Pathology Week 6 p36-49

7/30/2019 Pathology Week 6 p36-49

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More on Markers:Troponin I

Is a specific indicator of MI Appears 4-6 hours post infarction, maybe not until 12 hours Peaks at 16 hours and decrease in 9-10 days.

CK-MB MB fraction is specific for cardiac muscle, esp when there is no skeletal muscle damage in patient's history Appears to rise 4-6 hours post MI Not elevated in all patients until 12 hours post MI Level returns to baseline in 36-48 hours

Myoglobin Elevates within 1-4 hours, most sensitive during early time period Lacks specificity

BNP (marker for CHF) Beta natriuretic peptide is the active product of a split prohormone in response to atrial or ventricular wall stretch. In this case it is a response to the acute congestive heart failure secondary to acute myocardial infarction. 400 CHF likely (MI survivors are likely to develop heart failure)

Six weeks post-MI, this 56-y.o. male has chest pain, SOB, precordial friction rub. He dieswithin days. The cause of the pathology (photo) is?

A. Granulomatous inflammationB. Dresslers syndromeC. Metastatic carcinomaD. Ruptured LVE. Viral infection

Friction rub pericarditis autoimmune reaction Dresslers syndrome.

Can see bread-and-butter appearance

Apoptosis: Cells activate enzymes that degrade DNA and proteins (ATP/energy-dependent); cell membrane remainsintact; organelles are intact; NO INFLAMMATION.

Necrosis: Cell membrane ruptures; organelles rupture; enzymatic digestion of the cell; inflammation

Apoptosis is important in neoplasia and infectious disease. If apoptosis is intact, tumor cells die. If you have things thatprevent apoptosis from occurring, will promote neoplasia and favor infection.


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Apoptosis is common in neutrophils usually die after several hours. Also seen in Lichen Planus.

Above: intrinsic and extrinsic pathways of apoptosis.Sometimes receptors on the cell can trigger apoptosis

Defective Apoptosis: Tumors with p53 mutations Follicular lymphomas express high levels of bcl-2

(translocation of bcl-2 gene) HPV- protein E6 binds and inactivates p53 EBV- proteins that mimic or increase production of

bcl-2 Autoimmune disorders

Sensitivity, specificity and predictive value:Screening testsConfirmatory testsPrevalence and predictive value

Given the photo, what enzyme abnormality would you expect? A. Increased alkaline phosphataseB. Decreased alkaline phosphataseC. Decreased gamma GTD. Markedly increased AST and ALTE. Decreased direct bilirubin

Answer: A, increased AP: The photos show a gallbladder with stones and a large stone in the common bile duct.AP is made by the cells lining the bile canaliculi. During obstruction bile enters the lining cells and damages cellmembranes, releasing AP. The yellow area represents galbladder adenocarcinoma


4/14

The PAP smear labeled B suggests:A. Herpes virus infectionB. Human papillomavirus infectionC. CMV infectionD. Carcinoma insituE. Invasive cervical cancer

Answer: B, HPV infection. Koilocytes are presentc/w a low grade dysplasia (LGSIL)

Dysplasia: Atypical proliferative changes due to chronic

irritation or inflammation; PREMALIGNANT CHANGE

Metaplasia:A REVERSIBLE change in which one ADULT celltype is replaced by another ADULT cell type.

The architecture of this bladder tumor can be described as: A. MucinousB. SquamousC. SarcomatousD. PapillaryE. Signet ring cell

Papillary tumor = finger-like or Hawaiian island-like (if cross section).Here, can see finger-like projections

Answer: D, papillaryFinger-like. In this case a papillary transitional cell carcinoma.

Above: Pap smear. B will be HPV and probably low-grade lesionbecause nucleus is not very big. C moderate dysplasia.D severe dysplasia. Note nucleus:cell ratio to help tell them apart

Above: Cervical dysplasia. Normal the only dark blue cells aredown at the bottom. Low-grade dysplasia: goes up halfway. As itgets higher and higher, dysplastic cells fill more and more of theepithelium. CIN III carcinoma in situ.


