave been determined, inject slowly into the chemother-apeutic drug vial. Surround the drug vial stopper with analcohol-dampened 4 � 4-inch gauze pad prior to with-drawing the needle from the drug vial. Both needle andsyringe should be withdrawn together. Discard thesyringe and needle into an appropriate puncture-proofwaste container. Do not recap the needle. When with-drawing admixed drugs from a drug vial, the syringeshould be filled to no more than two thirds. Avoid largefluctuations between atmospheric pressure and pressurewithin vials. Venting devices can be useful for capturingaerosolized droplets that have resulted from sudden pres-sure changes. If multiple syringes are to be filled, the vialshould be fitted with a stopcock. Use syringes and intra-venous (IV) sets with Leur-lock fittings as a precautionagainst the accidental separation possible with standardfriction fittings. Aspirating the fluid slowly may createfewer air bubbles in the syringe. Do not tap the syringe toconcentrate air bubbles. This increases drug aerosoliza-tion. Injecting the bubbles into an alcohol-moistened cot-ton ball may safely eliminate those present.

Do not recap needles. Recapping, crushing, or clip-ping needles increases the risk of cutaneous oraerosolized drug exposure. Using venting devices towithdraw the admixed drug can minimize cutaneousexposure. Discard unused chemotherapeutic drugs intoan appropriate chemotherapeutic drug waste container.


When breaking an ampule, wear protective gloves. Thisreduces the possibility of cutaneous absorption. Place analcohol-dampened 4 � 4-inch gauze pad at the neck ofthe ampule. This will absorb any aerosolized drug.Remove the drug slowly from the ampule to minimizespillage or aerosolization. Inject excess air bubbles intoan alcohol-moistened cotton ball.

Count tablets and capsule forms of chemotherapeu-tic drugs on separate counting trays from those used forother hospital drugs. Minimize reducing tablet size forthe convenience of smaller-sized patients. Reducingtablet size may result in the aerosolization of drug dust.

After preparation has been completed, label all vialsand bottles with the date and time. Seal reconstituteddrugs that are ready for administration in a properlymarked zipper closure bag or leakproof container fortransport to the administration area. Place all brokenampules, needles, and other sharp items into a sealedpuncture-proof container that is separate from otherhospital trash. Clean the preparation area by discardingthe plastic-backed absorbable paper liner and then wash-ing the surface with soap and water. Use paper towels todry this area. All contaminated clothing should beremoved prior to leaving the work area. Discard all itemsin a properly marked waste container. Discard the gownand latex gloves. Thoroughly wash hands with soap andwater to remove any possible drug residue. Rememberhand washing is no substitute for wearing gloves; and if


medication is sent home with the patient, supply theowner with protective latex gloves.

Drug Administration

All drugs should be transported in a properly markedleakproof container or zipper closure bag. Prior toadministration, double-check drug selection and dosecalculations. All personnel involved in drug administra-tion must wear protective gowns, gloves, and faceapparel. When administering IV chemotherapeuticdrugs, place a plastic-backed absorbent liner under thepatient. Place an alcohol dampened 4 � 4-inch gauzepad under and around the IV injection port to preventaerosolization of the drug. Monitor the administrationset carefully for leaks. Administer IV chemotherapeuticdrugs through a patent indwelling catheter that hasbeen placed aseptically. Flush IV catheters with a solu-tion compatible with the drug prior to and followingchemotherapeutic drug administration. This informa-tion can be obtained from the drug insert. Cover theneedle with a 4 � 4-inch gauze pad when removing theneedle from the injection port.

Discard contaminated needles and syringes into apuncture-proof container designated only for chemo-therapeutic drugs. Dispose of contaminated soft goodssuch as catheters, IV administrations sets, venosets, gloves,and gowns with other chemotherapeutic drug wastes.Although there is no evidence to date that exposure to


urinary or fecal waste from a patient receiving chemo-therapeutic drugs is harmful, hospital personnel, as aregular part of the hospital clean hygiene plan, shouldalways wear gloves when handling body wastes frompatients. Ward cages or runs housing patients treatedwith chemotherapeutic drugs should display a warninglabel to alert hospital personnel. Body waste fromchemotherapeutic patients should be disposed of withother biohazardous waste.

Drug Disposal

Written policies regarding the identification, contain-ment, segregation, disposal, and collection of chemother-apeutic drug wastes should be established and posted inthe workplace. All containers should carry a hazardousdrug waste label. Segregate all chemotherapeutic-drug-contaminated waste containers from other hospital trash,and dispose of the waste according to local, state, and fed-eral regulations. Frequently, human hospital pharmaciescan be persuaded to accept the small amounts of wastegenerated by veterinary hospitals.

Accidental Spills

Place an accidental spill kit in the preparation andadministration areas. The spill kit should contain an iso-lation gown made with low permeability fabric, two pairsof latex gloves or necropsy gloves, face mask, shoe covers,


eye goggles, cat litter, paper towels or absorbent pads, ahemostat, and a thick resealable plastic bag that carriesan appropriate hazardous waste label. If an accidentalspill occurs, restrict access to the area immediately andallow some time to pass to allow spilled drug to settleonto surfaces, decreasing the risk of aerosolized expo-sure. The spill then should be cleaned at once.

If a human or animal has become contaminated bythe spill, the contaminated skin should be washed withsoap and water and contaminated eyes should be flushedwith an eyewash or water-based solution for a minimumof five minutes. A physician should be contacted imme-diately regarding additional emergency medical meas-ures. Contaminated clothing must be removed anddiscarded with all other contaminated waste. One personshould be designated for cleanup. Protective apparelmust be worn and the spill kit used. Promptly obtain andwear the protective isolation gown, two pairs of latexexamination gloves or heavy necropsy gloves, eye gog-gles, shoe covers, and face mask. Collect broken glasswith a broad edge tray or hemostat and place into a sep-arate puncture-proof container. Absorb liquids with dis-posable towels, pads, or cat litter. Collect powders with adamp disposable towel or pad. Rinse the contaminatedsurface with water and then clean with detergent. Do notuse chemical deactivators. Detergent-cleaned surfacesshould be cleaned again with water. Clean the spill areaonce more with soap and water and minimize use of this


area for 24 hours. Place all contaminated materials in aresealable, disposable thick, plastic bag that carries anappropriate warning label. Wash hands thoroughly aftercleanup.

Use Common Sense

The preceding guidelines should be evaluated for suit-ability in each veterinary hospital. The costs of imple-menting all of the guidelines may be consideredimpractical in some situations. It is recommended thateach veterinary hospital adopt some form of safetyguidelines for handling chemotherapeutic drugs andreview these with the hospital staff on a regular basis.Remember, common sense, good techniques, and inex-pensive safety precautions should eliminate the likeli-hood of exposure. If you have additional questions,contact an oncologist or oncology technician in yourarea.

Management of Chemotherapy Side Effects Prevention

Chemotherapy-associated complications should be andusually are rare events in veterinary oncology. The singlemost important method for avoiding chemotherapy tox-icity is to know the potential side effects of the drugs youintend to use. Many complications are avoidable, and it


is imperative that research on utilization of these drugsbe performed before use. It is also important to knowany synergistic toxicity that may exist if a combination ofchemotherapeutic agents (or other medications) isplanned. Several texts contain valuable informationabout chemotherapeutic drug handling and toxicity,and veterinarians are encouraged to consult experi-enced individuals before using these agents. A completeblood count (CBC), serum biochemical panel, and uri-nalysis (UA) should be performed prior to the firstchemotherapy treatment; and these tests should berepeated as necessary, depending on the drug adminis-tered. With rare exceptions, treatment with myelosup-pressive agents should not be performed if theneutrophil count is less than 2,500 cells/μl or theplatelet count is less than 100,000/μl (some individualsuse 75,000/μl as a guideline for platelets). A urinalysisshould be performed to rule out preexisting cystitis priorto use of drugs such as cyclophosphamide, to identifyoccult urinary tract infections (UTI), and to identifyearly renal dysfunction that may affect excretion ofchemotherapeutic drugs. Renal dysfunction is anabsolute and relative contraindication for use of cisplatinand carboplatin, respectively. Patients receiving doxoru-bicin should be carefully evaluated for cardiac disease(dog or cat) or renal disease (cat). Some veterinariansperform an electrocardiogram (ECG) prior to eachtreatment with doxorubicin. Others require thoracicradiography and echocardiography on patients at high


risk for cardiomyopathy or congestive heart failure (box-ers, doberman pinschers, dogs with heart murmurs andcardiac silhouette or vessel abnormalities on thoracicradiography, or cats with heart murmurs) prior toadministration of doxorubicin.

Chemotherapy administration should take place inan area of the hospital that is relatively traffic free toensure full concentration of the staff administeringchemotherapy as well as a calm environment for thepatient. This may require that chemotherapy treatmentsbe performed at a time of day that is less hectic thanusual. You should be sure that all required materials areprepared ahead of time and additional materials arewithin easy reach. It is important to remember that manychemotherapy agents are dosed using the body surfacearea method. It is equally important to remember thatthe m2 charts use body weight expressed in kilograms. Itis a good practice to have chemotherapy doses deter-mined by two individuals to verify calculations, and drugconcentrations should be verified to ensure that finaldrug volumes are appropriate. At times, it is necessary toadjust chemotherapy dosages for individual patients.Doxorubicin and other drugs are sometimes dosed on amg/kg basis for very small patients. Additionally, dosagesshould be decreased by 20–25% for those patients whoexperience side effects of severe gastrointestinal distressor marked myelosuppression.

Use of premedications varies considerably amongthose who administer chemotherapeutic drugs routinely.


Despite this variation in protocols, certain antineoplasticagents always require premedications. It is imperative toadminister antiemetics to dogs prior to use of cisplatin.Butorphanol (0.4 mg/kg subcutaneously [SQ] or intra-muscularly [IM] 30 minutes before cisplatin) orondansetron (Zofran, 0.3 mg/kg continuous rate infu-sion [CRI] over 30 minutes just prior to administrationof cisplatin) are commonly used for this purpose.

Most chemotherapy drugs have very specific routesof administration, and if not properly administered, dis-astrous results may ensue. Complications resulting fromextravasation of vesicants and the requirement for salinediuresis with use of cisplatin are examples. In addition, itis important to know the difference in the degree ofmyelosuppression associated with various routes ofadministration and dosing schedules of chemotherapyagents. For example, a single subcutaneous dose of cyto-sine arabinoside results in less myelosuppression thanadministration of the same dose as a CRI over severalhours. In contrast, administration of a single large dose ofcyclophosphamide results in a greater degree of myelo-suppression than dividing the same dose over severaldays. Avoid using peripheral veins for phlebotomy whenpossible. Only highly qualified staff members should beresponsible for treating chemotherapy patients withdrugs that are capable of causing extravasation reactions.

Venipuncture sites should be clipped adequately toallow visualization of the vein and prepared aseptically.Avoid sites of previous venipuncture that have taken


place within the prior 24 hours. Aspirate to check forgood blood flow and flush the catheter well with at least5 cc of nonheparinized saline solution prior to adminis-tration of the chemotherapeutic drug. After administra-tion of the chemotherapy agent, do not aspirate backinto the saline-filled syringe prior to flushing with thesaline, as you will contaminate the flush with thechemotherapy drug. Various catheter types are utilized,chosen based on the drug to be administered, individualpreference level, and patient characteristics. At times, itbecomes necessary to place venous access ports toensure appropriate administration of intravenouschemotherapy agents. The site of administration shouldbe recorded for each treatment for future reference.

Histaminic (anaphylactoid) reactions are reportedwith the use of doxorubicin, L-asparaginase, and pacli-taxel (Taxol). This toxicity is rarely observed with use ofdoxorubicin or L-asparaginase but prompts some veteri-narians to premedicate with diphenhydramine (1 mg/kgin cats and 2 mg/kg in dogs SQ or IM 30 minutes priorto administration of chemotherapy drug) and dexam-ethasone sodium phosphate (dex SP, 0.5 mg/kg IVimmediately prior). Premedication with these drugs isrequired when using Taxol due to the high incidence ofthese reactions, and some oncologists advise administra-tion of oral prednisone the night before treatment inaddition to the premedications just described. Histaminicreactions may be characterized by cutaneous erythema,pruritus, wheals, vomiting, vocalization, or cardiovascular


collapse (similar in nature and variability to the immuneresponse elicited by beestings or vaccinations). If such areaction occurs, chemotherapy administration should bediscontinued and treatment with diphenhydramine, dexSP, with or without epinephrine initiated.

Acute vomiting is a rare side effect unless accompa-nying a histaminic reaction. One exception is emesisseen routinely following treatment with cisplatin unlesspretreatment with butorphanol or ondansetron is per-formed as described previously. Cimetidine (4 mg/kg IM30 minutes prior to chemotherapy) is given as an addi-tional premedication when Taxol is administered toavoid vomiting secondary to histaminic gastritis. Otherpatients may require treatment with antiemetic medica-tion immediately preceding or following administrationof other antineoplastic agents. If a patient has exhibitedvomiting as an acute or subacute side effect to drugssuch as doxorubicin, administration of metoclopramideimmediately preceding chemotherapy and for one tothree days afterward may be warranted. Some veterinar-ians advise fasting chemotherapy patients before treat-ment in an effort to prevent nausea.

Subacute Toxicity

Subacute toxicity syndromes include myelosuppression,gastrointestinal disturbance, and sterile hemorrhagiccystitis. When highly myelosuppressive agents are admin-istered (usually these drugs are given every 3–4 weeks), a


CBC should be obtained at the time of the first expectednadir (usually 10–14 days), to establish the degree ofmyelosuppression caused by the drug. Subsequent dosesshould be reduced by 20–25% if the neutrophil count isless than 1,000 cells/μl. If the neutrophil count is <1,000cells/μl, administer prophylactic oral antibiotic therapy,usually trimethoprim-sulfa (22 mg/kg bid) or enro-floxacin (5 mg/kg bid). Sometimes, it is appropriate toinstruct the clients to take their dog’s temperature sothat they are able to do this at home if the dog feelsunwell. If neutropenia and fever or hemorrhagic fecesare present simultaneously, then hospitalize the patientfor IV antibiotic therapy: cephazolin (22 mg/kg tid–qid),with or without enrofloxacin (5 mg/kg IV sid), with orwithout metronidazole (7.5–10 mg/kg orally [PO] bid).Intravenous fluids may be administered if GI signs aresevere or in an attempt to help diminish a febrileepisode; the choice of IV fluids used varies with elec-trolyte and glucose requirements. Blood glucose levelsshould be evaluated for suspected septicemic patients. Ifthe patient is suffering from severe lethargy or GI dis-tress, a full biochemical profile should be performed toevaluate renal and hepatic function, as well as serumelectrolyte levels. Urine should be collected to identifypossible UTI and assess urine specific gravity, prior to ini-tiation of fluid therapy, as a complement to blood ureanitrogen and creatinine to evaluate hydration status andrenal function.


Use of granulocyte colony-stimulating factor (hrG-CSF, Neupogen) has become commonplace for neu-tropenic, febrile patients, though some clinicians reservethis treatment for those cases in which neutrophilrebound does not occur within 24–36 hours or thosewith neutrophil counts less than 500 cells/μl. The doseof hrG-CSF is 5 μg/kg SQ once daily. A daily CBC shouldbe obtained until the neutrophil count is above 2,000cells/μl (usually 1–3 days), at which time treatment withhrG-CSF is discontinued. Occasionally, oncologists initi-ate treatment with hrG-CSF at the time of the expectedneutrophil nadir if a particularly myelosuppressivechemotherapy protocol is in use. It is important toremember that hrG-CSF should not be administeredwithin the first few days following myelosuppresive ther-apy, as this places stem cells at risk for injury by thechemotherapy agent as they are stimulated to enter thecell cycle. Neutropenia-associated fever and sepsis is veryrare in cats. Chemotherapy-associated anemia is gener-ally mild and self-limiting. Treatment of chemotherapy-induced thrombocytopenia remains supportive in theform of blood transfusions if a bleeding diathesis causessevere anemia. Thrombopoietin (a bone marrow stimu-latory factor for platelets) may become commerciallyavailable in the future and could prove useful in thesepatients.

Subacute vomiting is generally mild and self-limit-ing, and the usual recommendations are for fasting or


nothing by mouth, followed by small, frequent feedingsof a bland diet. Use of antiemetic drugs, such as meto-clopramide or chlorpromazine, may be initiated forpatients with more than one episode of vomiting. It maybe necessary to administer these drugs parenterally if thepatient is unable to tolerate oral dosing. For refractorycases, butorphanol (0.2–0.4 mg/kg SQ tid–qid) is veryeffective. Intravenous fluids are required for patientsintolerant of oral hydration methods. Episodes of diar-rhea or hematochezia usually require little more than abland diet as treatment. For cases that last more thanone or two days, treatment with loperamide (ImodiumA/D, 0.08–0.2 mg/kg, or 2 mg/25 kg PO q8–12hr—caution if using for dogs <10 kg; 0.08 mg/kg POq12–24hr for cats, with caution) or diphenoxylate(Lomotil, 0.05–1.0 mg/kg PO qid for dogs; 0.063 mg/kgor 0.25 mg/cat PO q8–12hr for cats). Sucralfate(Carafate, 1/4 gm PO q8–12hr) may provide relief fromdiarrhea in some cats. The diagnosis of sterile hemor-rhagic cystitis (SHC) secondary to use of cyclophos-phamide is made in the presence of pollakiuria,stranguria, and hematuria with no evidence of UTI. Thissyndrome is generally observed three to seven days fol-lowing administration of cyclophosphamide. SHC mayoccur following the first treatment with cyclophos-phamide or following several doses of the drug. SHC isself-limiting but can be severe and a source of great stressto the patient and the client; cases may last as long as


8–10 weeks in my experience, although most resolvewithin 1–2 weeks. Attempts at treatment of SHC with cor-ticosteroids and NSAIDS have been generally unreward-ing despite anecdotal reports of success withantispasmodic agents (such as propantheline). It is rec-ommended that a patient with SHC should not betreated with cyclophosphamide (or related agents) againin the future.

Cumulative or Delayed Toxicity

The classic type of cumulative, delayed toxicity is car-diomyopathy associated with use of doxorubicin. Thistoxicity is generally avoidable by limiting the lifetimecumulative dose to 180–240 mg/m2, but even with thisprecaution, cases of cardiomyopathy may occur. Unfor-tunately, once cardiomyopathy has developed, it is gen-erally irreversible, and fatal congestive heart failuretypically ensues within 6 months. Careful prescreeningof patients to rule out preexisting myocardial disease iswarranted before using doxorubicin. Blood urea nitro-gen, creatinine, and urine specific gravity values shouldbe evaluated in these patients prior to each treatment.Chronic use of alkylating agents such as melphalan andchlorambucil is associated with severe, possibly irre-versible myelosuppression, particularly of the platelets.Careful, regular monitoring of trends of peripheralblood cells is vital to prevent such toxicity.


Client Communication

Above all, inform your clients what they may expect andimpress upon them the importance of rapid communi-cation with you in the event of any complications, nomatter how minor. This information will help you pre-plan any future treatment adjustments as well as preventminor complications from becoming major ones.


5 Chemotherapy Dosages, Indications,

and Adverse Reactions

Asparaginase (Elspar)Dosage: 10,000 IU/m2 intramuscularly

(IM) every 1–4 weeks.400 IU/kg IM every 1–4 weeks.

Indications: Lymphoma, leukemia.Adverse Reactions: Anaphylaxis.

Azothioprine (Immuran)Dosage: 2 mg/kg orally (PO), once daily

for 2 weeks; then 0.5–1.0 mg/kgPO every 48 hours thereafter.

167

Indications: Immune suppression (IMHA,IMTP, Evans’s syndrome).

Adverse Reactions: Myelosuppression, nausea.

Bleomycin (Bleoxane)Dosage: 2 mg/m2 subcutaneously (SQ)

weekly.Indications: Carcinomas, lymphoma,

leukemias.Adverse Reactions: Myelosuppression.

