Path 7-11: Neoplasia I-Iv And Cc

Front 1

define neoplasia

Back 1

"new growth", abnormal mass of tissues, the gro of which exceeds and is uncoordinated with that of normal tissues, persists after the cessation of stimuli

Front 2

define tumor

Back 2

swelling, not the same as neoplasia

Front 3

Compare and contrast benign and malignant tumors in terms of: nomeclature

Back 3

benign="oma", malignant= "carcinoma" (epithelial) or "sarcoma" (mesenchymal)

Front 4

Compare and contrast benign and malignant tumors in terms of resembleance to normal tissue

Back 4

benign-resmebles normal, malignant-varies, can resemble or extremely different

Front 5

Compare and contrast benign and malignant tumors in terms of growth rate

Back 5

benign=slow, malignant=variable

Front 6

Compare and contrast benign and malignant tumors in terms of invasion and metastasis

Back 6

benign=non-invasive, encapsulated, do not metastasize; malignant-invasive, capable of metastasizing

Front 7

tumors of epithelial origin usually arise from which germ layer

Back 7

ecto or endoderm

Front 8

tumors of mesenchymal origin arise from which germ layer

Back 8

mesoderm (fibroblasts, adipocytes,muscle, bone, cartilage, blood vessels)

Front 9

what are the prefixes used for neoplasms arising from smooth and skeletal muscle

Back 9

smooth-leio, skeletal-rhabdomyo

Front 10

tumors of melanocyte origin arise from which germ layer

Back 10

neural crest

Front 11

Give four possible cells of origin of tumors

Back 11

1. epithelial 2. mesenchymal 3. hematolymphoid 4. Melanocytic

Front 12

what components make up a benign mixed tumor

Back 12

epithelial and mesenchymal components, e.g. pleomorphic adenoma

Front 13

describe a teratoma

Back 13

predominately benign tumors composed of tissue deribed from multiple germ layers, totipotent cells

Front 14

define hamartoma

Back 14

a tumor like condition, mass of disorganized, mature tissue which is specific to the site of development, represents anomalous development

Front 15

define choriostoma

Back 15

ectopic tissue in a goreign location e.g. gastric heterotopia

Front 16

define tumor differentiation

Back 16

the extent to which tumor cells morphologically and functionally resemble the normal tissue counterpart

Front 17

describe the categories of tumor differentiation

Back 17

1. well-diff=resemble normal tissue (benign) 2. moderately diff 3. poorly diff-primitive, vague resemblance, can't really tell where its from 4. anaplastic-complete lack of differentiation (malignant are poor-anaplastic)

Front 18

Describe the qualities of a well diff tumor

Back 18

1. close resembalance to normal tissue 2. evidence of maturation/ function

Front 19

describe the qualities of  a poorly differentiated tumor

Back 19

1. spectrum of vague to no resembalance to normal 2. do NOT retain functionality

Front 20

describe the qualities of an anaplastic tumor

Back 20

Pleomorphic, hyperchromatic nuclei, high N/C ratio, coarsely clumped chromatin, large nucleoli, atypical mitoses, loss of polarity, giant cells

Front 21

What are the components of the TNM staging system

Back 21

T=tumor size, N=nodal involvement M=metastasis

Front 22

Describe the features of carcinoma in situ, a pre-invasive stage of tumor spread

Back 22

frequently seen in proximity to invasive tumor, malignant cells do not penetrate beyond the basement membrant but there is "full thickness dysplasia"

Front 23

list some features that would lead to  Dx of dysplasia

Back 23

disorganized growth=loss of polarity, increased mitoses, loss of maturation, crowded, hyperchromatic nuclei, atypia

Front 24

compare and contrast benign and malignant tumors in terms of local invasion

Back 24

benign-frequently well-circumscribed and/or encapsulated, DO NOT INVADE; malignant-well to poorly circumscribed, frequently infiltrate surronding tissue,

Front 25

T/F invasion=metastasis

Back 25

false, invasion is a local process, metastasis is a systemic process

Front 26

Describe the sequence of invasion by malignant tumors

Back 26

1. Loss of intercellular adhereance (E-cadherin is not produced) 2. Attachment to laminin (glycoprotein in basement membrane) 3. Degradation of basement membrane using type IV collagenase 4. Migration beyond BM via attachment to fibronectin in the ECM and production of autocrine cytokines to stimulate locomotion 5. Stimulation of angiogenesis

Front 27

T/F all malignant tumors metastasize

Back 27

false, basal cell carcinomas and gliomas are malignant but do not metastasis

Front 28

By which pathway do sarcoma's usually metastasize? To where?

