Pathology Week 5 p29-40

7/30/2019 Pathology Week 5 p29-40

1/12

HER2 Patient Outcome Data: If negativefor HER2, survival for breast cancer is alot higher.

Clinical Implications of HER-2/neu- Monoclonal antibody, Herceptin, recently approved for treatment of invasive breast cancer.- Clinical trials indicate that this antibody has a significant effect on survival .- Both FISH and IMC available at major medical centers to assess HER-2/neu gene or protein amplification in tumors.

- Problem: increase in heart problems because of Herceptin.

Predictive Medicine/Targeted Therapy- New clinical biomarkers will dictate clinical chemotherapy (eg. HER2/neu)- These biomarkers may predict patient survival and eliminate some of the current toxicities seen with standardchemotherapy.

Biomarkers Conventional (one-size-fits-all) Chemotherapy:

Goal: to use biomarkers to move the diagnosticparadigm way over to the left.

Metabolomics

Trying to find a way to diagnose cancer earlier and treat it quicker.

HER2 Protein Overexpression Br Ca: HER2 FISH Overexpression:

Located on cell membrane. There is one area of Her2neu geneon chromosome 17 can seeoverexpression above.

Targeted therapy wants to eliminate the drugs thatgenetically will not work on your tumor and only giveyou the treatment that works.

Test q: Optimal use of most tumor markers in the US as of

2009 are for: monitoring response to chemotherapy


2/12

New EGFR Inhibitors for Oncology Targeted Therapy (Most solid tumors)- Imclone- Iressa only ~8% of people saw improvement- Tarceva low toxicity- Approximately 170 new inhibitors in development

EGFR structure and distribution of types of mutation: Tremendous amount of mutations in EGFR some affectsurvival, some affect proliferation.(A) Ligand binding to EGFR stimulates autophosphorylation(B) and activation of signaling pathways, promoting both cell(C) proliferation (via MAPK/ERK) and survival (via AKT/STAT).(D) In addition to altering downstream signaling, EGFRmutations are within the tyrosine kinase inhibitor binding site andenhance inhibition of receptor activation.(E) Distribution of the types ofEGFRmutations within the tyrosine kinase domain.

Above: Women w/DCIS (ductal carcinoma in situ) that hasnot spread yet. Using markers to predict who should getchemotherapy and who should not. Followed patients over10 years to look at survival curves big markers are p16 andKi67. If you have high Ki67, survival is down. If you havehigh p16 AND Ki67, death occurs fairly quickly. These arethe ones who should be aggressively treated.

Above: If you have high COX2 in the tumor, poorsurvival. Low COX2 survival rate is better.


3/12

Graph showing the higher and lower % of EGFr indifferent tumor types:

Above: EGFR is highly expressed in a lot of different kinds of tumors. Notlike Her2neu (which is very predictive). (See breast goes from 10 to 90%.)

Does EGFR expression predict response?

Genetic Mutations in EGFR receptor

- Researchers found that patients who haddramatic responses to gefitinib (>50%tumor shrinkage) had lung tumors withEGFR-TK (tyrosine kinase receptor area)mutations- Paez also noted that the frequency ofthese mutations correlated with clinicalfactors identified as being associated withresponse to gefitinib (female,adenocarcinoma, no smoking, Japaneseethnicity)

Prognostic biomarkers in tumors that maypredict response to Cancer:

Caption from this slide: Tumor biopsies were taken between diagnosis and start of gefitinibtreatment from 87/209 patients recruited into the IDEAL 1 trial.Forty-seven patients received 250 mg/day gefitinib and 40 patients

received 500 mg/day; 18 of these patients experienced objectiveresponses.

Tumor EGFR expression levels did not predict response togefitinib; indeed, some patients with partial response hadundetectable levels of EGFR. Similar results were also observedfor the IDEAL 2 analysis(data not shown). Comparable analyses using data from Phase II clinical trials oferlotinib and cetuximab in NSCLC have also found no correlationbetween EGFR expression and tumor response.