5/14

These endocervical biopsies show:A. Glandular metaplasiaB. Squamous metaplasiaC. CISD. Invasive squamous cell carcinomaE. Invasive adenocarcinoma

Answer: B, squamous metaplasiaThe endocervical glands have columnar epithelium. At earlyages the female endocervix also has a columnar surface. Withage, sexual activity, childbirth etc a mature squamousepithelium replaces the glandular epithelium.

This brain tumor superficially invades bone, but not brain tissue. Name thetumor.A. Glioblastoma multiforme/astrocytoma grade IVB. MeningiomaC. Metastatic lung CAD. Metastatic breast CA

E. Metastatic melanoma

Psamomma bodies = dystrophic calcification (pictured in stained section below).Meningiomas, although benign, could grow into the bone. Will not spread to brain,etc. only invades via expansion.

Answer: B, meningioma. There is no invasion of the brain parenchyma. Thetumor is well demarcated but can kill by compression of the brain. It can locallyinvade bone, but does not metastasize.

The following two test qs can be answered using the lab manual Neoplasia III session:Test q: Meningiomas are differentiated from Schwannomas by the presence of: Psammoma bodies

Test q:A 45y/o male is seen by an ear, nose, and throat specialist for unilateral tinnitus and hearingloss. A neoplasm associated w/this clinical history is: Schwannoma.

This cut-section of liver is c/w: A. CongestionnB. CirrhosisC. HepatitisD. Metastasis

Answer: D, metastasesThe tumor nodules are diffuse (not a primary) and are too big to be cirrhoticnodules- there is also an absence of white connective tissue. Multiple nodules ofvariable sizes metastatic disease.

Big and yellow or orange. Triglycerides push nucleus off to the Oil Red O Stain for fatty changeIf fixed, may be pale. side in fatty change.

Psamomma bodies


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Brick red liver answer will either be Iron in parenchymal cells of pancreas.hemosiderosis (iron in Kuppfer cells) Patient may be diabetic.or hemochromatosis (iron in hepatocytes).

Bile looks brown in H&E like iron exceptsmudgy rather than granular.

CONSISTENCY: Organs become stiff, hard, soft, waxy or greasy in disease Alcoholism or hepatitis cause extensive fibrosis (scar tissue) in the liver and the liver is pale, shrunken and firm with

round NODULES (firm, circumscribed areas)

These photos of uterus are c/w: Well-circumscribed nodular tumors:A. LeiomyomaB. LeiomyosarcomaC. Endometrial adenocarcinomaD. Squamous cell carcinoma ofcervix

Answer: A, leiomyomaLeiomyosarcomas are bigger,necrotic and often have areas ofhemorrhage- and they are rare. Thetumor arises in the myometrium(smooth muscle)

This H & E section of colon is c/w A. AdenomaB. FibroadenomaC. CystD. Bulla

Answer: A, adenoma. POLYP = precursor foradenocarcinoma.Tubular adenoma andadenomatous polyp are synonyms.


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Cancer Precursor LesionsAdenomatous polyp Colon AdenoCAActinic keratosis SC SAHyperpl./breast Ductal CAUlcerative Colitis Adeno CA colonEndom. Hyperplasia Adeno CA endom.Esoph. Metaplasia (Barretts) Esoph. Adeno CAGastric metaplasia (Helicobacter) Gastric Adeno CA/lymphomaCirrhosis Adeno CA liver

METASTASIS: LIVER: (portal circulation) GI tract and pancreas; lung, breast, melanomas LUNG: breast, stomach, sarcomas, renal cell carcinoma (vena caval system) BONE: 3

rdmost frequent site for metastases; lung, breast, prostate, kidney,

thyroid; PROSTATE to bone gives osteoblastic lesions on Xray (more dense)and high serum alkaline phosphatase

ADRENAL: most common endocrine site

Metastasis#1 marker of malignancy. If that is not an option, look for invasiveness.Exceptions: gliomas (astrocytomas) of the brain and basal cell carcinomas of the

skin RARELY metastasize; also, meningiomas LOCALLY invade skull bone, but donot metastasize and are considered benign.

