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1 INTRODUCTION : PR INC IPLES AND PRACTICESFOR SMALL T I S SUE SAMPLES IN THEDIAGNOS I S OF PANCREATIC MASSESBrian Morse and Junsung Choi

INTRODUCTION

Fine-needle aspiration and small-core biopsy of the pan-creas are now the standard of care for the sampling ofpancreatic masses. Wedge biopsy of the pancreas at thetime of laparotomy was the traditional method of sam-pling the pancreas until the introduction of needle-corebiopsy in the 1950s. The first needle type was the Vim-Silverman needle, which was typically used under directpalpation by the surgeon at the time of laparotomy. Theadvantages were better sampling, and access to deeplyseated lesions; however, the complication rate was report-edly worse compared to wedge biopsy, probably becausethe needle sampled deeper lesions. Both were associatedwith hemorrhage, pancreatitis, fistulas, abscess formation,and death.

The first reports on fine-needle aspiration biopsy(FNAB) of the pancreas came from Sweden in 1970, per-formed on autopsy samples and preoperatively on livepatients. Preoperative FNAB was found to be safer thancore biopsies and more accurate than wedge excisionalbiopsy, and, thus, for years was the preferred method ofconfirming the diagnosis of pancreatic carcinoma beforedefinitive surgical intervention. No false positives werereported.

The next advance came with the development ofimage-guided FNAB. The first percutaneous image-guided biopsy was performed under angiography andreported in 1972. In 1975, transabdominal ultrasoundwas reported to guide FNAB. Computed tomography(CT) was reported in 1976 and endoscopic retrogradecholangiopancreatography was used in 1978. Endoscopicultrasound was introduced in the 1990s, and now is themost frequently used modality to guide FNAB of thepancreas, followed by CT scan (see Chapter 2). FNABis recognized as a safe and effective means of samplingthe pancreas.

ALGORITHMIC APPROACH TO THEINTERPRETATION OF PANCREATIC FNAB

The interpretation of a pancreatic FNAB should begin withknowledge of the clinical and imaging findings. From animaging standpoint, lesions of the pancreas are broadlydivided into cystic lesions, solid lesions, and solid and cysticlesions. The imaging appearance determines the differentialdiagnosis and algorithmic approach to biopsy evaluation(Figure 1.1), making the imaging findings the most criticalpiece of information to have before assessing the biopsysample. The differential diagnosis for solid masses includes anumber of neoplastic processes, such as neuroendocrinetumors, acinar cell carcinomas, and pancreatic ductal adeno-carcinomas (Table 1.1). The imaging characteristics of thesolidmass are also very helpful in further refining the differen-tial diagnosis. Adenocarcinomas are hypoechoic masses withirregular borders, whereas the other solid tumors are roundedmasses with well-defined borders. The differential diagnosisfor cystic lesions includes pseudocysts, developmental cysts,and cystic neoplasms (Table 1.2). The characteristics of thecyst are also helpful in further refining this differential diag-nosis. For example, a lobulated mass composed of numeroussmall microcysts and a central stellate scar is virtually pathog-nomonic of a serous cystadenoma and a septated cyst is veryunlikely to be a pseudocyst (see Chapter 7). It should always beremembered that any solid mass may undergo cystic degener-ation secondarily and present as a cystic mass, usually a solidand cystic mass. A solid pseudopapillary neoplasm typicallypresents as a solid and cystic mass.

GUIDELINES FOR PANCREATOBILIARYCYTOLOGY REPORTING TERMINOLOGY

The Papanicolaou Society of Cytopathology (PSC) recentlypublished guidelines for pancreaticobiliary cytology which

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address indications, techniques, terminology and nomen-clature, ancillary studies, and postprocedure management.The guidelines were drafted by committees composed of agroup of multidisciplinary experts in diagnosing, managing,

and treating patients with pancreaticobiliary disease. Theproposed Pancreaticobiliary Terminology classificationscheme has six categories (Table 1.3). While a terminologyclassification is not absolutely necessary for all cytologicaldiagnoses (in other words, the diagnosis of adenocarcinomadoes not need an interpretation category of "positive ormalignant"), some laboratory information systems requiresuch a category. If a category is going to be used, the systemproposed by the PSC offers a standardized method that canbe universally understood while offering a reporting systemfor maximum flexibility in patient management. Onecaveat is that the clinical and imaging findings should