Busulfan (Myleran)Dosage: 0.2 mg/kg PO daily.Indications: Myeloblastic leukemias.Adverse Reactions: Myelosuppression.

Carboplatin (Paraplatin)Dosage: Dogs—300 mg/m2 intravenously

(IV) every 3–4 weeks.Dogs—90 mg/m2 IV weekly.Cats—200 mg/m2 IV every 3–4weeks.

168 Chemotherapy Dosages, Indications, and Adverse Reactions

Indications: Osteosarcoma, melanomaAdverse Reactions: Myelosuppression, vomiting.

CCNU (Lomustine)Dosage: 60–90 mg/m2 PO every 3 weeks.Indications: Relapsed lymphoma, mast cell

tumors, cutaneous lymphoma,mycosis fungoides.

Adverse Reactions: Myelosuppression, vomiting.

Chlorambucil (Leukeran)Dosage: 0.2 mg/kg PO daily for 10 days

then every 48 hours thereafter.Indications: Lymphoma, leukemias, soft tissue

malignancies, mast cell tumors.Adverse Reactions: Myelosuppression.

Cisplatin (Platinol)Dosage: 70 mg/m2 IV every 3–4 weeks or

30 mg/m2 IV weekly; use a 3- to 4-hour saline diuresis.

Indications: Osteosarcoma, melanoma.Adverse Reactions: Myelosuppression, vomiting, renal

failure.

Chemotherapy Dosages, Indications, and Adverse Reactions 169

Cyclophosphamide (Cytoxan)Dosage: 200–350 mg/m2 PO or IV every

1–3 weeks or 50 mg/m2 PO dailyfor 4 days per week.

Indications: Lymphoma, leukemias, soft tissuemalignancies.

Adverse Reactions: Myelosuppression, hemorrhagiccystitis.

Cyclosporine (Sandimmune)Dosage: 3–10 mg/kg PO daily.Indications: Immune suppression, atopy.Adverse Reactions: Vomiting, diarrhea, anorexia.

Cytarabine (Cytosar-U)Dosage: 100 mg/m2 SQ TID for 3 days or

10 mg/m2 SQ q12hr until remis-sion occurs.

Indications: Leukemias.Adverse Reactions: Myelosuppression.


Dacarbazine (DTIC)Dosage: 200 mg/m2 IV daily for 5 days.Indications: Relapse lymphoma.Adverse Reactions: Severe vomiting, myelo-

suppression.

Doxorubicin (Adriamycin)Dosage: >20 lbs = 30 mg/m2 IV every 2–3

weeks (maximum five times).<20 lbs = 1 mg/kg IV every 2–3weeks (maximum five times).

Indications: Lymphoma, soft tissue tumors.Adverse Reactions: Myelosuppression, anaphylaxis,

vomiting, cardiomyopathy (do notexceed 180 mg/m2 cumulativeadministration).

Epirubicin (Pharmorubicin, Ellence)Dosage: 30 mg/m2 IV every 2–3 weeks.Indications: Lymphoma, soft tissue malignan-

cies, carcinomas.Adverse Reactions: Myelosuppression, vomiting, diar-

rhea, acute hypersensitivity.


Fluorouracil (5-FU)Dosage: 50 mg/m2 intralesionally mixed

in sesame oil (10 mg/ml finalconcentration).

Indications: Soft tissue malignancies.Adverse Reactions: Seizures, ataxia.

Gemcitabine (Gemzar)Dosage: 90–250 mg/m2 IV every 3 weeks.Indications: Pancreatic and hepatocellular

carcinomas.Adverse Reactions: Myelosuppression, vomiting,

anaphylaxis.

Hydroxyurea (Hydrea)Dosage: 50 mg/kg PO daily until remission.Indications: Leukemias.Adverse Reactions: Myelosuppression.

Ifosfamide (Ifex)Dosage: 375 mg/m2 diluted to 9.75 mg/kg

in saline, IV every 2–3 weeks withconcurrent MENSA (Mesnex®),


2-Mercaptoethanesulfonic acid;used to prevent bladder toxicity,such as sterile hemorrhagic cysti-tis, from ifosfamide orcyclophosphamide metabolites)administration.

Indications: Soft tissue malignancies, lym-phoma, lung tumors.

Adverse Reactions: Hemorrhagic cystitis (profound),myelosuppression, vomiting.

Melphalan (Alkeran)Dosage: 0.1 mg/kg PO daily for 10 days

then every 48 hours thereafter.Indications: Leukemia.Adverse Reactions: Myelosuppression.

Methotrexate (Methotrexate)Dosage: 0.5 mg/kg IV every 3 weeks.Indications: Lymphoma, leukemia.Adverse Reactions: Myelosuppression, vomiting.

Mitoxantrone (Novantrone)Dosage: Dogs—5–6 mg/m2 IV every 2–3

weeks.


Cats—5–6.5 mg/m2 IV every 3–4weeks.

Indications: Lymphoma, soft tissue tumors.Adverse Reactions: Myelosuppression, anaphylaxis,

vomiting.

Paclitaxel (Taxol)Dosage: 165 mg/kg, diluted to 0.6 mg/ml

in 0.9% saline, given as a continu-ous IV infusion over at least 2hours every 21 days; 5-day premed-ication with prednisone, cimeti-dine, and benadryl required.

Indications: Lymphoma, soft tissue tumors,mammary tumors.

Adverse Reactions: Anaphylaxis, vomiting, diarrhea,myelosuppression, alopecia.

Piroxicam (Feldene)Dosage: Dogs—0.3 mg/kg PO daily

or every 48 hours with or without concurrent antacidadministration.Cats—0.3 mg/kg PO every 3–4days with our without concurrentantacid administration.


Indications: Transitional cell carcinoma,melanomas, carcinomas.

Adverse Reactions: Gastrointestinal ulceration.

Prednisone (Prednisone)Dosage: 40 mg/m2 PO divided bid, sid, or

every 48 hours.Indications: Lymphomas, leukemias,

insulinomas.Adverse Reactions: Polyuria, polydypsia.

Streptozotocin (Zanosar)Dosage: 500 mg/m2 IV every 3 weeks with

concurrent 3-hour saline diuresis.Indications: Insulinomas.Adverse Reactions: Nephrotoxicity.

Tamoxifen (Nolvadex)Dosage: 2.5–10 mg PO bid.Indications: Mammary tumors, brain tumors,

anticancer drug resistant tumors,melanomas.

Adverse Reactions: Vaginal discharge, pyometra.


Vinblastine (Velban)Dosage: 2 mg/m2 IV slowly every 1–3

weeks.Indications: Lymphoma, Leukemias, mast cell

tumors, soft tissue tumors.Adverse Reactions: Myelosuppression.

Vincristine (Oncovin)Dosage: 0.5–0.75 mg/m2 IV every 1–3

weeks.Indications: Lymphoma, leukemias, mast cell

tumors, soft tissue tumors.Adverse Reactions: Myelosuppression.


6Chemotherapy Dosage

Conversion Chart

The following values are derived from the equation m2 = 10.0 (10.1 in cats) � (weight in grams)2/3/10,000.Always confirm all dosage calculations before drugadmixing and administration. In the following chart, thefirst and fourth columns are body weight in kilograms,the second and fifth columns are body weight in pounds,and the third and sixth columns are the calculated valuein body surface area (in square meters).

177

Kg Lb m2 Kg Lb m2

0.5 1.1 0.06 33 72.6 1.031 2.2 0.10 34 74.8 1.052 4.4 0.15 35 77.0 1.073 6.6 0.20 36 79.2 1.094 8.8 0.25 37 81.4 1.115 11.0 0.29 38 83.6 1.136 13.2 0.33 39 85.8 1.157 15.4 0.36 40 88.0 1.178 17.6 0.40 41 90.2 1.199 19.8 0.43 42 92.4 1.21

10 22.0 0.46 43 94.6 1.2311 24.2 0.49 44 96.8 1.2512 26.4 0.52 45 99.0 1.2613 28.6 0.55 46 101.2 1.2814 30.8 0.58 47 103.4 1.3015 33.0 0.60 48 105.6 1.3216 35.2 0.63 49 107.8 1.3417 37.4 0.66 50 110.0 1.3618 39.6 0.69 52 112.2 1.4119 41.8 0.71 54 114.4 1.4420 44.0 0.74 56 116.6 1.4821 46.2 0.76 58 118.8 1.5122 48.4 0.78 60 121.0 1.5523 50.6 0.81 62 123.2 1.58

178 Chemotherapy Dosage Conversion Chart

(continued)

Kg Lb m2 Kg Lb m2

24 52.8 0.83 64 125.4 1.62 25 55.0 0.85 66 127.6 1.6526 57.2 0.88 68 129.8 1.6827 59.4 0.90 70 132.0 1.7228 61.6 0.92 72 134.2 1.7529 63.8 0.94 74 136.4 1.7830 66.0 0.96 76 138.6 1.8131 68.2 0.99 78 140.8 1.8432 70.4 1.01 80 143.0 1.88

Chemotherapy Dosage Conversion Chart 179

7Ten Commonly Used

Chemotherapy Protocols

The following protocols are derived from clinical trialresults and personal experience with the expectation ofachieving an overall remission rate (the sum of all com-plete and partial responses) of greater than 50% with a6-month minimum duration of clinical response. Someof these protocols have shown remission rates exceeding80% and remission durations exceeding 2 years. Remem-ber that most clinical protocols rarely exceed a 20% com-plication rate and so never truly achieve an expectationconsistent with an intent to cure. Increasing the dosageof a drug, shortening the frequency between drug

181

administrations, or including additional drugs mayincrease protocol efficacy and clinical toxicity. Pleasereview the section on managing chemotherapy sideeffects. The concurrent use of radiation therapy may alsobe indicated. Consult with a local veterinary oncologistand have an open dialogue with the pet owner regardingtherapy goals.

Protocol IndicationsProtocol 1: Induction protocol for canine osteosar-

coma, canine hemangiosarcoma, caninesoft tissue carcinomas and adenocarcino-mas (thyroid, sweat gland, anal sac). Con-sider protocol 10 as maintenance therapyfor 6–9 additional months. Consider con-current radiation to the tumor site. Con-sider mitoxantrone as an alternative toAdriamycin in patients suspect for cardiacdisease.

Protocol 2: Induction protocol for canine osteosar-coma, canine bladder tumors. Considerprotocol 10 as maintenance therapy for6–9 additional months. Consider concur-rent radiation to the tumor site. Considermitoxantrone as an alternative to Adria-mycin in patients suspect for cardiacdisease.

182 Ten Commonly Used Chemotherapy Protocols

Protocol 3: Induction protocol for canine osteosar-coma, thyroid carcinoma, and lungtumors. Consider protocol 10 as mainte-nance therapy for 6–9 additional months.Consider concurrent radiation to thetumor site.

Protocol 4: Canine bladder tumors, feline injection-site associated sarcomas (consider concur-rent irradiation). Consider protocol 10 asmaintenance therapy for 6–9 additionalmonths.

Protocol 5: Canine oral and subungal melanomas(carboplatin is 90 mg/m2 intravenously[IV] weekly). Tamoxifen may also beindicated.

Protocol 6: Canine and feline lymphoma (continue asscheduled for 18 months).

Protocol 7: Canine and feline lymphoma (continue asscheduled for 18 months). Canine andfeline soft tissue tumors (excluding theuse of Elspar).

Protocol 8: Canine and feline mast cell tumors (con-tinue as scheduled for 12 months). Con-sider concurrent radiation therapy forgrade III tumors.

Protocol 9: Induction protocol for canine and felinetonsillar squamous cell carcinoma. Con-sider concurrent radiation therapy.

Ten Commonly Used Chemotherapy Protocols 183

Protocol 10: Maintenance protocol for various malig-nancies including canine hemangiosar-coma, canine and feline soft tissuecarcinomas and adenocarcinomas, canineand feline lymphoma.

Supportive Drugs Considered Optional toPrevent or Relieve Adverse Reactions

Nausea or Metoclopramide (Reglan), 0.5 mg/kg Vomiting: orally (PO) every 8 hours for 5 days.Colitis: Sulfasalazine (Asulfadine), 33 mg/kg PO

every 8 hours for 5 days.Gastric Cimetidine (Tagamet), 4 mg/kg PO everyUlceration: 8–12 hours regularly during piroxicam

administration.

184 Ten Commonly Used Chemotherapy Protocols

Ten Commonly Used Chemotherapy Protocols 185

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8Supportive Care and Rehabilitation

The complications of cancer and chemotherapy areoften the most difficult for owners. When treating theveterinary cancer patient, the clinician needs to clearlycommunicate treatment goals with owners. If animalsare apparently made worse by the treatment, owners maybe reluctant to continue. Because anorexia, nausea, vom-iting, and diarrhea are obvious outward signs, they maybe more disturbing than neutropenia, hypercalcemia,lymphadenopathy, or other complications. These signsmay also be due to the tumor itself, and distinguishingwhat is caused by the treatment and what the diseasecauses may be difficult. Supportive care should be timelyand aggressive.

187

Long-term complications are the chronic or linger-ing problems after the cessation of therapy, while lateeffects are delayed problems occurring months to yearsafter treatment. Long-term follow-up will not necessarilyeliminate the chronic or delayed effects of therapy, but itwill enable pet owners to make better informed deci-sions about issues affecting the quality of their pets’ lives.Awareness of risk can encourage changes in behaviorthat promote health (e.g., proper diet) and early detec-tion of tumor recurrence (e.g., regular veterinary exam-inations), thus optimizing the chances for long-termsurvival.

System-specific or organ damage or failure and pre-mature aging due to chemotherapy, radiation therapy,biologic modifiers, surgery, or any combination of thesehave been described. Some examples include (1) car-diomyopathy, renal insufficiency, bladder damage,cataracts, muscle atrophy; (2) compromised immune sys-tems causing increased risk of infection (viral, bacterial,or fungal) and possible increased risk of malignancy; (3) damaged endocrine systems leading to thyroid dys-function, hypothalamic-pituitary dysfunction, or repro-ductive problems; (4) recurrence and secondarymalignant neoplasms; (5) increased risk associated withcertain therapies (e.g., bladder cancer as a result ofcyclophosphamide therapy).

Other problems associated with cancer therapy may

188 Supportive Care and Rehabilitation

include (1) functional changes, such as incontinence,immobility due to weakness or orthopedic problems,orthodontic problems, lymphedema, sleep disturbances,pain syndromes, fatigue, or mucosal dryness; (2) cos-metic changes, such as amputations, ostomies, or skinand hair changes; (3) chronic illnesses, such as osteo-porosis, arthritis, scleroderma, or hypertension; and (4)psychosocial effects related to physiologic morbidity,such as anxiety, mood changes, or depressed behavior.

Cooperation is required between oncologists, pri-mary care veterinarians, and other veterinary care stafffor continued follow-up appropriate to the pet’s cancerhistory. Once cancer therapy begins, emphasis onpromotion of health and wellness is necessary, such asnutritional and pain support. Furthermore, everyoneinvolved in the care of the cancer-bearing pet shouldhave a clear understanding regarding the role of cyto-toxic agents, radiation therapy, or combinations of bothon the incidence and type of long-term complicationsand late effects of the prescribed cancer treatment plan.Offer appropriate owner education that includes full dis-closure of all potential long-term or late complications oftreatment, warning signs of possible problems, andsymptom management strategies. Promote appropriatebehavioral modifications, such as proper nutrition andexercise, to improve and strengthen damaged immunesystems and prevent future iatrogenic late effects.

Supportive Care and Rehabilitation 189

NutritionA variety of factors may predispose cancer patients to mal-nutrition during treatment. Maintenance of an optimalweight and prevention of nutritional deficiencies (andexcesses) can improve the patient’s outcome. In addition,nutritional modulation may be beneficial in the treat-ment of the disease. Therefore, nutrition should be anintegral part of the management for every cancer patient.

Nutritional Alterations in Cancer Patients

Researchers have shown that a number of metabolicalterations occur in dogs with cancer. Carbohydrate, pro-tein, and lipid metabolism is altered in dogs with a vari-ety of tumors, although the clinical implications and theeffect of diet on these alterations are still being investi-gated. Whether similar metabolic alterations occur incats with cancer still needs to be determined. Weight lossor cancer cachexia is a very common problem in peoplewith cancer. Unlike simple starvation, in which primarilyfat is lost, cancer cachexia involves a loss of both proteinand fat. In people, this weight loss is associated withshortened survival and poor quality of life. Two veteri-nary studies have shown that weight loss is uncommon inoncology patients.1,2 However, some individuals or evencertain patient populations may be more susceptible toweight loss. This might include animals undergoing radi-ation therapy, since they often undergo prolonged


hospitalization and daily sedation as part of the therapy.A recent study of dogs and cats undergoing radiationtherapy showed a median weight loss of 9.4% in dogsand 10.5% in cats. This suggests that preemptive nutri-tional support may be indicated. When weight loss doesoccur in the cancer patient, it is important to address thisproblem. While cancer cachexia is not a common issuein pets, obesity can often be a problem in dogs undergo-ing chemotherapy. This may be the result of prednisoneuse as part of the chemotherapy protocol or from own-ers who indulge their sick pet. In some of these patients,obesity can be severe enough to interfere with thepatient’s quality of life (e.g., reduced mobility, muscu-loskeletal disorders). Early discussion of the problems ofobesity with owners is recommended when weight gain isfirst noted, not after it is too late. It is extremely difficultto convince an owner of a cancer patient to put their peton a strict reduction diet.

Nutritional Assessment of the Cancer Patient

A careful diet history can help identify the presence andsignificance of the following factors that put patients atrisk of malnutrition (e.g., weight loss, changes inappetite) or overnutrition (e.g., obesity, vitamin or min-eral excesses from supplementation). Sometimes, a care-ful diet history reveals an inappropriate diet, excessivesupplementation, or other nutritional problems. Moni-toring body weight and body condition throughout


therapy for cancer patients is critical. Trends in bodyweight can identify weight gain or loss before it becomesa problem. Body condition scoring provides additionalinformation on whether the body weight is appropriatefor that animal (e.g., a 1–9 scale with 5 = optimal bodycondition). Other physical examination findings mayindicate the presence of malnutrition (e.g., muscle loss,poor hair coat, poor wound healing), although thesesigns are not usually seen until a relatively advancedstage of malnutrition. It is much better to identify an ani-mal at risk for malnutrition (e.g., frequent anesthesia,reduced appetite) and prevent malnutrition from occur-ring than try to correct it. It is important to ask ownersspecifically about nutritional supplement use in dogsand cats with cancer. A large percentage of owners whosepets have cancer are administering nutritional or herbalsupplements, and they may not voluntarily provide thisinformation unless specifically asked. Ask both whattypes of supplements are given and the doses. This infor-mation can help determine whether the supplement useand the dose are appropriate and whether any drug-nutrient interactions might occur with other forms oftherapy being used.

Anorexia

Many patients undergoing chemotherapy or radiationtherapy develop anorexia at some time during thecourse of the treatment. Anorexia can have direct detri-


mental effects because it can lead to weight loss. In addi-tion, anorexia is a common contributing factor to anowner’s decision for euthanasia. Appetite stimulationwith cyproheptadine or benzodiazepine derivatives is notusually very effective but sometimes may help to give ananimal a “jump-start” back into eating. Dietary changescan be helpful for anorexic animals. Switching to a morepalatable food may enhance food intake (changing fromdry to canned, from canned to dry, or to a differentbrand of food). Palatability enhancers also can improveappetite (e.g., low-salt tomato sauce, honey, yogurt fordogs; tuna juice, cooked meat for cats). Fish oil supple-mentation, which is high in n-3 fatty acids, also mayreduce anorexia in some animals. The method of feed-ing may influence eating behavior. A recent studyshowed that food intake of hospitalized animalsimproved significantly when they were hand-fed com-pared to voluntary eating. If the pet will not eat enoughby mouth, however, nutrition support is indicated.