Venous DrainagePortal: liverCaval: lungsParavertebral plexus: thyroid and prostate carcinomas metastasize to thevertebrae. Colon cancer can present as brain met w/no mets in liver or lung.Renal Cell CA: invades renal vein and grows in the vena cava

Steps in Metastasis: Cell must break apart break through basement membrane and ECM through wall of blood vessel mustsurvive in blood vessel must exit the blood vessel, attach, reenter the ECM. Once there, must establish a new blood supply.Difficult. So out of every 100,000 tumor cells that are potentially metastatic, only 1 or 2 actually make it.

If a tumor has an overexpression of cadherins, it will be less likely to metastasize because the cells cannot break apart. If cadherin isunderexpressed, will be more likely to metastasize. If there are increased laminin receptors, also more likely to metastasize.

Below: TNM Staging System.


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Different kinds of lung carcinoma:

If making keratin pearls SCC. If making glands adenoCA. If there are large cells w/no differentiation = large cell CA. If there aresmall cells w/no differentiation = small cell CA. All are treated differently Small cell chemo ALWAYS, no surgical option. For the

others, staging is critical. Could do surgery, radiation, chemo.

Well-differentiated if exhibition of squamous pearls and/or intercellular bridges. Above: Poorly differentiated

These H&E sections of breast nipplesuggest:A. MelanomaB. Underlying adenocarcinomaC. Underlying squamous cell carcinomaD. HPV infectionE. Marked epithelial dysplasia

Answer: B, Pagets DiseasePagets disease of nipple (usually crusty or scaly on clinical exam) represents anadenocarcinoma in the breast tissue that has grown up the lactiferous ducts. Theunderlying carcinoma may be intraductal or invasive. How do you know it isNOT a melanoma? It is the nipple, so first choice will always be Pagets disease.Can do special stains if deciding between melanoma and adenocarcinoma, cando mucin stain adenocarcinoma is mucin +, melanoma is mucin -. Can also do

melanoma stain.

Most of thechange that

occurs in thebreast occurs in

terminal ducts.

Lobule is acollection of

ducts (only infemale breast).


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Above: Proliferation of fibrous tissue (see Gland-in-gland appearance: cribbiforming.fibroblasts) also shows proliferation of

benign ducts (so adenoma). Fibroadenomasare benign.

What is the grade of this breast adenocarcinoma:A. IB. IIC. IIID. T1E. T2

A, Grade I. T1 and T2 are staging, so not D or E. Grading is what it lookslike staging is how far it has spread. Can see that most of the tumorexists as well-formed glands, no mitoses evident. No nuclear atypia. Well-differentiated adenocarcinoma. Remember: Architecture (glands) 1-3.Mitoses 1-3. Nuclear pleomorphism 1-3. For this one, glands = 1.Mitoses = 1. Nuclear atypia/nucleoli = 1.

Stage the tumor: The word tumor tells us that it is invasive.A. T0N0M0B. T0N1M0C. T1N1M0D. T1N1M1E. T2N1Mx

T0 = in situ, would not see lymph node involvement

Inflammatory carcinomas of the breast show:A. Neutrophils in malignant ductsB. Lymphocytes in malignant ductsC. Pagets DiseaseD. Lymphatic invasionE. Liver metastases

In inflammatory carcinomas of the breast, tumor invades and blocks thelymphatics. Test q: Inflammatory carcinomas of the breast exhibit: lymphatic invasion by tumor

How do we test for HER-2-neuoverexpression?A. Mucin stainB. counting mitosesC. FISHD. Flow cytometryE. Gene sequencing

C, fluorescence in situhybridization. FISH is moreaccurate thanimmunohistochemistry. Testingat IU is in Medical Genetics

Tumor is 1.1cm in diameter (


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Which of the following breast cancers has the WORST prognosis?A. Invasive ductal carcinomaB. Tubular carcinomaC. Medullary carcinomaD. Mucinous (colloid) carcinoma(This was a test q!)