Imaging Appearance

Solid

Benign/Non-Neoplastic

Acute pancreatitis

Neoplastic

Ductal adenocarcinoma

Neuroendocrine tumors

Acinar cell carcinoma

Pancreatoblastoma

Lymphoma, plasmacytoma

Metastasis

Mixed Solid and Cystic


Groove pancreatitis

Neoplastic

Solid-pseudopapillaryneoplasm

Neuroendocrine tumors

Ductal adenocarcinoma

Acinar cell carcinoma

Metastases and secondary tumors

Cystic


Mature teratoma

Epidermoid cyst in ectopic spleen

Lymphoepithelial cyst

Pseudocyst

Squamoid cyst of pancreatic ducts

Neoplastic

Intraductal papillary mucinous neoplasms

Mucinous cystic neoplasms

Cystic neuroendocrine tumors

Serous cystic neoplasm

Acinar cell cystadenocarcinoma

Chronic pancreatitis

Autoimmune pancreatitis

Ectopic spleen

Figure 1.1 Algorithmic approach to the evaluation of pancreatic masses based on whether they are solid, solid and cystic, or cystic. This will guide thedifferential diagnosis and, therefore, the clinical management decisions.

Table 1.3 PSC reporting terminology categories.

I Nondiagnostic

II Negative for malignancy

II Atypical

IV NeoplasticBenignOther

V Suspicious for malignancy

VI Diagnostic for malignancy

Table 1.1 Differential diagnosis of solid masses.

Benign/non-neoplastic Neoplastic

PancreatitisAcuteChronicAutoimmune

Ectopic spleen

Ductal adenocarcinomaNeuroendocrine tumorsAcinar cell carcinomaPancreatoblastomaMetastases

Table 1.2 Differential diagnosis of cystic masses.

Benign/non-neoplastic Neoplastic

Lymphoepithelial cyst of thepancreasSquamous cyst of pancreaticductsDermoid cystSquamoid cyst in ectopic spleen

Serous cystadenomaMucinous cystic neoplasmIntraductal papillary mucinousneoplasmIntraductal papillary oncocyticneoplasmAcinar cell cystadenocarcinomaCystic pancreatic neuroendocrinetumor

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always be taken into consideration when determining theadequacy and categorization of a sample. The categories, asthey pertain specifically to pancreatic FNAB, are describedas follows.

Category I. Nondiagnostic. This category is used when thesample provides no diagnostic or useful information.An example would be an acellular cyst fluid that lacksbackground mucin and on which ancillary testing wasnot performed. Another example is an aspirate of asolid mass with only gastrointestinal contaminant. Asfor any cytology specimen, any aspirate with cytologicalatypia cannot be classified as nondiagnostic regardlessof other factors.

Category II. Negative for malignancy. A sample deemednegative for malignancy contains adequate cellular and/or extracellular material to evaluate a mass identifiedon imaging studies. A definitive diagnosis should berendered whenever possible, but is not always possible.In such cases, a description of the cytological findingsis appropriate. For example, an aspirate of benignpancreatic tissue in the setting of a vague abnormalityor irregularity is negative for malignancy. Anotherexample is nonspecific cyst debris with low carcinoem-bryonic antigen (CEA) and amylase levels, which maywell be representative of a pseudocyst, but the absenceof characteristic morphology (see Chapter 7) andabsence of documented pancreatitis preclude such aspecific diagnosis.

Category III. Atypical. This category applies when cells areidentified that have architectural, cytoplasmic ornuclear features that are not normal, but are insufficientfor classification as a neoplasm or suspicious for malig-nancy. These include atypical reactive changes, lowcellularity specimens, and specimens with atypical/dysplastic changes outside of a defined neoplasm.Aspirates suspected of being a neuroendocrine tumorwithout diagnostic cytomorphology or insufficienttissue for confirmatory ancillary testing are placed inthe atypical category.

