Principles of Neoplasia

Question 1

Name for Cancers of Epithelium

Answer 1

B = Adenoma, papilloma
M = Adenocarcinoma, papillary carcinoma

Question 2

Name for Cancers of Mesenchyme

Answer 2

B = Lipoma
M = Liposarcoma
Mesenchyme = connective tissue (fat, bone, blood vessels, cartilage)

Question 3

Lymphocyte

Answer 3

M = Lymphoma/Leukemia

Question 4

Melanocyte

Answer 4

B = Nevus (mole)
M = Melanoma

Question 5

Aflatoxins causes

Answer 5

Hepatocellular carcinoma. Find this chemical in Aspergillus which can contaminate rice and grains so see commonly in Africa

Question 6

Alkylating Agents cause

Answer 6

Leukemia/lymphoma. Side effect of chemotherapy

Question 7

Arsenic causes

Answer 7

Squamous cell carcinoma of oropharynx and upper esophagus. Also hepatocellular carcinoma. Find in cigarette smoke

Question 8

Asbestos Causes

Answer 8

Primarily lung carcinoma but also mesothelioma.

Question 9

Cigarette Smoke Causes

Answer 9

Carcinoma of oropharynx, esophagus, lung, kidney, bladder, and pancreas. The polycyclic hydrocarbons are the most carcinogenic

Question 10

Nitrosamines Cause

Answer 10

stomach carcinoma. See in smoked foods so common in Japan

Question 11

Napthylamine Casues

Answer 11

Urothelial carcinoma of bladder. Find in cigarette smoke

Question 12

Vinyl Chloride Casues

Answer 12

Angiosarcoma of liver. See in workers that make PVC pipes

Question 13

Nickel, chromium, beryllium, or silica Casues

Answer 13

Lung carcinoma

Question 14

Epstein Barr Virus Causes (EBV) Causes

Answer 14

Nasopharyngeal carcinoma in chinese males or Africans. Usually present with a neck mass
Burkitt lumphoma
CNS lymphoma in AIDS

Question 15

Herpes Virus (HHV8) Causes

Answer 15

Kaposi Sarcoma. Find in Eastern European males, AIDS patients, or organ transplant (immunocompromised)

Question 16

Hepatitis B (HBV) and C (HCV) causes

Answer 16

Hepatocellular Carcinoma

Question 17

Human T-lymphotropic Virus 1 Causes

Answer 17

Adult T-Cell leukemia/lymphoma

Question 18

HPV Causes

Answer 18

Squamous cell carcinoma of vulva, vagina, anus, and cervix. Also get adencarcinoma of cervix

Question 19

Ionizing Radiation (nuclear accidents and radiotherapy) Causes

Answer 19

AML, CML, and papillary carcinoma of the thyroid

Question 20

Nonionizing (UV sun rays)

Answer 20

Basal cell carcinoma, squamous cell carcinoma, and melanoma of the skin

Question 21

Platelet Derived Frowth Factor B Associated w/

Answer 21

Astrocytoma (brain cancer). Overexpression so astrocyte is bombarded with PDGFB and grows and divides rapidly.

Question 22

ERBB2 (HER2/neu) Associated w/

Answer 22

Subsets of breast carcinomas. Amplification of these growth factor receptors causes the cell to be hyperresponsive to growth factors and grow and divide

Question 23

RET is associated w/

Answer 23

Neural Growth factor receptor. A point mutation can cause MEN2A or B and medullary carcinoma of thyroid

Question 24

KIT assoicated w/

Answer 24

Stem cell growth factor receptor. Point mutation can cause GI stromal tumor

Question 25

RAS gene family associated w/

Answer 25

Signal transducer that is a GTP binding protein. Point mutation results in a prolonged activated state and it sends too much message and get cancers of all kinds

Question 26

ABLassociated with

Answer 26

Signal transducer that is a tyrosine kinase. Get Philladelphia chromosome t(9:22) with BCR leading to overactivation of the tyrosine kinase and lots of cell growth. See in CML and some types of ALL. Philadelphia chromosome is poor prognosis

Question 27

C, N, and L MYC

Answer 27

All are nuclear regulators that cause upregulation of genes needed for cell growth. C- see a t(8:14) involving IgH. IgH is on chromosome 14 and usually on so translocation of c-MYC from 8 to Cr 14, get chronicall on c-MYC and get Burkitt Lymphoma N - neuroblastoma L = lung carcinoma

Question 28

CCND1 (Cyclin D1)

Answer 28

t(11:14) involving IgH. Overexpression of Cyclin D1 so cell moves from G1 to S phase rapidly. Get Mantle Cell lymphoma