Caption from this slide: Identification of factors that are associated with response to epidermal growth factor

receptor (EGFR)-targeted therapies may optimize the treatment of individual patients. Biologic markers that are associated with the EGFR signaling pathway(eg EGFR expression, MAPK, and pAkt levels), proliferation (eg Ki67 levels), and apopto

(eg Bcl-2 or TUNEL levels)may predict whether some patients are more likely to respondEGFR-targeted therapies. In addition, analysis of tumor gene expression may enable atreatment plan depending on each patients individual needs by identifying those patients

with a resistant or susceptible phenotype to EGFR-targeted therapy. Clinical benefit using EGFR-targeted therapies may also be affected by baselinedemographic factors such as disease characteristics (histology and metastasis), poor

performance status, and weight loss.

Surrogate markers (improvements in disease-related symptoms or quality of life, or theincidence of adverse events such as skin rash) may also identify patients who are morelikely to gain clinical benefit.

Caption from this slide: In the study described by Lynch et al, EGFR gene sequencing identified EGFR-TK

mutations in 8/9 patients who had responded to gefitinib. In contrast, no mutations wereseen in 7 patients with NSCLC who had not responded to gefitinib. Furthermore, Paez et al correlated the frequency of these mutations with previous clinical

demographic factors (female gender, adenocarcinoma histology, never having smoked andJapanese ethnicity) that have been associated with response to gefitinib. If confirmed, thesecorrelations would explain the variability of response within these subsets of patients.

A further analysis of 9 primary tumors from patients treated with gefitinib found that all 5patients who had responded to gefitinib had EGFR-TK mutations. In contrast, none of thepatients who progressed while receiving gefitinib had EGFR-TK mutations.

Additional molecular analyses are required in order to clarify the frequency of these EGFR-TK mutations in all patients who experience clinical benefit (stable disease or symptomimprovement) with gefitinib.


4/12

Biomarkers - Biofluids & TissuesTissue IHC, IMF & FISH of target pathway proteinsBiofluids & Tissue Use metabolomics (DNA, RNA, protein)Blood CTC (circulating tumor cells) CEC (circulating endothelial cells) CEPC (endothelial progenitor cells) CPC (circulating Progenitor cells)

Using Skin Biopsies as Biomarkers to predict clinical efficacy:

Figure: K Ras Mutation poor survival.

Colorectal Cancer Found in Blood

Survival Curves ASCO 2008

Fig 3. Pharmacodynamic effects of

EMD72000 punch biopsy of the skin.Pretreatment (left panel) and on-treatment(right panel) for (A) hematoxylin and eosin(HE); (B) epidermal growth factor receptor(EGFR): no changes in expression wereobserved after treatment; (C) transforminggrowth factor alpha (TGF-): no changes inTGF- were detected; (D) phosphorylatedEGFR (pEGFR): activated EGFR wascompletely inhibited in basal keratinocytesof epidermis after drug administration.

Fig 4. (E) Phosphorylated mitogen-

activated protein kinase (pMAPK):activated MAPK was inhibited in thebasal layer of epidermis; (F)phosphorylated signal transducerand activator of transcription protein3 (pSTAT-3): expressed in basal andsuprabasal layers of epidermis aftertreatment; (G) Ki-67: exhibited inproliferating cells and decreasedunder treatment; and (H) p27kip1:staining increased in keratinocytesafter treatment, preferentially in basallayers of epidermis.

Figures: If you do a punchbiopsy before and after treatment,EGFR is knocked down. Map kinaseis also knocked down. Stat3 (oninflammatory pathway) is up.P27 tumor suppressor gene isturned on and up.

AYA Tumors:

Above: mRNA expression of estrogen receptor (ER), progesterone receptor(PR), human epidermal growth factor receptor 2 (HER-2), and epidermalgrowth factor receptor (EGFR) among youngerversus olderwomen.

