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Pathology > Neoplasia II > Flashcards

Neoplasia II Flashcards

1
Q

Who is the guardian of the genome?

A

p53

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2
Q

What hereditary germline mutations lead to breast cancer at an early age?

A

BRCA-1 and 2

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3
Q

What are Gatekeepers?

A

genes that directly control tumor growth, i.e. tumor suppressors and oncogenes

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4
Q

What are Caretakers?

A

genes that affect genetic stability by causing defective DNA repair

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5
Q

What are some defects in gene repair?

A 
BRCA 1, 2
HNPC
Xeroderma pigmentosa
Ataxia telangiectasia
Bloom syndrom
Fanconi anemia
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6
Q

Follicular B cell lymphomas have a blank translocation that fuses with what?

A

Have a t translocation that fuses with BCL2 gene (chr. 18)

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7
Q

What is the primary mechanism of follicular B cell lymphomas?

A

Evasion of apoptosis. Fusion of BCL2 gene with active IgH locus on chromosome 14 results in over production of BCL2 (anti-apoptotic)

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8
Q

Sustained angiogenesis is required for a tumor to grow over?

A

2 mm

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9
Q

What is angiogenesis normally inhibited by?

A

Thrombomodulin (p53 induced) and destruction of HIF-1alpha (VHL)

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10
Q

What happens with HIF and VHL during tumor hypoxia?

A

Tumor hypoxia turns of VHL, so that HIF-1alpha produces VEGF

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11
Q

What are the four steps of cancer invasion?

A
  1. Detachment of tumor cells from each other
  2. Degradation of basement membrane and ECM
  3. Attachment of tumor cells to basement membrane
  4. Migration
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12
Q

What is bevacizumab?

A

Anti VEGF agent. Only mildly helpful

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13
Q

What is the angiogenic switch mediated by?

A

HIF1alpha, FGF, loss of p53, decreases thromodulin 1

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14
Q

Tumors need to overcomes what anti-angiogenic factors for sustained angiogenesis?

A

Angiostatin, Endostatin, and Vasculostatin

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15
Q

For cancer invasion, detachment of cells is mediated by what?

A

Down-regulation of E cadherin or mutated catenin

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16
Q

For cancer invasion, attachment of cells to exposed basement membrane is mediated by what?

A

Fibronectin and laminin receptors

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17
Q

Where does colon cancer generally metastasize to?

A

Liver

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18
Q

Where do prostate and breast cancer generally metastasize to?

A

Bone

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19
Q

What is the mechanism for metastatic organ tropism?

A

Differential concentration of endothelial cell ligands for adhesion molecules in different organs
Chemokines (ie CXCR4 and CCr7 receptors in breast cancer)

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20
Q

What is tumor embolus?

A

Tumor cells that invade veins go to the lungs and elicit formation of blood clot around them

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21
Q

What is responsible for the organization of a tumor embolus?

A

Organized by fibroblasts

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22
Q

What are chemical carcinogens?

A

Initiators cause mutations, which can potentially become irreversible

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23
Q

Do promoters cause reversible or irreversible proliferation of initiated cells?

A

Reversible

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24
Q

What are direct chemical carcinogens?

A

Electrophiles

25
Q

What are indirect chemical carcinogens?

A

Require metabolic activation of procarcingens commonly by CYP450 mono-oxygenases

26
Q

What are some examples of indirect chemical carcinogens?

A

Estrogen, alcohol, anti-cancer drugs, asbestos, polycyclic and heterocyclic aromatic hydrocarbons, aromatic amines, amides, and azo dyes, etc

27
Q

What carcinogens have long latent period (yrs-decade)

A

Radiation

28
Q

UV light causes what?

A

Skin cancer

29
Q

Radiation therapy can cause what type of cancer?

A

Sarcomas

30
Q

Nuclear power plant leaks cause what type of cancer?

A

Thyroid Cancer

31
Q

What are some microbial carcinogens?