Question 29

CDK4

Answer 29

Cell cycle regulator whose amplification leads to melanoma

Question 30

Tumor Suppressor Genes

Answer 30

Regulate cell growth and check to make sure cell is ok to move from G1 to S. When working properly they reduce risk of cancer formation. p53 and Rb are classic examples Need both copies of gene to be mutated to get cancer (as compared to proto-oncogenes where only need 1 mutation)

Question 31

p53

Answer 31

regulates progression from G1 to S. When DNA is damaged it upregulates repair enzymes If DNA damage is so bad it induces apoptosis by upregulating BAX which dirupts Bcl2 allowing ytochrome C to leak out of mitochondria and apoptose. Need both genes to be knocked out to get cancer. Germline mutation results in Li-Fraumeni Syndrome.

Question 32

Rb

Answer 32

Rb "holds" E2F transcription factor, which is needed to move to S phase. Rb mutation results in constitutively free E2F, allowing progression through cell cycle. Sporadic mutation (both hits are somatic) get unilateral retinoblastoma but it is very rare Germline mutation results familial retinoblastoma and can frequently see it bilaterally. Also more prone to osteosarcoma

Question 33

Bcl2

Answer 33

Normally stabilizes mitochondiral membrane and prevents release of cytochrome c and apoptosis. Overexpressed in follicular lymphoma. Get t(14:18) Bcl2 on 14 and Ig heavy chain on 18. See increased Bcl2 so get a bunch of B cells that would normally undergo apoptosis during somatic hypermutation in the lymph node germinal center are now living and circulate as useless B cells.

Question 34

Telomerase

Answer 34

Cancers upregulate telomerase so can live longer

Question 35

FGF and VEGF

Answer 35

Tumor cells express these a lot for angiogenesis so they can get nutrients to thrive

Question 36

MHC1

Answer 36

Cancers avoid immune surveilance by downregulating MHC1. (Also reason you see cancers in immunocompromised)

Question 37

Tumor Progression

Answer 37

1) Downregulation of E-cadherin so dissociate from neighboring cells 2) Cells attach to laminin and destroy basement membrane via colleganse 3) Attach to fibronectin in ECM and spread locally 4) Entry into blood or lymphatics allows them to spread all over

Question 38

Cancers that spread via Lymphatics

Answer 38

Carcinomas

Question 39

Cancers that spread hematogenously

Answer 39

Sarcomas + the following carcinomas | Renal cell, hepatocellular, follicular, and chorio

Question 40

Clinical Features of Benign Tumors

Answer 40

slow growing well circumscribed distinct mobile

Question 41

Clinical features of Malignant Tumors

Answer 41

Rapid growing poorly circumscribed Infiltrative Fixed to surrounding tissues and structures

Question 42

Histologic Features of Benign Tumors

Answer 42

``` Organized growth Uniform Nuclei low nuclear:cytoplasmic minimal mitotic activity lack invasion no metastatic potential ```

Question 43

Hitologic Features of Malignant Tumors

Answer 43

``` Disorganized growth Nuclear pleomorphism and hyperchromasia High nuclear:cytoplasmic High mitotic activity Invasion ```

Question 44

Immunohistochemical Stains indicate tumor of what origin: | Keratin, Vimentin, Desmin, GFAP, Neurofilament

Answer 44

``` Keratin = Epithelium Vimentin = Mesenchyme Desmin = Muscle GFAP = neuroglia Neurofilament = neurons ```

Question 45

Immunohistochemical Stains indicate tumor of what origin: | PSA, Estrogen Receptor, Thyroglobulin, Chromogranin, S-100

Answer 45

PSA= Prostatic epithelium Estrogen Receptor = breast epithelium Thyroglobulin= thyroid follicular cells Chromogranin = neuroendocrine cells (small cell carcinoma of lung and carcinoid tumors) S-100 = Melanoma, Schwannoma, and Langerhans Cell Histiocytosis

Question 46

Grading of cancer Low vs High

Answer 46

``` Low = well differentiated (resembles normal parent tissue) High = poorly differentiated (does not resemble parent tissue) ```

Question 47

Serum Tumor Markers

Answer 47

Useful for screening, monitoring response to treatment, and monitoring reccurence. CANNOT be used to diagnose someone with cancer. Only a biopsy can diagnose. If serum levels are high the next step is biopsy not surgery or treatment.

Question 48

Staging of Cancer : TNM

Answer 48

T- tumor size and depth of invasion N = spread to regional lymph NODES M = Metastasis