Disease-free survival (DFS) by age -

AYA Tumors

Above: FYI. If younger people (less than 30-40) get a tumor that normally occurs in olderpeople, it will be very aggressive andresistant to treatment.


5/12

Age Differences in Pathway Deregulation Seen in Breast Tumors

Cancer Is a Multi-Step Process:- Mutation of one oncogene or tumor suppressor gene does not lead to tumor formation- e.g. colon cancer --mutation of 4-6 critical genes (e.g. TSG, oncogenes, apoptosis genes) is required for tumor formation

Pathology Conference Neoplasia Review Fri. 09/17/10Note: This day, the lecture was only 30min long not sure where Dr. Davis stopped, but much of the material was not discussed in class.

1. A new test for prostate cancer (PC) is developed. 90% of men with PC test positive. 80% of men without PC testnegative.

2. In a population of 1000 men, 30% (300 men) have the disease (the prevalence is 30%). Calculate sensitivity,specificity and PPV.

Sensitivity and specificity: 90% sensitivity 90% of 1000 or 900 would be the truepositives 10% of 1000 or 100 would be the false negatives

80% specificity 80% of 1000 or 800 would be the true negatives 20% of 1000 or 200 would be the false positives

PPV (predictive value of a +) with a prevalence of 30%

410 men have a positive test: 270 TP (90%x300) and 140 FP (20%x700)PPV= TP/FP+TP = 270 / (270 + 140) = 270/410 or about 66%

Skin RR-1: 29 y.o. male with waxing and waning lesions like thosepictured. Which of the following physical findings are most likely:A. Guiac-positive stoolB. Friction rubC. HyperreflexiaD. Nail damageE. Hypertension

D, psoriasis: Discolorization, pitting, separation from the nail bed

Skin RR-10: What disorder produces the blister andimmuno stain pictured?A. ImpetigoB. Pemphigus vulgarisC. Bullous pemphigoidD. Eczematous dermatitisE. Urticaria

Need to know if it is IgG or IgA pretty linear pattern, so go with IgG.

C, Bullous pemphigoid: Subepidermal; linear IgG at hemidesmosomes ofbasal cell-basement membrane interface. Remember: The bull sees red. (red = eosinophils)

Figure: Non-parametric T test evaluatingpathway probability between tumors arising inyounger versus older women. Red representswomen aged 45 years. Blue represents womenaged 65 years. The line represents the median.

B catenin was up in younger women.

Above: (sub-epidermal blister)


6/12

39 y.o. male has unusual rash on histrunk and atypical lymphocytes.A. Langerhans cell tumorB. Langhans cell granulomaC. Mycosis fungoides

D. Maligmant melanomaE. Multiple myeloma

Nuclei look like a brain Cerebriform nuclei = mycosis fungoides w/Sezary syndrome. EM lymphocytes look like this ^

C, Mycosis fungoides: Sezary cells = Sezary syndrome of mycosis fungoides; CD4+ cells.

MF is a dermatologic condition w/CD4+ cells in the skin. In Sezary syndrome, these atypical T cells circulate in the blood.If you saw atypical bean-shaped cells w/CD1a and S100 positivity, tumor would be Langerhans.

Skin RR- 18 A 68 y.o.male has pearly nodule onhis upper lip. Dx?A. Malignant melanomaB. DermatofibtomaC. Actinic keratosisD. Nevocellular nevusE. Basal cell carcinoma

E, BCC: Ulcerated, Pearly,Peripheral palisading

Skin RR 21 45 y.o. i.v dug user has scalp lesion. Diagnosis?A. PsoriasisB. Lichen planus

C. DermatofibromaD. Squamous cell carcinomaE. Erythema multiforme

Think: IV drug user may have HIV immune suppressed squamouscell carcinoma (SCC IS RELATED TO IMMUNE SUPPRESSION!) Cansee in scan that it has grown all the way through dermis and subcutaneoustissue into the skull.

D, Squamous cell carcinoma: Aids patient (drug abuse); Immune supression

Above: If this was an IgA stain, itwould be dermatitis herpetiformis.On the histopathology of dermatitisherpetiformis, see neutrophils

micro-abscesses .