Answer: A. Tubular is aka well-differentiated adenocarcinoma. Medullary andmucinous carcinomas tend to grow rapidly, have more volume, diagnosed sooner.All have a better prognosis than invasive ductal carcinoma.

Targeted Therapy: Signal-transductionInhibitors Block enzymes and Growth Factor

Receptors GLEEVEC - GIST and CML

(abnormal tumor enzymes); IRESSA-non-small-cell lung cancer (EGFR)

C-kit is the abnormal protein in GISTTarget: Monoclonal Antibodies

Herceptin - invasive breastcarcinomas (that showoverexpression of HER-2-neu)

Generic names: Gleevec = Imantinib.Herceptin = Trastuzumab.

What is a diagnostic test foramyloid?A. Prussian blueB. Oil Red OC. Sudan black

D. Congo redE. Congo red with polarization

E will see apple greenbirefringence (pictured)

Amyloid: 15 types- 3 major AL (light chain); Ig light chains AA (amyloid associated); liver

product A-beta (amyloid in Alzheimer) And beta-2-microglobulin

(dialysis) All are beta-pleated sheet

proteins and all stain with CongoRed

What type of hypersensitivity reaction is acute rheumatic fever?A. IB. IIC. IIID. IVE. II and IV

Above: INDIAN FILING. If yousee a picture of cell lining upw/nucleoli think breast cancer,and more specifically lobular.

The original insult (cross-reacting antibodies) istype II, but what we see is a granuloma in tissu(seems like IV). WILL NOT BE ASKED becausits controversial.


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Rheumatic Heart Disease Acute rheumatic fever follows Streptococcus pyogenes pharyngitis Antibodies vs. M-protein of the bacterium cross-react with glycoprotein

antigens in the heart Pancarditis involves all 3 layers of the heart. Esp. mitral, then aortic Fibrinous pericarditis Deformed valves subject to endocarditis due to alpha-streptococci

(streptococcus viridans) endocarditis is NOT during the rheumatic fever appears later in life when the patient gets infected by other organisms.

Will see Aschoff bodies in the myocardium collection of macrophages, sometimes called granulomas. Will get fibrinous pericarditis (bread-and-butter)

Aschoff bodies. Malformed heart valves (mitral most Endocarditis.common, then aortic)

What tumor markers are useful in management of colon cancer?A. CEA is used to monitor tumor recurrenceB. CEA is used as a screening test for colon cancerC. CEA is used as a confirmation test if the test for occult blood is positiveD. High PSA in serum is diagnosticE. High AFP in serum is diagnostic(This was a test q!)

Answer: A, used to monitor tumor recurrence. CEA is not specific for colon cancer and not a sensitive test. CEAlevels are determined pre- and post-surgery. The CEA level should fall to near zero. If the level falls and then increases,the patient may receive chemotherapy for the recurrence. NOT used as a diagnostic test.

Tumor Markers: Management Detection (staging) Diagnosis (screening)-

PSA (prostate-specific antigen specificity is really bad lots of false negatives) CA 125 (marker for ovarian cancer, even worse than PSA)

Markers

CEA- colon, pancreas, stomach, lung, breast, (19% smokers, 3% gen. pop.) AFP- hepatocellular, germ cell (>500ng/ml) CA 125- 80% non-mucinousovarian CA CA 19-9- pancreatic CA (80%) PSA- (0-4 ng/ml normal) (>10 ng/ml highly suspicious); also AlkPhos elevation in prostate CA assoc. with bone

metastasis (osteoblastic) HCG- gestational trophoblastic tumors, testicular tumors


12/14

A 31y/o AIDS patient in the crisis phase has a BAL(bronchoalveolar lavage). The Giemsa and GMSstains are c/w:A. Blastomyces dermatitidisB. Candida albicansC. Coccidioides immitisD. Histoplasma capsulatumE. Mycobacterium avium

On Giemsa stain, can see macrophage, nucleus of themacrophage, and budding yeast. On silver stain, cansee tiny budding yeast.