Category IV. Neoplastic. This category is subdivided intobenign and other.Benign. This category is used for specimens contain-ing material diagnostic of a neoplasm that is knownto behave in a benign fashion. The primary lesion inthis category is serous cystadenoma.

Other. This category is used for pre-invasive, pre-malignant neoplasms, such as intraductal papillary

mucinous neoplasm and mucinous cystic neoplasm,and low-grade neoplasms regardless of malignantpotential, such as pancreatic neuroendocrine tumorand solid pseudopapillary neoplasm. This categorywas the most controversial aspect of the terminologyproposal, as both pancreatic neuroendocrine tumorsand solid pseudopapillary neoplasms are considered“malignant”. However, this category was devised torelate the cytological category to the WHO 2010classification that maintains the nomenclature oftumor and neoplasm for these entities, to separatethese low-grade neoplasms from the usual high-grade and aggressive ductal carcinoma, and to takeinto consideration the increasingly conservativemanagement approaches for small neuroendocrinetumors in some patients.

Category V. Suspicious for malignancy. A specimen isconsidered suspicious for malignancy when some butnot all of the features of a specific high-grade malig-nancy are present. An example would be cytology sus-picious for ductal carcinoma or suspicious for an acinarcell carcinoma with insufficient tissue for immunohis-tochemical confirmation.

Category VI. Positive for malignancy or malignant. Thisincludes neoplasms with unequivocal malignant fea-tures including pancreatic ductal carcinoma, acinar cellcarcinoma, lymphoma, metastases, and sarcomas.

WORK-UP AND MANAGEMENT OFTHE PATIENT PRESENTING WITH APANCREATIC MASS

The management of a patient presenting with a pancreaticmass should involve a team approach with input from sur-geons, gastroenterologists, medical and radiation oncolo-gists, radiologists, and pathologists. Assessment includesclinical evaluation, patient and family history, laboratorytests, serum tumor markers, and imaging modalities.

Clinical and patient and family history

Presenting symptoms and signs could indicate atumor-associated syndrome. Examples include hormonalsyndromes associated with functional pancreatic neuroen-docrine tumors, lipase hypersecretion syndrome associatedwith acinar cell carcinoma, or paraneoplastic syndromes

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associated with poorly differentiated neuroendocrinecarcinomas. Patient history provides information on riskfactors, genetic syndromes predisposing to certain neo-plasms, and previous history of malignancy. Family historyprovides information on whether the patient has familymembers with a previous history of carcinoma or othermalignancies, which could suggest a genetic predispositionto pancreatic carcinoma.

Serological studies

Elevated serum lipase levels could determine if thepatient has a lipase-secreting acinar cell carcinoma, evenif the patient does not have the signs and symptoms of alipase-hypersecreting syndrome. Chromogranins are afamily of glycoproteins belonging to the granin familyof proteins, which also includes the secretogranins foundin the secretory granules of endocrine and neuroendo-crine cells. Plasma chromogranin A (CgA) is the mostuseful marker for diagnosing and monitoring patientswith neuroendocrine tumors, including pancreatic neu-roendocrine tumors. Limitations to the use of CgA as abiomarker include treatment with proton-pump inhibi-tors, chronic atrophic gastritis-impaired renal function,and inflammatory bowel disease. Serum pancreatic poly-peptide levels are used less frequently due to lower sen-sitivity, but when used in combination with CgA canimprove sensitivity to 93%.

Hypersecretion of insulin is seen with insulinoma,which is associated with hypoglycemia (confusion, lethargy,seizures); hypersecretion of gastrin is seen with gastrinoma,which produces the Zollinger–Ellison syndrome (recurrentpeptic ulcer disease, diarrhea, and weight loss); hypersecre-tion of glucagon is seen with glucagonoma, which is char-acterized by necrolytic migratory erythema, cheilitis, weightloss, glucose intolerance, venous thrombosis, and diarrhea;and hypersecretion of vasoactive intestinal polypeptide(VIP) is seen with VIPoma, which is associated with asyndrome of watery diarrhea and hypokalemia.