Enteral Nutrition

When animals will not eat sufficient food voluntarily,nutrition support techniques are necessary to ensureadequate nutrient intake. Enteral nutrition is the pre-ferred method for nutrition support. Enteral nutrition issafer, more physiologic, and less expensive than par-enteral nutrition and helps maintain gastrointestinal(GI) structure and function. Enteral nutrition should be


used in any patient that will not or cannot voluntarily eatadequate calories orally. Contraindications include vom-iting, severe malabsorption, and an inability to guard theairway. A nasoesophageal tube can be used for short-term nutrition support (3–4 days), while esophagostomyor gastrostomy tubes are indicated for long-term man-agement. An esophagostomy or gastrostomy tube canoften be coordinated with sedation for other procedures(e.g., diagnostic procedures, surgery, or, anesthesia forradiation). Diets for tubes depend on the patient andtype of tube being used. Nasoesophageal tubes require aliquid diet, while esophagostomy and gastrostomy tubesare large enough to use either a blenderized pet food ora “critical care” diet (e.g., Hill’s a/d, Topeka, KS;Eukanuba Maximum Calorie, Dayton, OH). Humanenteral diets are used by some practices, but these areunbalanced for dogs and cats without supplementation.In cases where human enteral diets are preferred, sup-plementation with protein and B vitamins (for dogs andcats), plus taurine and arginine for cats is required toavoid deficiencies. Although other nutrients in these for-mulas also do not meet canine and feline requirements,they usually cause no problem with short-term use.Other nutrients, such as glutamine, arginine, n-3 polyun-saturated fatty acids, and micronutrients may have phar-macological benefits above and beyond their nutritionalrequirements, especially in the cancer patient.


Parenteral Nutrition

If the entire GI tract is nonfunctional or conditions pro-hibit the use of enteral nutrition, the other option is tofeed parenterally. Parenteral nutrition can be deliveredby a central vein (total parenteral nutrition, or TPN) or aperipheral vein (peripheral or partial parenteral nutri-tion, or PPN). Although PPN is no replacement for TPN,it can be useful for short-term nutritional support (<5 days) in a nondebilitated animal to help prevent mal-nutrition. It also can be used to supplement tube feedingin some cases. Since PPN can be formulated to meet only50–75% of a patient’s energy requirements, it should notbe used in a debilitated patient. Another temporaryoption for PPN is commercial mixes containing a proteinand carbohydrate source (e.g., Procalamine, McGaw,Irvine, CA; Quick Mix, Clintec, Deerfield, IL). Althoughthese solutions only provide approximately 25% ofenergy requirements when administered at maintenancefluid rates, they can be useful as an interim or short-term source for parenteral nutrition. Like TPN, PPN has potential complications, including metabolic dis-orders, mechanical complications, and sepsis; so carefulhandling of catheters, lines, and solutions is required.Monitoring for metabolic abnormalities is necessary toprevent complications from all forms of parenteralnutrition.


Patient Assessment and Nutritional Needs

The veterinary community is beginning to appreciatethe relationship between enteral nutritional support andproper medical and surgical management of companionanimals. The optimal route for meeting the nutritionalrequirements of companion animals is the gastrointesti-nal tract. Enteral nutritional support uses some part ofthe gastrointestinal tract to feed the patient that cannotor will not eat but can digest and absorb nutrients.Enteral feeding is the simplest, fastest, safest, and leastexpensive method of feeding companion animals thatrequire nutritional support. Assessment of the patientrequiring enteral nutritional support should include anassessment of the animal, the current diet, and feedingmanagement. The combined subjective and objectivedata collected can be used to formulate an appropriateenteral feeding plan and define the specific nutritionalgoals to manage the patient. The feeding plan then mustbe implemented and monitored; and if the animal goeshome with an enteral tube, the client must be educated.Frequently the veterinarian must rely on clinical judg-ment rather than objective data to decide to instituteenteral nutritional support. However, simple tools suchas a thorough clinical assessment are surprisingly sensi-tive. The primary goal of nutritional assessment is to pre-dict the animal that can benefit from nutritionalsupport. In the future, other techniques may be availableclinically to provide a more objective and quantitative


assessment of nutritional status. Anorexia and malnutri-tion, particularly protein calorie deficiency, is commonin companion animals requiring nutritional support.Malnutrition reduces synthesis of plasma proteins,impairs wound healing, and decreases the immuneresponse. It is essential for the veterinarian to assess thenutritional status of the patient on initial presentationand reassess the animal at appropriate intervals afternutritional intervention to determine whether a changein nutritional status has occurred.

PATIENT ASSESSMENT Nutritional assessment of thecompanion animal is a structured process that includesreview of the signalment, history, and medical record;physical examination; laboratory evaluation; and estima-tion of nutritional requirements based on physiologicalstate. Review of the signalment, history, and medicalrecord should include questions related to changes inbody weight, food intake, and drugs and other therapiesthat may affect appetite or nutrient metabolism. Themedical record may yield important objective informa-tion that may provide clues to the animal’s nutritionalstatus. Several drug-nutrient interactions may influencedietary intake or nutritional requirements. For example,animals receiving diuretics may have increased needs forpotassium, magnesium, and calcium. The patient’s phys-iological state should be determined by collecting infor-mation related to body weight, body condition score,growth rate, reproductive status, species, and the nature


and duration of the presenting illness. These parametersaffect the nutrient requirements of the animal for agiven nutrient. Furthermore, the client should be ques-tioned about environmental factors, such as activity andhousing, which could also alter nutrient requirements.The client should also be questioned about the animal’sdietary history, including the current diet, eating habits,and feeding management. The dietary history shouldstrive to identify all items of food being consumed by theanimal, including table scraps, treats, and supplements.The amount of each food offered and consumed shouldbe specified and factors that could affect intake, such asother animals in the household, should be recorded.Companion animals that have been anorexic or hadrestricted food intake for longer than 3 days may benefitfrom nutritional intervention.

Physical examination can help determine the nutri-tional status of companion animals. Body weight andbody condition score (score of 1 to 5, with 1 being thinand 5 being obese) provide a subjective estimation of theanimal’s body composition. Fat cover over the ribs, downthe topline, around the tailhead, and ventrally along theabdomen should be evaluated. A body condition scorecan be combined with zoometric measurements, such aspelvic circumference, to provide a better estimate of bodyfat. Body weight can be compared to usual or optimumbody weight and breed standards. Nutritional support isindicated if the patient recently lost more than 10% of its


usual or optimum body weight. The patient’s generalappearance should be assessed, including the presenceor absence of edema, ascites, and nonhealing wounds.Evaluation of hair coat, skin, and nails may provide anindication of malnutrition. Growth retardation, muscleweakness, or atrophy aids in the identification of cata-bolic, critically ill patients. Dysfunction of organs, such asthe liver, heart, kidneys, or lungs, may explain poor bodyweight and condition and help determine the mostappropriate nutrient profile for the enteral diet. Labora-tory evaluations may serve as objective indicators of nutri-tional status; however, no single laboratory parameteranalyzed routinely in veterinary medicine can accuratelyassess nutritional status. Laboratory tests, such as thosefor albumin, lymphocyte count, pack cell volume, andtotal protein, may provide insight into the patient’s nutri-tional status. For example, hypoalbuminemia mayindicate visceral protein depletion due to chronic under-nutrition or protein loss. In humans, hypoalbuminemiacorrelates with increased morbidity and mortality ratesand longer hospital stays. In the future, shorter half-lifeserum proteins, such as prealbumin, transferrin, retinol-binding protein, or fibronectin, may be available to assessshort-term changes in nutritional status. Serum glucose isimportant to assess in severely stressed, catabolic patients.Furthermore, since malnutrition affects the immune sta-tus of the patient, perhaps, in the future, an immune pro-file could be developed to provide a more sensitive


assessment of nutritional status. Serum biochemical pro-file changes associated with major organ dysfunction mayprovide indications of problems that may be nutrient sen-sitive and therefore affect the selection of the enteraldiet. For example, if the patient requiring enteral nutri-tional support has associated renal or liver disease, dietselection would dictate a modification in the levels of cer-tain nutrients. Other laboratory tests that may be of valuein nutritional assessment include urinalysis and fecalanalysis.

NUTRITIONAL NEEDS The patient’s nutrient and waterrequirements should be calculated and compared withthe nutrient and water intake of the animal. Nutrientintake can be estimated from the dietary history or bemonitored and evaluated if the animal is hospitalized. Inmost cases, the animal requiring enteral nutritional sup-port has an intake that is less than its requirements. Cal-culation of the nutrient requirements of the patientrequiring enteral nutritional support depends on thephysiologic state of the animal. Many of these animalsare critically ill, at least initially, and may have sufferedtraumatic injury, sepsis, or major organ disease in com-bination with food deprivation. Many conditions com-monly diagnosed in veterinary medicine increases theanimal’s risk of malnutrition. Disorders that may be asso-ciated with increased losses of protein and electrolytesinclude vomiting, draining wounds, ileus, diarrhea,


abscesses, chylothorax, enteropathy or nephropathy, andmalassimilation. Conditions that may be associated withincreases or decreases in nutrient requirements includeblood loss, liver disease, renal disease, trauma, sepsis,pulmonary disease, and cancer. Nutritional support maybe indicated in animals receiving antinutrients or cata-bolic drugs that result in anorexia or dysphagia. Catshave special nutritional requirements, as compared todogs, because they are strict carnivores. These specialdietary requirements of the cat should be consideredwhen considering the selection of an enteral product.Among the special physiologic and metabolic require-ments of cats are more protein than needed by dogs, anessential need for taurine, a requirement for arachidonicacid in their diet, more niacin and pyridoxine, and tak-ing into account the feline inability to convert B-9carotene to vitamin A. These differences become impor-tant when selecting an enteral product to feed a cat.Human liquid diets are not balanced for cats, and manyof the products lack sufficient taurine.

The following steps should be used to calculate thenutrient requirements of the patient (both dog and cat)and the feeding level for enteral nutritional support:

1. Calculate resting energy requirement. The restingenergy requirement (RER) is the amount of energyrequired by the animal in a postabsorptive resting stateand accounts for a thermoneutral environment and


physiological influences. In human medicine, RER isdetermined by indirect calorimetry, but this technique isnot widely used in veterinary medicine. In critically illcompanion animals, the goal is to meet resting energyrequirement on a daily basis. Critically ill animals arehospitalized, confined to a cage, and have energyrequirements below maintenance levels. Many timespatients have not eaten for several days and thereforeshould be adapted to the enteral diet over several days.The resting energy requirement is the starting point inmeeting daily energy requirements. If the animal toler-ates this level of feeding, then energy intake can beincreased over time. Patients sent home and fed longterm through feeding tubes are fed at higher levels,closer to maintenance levels. Again, the goals for energyintake are dictated by physiological state of the animal.In many of the enteral diets fed to dogs and cats, thenutrient content is balanced to the caloric content of thediet. Therefore, if you feed to meet the calculated dailyenergy requirement of the patient, all other nutrientrequirements are met. Water should be provided at therate of 1 ml for each kcal of calculated daily energyrequirement.

2. Select an enteral diet. Diet selection for enteralnutritional support depends on tube size and location,product availability and cost, functioning of the gastro-intestinal tract, and the experience of the veterinarian.Products available to feed include blended pet foods,veterinary-formulated critical care diets, and human


liquid enteral diets. Pet foods are higher in protein andfat than commercially available human liquid diets, havevarious nutrient profiles, are readily available, and arethe least expensive products to feed for the enteral sup-port of dogs and cats. Both blended pet foods and vet-erinary-formulated critical care diets cause fewercomplications, such as diarrhea, and usually requirefewer feedings per day than human enteral diets. In mostcases, a high energy and protein food should be chosenas the enteral diet. However, if the patient has renal orliver disease, a veterinary therapeutic diet can beblended and fed through the tube. Patients fed veteri-nary diets through the feeding tube may be fed the fooddirectly when they have regained their appetite, therebyeliminating a diet change. The veterinary-formulatedcritical care diets have increased levels of protein and fatas compared to average maintenance foods to aid insparing lean body mass and maintain host defenses.These diets may have increased levels of branched chainamino acids, n-3 fatty acids, B-9 complex vitamins,antioxidants such as vitamin E, glutamine, arginine andselected minerals (e.g., potassium, magnesium, andzinc). These diets may be formulated to be fed to bothdogs and cats. Such diets are contraindicated in animalswith renal or liver disease or for animals with gastroin-testinal problems that have resulted in fat intolerance.Human liquid enteral diets may cause diarrhea when fedto companion animals, and the diets are usually moreexpensive. Furthermore, the human liquid enteral diets


are not balanced for cats and must be modified withnutrient modules. Human liquid diets are available inpolymeric and monomeric formulations. Monomeric orelemental diets contain nutrients in their simplest formand require minimal digestion by the patient. Polymeric,or meal replacement, diets contain mixtures of proteins,fats, and carbohydrates from simple ingredients. Poly-meric diets require normal digestion. Human liquidenteral diets have the advantage that they can be fedthrough small feeding tubes and are available in a widevariety of nutrient profiles.

3. Determine food dosage. Calculate the total fooddose (ml), daily energy requirement (kcal), and energydensity of the product (kcal/ml). Initiate feeding bydividing the total daily amount to be fed by the numberof feedings per day. Begin by feeding one third of thefood per day and gradually increase the amount of theenteral diet per day. For example, a feeding schedule forthe first three days would be the following: calculateddiet + two thirds of the water on day 1, calculated diet +one third of the water on day 2, full calculated diet withno water added on day 3.

4. Determine feeding frequency. Frequency of feedingdepends on the diet type, route of feeding (tube type),and digestive and absorptive capacity of the patient. Forexample, an animal fed through an enterostomy tubemay require constant infusion of the diet.


5. Reassess. Reassess the patient to determine itsresponse to the diet and modify the feeding plan ifneeded.

Pain Management Management of pain constitutes an integral part of suc-cessful treatment for a wide variety of human diseases.This is particularly true for patients with malignancies,where the physiologic and psychological effects of painmay have a great impact. While advances in the under-standing and treatment of pain in animals have laggedsome years behind similar progress in the human field, itis now widely and increasingly accepted that appropriatetherapy for pain must accompany primary treatment ofmany animal diseases, including cancer.

Incidence

Approximately 50–80% of human patients with advancedcancer experience pain during the course of their dis-ease. The majority of these patients do not obtain satis-factory relief. This constitutes a major problem in themedical field, because unrelieved pain can significantlydiminish the patient’s quality of life. Among the factorsthat may contribute to inadequate pain management arethe overriding fears of addiction, health care profession-als’ lack of knowledge about pain medication and new


pharmacological interventions, and lack of confidence inthe efficacy of behavior techniques. Similar factors existin the veterinary medical community and are not limitedin application to pets with cancer.

Cancer pain can be acute or chronic. Acute paingenerally results from tissue damage and is of limitedduration. The physiological effects (e.g., tachycardia)observed result from stimulation of the autonomic nerv-ous system. Once the cause of pain has been identified,it can be successfully treated and is often completelyeradicated. Chronic pain, on the other hand, is persist-ent, usually longer than 3 months in duration. Becausethe pathology or cause of the pain cannot be altered, thenervous system eventually adapts and ceases to be hyper-active; the pain may then manifest itself as depression oranxiety.

Causes

The severity and prevalence of pain that cancer petsexperience depends on many factors, including the siteand stage of the disease and the location of metastases.Cancer-related pain can result from the disease processor cancer therapy. The most common causes of pain fromdirect tumor involvement are metastatic bone disease,nerve compression or infiltration, and hollow viscus (e.g.,bowel) involvement resulting in obstruction. All the


major treatment modalities may cause pain syndromes.Additionally, pets may have preexisting chronic painunassociated with either the disease or its treatment.

Pain affects each pet differently, depending on fac-tors such as age, perception, pain threshold, and pastexperiences with pain. Insomnia, fatigue, and anxietycan lower the pain threshold; while rest, sleep, and diver-sion can raise it.

Pain Assessment

An accurate assessment of the pet’s pain experience pro-vides a basis for an evaluation of various pain manage-ment techniques. A comprehensive assessment includesinformation about the following dimensions of pain:location, intensity, factors influencing its occurrence,observed behavior during pain, psychosocial variables(i.e., attitudes, situational factors), effects of pain, effectsof therapy, and patterns of coping. A variety of painassessment tools have been developed for use inhumans, ranging from simple self-reports about painintensity to detailed descriptive information. In veteri-nary medicine, assessment of chronic pain may beenhanced through the pet owner’s use of a pain diary, inwhich descriptions of the characteristics of the pain andthe effectiveness of management techniques can berecorded.


Treatment for Pain

The goal of pain management is not only relief frompain but also the maintenance of the pet’s normal qual-ity of life. All methods of pain management attempt toeither control the cause of the pain or alter the pet’s per-ception of it.

Although pain management techniques are manyand varied, therapeutic approaches can be classified aseither pharmacologic or nonpharmacologic. Pharmaco-logic pain control involves the use of analgesics as well asother medications that potentiate the analgesic’s effectsor modify the pet’s mood or pain perception. Nonphar-macologic approaches include behavioral techniques,radiation, surgery, neurological and neurosurgical inter-ventions, and traditional nursing and psychosocial inter-ventions; the latter measures attempting to promotecomfort and evaluate the effectiveness of the therapy.Because of the complex nature of cancer-related pain,successful management usually involves a combinationof techniques.

Cancer pain management in the geriatric pet callsfor special considerations. Aging pets are at an increasedrisk of drug reactions, because drug adsorption, distri-bution, metabolism, and elimination change with age,disease status, and medication interactions.

PHARMACOLOGIC MANAGEMENT Veterinary care per-sonnel must aggressively manage acute pain in the


cancer pet with medication to return the pet to a pain-free state as soon as possible. Once the pain is relieved,the pain medication is decreased to the lowest dosage ormildest analgesic that maintains the pain-free state.When the pain cycle is broken, pets can be sustained onminimal amounts of pain information.

Chronic pain, however, requires very different med-ication management. For example, a pet with chronicpain is usually started on a nonnarcotic analgesic andmoves to a narcotic as more effective pain control isneeded.

The World Health Organization (1987) states that“analgesic drugs are the mainstay of cancer pain man-agement” and advocates a three-step “analgesic ladder”for decision making. This schema is appropriate for usein veterinary medicine. Step 1 includes the use of anonopiod drug with or without an adjuvant drug (e.g.,aspirin + carprofen + misoprostil). If pain persists orincreases, pain management moves to step 2, a weak opi-oid plus a nonopioid, with or without an adjuvant drug(e.g., acetaminophen + codeine with or without carba-mazepine). If pain persists or increases, pain manage-ment moves to step 3, a strong opioid, with or without anonopioid, with or without an adjuvant drug (e.g., mor-phine with or without acetaminophen with or withoutdexamethasone).

Nonnarcotic pain agents are best used for mild can-cer pain. This category includes aspirin, acetaminophen,


and nonsteroidal anti-inflammatory drugs (NSAIDs).Nonnarcotic agents may also be used to potentiate theeffect of narcotic analgesics in pets with severe pain.However, these agents have a ceiling effect: Increasingthe dosage beyond a certain point produces no addi-tional pain relief. NSAIDs reduce the production ofprostaglandin by inhibiting cyclooxygenase (COX).Their analgesic properties are due primarily to their anti-inflammatory effects. Common side effects of these com-pounds include gastrointestinal and renal toxicity. Thenewer agents in this class include carprofen andetodolac. These compounds have a favorableCOX1:COX2, which in theory reduces the possible sideeffects associated with this class. Piroxicam is alsoincluded in this class. Other NSAIDs that may be usefulin the small animal patient include ketoprofen andketorolac.

Narcotic analgesics (opioids) are used for the treat-ment of moderate to severe cancer pain. They are cate-gorized as either narcotic agonist or narcoticagonist-antagonist drugs. This is the largest and perhapsmost valuable class of analgesic agents. These agentsinteract with specific receptors in the brain and spinalcord and are very efficacious. The side effects associatedwith this class are usually minimal, with respiratorydepression, bradycardia, and hypotension being of mostconcern. Using opiate antagonists can alleviate life-threatening side effects. The opioid agents most com-monly used include morphine, butorphanol, fentanyl,


and buprenorphine. Innovative modes for administra-tion include continuous rate infusion, epidural adminis-tration, and the transdermal fentanyl delivery system(patch).

