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STEP 1 Pathoma > Chapter 3 > Flashcards

Chapter 3 Flashcards

1
Q

What is neoplasia?

A

New tissue growth that is unregulated, irreversible, and monoclonal (all cells derived from a single mother cell)

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2
Q

Note that clonality was historically determined by the isozyme of G6PD (A,B, or C) or androgen receptor isoforms. Today, clonality of B lymphocytes is determined by what?

A

immunoglobulin (Ig) light chain phenotype- Ig is comprised of heavy and lght cahns, and each B cell expresses light chains that are either kappa or lambda (normal kappa:lambda ratio is 3:1 and is maintained in hyperplasia but is increased to 6:1 and inverted in lymphoma)

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3
Q

What are the most common cancers by incidence in adults?

A

1) breast/prostate
2) lung
3) colorectal

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4
Q

What are the most common cancers that cause death in adults?

A

1) lung
2) breat/prostate
3) colorectal

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5
Q

Cancer begins as a single mutated cell and typically 30 divisions occur befre symptoms present. Each division results in icnreased mutations and thus cancer that do not produce symptoms until late will have additional mutations (and tend to have a poor prognosis)

A

Cancer formation is initiated by dmaage to DNA of stem cells that overcomes DNA repair mechanisms, but is not lethal

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6
Q

Alfatoxin is associated with what cancer?

A

hepatocellular carcinoma (derived from aspergillus which can contaminate stored rice and grain)

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7
Q

Alkylating agents are associated with what cancer

A

leukemia and lymphoma (side effect of chemo)

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8
Q

Alcohol is associated with what cancer?

A

Squamous cell carcinoma of the oropharynx and upper esophagus, and HCC

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9
Q

Arsenic is associated with what cancer?

A

Squamous cell cancer of the skin, lung cancer, and angiosarcoma of the liver (arsenic is present in cigarette smoke)

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10
Q

Asbestos is associated with what cancer?

A

Lung carcinoma and mesothelioma (exposure to asbestos is more likely to cause lung cancer than mesothelioma)

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11
Q

Cigarette smoke is associated with what cancer?

A

carcinoma of the oropharynx, esophagus, lung, kidney, bladder, and pancreas

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12
Q

Nitrosamines is associated with what cancer?

A

Stomach carcinoma (found in smoke foods)

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13
Q

Vincyl chloride is associated with what cancer?

A

angiosacroma of the liver (PVC pipes)

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14
Q

Naphthylamine is associated with what cancer?

A

urothelial carcinoma of the bladder

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15
Q

Nickel, chromium, berllium and silica are associated with what cancer?

A

Lung carcinoma

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16
Q

EBV is associated with what cancers?

A

nasopharyngeal carcinoma, Burkitt lymphoma, and CNS lymphoma in AIDs

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17
Q

HHV-8 is associated with what cancers?

A

Kaposi sarcoma

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18
Q

HBV and HCV are associated with what cancers?

A

adult T-cell lymphoma/leukemia

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19
Q

HPV is associated with what cancers?

A

squamous cell carcinoma of the vulva, vagina, anus, and cervix

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20
Q

Ionizing radiation is associated with what cancers?

A

AML, CML, and papillary carcinoma of the thyroid (via free radicals)

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21
Q

Nonionizing (UVB sunlight) radiation is associated with what cancers?

A

basal cell carcinoma, squamous cell carcinoma and melanoma (from pyrimidine dimers in DNA)

22
Q

Tumor suppressors regulate cell growth and hence suppress the risk of tumor formation (p53 and Rb classic examples). What does p53 do?

A

regulates progression of the cell cycle from G1 to S phase. In response to DNA damage, p53 slows th cell cycle and upregulates DNA repair enzyes. If DNA repair is not possible, apoptosis is induced (p53 upregulates BAX, which disrupts Bcl2 causing cytochrome C release)

NOTE: BOTH copies of p53 gene must be knocked out for tumor formation (two hit hypothesis)

23
Q

What does Rb do?