Serum tumor markers

CA 19-9 is the tumor marker most commonly used in theevaluation of pancreatic ductal adenocarcinoma (PDAC).The CA 19-9 antigen is a sialylated oligosaccharide that isnormally present within the cells of the biliary tract. Thenormal reference range for CA 19-9 is 0–37 U/ml. Up to

75–85% of patients with PDAC present with elevated CA19-9 levels. False positives occur due to biliary disease, liverdisease, acute and chronic pancreatitis, cystic fibrosis, orthyroid disease. CA 19-9 is not specific for PDAC, as it canbe elevated in other cancers. The sensitivity and specificitydepend on the cut-off levels employed. A cut-off level of100 U/ml has a sensitivity of 68% and a specificity of 98% inthe absence of other factors, such as biliary tract disease.CA 19-9 is of greatest utility in the staging and follow-up ofpatients with PDAC, and is used to monitor response totherapeutic interventions. An increasing CA 19-9 followingresection, chemotherapy or radiation therapy suggests pro-gressive disease.

Carcinoembryonic antigen (CEA) is a high-molecular-weight glycoprotein found normally in fetal tissues com-monly used as a tumor marker in other gastrointestinalmalignancies. The reference range is 0–2.5 mg/ml. BecauseCEA is elevated in many gastrointestinal malignancies, andonly 40–45% of patients with PDAC have an elevated CEA,it is of limited usefulness for the monitoring of patientswith PDAC.

Alpha-fetoprotein (AFP) is a glycoprotein normallyproduced in fetuses by the liver, yolk sac, and gastrointest-inal tract. The normal range for healthy adults and non-pregnant females is 0–10 µg/l. AFP may be elevated in up to20% of patients with acinar cell carcinoma, and thereforemay be used as a marker to monitor the effect of therapyand recurrence in these patients.

Imaging modalities

Current imaging modalities used to evaluate pancreaticlesions include: transabdominal ultrasound (TUS), endo-scopic ultrasound (EUS), computed tomography (CT),magnetic resonance imaging (MRI) and occasionally posi-tron emission tomography (PET). These modalities havedifferent strengths and weaknesses. EUS will be discussed indetail in Chapter 2.

Transabdominal ultrasound (TUS) is no longer rou-tinely used for assessing patients with pancreatic masses,although it may be useful in distinguishing solid from cysticpancreatic lesions. For solid lesions, TUS may detect thelesion and can visualize obstruction of the main pancreaticduct (MPD). However, TUS has certain limitations. It canbe difficult to visualize the entire pancreas. Overlying bowelgas may obscure the pancreas and image quality may bedegraded in obese patients. In addition, TUS has lower

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spatial resolution than other modalities. TUS is notadequate for preoperative staging to evaluate involvementof the adjacent vascular structures and organs. For cysticmasses, TUS can characterize the internal features of thecysts under the right circumstances. However, TUS haslimitations for the evaluation of cystic masses. It may bedifficult to determine the exact relationship of the lesion tothe MPD. The characterization of internal contents mayalso be difficult using TUS. For example, it may be difficultto distinguish a mural nodule from debris or a blood clot ina lesion. It may also be difficult to distinguish a microcysticlesion from a solid lesion. Despite these limitations, TUS isa quick, inexpensive, and widely available modality that candetect lesions and narrow the differential diagnosis. Thecaveat is that findings detected with TUS usually requirefurther evaluation with CT or MRI.