One model explaining the actions and effects of theopioids, the multiple opioid receptor theory, proposesthat narcotic agonist drugs, such as morphine andcodeine, bind with specific opiate receptor sites. A drugcan bind to three kinds of receptor sites, or portions ofthe nerve cell: the μ (mu) receptor associated with anal-gesia and respiratory depression, the � (kappa) receptorwith sedative effects, and the � (sigma) receptor with psy-chomimetic effects.

Although the multiple opioid receptor theory is stillevolving and does not yet completely explain narcoticanalgesia, pure narcotic agonists such as morphine andcodeine are thought to occupy the μ receptor withoutantagonizing activity at the other receptor sites. Narcoticagonists-antagonists occupy the � receptor for painrelief, also antagonizing the effects of pure agonists atthe μ receptor. Three agonist-antagonists are butor-phanol, nalbuphine, and pentazocine.

Adjuvant analgesic drugs are also used to treat can-cer pain. This group includes amphetamines, anticon-vulsant agents, phenothiazines, tricyclic antidepressants,steroids, antihistamines, and levodopa. Although theirexact mechanisms of action for pain relief are not wellunderstood, these drugs relieve pain when used alone orin combination with other nonnarcotics or narcotics.


Pain medication may be given by the followingroutes: orally, rectally, subcutaneously, intramuscularly,intravenously, intrathecally, and epidurally. Conditionssuch as thrombocytopenia, neutropenia, and duration ofa medication’s effect must be taken into account whenselecting the route. The peak of a drug’s effect dependslargely on the route of administration. Oral medicationsusually peak in 2 hours, intramuscular drugs in 1 hour,and intravenous drugs in 15–30 minutes. The duration ofeffect varies widely and should be carefully considered.

The schedule for administering analgesics appearsto be an important factor in their effectiveness. Researchshows that around-the-clock (ATC) rather than asneeded (PRN) administration of analgesics is moreeffective in the control of chronic pain. In many cases,doses of analgesics may be decreased with ATC schedul-ing, because the pain intensity is consistently less.

Pets with cancer may be undermedicated for theirpain because veterinary care personnel believe thatcancer-bearing pets usually develop a tolerance to theeffects of opioids rather than an addiction. Tolerance tonarcotics can occur at any time and requires increasingdoses to produce the same level of analgesia. Pets alsodevelop tolerance to the serious side effects of narcotics(e.g., sedation, respiratory depression) at the same rateas tolerance to analgesia, so they can accept larger dosesof narcotics without overdosing.


Analgesics and Dosages Available for Use in Dogs and Cats

Nonsteroidal Anti-Inflammatory Narcotic Analgesics in Dogs Drugs in Dogs

Morphine, 0.25–5.0 mg/kg Aspirin, 10–25 mg/kg PO everyIM or SQ every 4 hours 8 hours

Oxymorphone, 0.2 mg/kg Phenylbutazone, 10–25 mg/kgIM, SQ, or IV every PO every 8–12 hours6 hours

Butorphanol, 0.4–0.6 mg/kg Carprofen, 1mg/lb PO everyPO, IM, SQ, or IV every 24 hours4–8 hours

Piroxicam, 0.3 mg/kg PO every 24 hours

Nonsteroidal Anti-Inflammatory Narcotic Analgesics in Cats Drugs in Cats

Morphine, 0.1 mg/kg IM, Aspirin, 10–20 mg/kg PO everySQ, or IV every 4 hours 48–72 hours

Oxymorphone, 2–4 mg/kg Piroxicam, 0.3 mg/kg PO everyIM every 2 hours 72 hours

Butorphanol, 0.4–0.8 mg/kg PO, IM, or IV every 3–8 hours

IM, intramuscularly; SQ, subcutaneously; PO, orally; IV, intravenously.

Like insulin, pain medications can be administeredon a continuous basis into subcutaneous tissue througha small-gauge butterfly needle taped in place. Narcotics


can also be continuously infused epidurally or intrathe-cally with the placement of an indwelling intrathecalcatheter. This technique is associated with fewer centralnervous system effects than systemic administration ofnarcotics. The major problem observed with intraspinaldelivery of narcotics is respiratory depression.

Fentanyl patches are labeled for managing chroniccancer pain in humans, specifically people who cannottolerate oral medications. The efficacy and convenienceof this delivery system have generated interest in the useof this treatment for postoperative pain in both humanand veterinary medicine. Fentanyl is not approved foruse as a single agent in dogs and cats. The patch consistsof a gel matrix containing fentanyl, a lipid-soluble opiodthat diffuses through the skin and achieves blood con-centrations high enough to produce analgesia. A varietyof sizes deliver 25, 50, 75, and 100 mg/hr, with the deliv-ery rate a function of the surface area of the patch.Patches are designed to provide continual release forabout 72 hours. In dogs, there appears to be a 6- to 12-hour latency to achieve plasma concentrations associ-ated with analgesia and up to 24 hours for plasma con-centrations to reach a plateau. The principal advantageof fentanyl patches is provision of hands-off analgesia.One disadvantage is body temperature; fever or othercauses of elevated body temperature (laying on a heatingpad) can increase drug delivery substantially. To circum-vent this, many apply the patch to the dorsal neck,


secured with a light wrap. For cats and small dogs, a 25mg patch is used. For medium-sized dogs (5–20 kg), a 50mg patch is used. Larger dogs (20–30 kg) may require a75 mg patch; and giant dogs (>30 kg) may require the100 mg patch. Side effects may include euphoria (incats) and increased appetite. Deleterious side effects mayinclude agitation, dementia, heightened response to theenvironment, and mild sedation or ataxia. However, sideeffects, when used properly, are uncommon.

NONPHARMACOLOGIC MANAGEMENT Nonpharmaco-logic pain management approaches include surgery,radiation, neurological and neurosurgical interventions,behavioral techniques, and nursing interventions. Bothradiation therapy and surgery may be used for cancerpets with enlarging tumors or advanced disease todecrease the tumor mass and reduce painful compres-sion of adjacent structures. These procedures are con-ducted for palliative purposes only.

Neurosurgical interventions are generally reservedfor pets that cannot obtain adequate relief with anal-gesics, palliative radiotherapy, or surgery. Most neuro-surgical procedures involve interruption or destructionof the pain pathway at some point along the route to thebrain or in the brain itself. The risks and benefits of thesetechniques must be discussed thoroughly with pet own-ers, because in many cases, the pet will have residualmotor or sensory deficits.


Neurostimulation techniques are based on the gate-control theory of pain. Some research indicates the path-ways in the spinal cord can accommodate only a certainamount of stimulation before sensory overload occurs.With neurostimulation, competitive nonpainful (e.g.,vibratory) impulses are used to block the transmission ofpainful impulses along nerve pathways. Neurostimulationcan be applied transcutaneously, as occurs with transcu-taneous electrical nerve stimulation (TENS), or via surgi-cally implanted electrodes in the spinal cord.

Behavioral techniques such as relaxation, distrac-tion, biofeedback, imagery, and hypnosis are now widelyused to manage cancer-related pain in people. In gen-eral, behavioral techniques are designed to alter theresponse to pain by fostering a deep relaxation and ashifting of attention to something other than the pain.These approaches, although controversial and likelyineffective for use on most pets, should be used in com-bination with and not as a substitute for appropriatemedication. Care must be taken not to misinterpret theefficacy of these techniques as an indication that the petis not really experiencing pain.

Oral ComplicationsEtiology

Identification of high-risk patients enables the veterinarycare providers to initiate pretreatment evaluation and


recommend prophylactic measures to minimize the inci-dence and morbidity associated with oral toxicity. Themost significant risk factors for the development of oralcomplications during and following treatment are pre-existing oral or dental disease, inadequate oral care dur-ing therapy, and any factors that may compromise theintegrity of the oral mucosa. Additional risk factors (notranked in order) include the type of malignancy(involved sites and histology); the antineoplastic agentsused, the dose, and the administration schedule; theradiation field, the dose, and the administration sched-ule; severity and duration of anticipated myelosuppres-sion; and patient age. Preexisting oral conditions, suchas dental calculus, broken teeth, faulty restorations, peri-odontal disease, gingivitis, and prosthodontic appli-ances, contribute to the development of local infectionsand may serve as a focus for systemic infections. Bacter-ial and fungal colonization of dental calculus, plaque,dental pulp, periodontal pockets, operculum defects,dentures, and dental appliances constitute a reservoir ofpathogenic and opportunistic organisms that maydevelop into local or systemic infections during episodesof immune suppression or neutropenia. Other sourcesof irritation may exacerbate mucosal thinning and atro-phy, producing local ulceration (stomatitis).

CHEMOTHERAPY-INDUCED COMPLICATIONS Becausegastrointestinal epithelial cells have a cell turnover rate


similar to leukocytes, the period of greatest damage tothe oral mucosa frequently correlates with the whiteblood cell nadir. Resolution of oral toxicity generallycoincides with granulocyte recovery. The lips, tongue,floor of the mouth, buccal mucosa, and soft palate aremore severely affected by drug toxicity than the hardpalate and gingiva; this may be due to their faster rate ofepithelial cell turnover. The role of vascularity in stom-atitis may be inferred from the effect of topical cryother-apy in preventing or lessening mucositis from agentssuch as fluorouracil (5-FU). The antineoplastic agentsmost likely to cause mucositis include bleomycin, dox-orubicin, 5-FU, methotrexate, vinblastine, and vin-cristine. The risk is exacerbated when chemotherapeuticagents that typically produce mucosal toxicity are givenin high doses, in frequent repetitive schedules, or incombination with ionizing irradiation (e.g., condition-ing regimens prior to bone marrow transplant).

RADIATION-INDUCED COMPLICATIONS Local irradia-tion to the head and neck region not only can cause thespecific histologic and physiologic changes of the oralmucosa caused by cytotoxic therapy but also structuraland functional alterations of underlying supportive tis-sues, including salivary glands and bone. High-dose radi-ation to tooth-bearing bone causes hypoxia, reduction invascular supply to the bone, and tissue breakdown lead-ing to bone exposure, infection, and necrosis. Both ion-izing radiation to the head and neck regions and


antineoplastic agents impair cell division, disrupting nor-mal replacement of the oral mucosa. Radiation damage,however, is anatomically site specific. It depends on theamount and kind of radiation used, total dose adminis-tered, and field size and fractionation. Radiation-induced damage also differs from that induced bychemotherapy in that tissue volumes treated with radia-tion continue to remain in jeopardy throughout the lifeof the patient; they are more easily damaged by subse-quent toxic drug or radiation exposures, and normalphysiologic repair mechanisms are compromised as aresult of permanent cellular depopulation.

SURGERY-INDUCED COMPLICATIONS In patients withosteoradionecrosis involving the mandible or facialbones, surgical debridement may be disfiguring, andreconstruction efforts may be futile unless tissue oxy-genation is improved prior to surgery. Hyperbaric oxy-gen therapy has been shown to stimulate new capillaryformation (angiogenesis) in affected tissues and is beingused as an adjunct to surgical debridement in humans.

Prevention

The incidence of oral complications in patients who donot have head and neck malignancies can be reducedsignificantly when an aggressive approach to oral care isinitiated prior to treatment. Primary preventive meas-ures, such as well-balanced nutritional intake, adequate


oral hygiene, and early detection of oral problems, areimportant pretreatment interventions. A veterinary careprovider familiar with the oral complications of cancertreatment should examine the patient prior to treatment(with chemotherapy as well as with radiation therapy tothe head and neck). Ideally, this examination is per-formed 2–4 weeks prior to treatment to permit adequatehealing of any required dental procedures. The exami-nation allows the veterinarian to determine the condi-tion of the oral mucosa and supportive structures priorto therapy and to initiate necessary interventions thatmay reduce oral complications during and after therapy.A program of oral hygiene should be initiated, and thepet owner should be instructed about the importance ofgood oral hygiene prior to initiating treatment.

Specific Oral Complications

MUCOSITIS AND STOMATITIS The terms mucositis andstomatitis are often used interchangeably but may includesome general distinctions. Mucositis describes a toxicinflammatory reaction affecting the gastrointestinal (GI)tract from mouth to anus, which may result from expo-sure to chemotherapeutic agents or ionizing radiation.Mucositis typically manifests as an erythematous, a burn-like lesion, or as random, focal-to-diffuse ulcerativelesions. It may be exacerbated by local factors. Stomatitisrefers to any inflammatory reaction affecting the oralmucosa, with or without ulceration, and may be caused


or intensified by local factors. Stomatitis can range frommild to severe; the patient with severe stomatitis isunable to take anything by mouth. In common practicalusage, however, mucositis and stomatitis are used indis-criminately to describe the same phenomena. Erythe-matous mucositis may appear as early as 3 days afterexposure to chemotherapy but more typically within 5–7days. Progression to ulcerative mucositis typically occurswithin 7 days after the start of chemotherapy. Veterinarycare providers should be alert to the potential forincreased toxicity with escalating dose or treatment dura-tion in clinical trials that demonstrate GI (mucosal) tox-icity. Combination or high-dose chemotherapy mayproduce severe mucositis. Drugs administered by con-tinuous infusion or on frequent, repetitive, intermittentschedules (e.g., vincristine) are more likely to causemucositis than equivalent amounts of the same drugsgiven in a single bolus. Mucositis is self-limiting when notcomplicated by infection and typically heals completelywithin 2–4 weeks. Systematic assessment of the oral cavityfollowing treatment permits early identification of toxic-ity and initiation of oral hygiene measures designed toprevent or decrease further complications. Once muco-sitis has developed, its severity and the patient’s hemato-logic status guide appropriate oral management.Meticulous oral hygiene and palliation of symptomsbecome the focus of care. In the absence of controlledclinical trials, many of the management recommenda-tions are anecdotal.


INFECTION Oral mucositis can be complicated by infec-tion in the immunocompromised patient. Not only canthe mouth itself become infected, but the loss of the oralepithelium as a protective barrier results in local infec-tions and provides a port of entry for microorganismsinto the systemic circulation. Once mucosal integrity isaffected, indigenous oral flora, as well as nosocomial andopportunistic organisms can cause local and systemicinfections. As the absolute neutrophil count falls below1,000/mm3, the incidence and severity of infection rise.Patients with prolonged neutropenia are at higher riskfor the development of serious infectious complications.Nonpharmacologic approaches to preventing infectionand prophylaxis with antimicrobials are being evaluatedin controlled trials. Antibiotics used during prolongedneutropenia alter oral flora, creating a favorable envi-ronment for fungal overgrowth that may be exacerbatedby concurrent steroid therapy. The majority of oral bac-terial infections are gram-negative due to the shift in thecolonization of the oral cavity from predominantly gram-positive to enteric gram-negative organisms.

HEMORRHAGE Hemorrhage may occur during treat-ment-induced thrombocytopenia or coagulopathy. Sitesof underlying periodontal disease may bleed sponta-neously or from minimal trauma. Oral bleeding may beminimal, with petechiae located on the lips, soft palate,or floor of the mouth, or it may be severe, with oral hem-orrhage, especially in the gingival crevices. Spontaneous


gingival oozing may occur when platelet counts diminishto less than 50,000/mm3.

XEROSTOMIA Xerostomia is a marked reduction in sali-vary gland secretion. Clinical symptoms and signs ofxerostomia include dryness, a sore or burning sensation(especially involving the tongue), cracked lips, slits or fis-sures at the corners of the mouth, changes in the tonguesurface, and increased frequency or volume of fluidintake. A preventive oral care regimen must be initiatedto halt the destruction. Xerostomia can result from theinflammatory and degenerative effects of ionizing radia-tion on salivary gland parenchyma, especially serous aci-nar cells. These changes are often rapid and irreversible,especially when the salivary glands are included in theradiation fields. Salivary flow measurably decreaseswithin 1 week after starting treatment and diminishesprogressively with continued treatment. The degree ofdysfunction is related to the radiation dose and volumeof glandular tissue in the radiation field. Xerostomiaalters the mouth’s buffering capacity and mechanicalcleansing ability, often contributing to dental caries andprogressive periodontal disease.

RADIATION NECROSIS Necrosis and infection of previ-ously irradiated tissue (osteoradionecrosis) is a seriouscomplication for patients who have undergone radiationfor head and neck tumors. Radiation-induced oral com-plications require aggressive dental therapy before,


during, and after radiation therapy to minimize theoccurrence of severe sequelae: permanent xerostomia,ulcerative caries, radiation-induced osteomyelitis, andosteoradionecrosis.

Intervention Options

ORAL CARE CONSIDERATIONS Routine systematic oralhygiene is extremely important in reducing the incidenceand severity of the effects of oncologic treatment such asradiation caries, mucositis, and stomatitis. In patients withmild, occasional xerostomia or with resection involvingoral structures, an inspection identifies areas that requireattention. Oral hygiene methods include rinsing or irri-gation and mechanical plaque removal. Telling pet own-ers how to perform mouth care is just as important asinforming them how to administer a medication. Aftermeals, the oral cavity should be rinsed or wiped; wipingthe oral cavity is almost always necessary for patients withxerostomia. Rinsing the oral cavity may not be sufficientfor a thorough cleansing of the oral tissues. After a rou-tine is developed, mechanical plaque removal may benecessary to assist rinsing. Mechanical plaque removalincludes use of gauze, toothettes, toothbrush, and inter-dental aids such as floss, proxybrush, wooden wedge, ordenture brush. Toothettes do not thoroughly cleanse thedentition, although they work very well to clean surgicalareas following maxillectomy or hemimandibulectomy.Toothettes are also good for cleaning the maxillary and


mandibular alveolar ridges of edentulous areas, thepalate, the palate with a prominent torus, and thetongue. If xerostomia is present, plaque is thicker andheavier than usual and will not rinse away. Oral careproducts should be selected carefully; those that pro-duce symptoms or injure the mucosa should not be used.Rinses containing alcohol should be avoided. Since theflavoring agents in toothpastes can irritate or burn gin-giva and mucosa, a mild toothpaste should be chosen,such as a child’s toothpaste. Lip care is important andshould include using a moisturizer.

MANAGEMENT OF MUCOSITIS AND STOMATITIS Oralcare protocols generally include atraumatically cleansingthe oral mucosa, moisturizing the lips and oral cavity,and relieving pain and inflammation. A soft toothbrushor foam swab (toothette) cleans teeth effectively andatraumatically. Options for cleansing and debridingagents include salt and soda (1/2 teaspoon each of saltand sodium bicarbonate in 8 ounces of warm water),normal saline, sodium bicarbonate (1 teaspoon in 8ounces of water), sterile water, and hydrogen peroxide(diluted 1:1 with water or normal saline). Indications foruse of hydrogen peroxide include crusting and need forgentle debridement. Use should be time limited (for 1or 2 days maximum) since chronic use may impair timelyhealing of stomatitis. In patients with stomatitis, irriga-tion or rinsing with mild saline or salt and soda should


be performed every 2 hours. Gentle wiping with wetgauze immersed in a saline solution aids in removal ofdebris. Toothettes may be too harsh for some areas. Irri-gation should be performed prior to topical medication,as removal of debris and saliva allows penetration to theoral tissues and prevents material from accumulating.Frequent rinsing cleans and lubricates tissues, preventscrusting, and soothes sore gingiva and mucosa. Frequentrinsing also removes debris and prevents debris and bac-teria from accumulating. Agents that produce symptomsor injure the mucosa should not be used. Toothpastemay be used if tolerated; however, over-the-countermouthwashes generally contain alcohol and should beeliminated. Glycerin is hygroscopic (i.e., takes up andretains moisture) and may dry tissues. Topical anesthet-ics may minimize pain temporarily but are frequently for-mulated with excipient ingredients (additives) that canintensify and prolong mucositis. Systemic analgesics(including opioids) are indicated to alleviate discomfort,but veterinarians need to be aware of agents that pro-duce gastrointestinal irritation or affect hemostasis.