A

HCV, HBV, HPV, and helicobacter pylori

32
Q

What microbial carcinogens cause hepatic cancer?

A

HCV and HBV

33
Q

What microbial carcinogens cause lymphoma?

A

HBV

34
Q

What microbial carcinogens cause uterine cervical cancer?

A

HPV

35
Q

What microbial carcinogens cause gastric carcinoma and lymphoma?

A

Helicobacter pylori

36
Q

What are some tumor antigens?

A

Mutated oncogene products
Products of other mutated genes
Overly or aberrantly expressed proteins
Oncogenic viral products

37
Q

What are even more tumor antigens?

A 
Oncofetal antigens (CEA, AFP)
Altered cell surface glycolipids (CA-125, CA-19-9)
Cell type specific differentiation antigens
38
Q

What is the principal immune surveillance mechanisms?

A

CD8

39
Q

What are other immune surveillance mechanisms?

A

NK cells (activated by IL2), macrophages, and antibodies

40
Q

What are some resistance mechanisms to immune surveillance?

A 
Selective outgrowth of Ag-neg cells
Decreased MHC molecules
Lack of co stimulation
Ag masking
Apoptosis of CD8's
Immunodeficiency
41
Q

What are paraneoplastic syndromes?

A

Symptoms not attributable to direct effects of tumor ( or hormones native to primary tumor organ)

42
Q

What percentage of patients do paraneoplastic syndromes occur in?

A

10%, not counting cachexia

43
Q

What can be the earliest manifestation of occult tumor?

A

paraneoplastic syndrome

44
Q

Can paraneoplastic syndrome be sickening or fatal by themselves?

A

Yes

45
Q

Can paraneoplastic syndrome mimic metastatic disease?

A

Yes

46
Q

What are examples of paraneoplastic syndromes?

A 
Hypercalcemia (most common)
Cushing syndrome
Syndrome of inappropriate ADH
Hypoglycemia
Carcinoid syndrome (serotonin)
eaton-lamberts syndrome (myasthenia)
47
Q

What are symptoms of hypercalcemia of malignancy?

A

nausea, vomiting, constipation, polyuria, disorientation, lethargy, seizures

48
Q

What are mechanisms of hypercalcemia?

A

Parathyroid hormone related protein

49
Q

How do you treat hypercalcemia?

A

Hydration and biphosphonates

50
Q

What lung cancer types most commonly causes hypercalemia?

A

Squamous cell carcinoma

51
Q

What are signs and symptoms of Cushing syndrome?

A

Weight gain, central obesity, moon face, weakness, hirutism, HTN, glucose intolerance, depression, psychosis, broad red abdominal striae, buffalo hump deposition, plethora, osteoporosis, menstrual irregularity, muscle wasting

52
Q

What is the most common source of cushing syndrome?

A

Pituitary carcinoma: ACTH

Small cell carcinoma of lung as well

53
Q

What are symptoms of Carcinoid syndrome?

A

cutaneous flushing, diarrhea, cramps, nausea, vomiting, cough

54
Q

What are more random examples of paraneoplastic syndromes that no one gives a fuck about?

A

Acanthosis
Dermatomyositis
Hypertrophic osteoarthropathy
Migratory thromboplebitis (Trousseau syndrome)
Marantic (non bacterial thrombotic) endocarditis

55
Q

What determines tumor stage?

A

Anatomic extent, including primary tumor size, extent of lymph node, and distant metastases

56
Q

What is tumor grade?

A

Qualitative assessment of the differentiation of a tumor. In other words, the extent to which it resembles normal tissue at primary site?

57
Q

What are the two stages of cancer diagnosis?

A
  1. Discovery

2. Specific diagnosis

58
Q

What is the discovery phase of diagnosing cancer?

A

Symptoms, signs, radiology, and serum markers

59
Q

What is the specific diagnostic phase of diagnosing cancer?

A

Biopsy: fine needle aspiration cytology, exfoliative cytology

Pathology (6 decks)

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