Above: Intra-epidermal split =pemphigus vulgaris

Above: Pemphigus Vulgaris. Every cellis stained, but no stain associatedw/basement membrane, dermal papillae,etc. is between each of the cells(desmosomes).


7/12

Cancer Precursor Lesions HAVE TO KNOW. MEMORIZE THIS LIST.Actinic keratosis Sq. Cell CAAtyp. Hyperplasia Breast Ductal CAUlcerative Colitis Adeno CA colonEndom. Hyperplasia Adeno CA endom.Esoph. Metaplasia (Barretts) Esoph. Adeno CAGastric metaplasia (Helicobacter) Gastric Adeno CACirrhosis Adeno CA liverScar in lung Adeno CADysplasia/cervix, lung/larynx Sq. Cell CAAdenomatous polyp Adeno CA colonHashimotos D. Lymphoma

Helicobacter gram-negative organism that causes stomach ulcers more susceptible to adenocarcinoma or gastriclymphoma.

Hashimotos overproliferation of lymphocytes. MUST be treated. If not, at high risk for lymphoma. If givenSynthroid, not at increased risk (lifelong drug).

Malignant Tumors and Endocrinopathies (these tumors canproduce these substances)Small Cell, Med. CA ACTH/CushingsChorioCA/testis HCG/gynecomastiaSC CA/lung PTH/hyperCa++

Med CA/thyroid Calcitonin/hypoCa+Islet cell Insulin/hypoglycemiaSmall Cell ADH/hypoNa+Renal Cell, Hepatocellular CA Erythropeitin/>Hct

The following image is most c/w which malignancy:A. Medullary Carcinoma of ThyroidB. Small cell carcinoma of LungC. Sq. Cell Carcinoma of LungD. Metastatic melanomaE. Renal Cell Adenocarcinoma

Figure: The walls are blue because they are filled w/calciummetastatic calcification. Squamous cell carcinoma of lung is mostlikely to make parathormone-like substance.

Ans. C, SCC of LungThese tumors frequently make a parathormone-like substance.

Anaplasia = Lack of differentiationAnaplasia is considered a hallmark of malignant transformation.Anaplastic features include:

- Cellular/nuclear pleomorphism- Increased nuclear-cytoplasmic ratio

- Nuclear hyperchromasia (increased DNA content)- Large nucleoli

- Undifferentiated, poorly differentiated, high grade- Small cell undifferentiated carcinoma of the lung = very aggressive, undifferentiated tumor. Not very successful in

treating.

GRADING TUMORS: Malignant tumors only- Differentiation and mitotic rate- Grades I-III/IV (higher grades are more anaplastic)- Important for some tumors: breast, prostate, endometrium, astocytomas- Dysplasias of the cervix are graded- Based on microscopic features

Test q:A 49y/o man experiences an episode of hemoptysis.On phys exam, he has puffiness of the face, pedal edema,

and systolic hypertension. A chest radiograph shows a 5cmmass of the right upper lobe of the lung. A fine-needleaspiration biopsy of this mass yields cells consistent w/small-

cell anaplastic carcinoma. A bone scan shows nometastases. Immunohistochemical staining of the tumor cellsis most likely to be positive for which of the following? ACTH

Glioblastomas of the brain are graded I-IV.Grades III & IV are called glioblastomamultiforme most malignant, aggressiveform of a glioblastoma.


8/12

Squamous pearls can sometimes have a lot of keratin, sometimes are swirls of malignant cells.