MANAGEMENT OF INFECTION Prophylaxis against fun-gal superinfections is generally recommended andincludes use of topical antifungal agents such as nystatin-containing mouthwashes. Although topical antifungalprophylaxis and treatment may clear superficial oropha-ryngeal infections, topical agents are not well absorbedand are ineffective against more deeply invasive fungal


infections, which typically involve the esophagus andlower gastrointestinal tract. For this reason, systemicagents are indicated for treating all except superficialfungal infections in the oral cavity. Chlorhexidine oralrinse has been used in combination with fluoride gel tocontrol cariogenic flora in humans. Veterinarians shouldnote that chlorhexidine oral rinse may be used as amouthwash during routine dental hygiene examinationsunder anesthesia to prevent ingestion. Commerciallymarketed formulations may also contain appreciablequantities of alcohol, which may exacerbate xerostomia.This may be particularly important in the context thatxerostomia may change flora to more cariogenic types.

MANAGEMENT OF CANDIDIASIS Candidiasis is a yeastinfection that is generally an overgrowth of the fungusCandida albicans. The management of candidiasis mayinclude (1) cleaning the oral cavity prior to taking anti-fungal medication, irrigation and mechanical plaqueremoval may be necessary; (2) discarding toothbrushand replacing it with a new one after each use; and (3)disinfecting any object or appliance used in the mouth(e.g., mouthpiece used during radiation therapy).

MANAGEMENT OF HEMORRHAGE The use of tooth-brushes and dental floss in patients with platelet countsof less than 50,000/mm3 is controversial because of thepotential to induce bleeding with routine oral care. Top-ical thrombin can be used for local hemostasis in


patients with minor oral hemorrhage secondary tothrombocytopenia.

MANAGEMENT OF XEROSTOMIA It is imperative thatpatients who have xerostomia maintain oral hygiene toprevent dental problems. Periodontal disease can beaccelerated and caries can become rampant, unless pre-ventive measures are instituted. To prevent dental decaywhen xerostomia is involved, pet owners should (1) per-form systematic oral hygiene at least 4 times per day (aftermeals and before retiring at night), (2) rinse the mouthwith a solution of salt and baking soda 4–6 times per day(1/2 teaspoon salt and 1/2 teaspoon baking soda in 8ounces warm water) to clean and lubricate the oral tissuesand to buffer the oral environment, (3) avoid foods andliquids with a high sugar content, and (4) have free accessto water to alleviate mouth dryness.

Other Considerations

Client education and patient supportive care are impor-tant for pets experiencing oral complications related tocancer therapy. It is important to closely monitorpatients’ distress, ability to cope, and their response totreatment (quality of life); to show concern for the prob-lems they are experiencing; and to educate and supportthe pet owner. With full support from the veterinarystaff, the patient and the pet owner can be expected tobe able to deal with these complications.


Malignant EffusionsEffusions may be the presenting sign of cancer or theymay develop after the cancer is diagnosed. Only 50% ofthe effusions that develop in cancer-bearing pets duringthe course of their illness are malignant. Correct diag-nosis of the cause of pleural effusions is the necessaryfirst step in their management.

Pleural effusions are caused principally by conges-tive heart failure, malignancy, and infection. Pets com-monly present with the symptoms of cough, dyspnea,decreased exercise tolerance, and chest pain. Whilelarger effusions may be detected on physical examina-tion, radiographs or ultrasound of the chest may detecteffusions as small as 100 ml. A diagnostic thoracentesisshould be performed early in the course of investigation.In markedly symptomatic pets, removal of pleural fluidcan provide immediate, albeit temporary, relief; gener-ally 250–500 ml or more must be removed to improvesymptoms. Pleural fluid analysis should include protein,pH determination, cell counts, cytology, and cultures forbacteria, fungi, and mycobacteria. At least 50 ml of pleu-ral fluid is necessary for adequate cytologic examination.

Pleural effusions are classified as transudative orexudative. Most often, transudative effusions are causedby congestive heart failure, cirrhosis, nephrotic syn-drome, or occasionally by lymphatic blockade producedby cancer. Exudative effusions are caused by infection ormalignancy. In the absence of infection, an exudative


pleural effusion, especially if it is bloody, strongly sug-gests a malignant etiology. The cancer very likely causesan exudative pleural effusion in a pet with a current orpast cancer. Effusions due to lymphoma or mediastinalinvolvement by any tumor may be chylous and cytologi-cally negative. About half of effusions ultimately diag-nosed as malignant have a positive cytology from theinitial thoracentesis.

Diagnostic Approach

Two different approaches can be used to attempt to diag-nose the etiology of pleural effusions if the initial cyto-logic examination does not show malignant cells. Repeatthoracentesis and pleural biopsy will confirm malignancyin 80–90% of malignant effusions. The pleural biopsyhas a higher complication rate but a higher yield thanthoracentesis. Despite thoracentesis and pleural biopsy,10–20% of pets with malignant pleural effusions stillhave no diagnosis. In such pets, thoracoscopy or thora-cotomy is needed for diagnosis. Although thoracoscopicbiopsy requires local or general anesthesia, it increasesthe diagnostic yield greatly compared to thoracentesis.

The alternative diagnostic approach to pets withpleural effusions whose initial cytologic examinationdoes not show malignant cells is to go directly to thora-coscopy or thoracotomy with biopsy of visually identifiedabnormal areas of the pleura. The diagnostic yield of a


malignancy using this approach exceeds 90% if the effu-sion is caused by cancer.

Treatment Considerations

Once the diagnosis of malignant pleural effusion hasbeen made, treatment depends on the tumor type andprior, if any, antineoplastic therapy. About 25% of effu-sions require no immediate therapy; the effusions are small and stable. Malignant effusions caused bylymphomas may respond to systemic chemotherapy.Repeated percutaneous draining of effusions may leadto tumor growth along the needle track and through thechest wall. Pets who have received extensive prior sys-temic therapy and those with chemotherapy-resistanttumors are not likely to respond to systemic therapy. Pal-liative approaches to the management of malignantpleural effusions are necessary in such pets.

Pets with symptomatic malignant pleural effusionswhose underlying cancer is unlikely to respond to sys-temic treatment should have their pleural fluid drained.Pets with relatively large (>1,000 ml) recurrent effusionswhose symptoms resolve with drainage and whose lungscan fully expand are candidates for palliation. Two gen-eral approaches to the palliative management of symp-tomatic pleural effusions are chest tube drainage withinstallation of a sclerosing agent and thoracoscopicdrainage of the pleural effusion under local or general


anesthesia with intraoperative sclerosis of the pleuralspace.

Historically, many chemical agents have beeninstilled into the pleural space and shown to have someeffectiveness in controlling effusions, including tetracy-cline, doxycycline, minocycline, bleomycin, cisplatin,doxorubicin, mitoxantrone, interferon, Corynebacteriumparvum, methylprednisolone, and talc.

Chest tube drainage should be done by inserting thechest tube into the pleural cavity and draining the fluid.When the drainage reaches less than 50–100 ml in a 24-hour period, a sclerosing agent can be instilled. Infor-mation on the recommended sclerosing agent is cur-rently inconclusive. Small numbers and relatively shortfollow-up plague the few randomized studies on thistopic. Some comparative studies suggest advantages fortalc as the sclerosing agent compared to tetracycline andothers. In humans with breast cancer, thoracoscopy andinsufflation of talc controlled the pleural effusions intwice as many patients as tetracycline (>90% versus 50%,respectively).

Another approach that is appropriate for pets with asymptomatic malignant pleural effusion and good per-formance status who are capable of undergoing a proce-dure under local, regional, or general anesthesia is athoracoscopy with biopsy of suspicious pleural lesions,lysis of any adhesions, evaluation to see if the lung reex-pands, and instillation of the sclerosing agent during the


same procedure. This could shorten the hospitalizationbecause the whole procedure can be done in the oper-ating room in a single day. Since tetracycline is no longeravailable and similar efficacy has been shown for doxycy-cline, doxycycline has been substituted for tetracycline inhuman clinical trials. Pleural stripping (pleurectomy) viathoracotomy or thoracoscopy is nearly 100% effective incontrolling malignant pleural effusions, but the morbid-ity is so severe that this procedure is rarely used in vet-erinary medicine.

Prognosis

The prognosis for dogs and cats with malignant pleuraleffusions is poor—median survival time with treatment isabout 6 months—and in those with chemotherapy-resistant tumors that are not likely to respond to systemictherapy, the prognosis is grim.

Oncology EmergenciesCancer itself can present as an emergency. Internalblood loss from a ruptured abdominal mass or a peri-cardial effusion due to a bleeding heart-based tumormay present as shock. General and emergency veteri-narians who are able to recognize these signs early andinstitute appropriate shock therapy can give thesepatients and their owners’ time, a tissue diagnosis, andtreatment options for extended high-quality time.


Other examples of oncologic emergencies include meta-bolic derangements (hypercalcemia, hypoglycemia, andhyponatremia).

The treatment of cancer can also lead to manyunique yet predictable complications. The administra-tion of many chemotherapeutic agents is associated withknown side effects. Many of these agents irritate tissues,and extravasations will occur even to the most experi-enced oncologist. Some agents are associated with hyper-sensitivity reactions and even anaphylaxis. Many sideeffects are predictable. Bone marrow suppression andgastrointestinal disturbances are just some commoncomplications of these agents.

Metabolic Complications

Hypercalcemia is the most common metabolic distur-bance associated with neoplasia. Most commonly theresult of parathyroid-related peptides produced by sometumors, hypercalcemia is usually caused by lymphoma.Other tumors frequently implicated include anal sacadenocarcinoma, mammary adenocarcinoma, and pri-mary hyperparathyroidism. Emergency care for thehypercalcemic patient involves a diuresis with 0.9% NaClfor enhanced calciuresis. Furosemide (2–4 mg/kg bid)also enhances calcium elimination. Other drugs used totreat hypercalcemia include intravenous biphosphonates(etridronate, disodium palmidroate), gallium nitrate,mithramycin, and salmon calcitonin. Corticosteroids


prevent bone reabsorption, intestinal absorption, andincrease urinary calcium excretion. However, because oftheir rapid antitumor effects, corticosteroid use shouldbe withheld until a tissue diagnosis is made. Identifica-tion and treatment of the primary disease becomes thehighest priority. Lymph node aspiration and biopsy,chest radiographs, abdominal ultrasound, and bonemarrow evaluation should follow physical examination,including lymph node palpation and perianal examina-tion. Every effort should be made to rule out lymphomaand anal sac adenocarcinoma.

Hypoglycemia associated with neoplasia may resultfrom an insulin-secreting tumor, destruction of normalgluconeogenic tissues, or glucose consumption associ-ated with such systemic complications as bacterial sepsis.The most common tumors associated with hypoglycemiaare insulinoma, hepatoma, and carcinoma. Insulinomasare diagnosed by demonstrating inappropriately high lev-els of insulin in the face of hypoglycemia. Animals show-ing clinical signs of hypoglycemia (stupor, coma,seizures) can be treated with parenteral dextrose anddextrose-containing fluids. Prednisone (0.5–2 mg/kgdivided bid) increases hepatic gluconeogenesis andantagonizes the effects of insulin on peripheral tissues.Diazoxide (10–40 mg/kg divided bid) can directly inhibitinsulin secretion and may be useful in the medical man-agement of insulin-secreting tumors. Surgical excisionand medical management of metastatic lesions can leadto the temporary resolution of the clinical disease.


Shock

Animals with large intra-abdominal tumors may appearnormal to the owner until such time that these vasculartumors rupture and lead to acute blood loss, collapse,and hypovolemic shock. Acute collapse can also be seenwith pericardial tamponade secondary to vasculartumors on the heart or at the heart base. Both cases pres-ent with cool extremities, a rapid heart rate, decreasedmentation, and hypotension. It is important to differen-tiate pericardial tamponade from hypovolemia, asaggressive fluid therapy may actually worsen the patient’scondition. Jugular pulsation, elevated central venouspressure (distension of the lateral saphenous vein whenheld above the heart), decreased amplitude electrocar-diogram, and a rounded cardiac silhouette are oftenseen with tamponade. Tamponade is best treated imme-diately with pericardiocentesis. Internal blood loss froma ruptured vascular tumor should be treated with shockdoses of crystalloid fluids. Frequent rechecks of heartrate, blood pressure, and packed cell volume are manda-tory. If the packed cell volume drops precipitously, wholeblood, packed red blood cells, or cell-free hemoglobinshould be used to improve blood oxygen content.Patients should be carefully evaluated to identify thesource of the hemorrhage. When a patient’s conditionallows, radiographs of the chest and abdomen help stagethe disease and provide the veterinarian and ownermore information on the extent of the disease.


Exploratory surgery is necessary to remove the source ofblood loss and fully evaluate the extent of the disease.The acute nature of these cases requires compassion andunderstanding from the veterinarian. The diagnosis ofcancer when the only finding is an intra-abdominal masscan be overwhelming for owners. Clients need to beinformed and given every option. Surgical explorationand biopsy are the only ways to definitively diagnose andtreat these cancers.

Sepsis and septic shock are not uncommon in can-cer patients. Sepsis can be the result of the disease itselfor a complication of treatment. Intestinal neoplasia canlead to bacterial translocation and even rupture of a hol-low viscus. These animals present with signs of acuteabdominal distress and evidence of peritonitis on plainradiographs (free air, decreased abdominal detail). Thediagnosis can be confirmed with a diagnostic peritoneallavage. Animals with diffuse intestinal neoplasia mayhave a more chronic course of weight loss, panhypopro-teinemia, and nonspecific gastrointestinal symptoms,which may lead to weakened immunity and septic com-plications. Septic shock is characterized by fever orhypothermia, leukocytosis or leukopenia, and hypoten-sion associated with the systemic release of local inflam-matory mediators. Emergency management of thesecases centers around the quick identification andremoval of the septic focus, appropriate antibiotic ther-apy, and cardiovascular support with fluids, colloids, andif necessary, positive inotropes.


Extravasation

Some of the more common chemotherapeutic agentsused in veterinary medicine can cause significant tissueinjury when they extravasate into perivascular tissues.Some of the more serious compounds include the vincaalkaloids (vincristine and vinblastine) and doxorubicin.Other agents causing tissue damage include mithra-mycin, mitoxantrone, and cisplatin. Every effort shouldbe made to prevent extravasation. Veins used forchemotherapy should not be used for blood sampling.Multiple attempts to catheterize one vein or recentvenipunctures make the vein unsuitable for administra-tion of any cytotoxic drugs. A careful “first-stick”approach using a small (22–23 g) catheter should beused to administer large volumes of drugs like cisplatinand doxorubicin. Small volumes (<1 cc) can be giventhrough a small (23–25 g) butterfly catheter. Salineshould be flushed before and after administration of thechemotherapeutic to assess catheter placement andensure vessel integrity. The earliest sign of extravasationis pain. Animals become extremely agitated, even to thepoint of self-trauma, as these vesicants leak into sur-rounding tissues. Erythema may develop quickly or overseveral days, ultimately resulting in tissue necrosis andopen, draining wounds. When extravasation is sus-pected, do not remove the catheter. Instead, use thecatheter to remove as much drug as possible. Applywarm compresses to enhance systemic absorption. Then


apply cold compresses to affected area for up to 10 hoursto inhibit cytotoxicity. Keep in mind that, even with theuse of good first aid, intense wound management may berequired.

Anaphylaxis

Allergic complications are not common side effects ofchemotherapy. Reactions range from potentially lethalanaphylaxis to mild, delayed hypersensitivity reactions.Serious anaphylaxis has been associated with L-asparagi-nase. Because L-asparaginase associated anaphylaxis usu-ally occurs within minutes, it is advisable to observe thepatients for no less than 30 minutes after administration.Giving the drug by intramuscular injection can minimizethe risk of anaphylaxis. Intravenous and intraperitonealadministration is associated with higher incidence ofanaphylactic reactions. Anaphylaxis causes acute col-lapse and hypotension. Emergency management ofthese patients involves quick shock therapy. Intravenousaccess and shock volumes of crystalloid fluids (up to 90ml/kg/hr) are given along with 0.1–0.3 ml of a 1:1000dilution of epinephrine given IV or IM. Delayed hyper-sensitivity can be seen with any drug but has been mostcommonly associated with doxorubicin, etoposide, andpaclitaxel. These reactions typically result in erythemaand swelling of the ears, face, and paw. Delayed hyper-sensitivity reactions can be minimized by diluting drugssuch as doxorubicin with 250–500 ml of 0.9% NaCl and


administering them slowly over 30 minutes. Hypersensi-tivity reactions can be treated with rapid acting corticos-teroids, dexamethasone sodium phosphate (2 mg/kgIV), and an antihistamine, diphenhydramine (2–4mg/kg IM).

Acute Tumor Lysis Syndrome

Acute (hours to days) collapse and even death can beseen with the treatment of extremely chemosensitivetumors. The destruction of large tumor volumes canlead to massive release of inflammatory cellular debris.The resulting inflammatory cascade can mimic sepsisand septic shock and can best be described as a systemicinflammatory response. Electrolyte disturbances causedby the release of intracellular potassium and phospho-rous also contribute to cardiovascular problems. Thetumors most frequently associated with acute lysisinclude lymphoma and leukemia. Fast recognition oftumor lysis with appropriate cardiovascular support isrequired if the patient is to survive. Bradycardia in theface of shock should alert the clinician to possiblehyperkalemia. Hypocalcemia may result from high phos-phorous levels and can result in impaired cardiac con-duction and reduced cardiac output. Aggressive fluidresuscitation, normalization of electrolytes, and supportof cardiac output and vascular tone are necessary to seethe patient through the crisis.


Neutropenia

Bone marrow suppression is an expected complicationof many chemotherapeutic protocols. In addition, dis-eases like leukemia and lymphoma can invade the bonemarrow, causing primary granulopoiesis and even pan-cytopenia. Drugs that are highly myelotoxic includedoxorubicin, cyclophosphamide, cisplatin, and carbo-platin. Doxorubicin and cyclophosphamide usuallycause myelosuppression in 7–10 days. Recognizing theneutrophil nadir and taking steps to prevent bacterialcolonization should help prevent serious complications.Patients should be closely monitored during this period.Changes in appetite, attitude, body temperature,mucous membrane color, and pulse quality warrantcloser examination. Every effort should be made to pre-vent bacterial colonization during periods of neutrope-nia. Signs of bacterial colonization will also be affectedby neutropenia. Bacterial colonization of lungs and blad-der can result in infection without suppurative inflam-mation. Culture of urine, blood, and bronchial fluid canresult in the identification of causative organisms with-out cellular evidence of inflammation. Treatment ofneutropenia and septic complications is directed atmaintaining perfusion through the use of crystalloid andcolloid solutions and antibiotic therapy with bactericidaldrugs effective against likely organisms. Recombi-nant human granulocyte colony-stimulating factor (5 μg/kg/day SQ) can be administered to neutropenic


patients to decrease the duration and severity ofchemotherapy induced neutropenia.

Gastrointestinal Ulceration

Upper GI inflammation can be managed with antacidsand GI protectants. Symptoms of inflammatory colitiscan be managed with sulfasalazine, 10–30 mg/kg tid.Many chemotherapeutics stimulate the chemoreceptortrigger zone to cause a central nausea. Secondarily, theprimary disease can cause stimulation to the gastroin-testinal tract and peritoneal cavity, resulting in nauseaand vomiting. Early antiemetic therapy should be con-sidered in anorectic nauseous patients. Chemotherapy-induced emesis is mediated by 5-HT3-serotonergicreceptors. Antiemetic drugs, which antagonize thisreceptor, seem to work the best. Metoclopramide (1–2mg/kg/day) has some partial 5-HT3-antagonist proper-ties and can be given by continuous infusion. Specific 5-HT3 receptor antagonists such as ondansetron (0.5–1.0mg/kg), although expensive, work even better.