Computed tomography is the main modality used inthe evaluation of the pancreas. CT provides high-resolutionimages that can distinguish solid from cystic pancreaticlesions and determine the relationship of these lesions toadjacent structures. A typical CT (pancreas protocol) toevaluate a pancreatic lesion will consist of high-resolution(typically 3-mm slice thickness or less) multiplanar imagesand multiphase postcontrast images (noncontrast, arterial,and venous phases). The high-resolution images are neces-sary to evaluate small structures and their relationship tothe adjacent vasculature and the MPD. Multiplanar images,typically acquired in axial, coronal and sagittal planes, arecrucial in this application. Contrast is necessary to opacify

the vessels and postcontrast images are acquired at differenttimes to provide optimal enhancement of the pancreas,arteries, and veins. The postcontrast characteristics of alesion may narrow the differential diagnosis. For example,lesions with avid early enhancement include neuroendo-crine tumors and metastases from renal cell carcinoma(Figure 1.2). In contrast, pancreatic adenocarcinomaexhibits hypoenhancement relative to normal pancreaticparenchyma (Figure 1.3). Contrast will help identify enhan-cing mural nodules or complex internal architecture incystic pancreatic lesions that indicate dysplasia or malig-nancy (Figure 1.4).

Although CT is the main modality used for imaging thepancreas, MRI can provide useful information in certaincases, especially in the evaluation of cystic pancreaticlesions. Pancreas protocol MRI is emerging at some centersas an equivalent alternative to CT. MRI images are alsoacquired in multiple planes (typically axial and coronal)and provide high-resolution images. T2-weighted imagesare the main MRI sequence used in the evaluation of cysticpancreatic lesions. Lesions which contain fluid or mucinhave high contrast from pancreatic parenchyma and adja-cent structures on T2-weighted images, even without theadministration of intravenous contrast. MRI also utilizespostcontrast images to evaluate the internal architecture ofcystic lesions to exclude solid internal components, a high-risk feature for malignancy.

Figure 1.2 An axial image from a contrast-enhanced CT showsa hypervascular lesion in the tail of the pancreas with avid earlyenhancement. Biopsy showed pancreatic neuroendocrine tumor.

Figure 1.3 An axial CT image shows a hypoenhancing, irregular massin the body and tail of the pancreas (arrows). Biopsy showed ductaladenocarcinoma.

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Typically an MRI to evaluate a cystic pancreatic lesionwill include magnetic resonance cholangiopancreatography(MRCP). MRCP utilizes special parameters to acquire high-contrast, multiplanar, high-spatial resolution images of thebiliary system and main pancreatic duct (Figure 1.5). Itallows very accurate delineation of the internal architectureof cystic pancreatic lesions and their relationship to theMPD. These features are very important in narrowing thedifferential diagnosis of cystic pancreatic lesions. Forexample, the microcystic internal architecture of a serouscystadenoma can be distinguished from the larger cysticlocules of a mucinous cystic neoplasm. Another example isthe identification of the cyst communicating with the MPD,a key feature of an intraductal papillary mucinousneoplasm (IPMN).

Positron emission tomography (PET) uses 18F-fluorodeoxyglucose (FDG) to image the primary tumorand metastatic disease. PET scanning appears to be mostuseful for the imaging of metastatic disease. Its role in thework-up of the primary mass is not as evident. Studies ofPET-CT have suggested that PET-CT scanning is moresensitive than conventional imaging for the detection ofpancreatic cancer and that PET-CT scan findings sometimeschange clinical management. The National ComprehensiveCancer Network (NCCN) guidelines consider PET-CT anevolving technology; its role in the diagnosis of pancreaticcancer is not yet established.