STAGING TUMORS:- How far has the tumor spread (has NOTHING to do w/what the

tumor looks like)

- Malignant tumors only- Tumor size (T), lymph node (LN) involvement, distant metastases

(M big 3 are brain, lung, and liver.)- Staging often involves: the Pathologist, radiology or other imaging,

lab tests (tumor markers)- CIS is referred to as Stage Zero is malignant, but has not

gone through basement membrane.- T1N0M0 = very small tumor, no lymph node involvement, no

distant metastases.- T3N5M1 = large, 5 lymph nodes involved, 1 met could have

gone to liver or brain, for example

METASTASIS LIVER: (spreads through portal circulation) tumors from GI tract

and pancreas; lung, breast, melanomas LUNG: breast, stomach, sarcomas BONE: 3

rdmost frequent site for metastases; lung, breast,

prostate, kidney, thyroid In bone, either break down the bone or cause bone to

proliferate. Osteoblastic = proliferative, bone gets denser.Osteolytic lesions = break down bone, see holes in bone.

PROSTATE bone gives osteoblastic lesions on X-ray andhigh serum alkaline phosphatase

Breast bone is osteolytic, break down bone and get lyticlesions.

ADRENAL: most common endocrine site

Above:Adenocarcinoma is characterized bygland formation or evidence of glandulardifferentiation.

Above: Two squamous cell carcinoma (SCC) examples with squamous pearls(SP). Whats the difference between a squamous pearl and an intra-epidermalpseudo-horn cyst (since they look similar)? The difference is the setting.S uamous earl = SCC. Inclusion c st in skin = normal findin seen in nevi etc

Above: * = intercellular bridges. SCCs also haveintercellular bridges. Does not mean it is malignant normal skin has these. But if you look at a mass from thelung w/intercellular bridges, its a squamous cancer.

Above:Anaplastic rhabdomyosarcoma totallyundifferentiated.

Test q:A malignant tumor is removed from the liver.Microscopically the tumor exhibits squamous pearls and

intercellular bridges. The most likely origin of thisneoplasm is: lung. (Other choices pancreas, liver,gallbladder, thyroid) REPEATED x2

Test q:A 38y/o female has a left breast lumpectomy. A

mass which measures

cm in greatest diameter isexcised as are two sentinel lymph nodes from the leftaxilla. The tumor consists of well-formed glands(tubules), exhibits no mitoses and has no nucleoli. The

ductal adenocarcinoma is focally invasive and there isminimal desmoplasia. Both lymph nodes are negativefor adenocarcinoma and there is no evidence of distant

metastases in liver, lung, or bone. Special stains forEstrogen Receptor (ER) and Her-2 Neu are totallynegative. The stage of this tumor is: T1N0M0

Test q:A mass is biopsied from the left breast of a 42y/ofemale. Invasive ductal carcinoma is present. All tumor

cells are present as round glands. Mitoses are not seenand nucleoli are absent. This tumor can be describedas: low grade. (Other choices: anaplastic,

undifferentiated, hamartoma, or CIS) The tumor

measures 1.1cm in diameter. Three sentinel lymphnodes are all negative for tumor. Distant metastases are

not detected. The stage of this neoplasm is: T1N0M0

Test q:A 76y/o man has experienced lower back painfor the past year. On phys exam, the physician palpatesa firm nodule in the prostate. Lab studies show analkaline phosphatase level of 290 U/L and a serum

prostate specific antigen level of 17 ng/mL. Both areelevated. A prostate needle biopsy specimen shows amoderately differentiated adenocarcinoma. Which of the

following mechanisms best accounts for these findings?Osteoblastic metastases.

Test q: Which of the following tumors commonlymetastasize to bone? Renal cell carcinoma.


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Neoplasia Case: A 38-y.o. malehas a family history ofcolectomies performed betweenages 30 and 40. The slide showsthe total colectomy specimenfrom this patient.

Which of the following bestdescribes this disease?