Diarrhea

Simplified, diarrhea is the result of increased fecal water.A number of different pathophysiologic mechanismscan account for increased fecal water. Acute diarrhea ismost often caused by malabsorption (osmotic diarrhea),abnormal fluid secretion (secretory or inflammatorydiarrhea), and altered intestinal motility. Mucosal or


submucosal diseases that impair absorption in either thesmall or large bowel result in malabsorptive diarrhea.Impaired absorption of dietary substances interfereswith water resorption by altering osmotic gradients.Mucosal diseases also may directly impair sodium resorp-tion, in effect inhibiting water resorption, resulting indiarrhea. Enhanced intestinal secretion of water andelectrolytes can be induced by several stimuli, mostnotably bacterial enterotoxins. Bile acids and dietaryfatty acids also incite intestinal secretion, as does intes-tinal obstruction. Damage to the intestinal mucosa canresult in transudation of water and electrolytes. If theinjury is severe, plasma proteins and blood may also belost. It is unclear whether a diarrhea can be causedspecifically and only by abnormal motor function. Mostdiarrheal diseases that have been studied have beenshown to alter intestinal fluid and electrolyte transport aswell as smooth muscle function. Intestinal motility, mostnotably segmental contractions, is reduced in most diar-rheic conditions. Decreased segmental contractionsresult in transport of ingesta at a rate too fast for diges-tive and absorptive processes to occur. Diarrhea mayresult from one pathophysiologic mechanism; however,in most patients with diarrhea, more than one patho-physiologic mechanism is simultaneously operative.

Mild diarrhea causes few metabolic consequences;however, moderate or severe diarrhea may lead to pro-found hydration and electrolyte and acid-base distur-bances. Diarrhea most often results in loss of fluids


isotonic to plasma. Loss of isotonic fluid decreases circu-lating plasma volume and, if severe, precipitates hypov-olemic shock. The major solutes lost with diarrhea aresodium, chloride, and potassium. Initially, serum elec-trolyte concentrations remain normal because isotonicfluids are lost. Hypokalemia is the most common elec-trolyte disturbance. Renal loss secondary to aldosteronereleased in response to fluid volume depletion is themost important source of potassium loss. Significantlosses of potassium may also occur through the feces ifthe diarrhea is severe or protracted. Metabolic acidosismay develop secondary to the loss of intestinal bicarbon-ate and the production of lactic acid by anaerobicmetabolism in response to hypovolemia.

As with any medical problem, treatment for acutediarrhea is best based on knowledge of the cause. Inmany cases, however, the cause of acute diarrhea is notascertained because of the anticipated brevity of the diar-rhea, financial constraints of the owners, or the elusivenature of the disease process. As a result, symptomatictherapy of diarrhea is often utilized. Symptomatic ther-apy is also of importance in the adjunctive supportivetherapy in patients with acute diarrhea in which the pri-mary cause is known. The routine use of nonspecificantidiarrheal drugs in all patients with acute diarrhea isunnecessary and in many situations these agents are con-traindicated.

Opiates stimulate segmental contractions anddecrease peristalsis. The net effect is prolonged intestinal


transit that allows additional time for fluid and electrolyteabsorption. Opiate actions are attributed to the directeffect on intestinal smooth muscle. Additional antidiar-rheal effects are attributable to stimulation of absorption,and inhibition of secretion, of fluid and electrolytes. Thetwo most common opiates used are loperamide (0.1mg/kg PO q8hr) and diphenoxylate hydrochloride (0.1mg/kg PO q8hr). Although structurally similar, lop-eramide appears to be more potent, have a more rapidonset of action, and have a longer duration of effect.These properties may be attributable to loperamide’sprostaglandin synthetase inhibiting, calmodulin antago-nizing, and calcium channel blocking actions. Sideeffects of these two drugs most often are noted wheninappropriate dosages are used and include depression,vomiting, and excessive salivation. Opiates should not beused to treat acute diarrhea in which a bacterial cause issuspected. Increasing intestinal transit time prolongs res-idence time of the bacteria, allowing further proliferationof the organism, mucosal invasion, and the absorption oftoxins. If diarrhea is not controlled within 48–72 hours,opiates should be discontinued.

Bismuth subsalicylate (0.5–1 ml/kg PO q6–8hr)appears to be an effective agent for the treatment ofenterotoxigenic diarrhea. The salicylate moiety is felt todecrease intestinal secretion by interfering withprostaglandin production and by a more direct butundetermined effect on the enterotoxin. In addition,this drug appears to be anti-inflammatory, possess some


bactericidal activity, and may bind enterotoxin. Salicylateintoxication can result from overdosage, particularly incats. It is a useful and practical therapy for acute non-specific diarrhea. Silicates, such as kaolin, may bindenterotoxins but have no proven efficacy for the treat-ment of diarrhea.

Anticholinergics inhibit Cl– and water secretion bycrypt epithelial cells and stimulate Na+, Cl–, and waterabsorption by villus epithelial cells by antagonizing mus-carinic (M1 and M2) cholinergic receptors. Unfortu-nately, available muscarinic antagonists are nonselectiveand also inhibit smooth muscle contraction, causing amajor reduction in resistance to flow in the intestinaltract. For this reason, the effectiveness of these drugs isquestionable and their use can precipitate ileus by fur-ther reducing intestinal motility in an animal with diar-rhea whose intestine is already hypomotile.

Other drugs that might be of benefit in the treat-ment of severe, unexplained acute diarrhea wouldinclude 5-HT3 antagonists (ondansetron or granisetron0.5–1.0 mg/kg PO q12hr), a2-adrenergic antagonists(clonidine 5–10 mg/kg SQ, PO q8–12hr), calmodulinantagonists (chlorpromazine 0.2–0.4 mg/kg SQ, IMq8hr or prochlorperazine 0.25–0.5 mg/kg PO, SQ, IMq8hr), and calcium channel blockers (verapamil or dilti-azem 0.5–1.0 mg/kg PO). Because of limited clinicalexperience with the use of these drugs and their poten-tial side effects, these drugs should be used with caution.


References1. Mazzaferro EM, Hackett TB, Stein TP, et al. Meta-

bolic alterations in dogs with osteosarcoma. Am J VetRes 2001;62(8):1234–1239.

2. Ogilvie GK, Walters L, Salman MD, et al. Alterationsin carbohydrate metabolism in dogs with non-hematopoietic malignancies. Am J Vet Res 1997;58(3):277–281.


Case Illustrations

CASE 1: Canine OsteosarcomaA 6-year-old, 114-pound, castrated male Doberman pre-sented with a 1-month history of left forelimb lameness.A soft tissue swelling was palpated overlying the distalradius of the left forelimb. Following palpation, the dogwas unable to bear weight on the limb. Cytological exam-ination of a fine-needle aspiration biopsy obtained fromthe soft tissues surrounding the left distal radius showedcells suggestive of a mesenchymal neoplasm. Radio-graphs of the thorax and abdomen were normal inappearance. An aggressive, destructive lesion of the leftdistal radius was observed radiographically and found tobe highly suggestive of a primary bone neoplasm (FigureC1-1).

249

250 Case Illustrations

Figure C1-1 Survey radiograph of the distal radius.

A scintigraphic evaluation of the skeleton revealedno bony metastatic involvement but confirmed theaggressive nature of the primary neoplasm. The left fore-limb was amputated and histological examination of theleft distal radius confirmed a diagnosis of osteosarcoma(Figure C1-2).

The dog was given cisplatin chemotherapy onceevery 21 days for four treatments following the amputa-tion. Seventeen months later, the dog presented withacute abdominal enlargement, weight loss, and depressedactivity. Radiographic evaluation of the abdomen wassuggestive of multiple hepatic metastatic nodules. Thedog was euthanized, and metastatic disease was con-firmed on postmortem examination.

Key Points

Most tumors of the musculoskeletal system have a briefclinical course prior to diagnosis (acute lameness). Themost common bone tumor in the dog is osteosarcoma.These tumors progress rapidly with widespread micro-scopic metastatic lesions (micrometastases) present invirtually all tissues of the body. Because of the advancedstage at presentation (lysis of bone, possibly fracture),amputation of the affected limb is performed. To delaythe growth of micrometastatic lesions, chemotherapyconsisting of cisplatin, carboplatin or Adriamycin isgiven after amputation. Limb-sparing procedures havebeen reported but are rarely performed because of highcost and complications.

Case Illustrations 251


Figure C1-2 In this hematoxylin and eosin stain photomicro-graph of osteosarcoma, note the disorganized architecture of thespecimen and the presence of large, bizarre, multinucleated cells(osteoclasts).

CASE 2: Feline Cutaneous MelanomaA 10-year-old, intact female, 8-pound domestic shorthaircat was presented with a 3-month history of multiple der-mal melanomas on both ears. Several masses 3–8 mm indiameter were observed on each pinna (Figure C2-1).The masses were dark black in color, firm, fixed to theskin, but not painful on palpation.


Figure C2-1 Multiple dermal melanomas on the left pinna.

Cytologic examination of cells obtained by fine-needle aspiration biopsy (Figure C2-2) showed plumpspindloid to round cells containing melanin granules.Although the nuclei were obscured in most cells, a diag-nosis of a well-differentiated melanoma was made.

The pinna was amputated. Histological examinationof the surgical specimens confirmed a diagnosis of cuta-neous melanoma. The cat has had multiple lesions con-firmed as dermal melanomas arising along the face,neck, and body wall since the time of pinna amputation.All lesions have been excised and no evidence of lymph


Figure C2-2 Dermal melanocytes observed on a cytologicsmear obtained by fine-needle aspiration biopsy.

node or internal metastasis has been observed in the 12months since the cat first presented to our hospital.

Key Points

Cutaneous melanomas are extremely rare in cats. Sites ofoccurrence that have been reported include the digits,head, and lumbar skin. Surgical removal is the treatmentof choice, and metastases have been reported in one offive cats with dermal melanoma. Three of the remainingfour cats were alive and disease free more than 1 yearafter surgery.


CASE 3: Canine Mast Cell TumorA 9-year-old, spayed female, 47-pound cocker spanielmix presented with a 2-week history of a mass overlyingthe left midthoracic body wall. On examination, an 8-cm,soft tissue mass was palpated in the area of the 8th–11thmid-intercostal region. The mass was located in the sub-cutaneous tissues. Deep palpation revealed the mass tobe deeply attached to the intercostal musculature. Find-ings of a complete blood count (CBC), serum biochem-istry, and urinalysis were unremarkable. A fine-needleaspiration biopsy was performed, and examination washighly suggestive of a mast cell tumor (Figure C3-1).


Figure C3-1 Cytological appearance of a mast cell tumor.

Radiographs revealed a soft tissue mass on the leftthoracic body wall with no apparent invasion into thethoracic cavity. Ultrasonographic examination con-firmed the deep attachment to the 8th through 11thribs. No evidence of metastasis was noted within the liver,spleen, sublumbar lymph nodes, or thorax. The mass wasexcised with wide margins and “peeled” from the tho-racic body wall. Histologic examination revealed neo-plastic cells at the deep margin. A diagnosis of grade IIImast cell tumor was made. The dog was treated with tem-porary radioactive iridium implants (Figures C3-2, C3-3,and C3-4).


Figure C3-2 The grossly evident boundaries of the tumor arehighlighted. The radiation field will extend 3 cm in all directionsbeyond these boundaries.

The temporary implants were left in place until auniform dose of radiation sufficient to “kill” the remain-ing cancer cells was obtained. The dose and time dependon the activity of the radiation packets. The advantage ofan implant is that the distance the radiation travels isshort, thus sparing the deeper normal tissues such as the


Figure C3-3 The dog is positioned in lateral recumbency undergeneral anesthesia. Stylets are passed through the subcutaneoustissues, and several hollow tubes are placed at 1-cm parallel inter-vals (also see Figure C3-4).

pleural space and lung. The radiation site became hyper-emic and alopecic over the next 21 days; however, nosigns of pleural or pulmonary toxicity occurred adjacentto the radiation site and no evidence of tumor recur-rence or metastasis has been noted on repeated exami-nation over the past 3 years.


Figure C3-4 All tubes are placed, and the dog is transferred tothe radiation isolation room. During recovery, each tube is loadedwith a radioactive ribbon containing packets of iridium.

CASE 4: Canine ThymomaAn 8-year-old, spayed female, 51-pound English springerspaniel was presented because the owner noticed achange in the sound of the bark. Radiographic, ultra-sonographic, and magnetic resonance imaging (MRI)examination showed an extensive mediastinal mass thatengulfed the cardiac silhouette on the right side and par-tially on the left. The mass was touching the mediastinalvessels but not invading them. The lung was totally oblit-erated on the right side. The left side of the lung waspresent but somewhat compressed. Cytologic examina-tion was suggestive of round cell neoplasia, possibly thy-moma. The anterior mediastinum was irradiated (FigureC4-1). Objective shrinkage of the tumor was noted dur-ing the therapy; however, 1 month following the end oftherapy, the mass had enlarged to the preradiation size.

The dog was treated with weekly vincristine therapyfor 2 months. The mass decreased in size by >90% dur-ing this time. Vincristine treatments were continued for an additional 6 months at 2-week intervals. Eightmonths after beginning vincristine treatment, the masswas not observed on survey radiographs of the thorax.The dog was still alive and in remission 19 months fol-lowing treatment.

Key Points

Thymomas are malignant epithelial tumors containingmature lymphocytes and mast cells. Cytologic examina-


tion of cells obtained by fine-needle aspiration biopsycan be difficult. Differential diagnoses for an anteriormediastinal round cell tumor include lymphoma, thy-moma, mast cell tumor (metastatic), or an undifferenti-ated endocrine neoplasm.

Common clinical signs in dogs with thymomainclude cough and, less commonly, dyspnea and lethargy;some patients may have signs related to aspirationpneumonia secondary to myasthenia gravis and megae-sophagus.


Figure C4-1 Note the alopecia and erythema that occurs late in the course of an external beam radiotherapy treatment of thethorax.

Thymomas tend to be large, invasive, slow-growingtumors with a low metastatic rate. Surgical excision withneoplastic-free margins is the treatment of choice. Dogswith megaesophagus, polymyositis, hypercalcemia, andaspiration pneumonia have a poor prognosis.

Success using either localized irradiation or systemicchemotherapy has not been described in a large numberof dogs. Vincristine is commonly used in combinationwith other chemotherapy drugs in the induction, main-tenance, and reinduction of remission in dogs withlymphoma.


CASE 5: Canine Bladder TumorA 14-year-old, spayed female, 34.5-pound mixed breeddog was referred for signs of stranguria, hematuria, andinappetence of 2 weeks duration. CBC findings were nor-mal, the serum biochemistry showed increased bloodurea nitrogen (BUN; 33). Survey radiographs of theabdomen showed a mass present in the trigone of theurinary bladder when contrasted with air (pneumocys-togram; Figure C5-1).

An ultrasonographic examination of the abdomenshowed a polyploid mass arising from the trigone regionof the urinary bladder (Figure C5-2). Low-power resolu-tion cytologic examination of a urine sample (free catch)


Figure C5-1 Pneumocystogram of the urinary bladder.

showed many neoplastic transitional epithelial cells (Fig-ure C5-3).

Histologic examination of a biopsy obtained via arigid cystoscope inserted into the distal urethra con-firmed a diagnosis of transitional cell carcinoma (FigureC5-4). During the initial evaluation, the dog becameunable to urinate and acutely azotemic resulting indepressed activity and inappetence. A temporary cys-tostomy procedure was performed, allowing diversion ofurine through a Foley catheter (Figure C5-5).


Figure C5-2 Ultrasonographic image of a urinary bladder massarising from the trigone (lower right portion of the ultrasoundimage).

The dog was given two treatments of cisplatinchemotherapy. The temporary cystostomy tube wasremoved 2 months following the initiation of cisplatintherapy. The dog then was maintained on daily piroxi-cam chemotherapy. The dog was followed for 36months; clinical signs of stranguria were reported rarely.

The dog had a persistently elevated BUN and creati-nine with isothenuric urine, suggestive of chronic renalinsufficiency as a result from either intermittent urinaryoutflow obstruction from the tumor or from the combi-nation of cisplatin and piroxicam administration.


Figure C5-3 Low-magnification view of transitional epithelialcells from a urine sample.


Figure C5-4 High-magnification view of a urine sample from adog with transitional cell carcinoma.


Figure C5-5 Foley catheter placement in a dog for urinarydiversion during treatment of a transitional cell carcinoma.

CASE 6: Canine LymphomaA 5.5-year-old, intact female, 56.5-pound Doberman pre-sented with a mass on the soft palate and weight loss(about 20 pounds) over the previous 6 months. The sub-mandibular lymph nodes were enlarged (Figure C6-1)and the dog was having difficulty breathing.

A temporary tracheostomy tube (see Figure C6-1)was placed to relieve upper airway obstruction caused byenlarged lymph nodes. A CBC showed decreased packedcell volume (PCV; 30), hemoglobin (9.5 g/dl) and redblood count (RBC; 4.2 million/μl). No other abnormal-ities were noted. Cytological examination of a tissue


Figure C6-1 Enlarged submandibular lymph nodes in aDoberman.

imprint obtained from the mass in the caudal orophar-ynx progressing ventrally from the soft palate wassuggestive of lymphoma. Survey radiographs of the naso-pharyngeal region showed enlarged retropharyngeallymph nodes (Figure C6-2).

The retropharyngeal lymph nodes were biopsied,and histological examination confirmed a diagnosis oflymphoma. The dog was treated with a combination ofchemotherapy drugs including vincristine and Cytoxan.The retropharyngeal lymph nodes were irradiated in anattempt to palliate the signs of dyspnea. The dog died


Figure C6-2 Survey radiographs showing enlarged retropharyn-geal lymph nodes and tracheal compression. Thoracic radiographswere normal.

2 months following discharge from the hospital second-ary to respiratory complications.

Key Points

Canine lymphoma is a multisystemic disorder of lym-phocytic origin. Disease may originate in any one or alllymph nodes. Neoplastic cells, although few in number,can be readily identified in any organ of the lym-phoreticular system (liver, spleen, bone marrow).

These tumors progress rapidly with widespreadinvolvement, eventually affecting all lymph nodes withsignificant lymphocytic infiltrates present in the liver,lung, kidney, and bone marrow. Because of the advancedstage at presentation (lymph node enlargement, bonemarrow involvement) and possible paraneoplastic syn-dromes (hypercalcemia, cancer cachexia), the lifespanof dogs is short without treatment (30–60 days).

The dog with lymphoma can be successfully treated,not cured, with chemotherapy. Many protocols exist thatallow dogs to enjoy a significant, high-quality lifespan.


CASE 7: Canine Splenic HemangiosarcomaA 12-year-old, spayed female, 46-pound mixed breed dogwas presented with a decreased appetite and lethargy.Enlarged popliteal lymph nodes and an abdominal masscaudal and ventral to the liver were palpated. A CBCshowed a decreased PCV, hemoglobin, and RBC. Nucle-ated RBCs were noted as well as a decrease in plateletnumbers. Serum biochemistry revealed an increasedalkaline phosphatase and decreased potassium. Abdom-inal ultrasonography revealed masses within the spleenof mixed echogenicity. Thoracic radiographs showedpossible neoplastic pulmonary infiltrates. A splenectomywas performed and a histologic diagnosis of heman-giosarcoma was made. The dog was treated with fourcycles of Adriamycin. The dog died 15 months after sur-gery from complications due to metastases to the liverand lungs.


CASE 8: Canine Pituitary MacroadenomaAn 11-year-old, spayed female, 20.5-pound Boston

terrier was presented for a decreased appetite and thirst,with estimated weekly episodes of confusion with weak-ness lasting about 24 hours. The dog had a history ofskin tumors. A slight discharge from both nares wasnoted as well as mild bilateral cataracts. Several smallmasses on the cranium were noted and thought to bepossible benign sebaceous adenomas. A firm 3-cmnonpedunculated mass was palpated on the left shoul-der. Possible hepatomegaly was noted upon abdominalpalpation. CBC findings were within normal limits. Theserum biochemistry showed increased alanine transami-nase (ALT; 398) and alkaline phosphatase (ALP; 458).An MRI showed a large enhancing mass arising from theregion of the sella turcica. The primary considerationwas a pituitary mass. A macroadenoma was diagnosedbased on the MRI. The dog was treated with externalbeam radiation (25 daily 2-Gy fractions). The massresolved and the dog was still doing well 2 years followingradiation therapy.