Answer: D, Histoplasma Capsulatum. The Giemsa and GMS show small, intracellular yeasts. If you look at theGiemsa, you can see that the yeasts are smaller than RBCs and thus about 2-3 microns in diameter. 25-50% of the AIDSpatients in Indy get H. capsulatum infections

Biopsy and BAL from an AIDS patient:Diagnosis? Pneumocystis Pneumonia. H&E stain of tissue shows glassy pink

alveolar contents.

GMS (silver) stain of tissue showscysts can see dots/grooves in them,but they are not budding.

BAL fluid shows 8 trophozoites onGiemsa stain

HIV Remember that in the beginning of HIV infection,CD4 count is high and RNA viral load is also high. Forseveral years, the viral load will drop down to very lowlevels, the CD4 count will progressively drop, and whenyou get to have a CD4 count of


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Which of the following is poorly differentiated?

Anaplastic rhabdomyosarcoma. No resemblance to cell of origin.Large cells, bizarre nuclei, mitoses present.

A B

C D

Answer: C&D. C is small cellundifferentiated carcinoma (oat cell). D islarge cell undifferentiated (either a squamousor adeno carcinoma)

Small cell, undifferentiated always

metastatic, always treated w/chemotherapy.Large cell stage it. Three treatmentoptions: surgery, chemo, radiation.

Early HIV: Virus has affinity for macrophages anddendritic cells (APCs).Middle HIV: macrophages and lymphocytesCrisis/Late: Affinity for CD4 lymphocytes

Macrophages and HIV:- Provide a site to maintain the infection when

the CD4 count is very low.- Provide a route of infection for the brain.


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The Rest Here are all of the leftover test questions that I couldnt find the right spot for Some of them may notbe relevant anymore (since the tests date back to 2005), but some of them are probably still valid (and I just missedthe spot where they should go).

Which of the following groups of patients would be most likely to develop the symptoms of aluminum toxicity: renal failure,

Aluminum toxicity is most likely to develop in patient w/which of the following conditions: dialysis patients.

If a motor vehicle accident v ictim w/a breathalyzer ethanol result of 0.24% is transported to a hospital, you would expect the hospital lab ethanol

result to be approximately: 240 mg/dL.

A 57y/o chronic alcoholic male was diagnosed w/a seizure disorder as a child. He takes the recommended dose of his Phenobarbital but does not

stop drinking. Upon multiple repeat trips to his neurologist, the man is always subtherapeutic in his Phenobarbital levels and continues to seize.What hepatocellular organelle has adapted to the excess levels of alcohol and is responsible for the overmetabolism of the seizure medication?Smooth endoplasmic reticulum.

A 21y/o female is found unconscious in her bed w/an empty bottle of analgesic pills beside her. She is rushed to the hospital where her stomach is

pumped, revealing numerous pill fragments. She regains consciousness and seeks counseling. Three days later she becomes acutely illw/nausea, vomiting, and scleral icterus. Which molecule has been exhausted allowing for extensive liver damage? Glutathione.

A 25y/o female presents w/diarrhea, dysphagia, jaundice, and white transverse lines on the fingernails (Mees lines). What is the most likelydiagnosis? Arsenic poisoning.

A 52y/o male presents at urology clinic w/hematuria and what appears to be a flank mass. Further workup reveals an elevated hematocr it andhemoglobin. You suspect? Renal cell carcinoma

A 68y/o male presents w/weight loss, anorexia, nausea, and constipation. Mucous membranes and sclera are icteric. A 5cm mass is palpated inthe RUQ.

Bili (tot) = 7.1 mg/dL (

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Pathology Week 6 p36-49