A

regulates progression of G1 to S phase. Rb holds the E2F transcription factor which is necessary for transition to the S phase. E2F is released when RB is phosphorylated by the cyclinD/CDK4 complex.

RB mutation causes constitutively expressed free E2F, allowing progression hrough the cell cycle and uncontrolled cell growth. Again, both copies of Rb must be knocked out for this to happen.

24
Q

Germline mutation in Rb results in what?

A

BILATERAl familial retinoblastoma and osteosarcoma

25
Q

Overexpression/mutation of PDGF-B is associated with what cancer?

A

Astrocytoma

26
Q

Amplification of ERBB2 (HER2/neu) is associated with what cancer?

A

breast carcinoma

27
Q

Point mutation of RET (a neural growth factor receptor) is associated with what cancer?

A

MEN 2A, 2B, and sporadic medullary carcinoma of the thyroid

28
Q

Point mutation of KIT (a stem cell growth factor receptor) is associated with what cancer?

A

GIST

29
Q

Point mutation in the RAS gene family, a GTP binding protein) is associated with what cancer?

A

carcinomas, melanoma, and lymphoma

30
Q

t(9:22) with BCR translocation of ABL is associated with what cancer?

A

CML and some subtypes of ALL

31
Q

t(8:14) translocation of c-MYC (a transcription factor) with IgH is associated with what cancer?

A

Burkitt lymphoma

32
Q

Amplification of N-MYC, a transcription factor, is associated with what cancer?

A

Neuroblastoma

33
Q

Amplification of L-MYC, a transcription factor, is associated with what cancer?

A

Small cell lung carcinoma

34
Q

t(11:14) translocation of Cyclin D1 with IgH is associated with what cancer?

A

Mantle cell lymphoma

35
Q

Amplification of CDK4 is associated with what cancer?

A

Melanoma

36
Q

What does Bcl2 normally do?

A

Stabilizes the mitochondrial membrane, blocking release of cytochrome C (mutation- apoptosis)

37
Q

Bcl2 is overexpressed in what?

A

Follicular lymphoma in which a t(14:18) translocation exchanges Bcl2 on chrom 18 with the Ig heavy chain on chrom 14. This causes the mitochondrial membrane to be further stabilized, inhibiting apoptosis and leading to lymphoma

38
Q

_____ is needed for cell immortality

A

Telomerase - normally they shortern with serial cell division eventually resulting in cellular senscence (cancers often have upregulated telomerase

39
Q

Avoiding immune surveillance is key to tumor survival. How can this be accomplished?

A

Downregulation of MHC class I molecules

40
Q

How does tumor spread occur?

A

Mutations accumulate against E-cadherin which normally anchors cells together, allowsing th cells to attach to fibronectin in the extracellular matrix and spread locally.

41
Q

Lymphatic spread is classic of _______

A

Carcinomas- initial spread to regional regional lymph nodes

42
Q

Heme spread is classic of _______

A

Sarcoma and some carcinomas (renal cell carcinoma invades the renal vein, HCC invades the hepatic veins, follicular carcinoma of the thyroid, and choriocarcinoma)

43
Q

Seeding of body cavities is most common with what cancers?

A

Ovarian carcinoma which often involves the peritoneum

44
Q

_______ is the hallmark of malignancy

A

MET potential (benign tumors never MET)

45
Q

A keratin stain would be used to visualize what?

A

Epithelium

46
Q

A vimentin stain would be used to visualize what?

A

Mesenchyme

47
Q

A desmin stain would be used to visualize what?

A

Muscle

48
Q

A GFAP stain would be used to visualize what?

A

Neuroglia

49
Q

A neurofilament stain would be used to visualize what?

A

Neurons

50
Q

A chromogranin stain would be used to visualize what?

A

Neuroendocrine cells (e.g. small cell carcinoma of the lung or carcinoid tumors)

51
Q

A S-100 stain would be used to visualize what?

A

melanoma, Schwannoma and langerhans cell histiocytosis

52
Q

A thyroglobulin stain would be used to visualize what?

A

thyroid follicular cells

STEP 1 Pathoma (18 decks)

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