CASE 9: Feline Vaccine-Associated SarcomaA 10-year-old, castrated male, 8.5-pound domestic short-hair cat presented with a 5-cm diameter, firm mass over-lying the left scapula. The mass was first noticed 3months ago and began to rapidly increase in size duringthe last 7 days. The mass was broad-based and fixed tothe scapula. Thoracic radiographs were obtained and nopulmonary abnormalities were noted; however, two softtissue masses were seen caudal to the last rib on the leftlateral wall. No bony involvement was evident.

Ultrasonographic examination showed the massinfiltrating the tissues of the left paracostal region. Cyto-logic examination of a fine-needle aspiration biopsyrevealed large, multinucleated, pleomorphic mesenchy-mal cells (Figure C9-1). The masses were excised (FigureC9-2) and submitted for histologic examination. A malig-nant spindle cell tumor, giant cell sarcoma (containingsome areas that were morphologically consistent withosteosarcoma) was diagnosed.

The left scapular and thoracic wall region was irra-diated using temporary subcutaneous iridium afterload-ing implants. Three months later, the cat presented withclinical signs of weakness and nonproductive coughing.Thoracic radiographs (Figure C9-3) showed an anteriorthoracic mass and pleural effusion. Cytologic examina-tion of a thoracocentesis sample confirmed metastaticdisease and the cat was euthanized.


Key Points

Many investigations have suggested a causal relation-ship between vaccination and the development oftumors in cats. A Task Force by the American Veteri-nary Medical Association has been created to examinethe cause(s) and treatment(s) of vaccine-associated


Figure C9-1 Wright-Giemsa stained fine-needle aspirationsmear from the left scapular mass consistent with a mesenchymalneoplasm. Osteoid and malignant chondrocytes were observed inother areas, suggesting a diagnosis of either an osteosarcoma orgiant cell tumor.

tumors in cats. Unfortunately, these tumors are quiteinvasive and surgical excision with neoplastic-free mar-gins is uncommon. Regrowth following excision is sud-den in onset, and preliminary reports regarding the useof radiation or chemotherapy have mixed results. Vari-ous histologic forms have been identified. Giant celltumors are very uncommon in animals and known tobe highly metastatic.


Figure C9-2 The shaved area illustrates the outermost extentof the surgical area. Neoplastic cells were observed at all surgicalmargins.


Figure C9-3 Thoracic radiograph showing an anterior thoracicmass with pleural effusion 3 months following irradiation for avaccine-associated giant cell tumor.

CASE 10: Feline Bladder TumorAn 11-year-old, castrated male, 8-pound domestic short-hair cat presented with hematuria. The cat had been uri-nating throughout the house and had no previoushistory of a urinary tract infection. On palpation, thebladder was found to be irregular and hard; however, nopain was noted.

The following laboratory findings were abnormal:decreased lymphocyte count, slightly increased eosino-phil and basophil count, slightly elevated total protein,increased BUN (45), and increased total bilirubin (0.6).Urinalysis findings were specific gravity 1.033 with 3+blood, 2+ bilirubin, 1+ ketones, 4+ protein, 8–10 whiteblood count (WBC)/high-power field (HPF), and loadedwith RBC/HPF. Abdominal radiographs showed a largesublumbar lymph node, while the thoracic radiographsappeared normal. An ultrasound of the abdomenshowed a large, irregularly marginated granular massinvolving the wall of the urinary bladder that occludedthe major portion of the lumen. Further evaluationshowed a large medial iliac lymph node, and both kid-neys showed diffuse increased echogenicity. Cytologicalexamination of aspirates from the iliac lymph nodes andthe bladder were diagnostic of squamous cell carcinoma.

Abdominal exploratory surgery was performed, thebladder isolated, and a 5-cm mass firmly attached to the mucosa of the bladder was removed (Figure C10-1).The iliac lymph nodes were biopsied. The surgical


margins contained neoplastic cells. The lymph nodes didnot contain neoplastic cells. A diagnosis of squamous cellcarcinoma was confirmed. The pet owner declined fur-ther therapy, and although the cat was free of clinicalsigns for 3 months, urinary tract obstruction occurredand the cat was euthanized.


Figure C10-1 Exposed urinary bladder during a laparotomy.The bladder was opened and several biopsies obtained. Completeexcision of grossly evident neoplastic tissue could not beperformed.

Key Points

Tumors of the urinary bladder have a long clinical courseprior to diagnosis. These tumors progress very slowly andsigns can be misinterpreted for a complicated urinarytract infection. Because of the advanced stage at presen-tation, complete excision is often impossible. Whentumors become evident on gross examination, only asmall percentage of the tumor cells are responsible forfurther tumor enlargement (Gompertzian kinetics);therefore, many large-sized tumors are unresponsive tosystemically delivered anticancer drugs.


CASE 11: Canine Mediastinal LymphomaA 5-year-old, intact male, 17-pound West Highland whiteterrier presented with a 2-week history of nonproductivecough, regurgitation, and enlarged lymph nodes. A gen-eralized lymphadenopathy was noted on physical exami-nation. The findings of a complete blood count wereunremarkable. Results from a serum biochemical profileshowed a slight elevation in glucose, alkaline phos-phatase, and total bilirubin. Survey radiographs of thethorax showed enlargement of the anterior medi-astinum mass. Equivocal hilar lymphadenopathy was alsonoted. A fine-needle aspiration biopsy of the leftprescapular lymph node was diagnostic for lymphoma(Figure C11-1).

The dog was treated with a combination of Cytoxan,vincristine, and L-asparaginase. The dog was in completeremission for 7 months. The cancer then relapsed andwas reinduced into remission for an additional 8 monthsusing Adriamycin chemotherapy.

Key Points

Canine lymphoma is a multisystemic disorder of lympho-cytic origin. The disease may originate in any one or alllymph nodes. Neoplastic cells, although few in numbercan be readily identified in any organ of the lymphoretic-ular system (liver, spleen, bone marrow). These tumorsprogress rapidly with widespread involvement, eventually


affecting all lymph nodes with significant lymphocyticinfiltrates present in the liver, lung, kidney, and bone mar-row. Because of the advanced stage at presentation(lymph node enlargement, bone marrow involvement)and possible paraneoplastic syndromes (hypercalcemia,cancer cachexia), the lifespan of dogs is short withouttreatment (30–60 days). The dog with lymphoma can besuccessfully treated, not cured, with chemotherapy. Manyprotocols exist that allow dogs to enjoy a significant, high-quality lifespan.


Figure C11-1 In this fine-needle aspiration biopsy specimenobtained from a superficial lymph node, note the pleomorphicfeatures at low magnification.

CASE 12: Feline Intestinal LymphomaAn 8-year-old, spayed female, 7.5-pound domestic short-hair cat presented with a 1-month history of lethargy,recent anorexia, and weight loss (3 pounds in the past 6months). The cat had been recently tested and wasFeLV/FIV negative. A bone marrow aspirate at the refer-ring veterinarian showed significant lymphoprolifera-tion. The cat was lethargic and recumbent, which hadbecome normal to the owner in the past several months.An intestinal mass in the mid-abdomen was palpated.The CBC revealed a nonregenerative anemia, neutrope-nia, and thrombocytopenia. Results from a serumbiochemistry profile were unremarkable. An ultrasono-graphic examination of the abdomen was performed. Amass in the abdomen appeared to be arising from thesmall intestine. A Tru-cut biopsy was obtained from theenlarged mesenteric lymph nodes. Histologic and cyto-logic examination of mesenteric lymph node specimensconfirmed a diagnosis of lymphoma. The intestinal masswas removed (Figure C12-1) to relieve the obstruction.The cat was treated with single-agent asparaginase untilneutrophil counts returned to normal. Then the cat wasswitched to a combination of vincristine and Cytoxanchemotherapy. The cat has been in remission for aperiod of 10 months.

In some cases, resection of the mass not only resolvesthe clinical signs of obstruction and the resultinganorexia and weight loss but also alleviates the need for


adjuvant chemotherapy. However, for the most part, lym-phoma is a systemic disease and chemotherapy is neededto manage the disease.

Key Points

Feline lymphoma is a multisystemic disorder of lympho-cytic origin. Feline leukemia virus infection has beenshown to cause lymphoma in cats and a negative result ofa test for the virus does not guarantee against prior expo-sure to the virus. As a retrovirus, FeLV can insert an“oncogene” into lymphocytes, resulting in uncontrolled


Figure C12-1 Intestinal lymphoma in a cat.

growth of the cells (i.e., cancer). The disease may origi-nate in any one or all lymph nodes. Neoplastic cells,although few in number, can be readily identified in anyorgan of the lymphoreticular system (liver, spleen, bonemarrow). These tumors progress rapidly with widespreadinvolvement, eventually affecting all lymph nodes, withsignificant lymphocytic infiltrates present in the liver,lung, kidney, and bone marrow. Because of the advancedstage at presentation (lymph node enlargement, bonemarrow involvement) and possible paraneoplastic syn-dromes (hypercalcemia, cancer cachexia), the lifespanof cats with no treatment is short (30–60 days).

The cat with lymphoma can be successfully treated,not cured, with chemotherapy. Many protocols exist thatallow cats to enjoy a significant, high-quality lifespan. Apositive test for FeLV indicates a poor prognosis. BecauseFeLV infects cells of the myeloid series, profound andsustained neutropenia can result following chemother-apy administration. In this cat, significant bone marrowinfiltration with neoplastic cells resulted in neutropenia.To avoid further insult to the cells of the bone marrow,asparaginase was used.


CASE 13: Feline Mammary CarcinomaA 13-year-old, spayed female, domestic shorthair cat wasreferred for treatment after a mammary tumor wasremoved 3 weeks ago. The biopsy from the referring vet-erinarian was diagnostic of adenocarcinoma/carcinosar-coma with evidence of lymphatic invasion. A large masswas palpated on the midline of the abdomen, along theprevious incision site. A diagnosis following excisionbiopsy of mammary adenocarcinoma with lymphaticinvasion was made.

The cat was treated with Adriamycin three times.Two months after beginning treatment, radiographswere suggestive of metastatic disease in the left caudallung lobe. The cat was euthanized 3 months after begin-ning treatment, due to metastases.


CASE 14: Feline Lung TumorA 4-year-old, spayed female, 7.5-pound domestic shorthaircat presented with a 10-month history of a nonproductivecough and episodes of wheezing. On examination, the catwas found to have increased lung sounds and a nonpro-ductive cough was elicited on tracheal palpation. Thefollowing laboratory findings were abnormal: slightly ele-vated PCV, total plasma protein (TPP), and an increasedALT. Thoracic radiographs revealed a solitary lung massin the left caudal lung lobe and enlarged tracheo-bronchial lymph nodes (Figure C14-1). A surgical biopsyof the lung was cytologically examined, and squamouscell carcinoma with metastasis to the tracheobronchiallymph nodes was diagnosed.

Tumors of the respiratory tract are uncommon incats. The most common clinical signs in cats with lungtumors are weakness, lethargy, and weight loss, notcoughing or wheezing. Lung tumors tend to be solitarymasses affecting the caudal lung lobes (left more thanright) more than the cranial lung lobes, although pleu-ral effusion may be noted in over 50% of cats, masking amass or masses. If associated tracheobronchial lymphnodes are not enlarged, the median survival of cats isabout 1 year following excision of a solitary lung tumormass. The survival is poor (<60 days) in cats with poorlydifferentiated lung tumors or enlarged tracheobronchiallymph nodes.



Figure C14-1 Right lateral thoracic radiograph of a cat. Notethe solitary lung mass in the left caudal lung lobe and the dorsaldeviation of the trachea by enlarged tracheobronchial lymphnodes. Because of the poor prognosis, the owner declined furthertherapy for the cat.

CASE 15: Canine Oral MelanomaA 12-year-old, intact male, 63-pound golden retrieverpresented with a history of having growths removedfrom the oral cavity in the past. A round, pink mass onthe right side of the soft palate was noted. The left sub-mandibular lymph node seemed enlarged, and two smallgrowths were noted (one on the right thoracic wall andthe other on the middle dorsum, between the scapulae.The right prescapular lymph node was enlarged. A sub-dermal mass was noted over the right eye. Two or threehardened lumps were palpated in the testicle. Urinalysisshowed specific gravity 1.024, pH 7, 4+ protein, 1+ biliru-bin, negative for blood and hemaglobin, and 0–1 WBC +RBC/HPF. No other abnormalities were noted. Radi-ographs showed no evidence of thoracic involvement.Ultrasound showed testicular masses, most likely to beneoplasia. It also showed a focal enlargement of smallbowel. Cytologic examination of an aspiration of the tes-ticle was suggestive of an interstitial cell tumor. Cytologicexamination of the mass over the right eye was suggestiveof a mast cell tumor. The dog was neutered, the oralmelanoma was removed and the mast cell tumorremoved from over the eye. Histopathology confirmedthe diagnoses as mast cell tumor and interstitial celltumor. The dog was treated with bacillus calmette-guerin(BCG; a nonspecific immunomodulator that activelystimulates the immune system to respond to a wide vari-ety of substances that may harm the body, including


some cancers) given intralesionally and two doses of cis-platin. The dog never attained remission and died due tometastases and continual tumor growth.


CASE 16: Canine Maxillary MelanomaA 4-year-old, castrated male, 91-pound mixed breed dogwas presented for a mass behind the left upper canine,which the owner noticed 2 weeks earlier. The mass wasbiopsied at the referring veterinarian and diagnosed asmelanoma. An eroded mass was found on the ventralsurface of the gingiva. Serum biochemistry revealedincreased ALP (980) and ALT (740). No other abnor-malities were present. An MRI showed left-sided rostralmaxillary mass extending from the canine through thesecond premolar, invading partially through the cornerof the nasal cavity and infiltrating somewhat into thenasal turbinates, but the mass remained well marginated.A hemimaxillectomy and mandibular lymph node exci-sion was completed. Histological examination was diag-nostic of an amelanotic melanoma in the maxilla andpyogranulomatous inflammation in the lymph nodes.The dog was still in remission 15 months after surgery.


CASE 17: Canine Lung TumorA 13-year-old, spayed female, 33.5-pound cocker spanielpresented with a chronic cough of 3 weeks and a mass inthe cranial left dorsal lung lobe. The right front mam-mary gland had been removed 16 months earlier. Sev-eral small masses were found on examination: a 10 � 5cm mass on the left lateral abdominal wall, and a pea-sized mass in the right third mammary gland. A coughwas elicited, and harsh lung sounds were heard on bothsides of the lungs. All laboratory findings were withinnormal limits. Thoracic radiographs revealed a massassociated with the left cranial main stem bronchus withpossible extension to the hilar region or extension to thehilar lymph nodes (Figure C17-1). A diffuse increasedbronchial pattern was observed.

Cytologic evaluation of a fine-needle aspirate of thethoracic mass was suggestive of carcinoma, possiblybronchiolar alveolar in origin. The dog was given Adri-amycin therapy once every 3 weeks for a total of threedoses. However, the dog died at home 1 month aftercompletion of the therapy.

Key Points

Originally, the lung mass was believed to be metastaticmammary carcinoma. Histologic examination provedthe dog to have a new malignancy. Tumors of the respi-ratory tract are uncommon in dogs. The most common


clinical signs in dogs with lung tumors are weakness,lethargy, weight loss, not coughing or wheezing. Mostlung tumors are observed unexpectedly after taking rou-tine thoracic images. Lung tumors tend to be solitarymasses affecting the caudal lung lobes (right more thanleft) more than the cranial lung lobes; pleural effusion isuncommon. If associated tracheobronchial lymph nodesare not enlarged, the median survival of dogs is about 1year following excision of a solitary lung tumor mass.


Figure C17-1 This and other survey radiographs suggested aprimary bronchial alveolar carcinoma with mass extension to thehilus or metastasis to regional lymph nodes and possibly through-out the chest.

The survival is poor (<60 days) in dogs with poorly dif-ferentiated lung tumors or enlarged tracheobronchiallymph nodes.


CASE 18: Canine HemangiopericytomaA 10-year-old, castrated male, 62.5-pound German shep-herd presented with a mass overlying the left carpus. Themass had been removed twice and grown back rapidly.There was firm, ulcerated, lobulated, nonpainful masson mediolateral aspect of the left carpus (Figure C18-1).A fine-needle aspiration biopsy of the mass was per-formed (Figure C18-2). No evidence of pulmonarymetastasis was seen on survey thoracic radiographs, andan incisional biopsy was obtained (Figure C18-3).

The tumor and approximately 4 cm of surroundingnormal tissue on the left distal antebrachium were


Figure C18-1 Carpal mass in a German shepherd.

Figure C18-2 Cytologic examination showed a uniform popu-lation of pleomorphic mesenchymal cells with indistinct cytoplas-mic borders, suggestive of a fibrosarcoma or hemangiopericytoma.

exposed to a combination of radiation and hyperther-mia. The tumor mass decreased in overall size by >50%over the 6-week treatment period (Figure C18-4).



Figure C18-3 Histological findings were consistent with a diag-nosis of hemangiopericytoma. Note the typical whorled pattern ofmesenchymal tumor cells observed in canine hemangioperi-cytomas.


Figure C18-4 Two months following the completion of radia-tion therapy, the hemangiopericytoma was smaller in size. Thedog was able to enjoy full function of the limb. No further pro-gression in size of the tumor was noted after more than 2 years.

CASE 19: Canine Hepatic CarcinomaA 9-year-old, spayed female, 36-pound mixed breed dogwas referred because of a mass in the right cranialabdomen. The dog had a history of mast cell tumorremoval from the neck 2 years ago and basal cell tumorremoval from the neck 1 year ago. A large soft mass onthe cranial thorax was palpated. Also palpated was alarge firm mass in the cranial abdomen. The abdominalmass seemed to have the right kidney associated with it.The inguinal lymph nodes were enlarged. A CBCshowed decreased RBC and PCV and an increased WBC(25.2) count. Also, 3 nucleated RBC per 100 WBC werenoted. Serum biochemistry revealed increased ALP(2840), ALT (2370), and aspartate transaminase (AST;4420). Ultrasonic evaluation showed a right-sidedhepatic mass with secondary masses in the remaininghepatic parenchyma. The right kidney was seen to be dis-placed by the mass but not involved.

The mass was removed and the section examined his-tologically. It was diagnosed as hepatocellular carcinoma.The dog was treated with Adriamycin four times. Remark-ably, the dog was still alive 3 years following diagnosis.


CASE 20: Feline Nasal Plane Squamous Cell Carcinoma

A 10-year-old, intact female, 11-pound domestic short-hair cat presented with a 3-month history of an erosivelesion on the rostral aspect of the nasal plane (FigureC20-1). A topical antimicrobial ointment had beenapplied previously with no apparent effect. An erosivemass encompassing the left nares extending onto thenasal plane was observed. The remainder of the physicalexamination was normal. Using a scalpel blade, thelesion was gently scraped and the cells smeared onto amicroscope slide for cytologic evaluation (Figure C20-2).Histologic examination of a superficial pinch biopsy con-firmed a diagnosis of squamous cell carcinoma. Photo-dynamic therapy (PDT) was used to treat the rostralnasal plane of this cat. A circumferential necrotic lesionformed over 24 hours and the granulated wound reep-ithelialized over the next 6 weeks.



Figure C20-1 An erosive mass on the nasal plane of a cat.


Figure C20-2 Squamous cell carcinoma as observed on a cyto-logic smear of cells obtained by scraping the nasal plane lesionwith a scalpel blade.