The imaging evaluation of neuroendocrine tumors(NETs) deserves special attention because there are func-tional imaging methods that can be employed whenimaging these tumors. Radiolabeled somatostatin analogscan be used to image NETs by binding to somatostatinreceptors. 111In-pentetreotide (OctreoScan) was one of thefirst functional imaging methods used in the evaluation ofNETs (Figure 1.6). In addition to localizing the primarytumor and metastases, 111In-pentetreotide can be used toplan treatments and monitor therapy response. 111In-pentetreotide has low sensitivity for small (< 1 cm) anddedifferentiated tumors. A more recent development isthe imaging of NETs with gallium-labeled somatostatinanalogs. The somatostatin analogs are linked to 68Ga by achelate. One of the more commonly used chelatesis 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA). The three main 68Ga–DOTA-labeled somatosta-tin analogs currently in use are DOTA-NOC, DOTA-TATE, and DOTA-TOC. 68Ga-DOTA uses PET-CT ratherthan SPECT (single photon emission computed tomog-raphy) and has several advantages over imaging with111In-pentetreotide including: faster image acquisition,improved spatial resolution, higher affinity for somatostatinreceptors and the ability to quantify activity. 68Ga–DOTA-labeled somatostatin analogs are useful for detecting pri-mary lesions and the site of metastatic disease, as well asplanning and monitoring response to therapy. A pitfall tothe 68Ga–DOTA-TATE PET-CT scan, however, is thepotential false-positive results with high uptake in the

Figure 1.4 An axial image from a contrast-enhanced CTshows a large cystic lesion communicating with the main pancreaticduct. The appearance is compatible with intraductal papillarymucinous neoplasm involving the main pancreatic duct. Thereare enhancing mural nodules that are worrisome for malignanttransformation (arrows).

Figure 1.5 This image from an MRCP shows a normal common bileduct and main pancreatic duct.

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uncinate process due to the high concentration of somatos-tatin receptors in this location, especially in the setting ofendocrine hyperplasia and aggregation.

THE ROLE OF IMAGING STUDIES INTHE WORK-UP AND MANAGEMENTOF PANCREATIC MASSES

The primary roles of imaging in the preoperative work-upof pancreatic masses are to define the nature of the lesion,identify high-risk features in cystic masses, and assessresectability.

Solid masses

When a solid mass is identified by imaging, the mainobjective is to determine if the mass represents adenocarci-noma, mass-forming pancreatitis, or another solid pancre-atic lesion. There are certain imaging features which arecharacteristic of pancreatic adenocarcinoma, but again adefinitive diagnosis may be difficult by imaging alone. Ade-nocarcinoma typically appears as a mass that obstructs themain pancreatic duct and is hypoenhancing relative tonormal pancreatic parenchyma (Figure 1.7). However, thisappearance is not entirely specific for adenocarcinoma. Forexample, metastases to the pancreas may appear hypovas-cular and obstruct the MPD (excluding renal cell carcin-oma metastases which are hypervascular). So although

current imaging techniques can provide excellent anatomicdetail, in many cases lesions remain indeterminate utilizingimaging alone.

CT is the standard for staging and assessing the resect-ability of pancreatic adenocarcinoma. This is becauseaccurate staging and treatment of pancreatic adenocarci-noma requires exact analysis of the relationship of the massto adjacent vascular structures. The resectability of a tumordepends on its relationship to the superior mesentericartery, celiac axis, common hepatic artery, main portal vein,and superior mesenteric vein (SMV). If imaging revealsclear fat planes between these vessels and tumor, the lesionis considered resectable (Figure 1.7). A tumor that involvesgreater than 180 degrees of these arteries is considered to belocally advanced disease (Figure 1.8). Venous tumorinvolvement may be more extensive before it is consideredlocally advanced because venous reconstruction can beperformed during surgery. If there is involvement of themain portal vein or SMV that is not deemed reconstructi-ble, then that tumor is locally advanced. Other tumors(those with arterial involvement less than 180 degrees andvenous involvement that is minimal or reconstructable) areconsidered borderline resectable (Figure 1.9). Thesepatients may undergo neoadjuvant therapy followed byre-imaging to determine if the tumor was downstaged aftertherapy. A meta-analysis of 1823 patients with pancreaticcancer showed the sensitivity and specificity of helical CT

Figure 1.7 This axial image from a contrast-enhanced CT shows ahypoenhancing mass in the body of the pancreas (arrow) causingobstruction of the main pancreatic duct. The appearance is suspiciousfor pancreatic ductal adenocarcinoma. Adjacent vascular structures areuninvolved – it is a resectable mass.