A. Crohns DiseaseB. Ulcerative colitisC. Inactivation of a supressor

geneD. X-linked recessive inheritance

patternE. Autosomal recessive

inheritance pattern

Answer: C, inactivation of APC. This disorder is autosomal dominant with the APC suppressor gene on chromosome 5

COLON CANCER

- Grading is not very helpful- STAGING: predicts clinical outcome- TNM

Tumor Size (T)Tis- in situ; not through the muscularis mucosaT1- invades submucosaT2- into but not through the muscularis propriaT3- through muscularis propriaT4- invades adjacent organs

TNM Staging System:Test q: A 50y/o man w/a history of colon cancer undergoes a segmental resection of adysplastic polyp in the transverse colon. The polyp shows focal adenocarcinoma (1cm also show ras mutations

- CEA (carcinoembryonic Ag) can be used to follow patients after surgery-tumor monitoring- Deeply infiltrating tumors cause desmoplasia and apple core/napkin-ring appearance

Above: Apple core/napkin ring appearance.

adenomatouschange

Lymph Nodes (N)N0- no nodes involvedN1- 1-3 regional LNsN2- 4+ regional LNs

Distant Metastases (M)M0- no distant metastasisM1- distant mets present*note: Tx, Nx, Mx cannot beassessed


10/12

Name the most common human tumor supressor genes and protooncogene (RESPECTIVELY)A. P53 and RBB. P53 and RASC. RB and RASD. APC and P53E. APC and RB

Answer: B, P53 and RASP53 is the tumor supressor gene mutated in over 50%of human tumors. The mutation prevents DNA repairand inhibits apoptosis. The point mutation in theproto-oncogene RAS allows cell proliferation (GTPsignal transduction) and is seen 30+% of humantumors

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

Answer: A, used to monitor tumor recurrence

CEA is not specific for colon cancer and not a sensitive test. CEA levels are determined pre- and post-surgery. The CEAlevel should fall to near zero. If the level falls and then increases, the patient may receive chemotherapy for therecurrence.

Tumor Markers:- Management- Detection (staging)- Diagnosis (screening)- PSA and CA 125- 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 highlysuspicious); also AlkPhos elevation in prostateCA assoc. with bone metastasis (osteoblastic)

- HCG- gestational trophoblastic tumors, testiculartumors

Benign breast ducts and lobules: Fibroadenoma:

Test q: CEA is used to follow patients w/cancer of the: colon.

Test q: Cancer antigen 125 (CA-125) is used to follow patients w/cancer ofthe: ovary. REPEATED x2

Test q (shown above): How are tumor markers useful in management ofcolon cancer? CEA is used to monitor tumor recurrence

Test q: Which of the following tumor markers can be used clinically to screenpopulations for presence of malignancy? PSA.


11/12

Intraductal carcinoma with cribbiforming (C)

Fibroadenoma of breast: and comedonecrosis (CN): Breast Carcinoma:

BREAST CARCINOMA GRADING: Bloom and Richardson Tubules present (1-3) Nuclear atypia (1-3) Mitoses (1-3) Total score 3-5: Grade I Total score 6,7: Grade II Total score 8,9: Grade III

BREAST CARCINOMA STAGINGStage 0 (in situ or CIS): 5-year 92%Stage I. (4 LN+): 5-year 46%Stage IV. Distant mets: 5-year 13%

BREAST CARCINOMA (OTHER): Estrogen receptor (+): tumor is stimulated by estrogen and can be treated

with the anti-estrogen tamoxifen. This is palliation.

HER-2 Neu amplification: by immunostaining or FISH. If HER-2 Neu isamplified (20%), the patient can be treated with Herceptin. This is veryexpensive and tends to be used in high grade/high stage lesions that areHER-2 Neu positive.

All of the following questions were already written into the week 4 study guide:Test q:A 50y/o woman saw her physician af ter noticing a mass in the right breast. Physical exam showed a 2cm mass fixed to the underlying tissuesand three firm, nontender, lymph nodes palpable in the right axilla. There was no family history of cancer. An excisional breast biopsy was performed,and microscopic exam showed a well-differentiated ductal carcinoma. Over the next 6mo, additional lymph nodes became enlarged, and CT scans

showed nodules in the lung, liver and brain. The patient died 9mo after diagnosis. Which of the following molecular abnormalities is most likely to befound in this setting? Amplification of the c-erb B2 (HER2) gene in breast cancer cells REPEATED x5!! (Once, answer was Amplification of theERBB2 (HER2) gene)