CASE 21: Canine Nasal AdenocarcinomaA 13-year-old, intact male, 18-pound miniature poodlepresented with a nasal adenocarcinoma diagnosed bythe referring veterinarian. The carcinoma started in theleft nostril and crossed the septum to the right nostril. A5-month history of occasional epistaxis was noted. Agrade IV holosystolic left apical murmur and externalfacial asymmetry were noted. The following laboratoryfindings were abnormal: BUN (26), creatinine (1.4),ALP (285). The CBC was within normal limits. Magneticresonance images of the skull showed an aggressivelesion in the left nasal passage compatible with neoplasia(Figure C21-1).

Multiple pieces of nasal mucosa were cytologicallyexamined and a diagnosis of carcinoma was confirmed.A rhinotomy followed by the placement of iridiumimplants in the nasal sinuses for 4 days (radiation ther-apy) was performed. An additional 10 treatments withexternal beam irradiation to the ethmoid region of thenasal cavity was performed. The dog was alive 3.5 yearsafter the surgery and radiation procedures.

Key Points

Tumors of the respiratory tract are uncommon in dogs.Tumors of the nasal and paranasal sinuses are the mostcommon respiratory tract malignancies. The most com-mon clinical signs are epistaxis and sneezing. Metastatic



Figure C21-1 MRI scan of the nasal passages of a dog. Notethe increased soft tissue density along the left side.

disease is uncommon; however, a thorough examinationof the head, neck, and thorax should be performed. Thelifespan of a dog with a nasal malignancy is greatlyprolonged following localized radiation therapy to theentire nasal and frontal sinus regions of the head,generally 18–24 months with external beam radiationtherapy protocols and 36–48 months following brachy-therapy (implant radiation) protocols. Surgery withoutadjuvant radiation is not recommended; the survival ofthese dogs is generally <6 months. The survival time isshorter in dogs with mesenchymal nasal tumors (chon-drosarcomas), generally 12–15 months.


Recommended Reading

In addition to the guiding principle of “biopsy, biopsy,biopsy,” always consider the corollary “when in doubt,check it out.” Keep current on information published inpeer-reviewed scientific journals, comprehensive inter-nal medicine textbooks, and always seek the advice of aveterinary oncologist. The resources in print that I findhelpful on a regular basis in my clinic and used as thesole reference materials for this book are these:

DeVita VT, Hellman S, Rosenberg SA. Cancer: Princi-ples and Practices of Oncology (6th ed). Philadelphia:Lippincott-Raven, 2001.

Hahn KA, Richardson RC. Cancer Chemotherapy: AVeterinary Handbook. Baltimore: Williams andWilkins, 1995.

Morrison WB. Cancer in Dogs and Cats. Baltimore:Williams and Wilkins, 1998.

305

Ogilvie GK, Moore AS. Managing the Veterinary Can-cer Patient. Trenton, NJ: Veterinary Learning SystemsCompany, 1995.

Plumb DC. Veterinary Drug Handbook (3rd ed). Ames:Iowa State University Press, 1999.

Withrow SJ, MacEwen EC. Small Animal ClinicalOncology, Third Edition. Philadelphia: Saunders, 2001.

306 Recommended Reading

Aabnormal circulating cells, 38acute tumor lysis syndrome, 240adenocarcinomas, 15

anal sac, 67–68canine nasal case study,

302–304thyroid, 28–30

adjuvant analgesics, 211Adriamycin, 171Alkeran, 173alkylating agents, 139American Society of Hospital

Pharmacists, 147anal sac apocrine gland adeno-

carcinomas, 18–19, 67–68anaphylaxis, 159–160, 239–240anemia, bone marrow evaluation

and, 37anorexia, 192–193antibiotics, 139anticholinergics, 246antimetabolites, 139appetitice stimulation, 193asparaginase, 167assessment

nutritional, 196–200

of nutritional needs, 200–205of pain, 207

atopy, 170azothiprine, 167–168

Bbasal cell tumors, 16behavioral techniques of pain

management, 216benign tumors, cytologic criteria

for, 12biopsies

excisional, 55–56guidelines for, 50–63incisional, 54–55lymph node, 57methods, 53–57needle core, 56needles for, 52–53punch, 53–54specimen handling, 57–58Tru-cut, 8–9when to obtain, 50–52

bismuth subsalicylate, 245–246bladder tumors, 263–267

feline case study, 277–279bleomycin, 168

307

Index

Bleoxane, 168blood smear evaluation, 30–37

collection and slide prepara-tion for, 31

erythrocyte evaluation in, 33leukocyte evaluation, 34–36neoplastic cells, 36platelet evaluation, 34scanning, 32

bone marrow evaluation, 36–49cellularity evaluation, 43erythroid series, 45–46indications for, 36–39leukemias, 48–49marrow iron or hemosiderin,

43–44materials needed for, 39–40megakaryoctyes, 44–45myeloid series, 47–48sample collection, 40–43

bone scans, 60bone tumors, 68–69

appendicular skeleton, 110–111axial skeleton, 111–112canine case study, 249–252chemotherapy for, 168, 169nonosteosarcomas, 104–105

brain tumors, 69–70chemotherapy for, 175

busulfan, 168

Ccandidiasis, 227capillary action (nonaspiration)

technique, 8

carboplatin, 168–169carcinomas, 15

canine hepatic case study, 298chemotherapy for, 168, 171,

172, 174–175cutaneous squamous cell,

75–77feline mammary case study,

285feline nasal plane case study,

299–301cardiac hemangiosarcomas,

70–71case studies, 249–304

canine bladder tumor,263–267

canine hemangiopericytoma,294–297

canine hepatic carcinoma, 298canine lung tumor, 291–293canine lymphoma, 268–270canine mast cell tumor,

256–259canine maxillary melanoma,

290canine mediastinal lymphoma,

280–281canine nasal adenocarcinoma,

302–304canine oral melanoma,

288–289canine osteosarcoma, 249–252canine pituitary macroade-

noma, 272

308 Index

canine splenic hemangiosar-coma, 271

canine thymoma, 260–262feline bladder tumor, 277–279feline cutaneous melanoma,

253–255feline intestinal lymphoma,

282–284feline lung tumor, 286–287feline mammary carcinoma,

285feline nasal plane squamous

cell carcinoma, 299–301CCNU, 169chemotherapy, 133–165

accidental spills in, 153–155administration, 145–146,

152–153client communication and,

165combinations and scheduling

of, 141–142cumulative or delayed toxicity

in, 164dosage conversion chart,

177–179dosages, indications, and

adverse reactions,167–176

dose determination, 143–144dose response curves, 137–138drug classes, 139drug disposal, 153drug storage and preparation

for, 148–152

extravasation from, 238–239goal of, 4–5multimodal, 143pharmacologic principles of,

136–146premedications, 157–158protocols, 141–143, 181–185resistance to, 140–141safety guidelines, 146–155selecting appropriate, 4–5side effect prevention,

155–160subacute toxicity syndromes,

160–164therapeutic index, 138–139tumor growth and response

to, 134–136when to consider, 133–134workplace concerns in,

146–148chlorambucil, 169cisplatin, 169client education, 228coagulation abnormalities, 51color flow doppler imaging, 62communication with clients, 165cumulative/delayed toxicity, 164cutaneous lymphomas,

chemotherapy for, 169cutaneous squamous cell carci-

nomas, 75–77cyclophosphamide, 170cyclosporine, 170cytarabine, 170cytologic criteria, 11–30

Index 309

cytologic criteria, cont.benign vs. malignant, 12inflammation and malignancy,

13tumor types and locations,

13–30cytoplasmic toxicity, 35–36Cytosar-U, 170cytotoxicity, 136–137, 146–148.

See also chemotherapyCytoxan, 170

Ddacarbazine, 171delayed toxicity, 164diagnosis

biopsy guidelines, 50–63blood smear evaluation, 30–36bone marrow evaluation,

37–49fine-needle aspiration, 7–11importance of, 1malignancy cytologic criteria

in, 11–30diagnostic imaging, 58–63

magnetic resonance imaging,62–63

nuclear medicine, 59–61plain film survey radiography,

58–59ultrasonography, 61–62

diarrhea, 242–246disposal, of drugs, 153dose determination, 143–144dose response curves, 137–138

doxorubicin, 171drug classes, 139DTIC, 171dysplasia, 38

Eelectrocardiograms, 156–157Ellence, 171Elspar, 167emergencies, oncology, 233–246

acute tumor lysis syndrome,240

anaphylaxis, 239–240diarrhea, 242–246extravasation, 238–239gastrointestinal ulceration, 242metabolic complications,

234–235neutropenia, 241–242shock, 236–237

enteral nutrition, 193–194,202–204

epirubicin, 171epithelial neoplasms, 15–19

adenocarcinomas, 15anal sac apocrine gland ade-

nocarcinomas, 18–19basal cell tumors, 16carcinomas, 15perianal gland adenomas,

17–18erythrocyte evaluation, 33erythrocytosis, 77erythroid series, 45–46euthanasia, 5

310 Index

Evans’s syndrome, 167–168excisional biopsies, 55–56extramedullary plasmacytomas,

24–25extravasation, 238–239

Ffamily considerations, 5–6feeding frequency, 204Feldene, 174–175fibroplasia, 15fine-needle aspiration, 7–11

capillary action technique for,8

fluid for analysis in, 10–11sample prepartion and han-

dling, 9–11slide preparation for, 11standard technique for, 7–8Tru-cut biopsies, 8–9

fluorouracil, 172

Ggallium, 60–61gastrointestinal ulceration, 242gemcitabine, 172Gemzar, 172gene amplification, 141granulocyte colony-stimulating

factor, 162

HHaemobartonella felis, 31hemangiopericytoma case study,

294–297hemangiosarcomas

canine splenic case study, 271cardiac, 70–71in cats, 78–79cutaneous, 73–74splenic, 122–123

hemorrhage, 222–223management of, 227–228

hemosiderin, 43–44hepatic carcinoma case study,

298histaminic reactions, 159–160,

239–240histiocytomas, 19–20histiocytosis, malignant, 20Hydrea, 172hydroxyurea, 172hyperadrenocorticism, 79–80hypercalcemia, 39, 234–235hyperplasia

erythroid, 46myeloid, 47–48

hypersinophilic disease, 80–81hypocalcemia, 240hypoglycemia, 235hypokalemia, 244

IIfex, 172–173ifosfamide, 172–173immune suppression, 167–168,

170Immuran, 167–168incisional biopsies, 54–55infections, 222

management of, 226–227

Index 311

inflammation, 13sarcoma vs. reactive fibroplasia

and, 15injection site–associated sarco-

mas, 81–82, 273–276insulinoma, 82–83

chemotherapy for, 175intestinal tumors, 83–85

case study, 282–284

LL-asparaginase, 139, 146lead poisoning, 38leiomyosarcomas, 14leukemias

acute lymphoid, 65–66acute nonlymphoid, 66–67bone marrow evaluation for,

48–49chemotherapy for, 167, 168,

169, 170, 172, 173, 176chronic lymphocytic, 71–72

Leukeran, 169leukocyte evaluation, 34–36leukocytosis, bone marrow evalu-

ation and, 37leukopenia, bone marrow evalua-

tion and, 37liver tumors, 86–87Lomustine, 169lung tumors, 89–90

canine case study, 291–293chemotherapy for, 172–173feline case study, 286–287

lymph node biopsies, 57lymphoid leukemias, 65–66lymphomas, 20–21

canine case study, 268–270canine mediastinal case study,

280–281in cats, 90–91chemotherapy for, 167, 168,

169, 170, 171, 172–173,174, 175, 176

in dogs, 91–93feline intestinal case study,

282–284

Mmagnetic resonance imaging

(MRI), 62–63malignant effusions, 229–233

diagnostic approach to,230–231

prognosis for, 233treatment considerations for,

231–233mammary tumors, 93–95

chemotherapy for, 174, 175mast cell tumors, 21–23

canine case study, 256–259in cats, 95–96chemotherapy for, 169, 176in dogs, 97–98

megakaryocytes, 44–45melanomas, 25–27

canine maxillary case study,290

312 Index

canine oral case study,288–289

chemotherapy for, 168, 169,175

cutaneous, 74feline cutaneous case study,

253–255melphalan, 173mesenchymal neoplasms

cytologic criteria of, 13–15leimyosarcomas, 14myxosarcomas, 14sarcomas, 14

mesotheliomas, 98–99metabolic complications,

234–235methotrexate, 173mitotic inhibitors, 139mitoxantrone, 173–174monoclonal gammopathy, 39mucositis, 220–221

management of, 225–226multiple myelomas, 24–25

in cats, 99–100in dogs, 100–101

mycosis fungoides, chemother-apy for, 169

myelodysplasia, 101–102myeloid series, 47–48myeloproliferative diseases,

48–49myelosuppression, 168Myleran, 168myxomas, 14myxosarcomas, 14

Nnasal tumors

in cats, 102–103in dogs, 103–104

needle core biopsies, 56needles, biopsy, 52–53

aspiration, 53cutting, 52–53semiautomatic, 53

neoplastic cells, 36nerve sheath tumors, 113–114neuroendocrine neoplasms,

27–30canine thyroid tumors, 28–29feline thyroid tumors, 29–30

neurostimulation, 216neutropenia, 241–242Nolvadex, 175nonosteosarcoma bone tumors,

104–105Novantrone, 173–174NSAIDS, 164, 209–210nuclear medicine, 59–61nucleated red blood cells

(NRBCs), 33nutrition, 190–205

alterations in cancer patients,190–191

anorexia, 192–193assessment of in cancer

patients, 191–192,196–205

enteral, 193–194needs caluclation for, 200–205parenteral, 195

Index 313

Oocular tumors, 105–107Oncovin, 176opioids, 210–211, 244–245oral complications, 216–228

candidiasis, 227etiology of, 216–219hemorrhage, 222–223,

227–228infection, 222, 226–227intervention options for,

224–228mucositis, 220–221, 225–226oral care and, 224–225preventing, 219–220radiation necrosis, 223–224stomatitis, 220–221, 225–226xerostomia, 223, 228

oral tumorsin cats, 107–108in dogs, 108–109

osteosarcomasappendicular skeleton,

110–111axial skeleton, 111–112canine case study, 249–252chemotherapy for, 168, 169

ovarian tumors, 112–113

Ppaclitaxel, 174pain management, 205–217

administration schedules in,212–215

assessment of pain and, 207causes of pain and, 206–207incidence of pain and,

205–206nonpharmacologic, 215–216pharmacologic, 208–215treatment for, 208–217

palliative care, 133–134pancreatic tumors, 78Paraplatin, 168–169parenteral nutrition, 195patient evaluation, 1–2patient management, 1–6perianal gland adenomas, 17–18peripheral nerve sheath tumors,

113–114Pharmorubicin, 171piroxicam, 174–175pituitary macroadenoma case

study, 272plain film radiography, 58–59plasma cell tumors, 24–25plasmacytomas, cutaneous and

extramedullary, 72–73platelet evaluation, 34Platinol, 169platinum compounds, 139pleural effusions, 229–230

diagnosing, 230–231prognosis for, 233treatment considerations for,

231–233polycythemia, bone marrow eval-

uation and, 37

314 Index

power doppler imaging, 62prednisone, 175, 191prostatic tumors, 114–115protocols, 141–143, 181–185. See

also chemotherapyindications for, 182–184supportive drugs in, 184

punch biopsies, 53–54

Qquality of life, 4–5

Rradiation necrosis, 223–224radiography

complications from, 218–219plain film, 58–59

recommended reading, 305–306rehabilitation. See supportive

care and rehabilitationrenal dysfunction, 156renal tumors, 115–117reserve cells, 17resistance to chemotherapy,

140–141resting energy requirements

(RER), 201–202retrobulbar tumors, 117–118round cell neoplasms, 19–27

histiocytomas, 19–20lymphoma, 20–21malignant histiocytosis, 20mast cell tumors, 21–23melanomas, 25–27plasma cell tumors, 24–25

transmissible venereal tumors(TVTs), 23–24

Ssalivary gland tumors, 119Sandimmune, 170sarcomas, 14

injection site–associated,273–276

injection site–associated,81–82

soft tissue, 120–121synovial cell, 125–126

septic shock, 237shock, 236–237side effects of chemotherapy,

155–165acute tumor lysis syndrome,

240anaphylaxis, 159–160, 239–240cumulative/delayed toxicity,

164diarrhea, 242–246gastrointestinal ulceration, 242neutropenia, 241–242oral, 216–228in pain management, 214–215preventing, 155–160subacute toxicity syndromes,

161–164slide preparation, 11soft tissue malignancies,

chemotherapy for, 169,170, 171, 172, 174, 176

specimen handling, 57–58

Index 315

spinal tumors, 121–122splenic hemangiosarcomas,

122–123canine case study, 271

splenic tumors, 123–124staging

bone marrow evaluation in,38–39

lymph node biopsies in, 57sterile hemorrhagic cystitis

(SHC), 163–164stomach tumors, 124–125stomatitis, 220–221

management of, 225–226streptozotocin, 175subacute toxicity syndromes,

161–164supportive care and rehabilita-

tion, 187–247client education in, 228malignant effusions, 229–233nutrition, 190–205oncology emergencies,

233–246oral complications, 216–228pain management, 205–216

surgery, 3complications from, 219pain management with,

215–216synovial cell sarcomas, 125–126

Ttamoxifen, 175Taxol, 174

Technical Assistance Bulletins,147

testicular tumors, 126therapeutic index, 138–139thrombocytopenias

bone marrow evaluation and,37

megakaryoctyes and, 45thrombocytosis, bone marrow

evaluation and, 37thryoid tumors

in cats, 129–130in dogs, 130–131

thymomas, 127–128canine case study, 260–262

thyroid tumors, 28–30canine, 28–29feline, 29–30nuclear medicine and, 59–60

transmissible venereal tumors(TVTs), 23–24, 131–132

treatment plans, developingappropriate, 2–6

Tru-cut biopsies, 8–9tumors, 65–132

acute lymphoid leukemias,65–66

acute nonlymphoid leukemias,66–67

anal sac adenocarcinomas,67–68

bone, canine, 104–105bone, feline, 68–69brain, canine, 69–70brain, feline, 69

316 Index

cardiac hemangiosarcomas,70–71

chronic lymphocytic leukemia,71–72

cytological criteria for, 13–30epithelial neoplasms, 15–19erythrocytosis, 77growth of and response to

chemotherapy, 134–136hemangiosarcomas, 78–79hemangiosarcomas, cuta-

neous, 73–74hyperadrenocorticism, 79–80hypereosinophilic disease,

80–81insulinomas, 82–83intestinal, 83–85liver, 86–87locations of specific types,

13–30lung, 89–90lymphomas, 90–93mammary, 93–95mast cell, 95–98melanomas, cutaneous, 74mesenchymal neoplasms,

13–15mesotheliomas, 98–99multiple myelomas, 99–101myelodysplasias, 101–102nasal, 102–104neuroendocrine neoplasms,

27–30nonosteosarcoma bone,

104–105

ocular, 105–107oral, 107–109osteosarcomas, 110–112ovarian, 112–113pancreatic, 78peripheral nerve sheath,

113–114plasmacytomas, cutaneous and

extramedullary, 72–73prostatic, 114–115renal, 115–117retrobulbar, 117–118salivary gland, 119sarcomas, injection site–associ-

ated, 81–82sarcomas, soft tissue, 120–121spinal, 121–122splenic, 123–124splenic hemangiosarcomas,

122–123squamous cell carcinomas,

cutaneous, 75–77stomach, 124–125synovial cell sarcomas,

125–126testicular, 126thymomas, 127–128thyroid, 129–131transmissible venereal,

131–132urinary tract, 87–89vaginal and uterine, 132

Uultrasonography, 61–62

Index 317

urinalysis, 156urinary tract infections, 156urinary tract tumors, 87–89uterine tumors, 132

Vvaginal tumors, 132Velban, 176vinblastine, 176vincristine, 176vomiting, 160, 162–164

Wworkplace safety guidelines,

146–148accidental spills, 153–155drug disposal, 153

World Health Organization, 209

Xxerostomia, 223

management of, 228

ZZanosar, 175

318 Index

Documents

Practical Veterinarian Veterinary Oncology