Figure 1.6 OctreoScan demonstrating numerous metastases to the liverfrom a neuroendocrine tumor.

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to be 81% and 82%, respectively, for determining resect-ability, and also demonstrated that CT was superior to bothMRI and US. Most patients only require CT scans as part oftheir work-up. It is important to note that while a definitivediagnosis of a mass lesion is not required prior to resection,it is required prior to instituting chemoradiation therapy.

Staging pancreatic cancer also requires evaluation of thepatient for metastatic disease. Common sites of metastaticdisease (liver metastases and abdominal lymphadenopathy)are easily detected and characterized by CT. MRI may be

used as a problem-solving tool for indeterminate liverlesions or as an adjunct in high-risk patients in whom nometastases are identified initially. CT is also the modality ofchoice to exclude pulmonary metastases at initial staging.

PET-CT utilizing FDG is used in some centers in thestaging of pancreatic cancer. PET-CT does have a relativelyhigh sensitivity for distant metastatic disease, but will detectdisease not already identified by CT in only a minority ofcases. Work is ongoing determining the utility of PET-CTto evaluate response to therapy and to better distinguishbenign from malignant processes.

Cystic masses

The imaging features of the most common cystic pancreaticlesions overlap. Therefore, it can be difficult to make adefinitive diagnosis of a cystic pancreatic lesion by imagingalone (Figures 1.10 and 1.11). This is particularly true whena pancreatic pseudocyst is a possibility, as the imagingfeatures of a pseudocyst can overlap with neoplastic pan-creatic lesions. There are some imaging features that dohelp clinch a specific diagnosis. For example, the microcys-tic appearance of a serous cystadenoma has an imagingappearance that is fairly pathognomonic. Communicationwith the main pancreatic duct is a key feature of IPMN(Figure 1.11). Imaging can also help distinguish a side-branch IPMN from an IPMN with involvement of theMPD. Imaging evaluation of cystic pancreatic lesions mustinclude a detailed analysis of the internal architecture of the

Figure 1.8 Axial contrast-enhanced CT image shows a patientwith pancreatic adenocarcinoma with perineural tumorextension that encases the celiac axis – an unresectable locallyadvanced tumor.

(A) (B)

Figure 1.9 Borderline resectable. (A) Axial image showing partial encasement of the superior mesenteric vein. (B) Coronal image showing the same.

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lesion and the MPD to identify these features and othersthat help narrow the differential diagnosis. The role ofimaging in the work-up of pancreatic cystic lesions is fur-ther discussed in Chapter 7.

PERCUTANEOUS IMAGE-GUIDEDBIOPSY OF THE PANCREAS

Percutaneous image-guided needle pancreatic biopsy is awell-established method for obtaining tissue specimens forthe diagnosis of pancreatic masses. Image-guided biopsy isindicated to establish a malignant diagnosis, either primaryor metastatic, establish a benign diagnosis, or obtain mater-ial for culture or other laboratory studies. Image guidanceprovides safe access and needle passage into the targetedlesion for cytologic or histologic evaluation. In addition, therequests to obtain tissue for additional studies includingmolecular testing and to meet requirements for clinicaltrials may increase the demand for these procedures thanhas been required traditionally.

Image-guided biopsy can be performed as an outpatientprocedure, which is less invasive with lower morbidity,mortality, and cost compared to open biopsy techniques.Successful diagnosis of a lesion depends on several factors.For image-guided needle biopsy these factors includewhether the target lesion is amenable to a percutaneousimage-guided approach, the technical expertise of the radi-ologist and cytopathologist, and proper specimen prepar-ation. On-site evaluation of FNAB specimens by acytopathologist is important as this increases diagnosticyield and accuracy of needle biopsies of the pancreas(see below).

