Pathoma Ch. 3 - Neoplasia Basics

Question 1

Determining clonality in somatic cells vs. B cells

Answer 1

Somatic - G6PD isoform (normal = A:G 1:1)

B cells - Ig light chain (normal = kappa:lambda 3:1)

Question 2

Leading causes of death in adults vs. children

Answer 2

Adults: Cardiovascular, cancer, cerebrovascular
Kids: Accidents, cancer, congenital defects

Question 3

Why is lung cancer the most popular killer?

Answer 3

No good detection mechanism

Question 4

Classes of oncogenes (w/ classic examples)

Answer 4

Growth factors (ex. PDGF-beta)
Growth factor receptors (ex. HER2, RET, KIT)
Signal transducers (ex. RAS, ABL)
Nuclear regulators (ex. Myc)
Cell cycle regulators (ex. cyclin D1, CDK4)

Question 5

Classic tumor suppressor genes (w/ fxns of each)

Answer 5

P53 (slow G1 –> S cell cycle, upregulate DNA repair, and/or induce apoptosis via BAX if DNA damage can’t be repaired)

Rb (slow G1 –> S cell cycle by holding E2F inactive)

Question 6

Rb phosphorylated vs. dephosphorylated

What inactivates it?

Answer 6

Phosphorylated = release E2F
Dephosphorylated = hold E2F

Cyclin D/CDK4

Question 7

What is true regarding the mutations for both p53 and Rb?

Answer 7

1. Inactivating mutations

2. BOTH copies must be knocked out

Question 8

Bcl overmutation

Result?

Answer 8

Follicular lymphoma

No apoptosis –> increased germinal centers, etc.

Question 9

Overactive…

- PDGF-beta
- RET
- KIT
- ABL
- CKD4

Answer 9

Astrocytoma
MEN2, Sporadic medullary thyroid cancer
GIST
CML, adult ALL
Melanoma

Question 10

Contaminated stored grains

Answer 10

Aflatoxins – HCC

Question 11

Alcohol - cancers (4)

Answer 11

Oropharynx SCC, Upper esophagus SCC, Pancreas, HCC

Question 12

Arsenic - cancers (3)

Answer 12

SCC of skin, Lung cancer, Liver angiosarcoma

Question 13

Cigarette smoke - cancers (5)

Answer 13

Oropharynx, Esophagus, Lung, Kidney, Bladder

Question 14

Smoked foods in japan

Answer 14

Nitrosamines - intestinal stomach cancer

Question 15

Naphthylamine

Answer 15

Urothelial carcinoma of bladder

Question 16

Vinyl chloride

Common route of exposure here

Answer 16

Angiosarcoma of liver

PVC pipe

Question 17

Nickel, chromium, beryllium, or silica

Answer 17

Lung cancer

Question 18

EBV

Answer 18

Nasopharyngeal carcinoma (Asia, Africa), Burkitt lymphoma (endemic), primary CNS lymphoma (AIDS)

Question 19

HHV-8 in eastern european male

Treatment?

Answer 19

Kaposi sarcoma

Excise it

Question 20

High risk HPV

Answer 20

SCC of vulva, vagina, anus, cervix

Adenocarcinoma of cervix

Question 21

Ionizing radiation (Chernobyl, cancer)

Answer 21

AML, CML, papillary thyroid cancer (free radicals)

Question 22

UVB sunlight

Answer 22

BCC, SCC, Melanoma (pyrimidine dimers)

Question 23

Angiogenesis in cancers occurs via what?

Answer 23

FGF and VEGF

Question 24

Tumor cells dissociate via ____
Tumor cells attach to ___ on BM and destroy it via ____
Tumor cells attach to ___ in the ECM to spread locally

Answer 24

Down-regulation of E-cadherin
Laminin; Collagenase (type 4 collagen destruction)
Fibronectin

Question 25

IN GENERAL, carcinomas spread via ___ Exceptions? (4)

Answer 25

Lymphatics (regional LNs) 1. RCC (renal vein) 2. HCC (hepatic vein) 3. Follicular thyroid carcinoma 4. Choriocarcinoma (trophoblasts find BVs)

Question 26

Classic characteristics of malignant tumors (7)

Answer 26

1. Poorly differentiated 2. Disorganized growth 3. Nuclear pleomorphism 4. Hyperchromasia 5. High nuclear:cytoplasm ratio 6. High mitotic activity w/ atypical mitoses 7. Invasion (metastatic potential)

Question 27

Cancer types... - Keratin - Vimentin - Desmin - GFAP - Neurofilament

Answer 27

``` Epithelium Mesenchyme Muscle Neuroglia Neuron ```

Question 28

Cancers... - Thyroglobulin - Chromogranin - S-100

Answer 28

Thyroid FOLLICULAR cells Neuroendocrine cells Melanoma, LC Histiocytosis

Question 29

Elevated serum tumor marker (ex. PSA)...must do what?

Answer 29

Biopsy

Question 30

Low grade means ___ | High grade means ___

Answer 30

Well-differentiated (looks like parent tissue) | Poorly-differentiated (does NOT look like parent tissue)

Question 31

Which is more important: stage or grade? Single most important prognostic indicator?

Answer 31

STAGE Metastasis (M)