Test q:A 38y/o female has a left breast lumpectomy. A mass which measures cm in greatest diameter is excised as are two sentinel lymph nodes

from the left axilla. The tumor consists of well-formed glands (tubules), exhibits no mitoses and has no nucleoli. The ductal adenocarcinoma is focallyinvasive and there is minimal desmoplasia. Both lymph nodes are negative for adenocarcinoma and there is no evidence of distant metastases in liver,lung, or bone. Special stains for Estrogen Receptor (ER) and Her-2 Neu are totally negative.

- The grade of this tumor is: I- The treatment plan for this patient will include: neither tamoxifen nor herceptin

Test q:A mass is biopsied from the left breast of a 42y/o female. Invasive ductal carcinoma is present. All tumor cells are present as round glands.Mitoses and nucleoli are absent. This tumor can be described as: low grade. (Other choices: anaplastic, undifferentiated, hamartoma, CIS)

Test q:A mass was removed from the breast of a 46y/o female. The surgery performed was a lumpectomy w/axillary tail dissection (to look formetastatic disease in lymph nodes). The tumor measured 5.4cm in greatest diameter. Stromal invasion was extensive and desmoplasia was identified.3-4 mitoses were present in every high-power field. Gland/tubule formation was not present and most of the tumor showed sheets and nests of

undifferentiated malignant cells w/prominent nucleoli and irregular chromatin clumping. 15 lymph nodes were harvested from the axillary tail and 6/15were positive for adenocarcinoma. 3 of the positive nodes were matted together and fixed (surrounded by fibrosis) to the surrounding soft tissue.Staining for estrogen receptors was entirely negative. Staining for Her2-Neu showed strongly positive cytoplasmic and membrane staining in 90% of the

tumor cells. There was no clinical evidence of distant metastases.- An accurate grade for this tumor would be: Bloom and Richardson Grade III. - Additional treatment for this patient would include: Herceptin.


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Test q: A 42y/o female has a 5.0cm tumor removed (lumpectomy) from her right breast. 2 senitel lymph nodes are negative for tumor. Histologically,the tumor is anaplastic and shows no tubules or ducts, approx 25% of the tumor cells exhibit mitoses, and the nuclei are pleomorphic w/prominent

nucleoli and irreg nuclear membranes. These features are consistent w/a Scarff Bloom Richardson grade of: III.

Squamous Carcinoma of Cervix: Squamous metaplasia Dysplasia CIS Microinvasive cancer (5mm below BM

Stage I: 5-year is 90% Stage II: 5-year is 70% Stage IV: 5-year is 10%

HPV and Cervical Cancer HPV DNA types 6 and 11: condyloma HPV 16, 18, 13 others: carcinoma Viral protein E7 acts via retinoblastoma gene protein Viral protein E6 acts via to P53 (TP53). Proliferation is stimulated and apoptosis is inhibited

Squamous metaplasia :

Test q:A Pap smear reveals the presence of severe cervical dysplasiain a 35y/o female. Which of the following viruses binds to pRb toincrease the risk for this lesion? HPV DNA type 16 or 18.

Test q:A 30y/o woman who has had multiple sexual partners sees herphysician because she has had vaginal bleeding and discharge for the

past 5 days. Pelvic exam shows an ulcerated lesion arising from thesquamocolumnar junction of the uterine cervix. A cervical biopsy isperformed. Microscopic exam reveals an invasive tumor containing

areas of squamous epithelium, with pearls of keratin. In situhybridization shows the presence of human papillomavirus type 16(HPV-16) DNA within the tumor cells. Which of the following molecular

abnormalities in this tumor is most likely related to infection with HPV-16? Functional inactivation of the RB1 protein.

Test q:A 25y/o female presents w/an exophytic condyloma on hercervix. What HPV DNA types would you expect? HPV 6, 11

Pathology Week 5 p29-40

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Transcript of Pathology Week 5 p29-40