PERCUTANEOUS BIOPSY

Percutaneous biopsy of the pancreas can be performed witha variety of imaging modalities. They include multidetectorCT, ultrasonography (US), MRI, and fluoroscopy. The pre-dominant image-guidance modalities remain CT and US.As with the biopsy of other abdominal lesions, CT- and US-guided biopsy of the pancreas has been the mainstay ofminimally invasive needle biopsy prior to the introductionof endoscopic US-guided biopsy of the pancreas. MR-guided needle biopsy of retroperitoneal lesions includingthe pancreas has also been performed safely and accuratelyand can be an alternative to CT- or US-guided biopsies

when lesion detection by MRI is more favorable. The role ofany image-guidance technique is to identify the target,identify a safe route of access, identify the entry site anddistance to the target along a safe access route, and toconfirm the proper position of the needle tip within thetarget during the biopsy procedure.

In addition to standard imaging techniques, additionalimaging-guidance techniques are available. CT fluoroscopyutilizes rapid sequential CT imaging at a fixed table positionto view the needle during needle manipulation. This canincrease the accuracy of needle placement and reduce pro-cedure time. Although this can reduce the radiation dose tothe patient, it has the disadvantage of potentially increasingthe radiation exposure to the operator. Navigation guidancetechnology utilizing electromagnetically tracked needles incombination with real-time US or fused CT imaging havebeen used to visualize a path and track needle positionduring needle advancement providing greater precision inneedle placement. This is particularly helpful in more com-plex off-axis approaches to reach the target. This has beenshown to reduce both needle placement times and thenumber of needle pullbacks needed for redirection duringthe biopsy. Although needle tracking navigation systemsare commercially available, in routine practice they arenot commonly used because they require additional timefor equipment setup which may offset the time savedduring the procedure as well as the added expense to theprocedure.

NEEDLE TYPES

There are a variety of needle types available for image-guided biopsies. FNAB needles typically range from 19 to25 g and may be beveled or non-beveled. These includenon-beveled Greene®, and beveled Chiba®, Franseen®, andWestcott® needles, among others. They come in standardlengths of 9, 15, and 20 cm. In comparison to core-biopsyneedles, FNAB needles have the potential benefit of beingsafer with the ability to traverse bowel or even vascularstructures, but this also requires the availability of goodcytology with on-site monitoring by a cytotechnologist orcytopathologist. A coaxial 18- or 19-gauge thin-wall guideneedle is often used to aid in obtaining multiple sampleswithout the need to repeat image-guided biopsy needleplacement each time. A beveled tip may make it harder tohit the target due to deflection of the needle path. However,it can also be used to its advantage to “steer” the needle

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based on bevel orientation. A prospective study to evaluatethe effect of four different FNAB needle tip configurationson the diagnostic yield of tissue samples in abdominallesions showed some variability, including yield from thepancreas. However, no one particular aspiration needle wasclearly superior to another for the biopsy of pancreaticmasses.

Core needles typically used for the pancreas are 18–20gauge “Tru-cut” type needles with 1 or 2 cm “throw”, which

is the length of extension of the inner stylet from the outercutting cannula. The length of the specimen notch withinthe inner stylet is slightly shorter than the throw of theinner stylet. An example of this type of core needle is theQuick-core® needle. Spring-loaded automated biopsy gun-type core needles are also commonly used. Compared toFNAB, core biopsy has the advantages of obtaining betterdefinitive benign diagnosis, and faster procedure time with-out the need for on-site monitoring. However, there can be

(A) (B)

(C)

Figure 1.10 These CT and MR images show a cystic lesion in the pancreas but the appearance is nonspecific. Differential possibilities include IPMN,mucinous cystic neoplasm, pseudocyst or more rare cystic lesions. (A) Axial contrast-enhanced CT image shows a small cystic lesion in the head ofthe pancreas. (B) Axial T2-weighted image from an abdomen MRI shows the cystic lesion. No internal mural nodularity is identified. (C) MRCPimage from an abdominal MRI shows the cystic lesion without complex internal architecture.

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1 INTRODUCTION: PRINCIPLES AND PRACTICES FOR SMALL …assets.cambridge.org/97811071/07823/excerpt/9781107107823_excerpt.pdf1 INTRODUCTION: PRINCIPLES AND PRACTICES FOR SMALL TISSUE