Back 28

hematogenous, veins> arteries, most common sites are portal, vena caval, and paravertebral plexus leading to liver, lung, and vertebral mets

Front 29

By which pathway do carcinomas usually spread

Back 29

lymphatic, sentinel node= first LN to drain the tumor

Front 30

describe seeding as a pathway for metastatic spread

Back 30

tumor cells displace from mass and implant/ invade serosal surfaces, peritoneal cacity most commonly involved, frequent in ovarian and peripheral lung cancers

Front 31

most common cancers in kids

Back 31

1. hematogneous 2. brain/CNS

Front 32

Top 3 cancer INCIDENCE male/female and death

Back 32

Incidence 1.prostate/ breast 2. Lung 3. colon, Death=1. lung 2. Prosate/ Breast 3. Colon

Front 33

cancer rank on US cause of death

Back 33

2nd leading cause of death

Front 34

what is the inheritance pattern of retinoblastoma

Back 34

autosomal dominant

Front 35

What is the normal function of Rb. What happens after two hits (one inherited, one aquired)?

Back 35

Rb binds E2F and prevents it from actvating the cell cycle. when the Rb gene is mutated, there is a failure of E2F regulation allowing for uncontrolled E2F activation and unregulated cell growth leading to retinoblastoma and osteosarcoma

Front 36

what is the inheritance pattern of Familial Adenomatous Polyposis

Back 36

autosomal dominant

Front 37

Mutations in which gene are associated with FAP? WHat is it's normal function? What happens when it is mutated?

Back 37

APC, normal fxn=tumor supressor, down regulated B catenin, mutation leads to B catenin accumulation, B catenin complexes with TCF and stimulates the transcription of growth factors leading to unregulated cell growth

Front 38

What is the inheritance pattern of Li-Fraumeni Syndrome? whihc gene is involved

Back 38

ausomal dominant, p53

Front 39

Which gene is mutated in LiFraumeni syndrome? Consequences?

Back 39

p53, normal function is cell cycle arrest and initiation of apoptosis, mutation  leads to a 25x increased risk of cancer, younger age, multiple cancers, wide variety

Front 40

What is the inhertaince pattern of the BRCA1/2 genes? Normal fxn Mutation?

Back 40

Autosomal dominant, normal fxn is tumor supression, mutation leads to increased risk fo breast CA at younger age, increased risk of other cancers

Front 41

What is the inheritance pattern of HNPCC? Gene target? Result of mutation?

Back 41

Autosomal dominant, mutation in MSH2, MLH1, DNA mismatch repair, leads to increased risk of colon CA at younger age, no adenoma, also increased risk of endometrial and ovarian CA

Front 42

what is the inheritance pattern of Xeroderma pigmentosum? Gene target? Result?

Back 42

autosomal recessive, defect in nucelotide excision repair, extreme photosensitivty, 2000x risk of skin cancer, +/- neuro abnormalities

Front 43

Describe familial cancer syndromes

Back 43

no clear inheritance pattern, early onset cancers, two or more close relatives, multiple, bilateral tumors

Front 44

list the 6 "pilars" of cancer

Back 44

1. evading apoptosis 2. self-suficiency in growth signals 3. insensitivity to anti-growth signals 4. sustained angiogenesis 5. limitless replicative potential 6. tissue invasion and metastasis

Front 45

give 4 examples of genetic alterations that can lead to cancer

Back 45

1. point mutations 2. balanced translocations 3. gene deletions 4. gene amplification/ over expression

Front 46

a protooncogene must be activated/inactivated to lead to cancer

Back 46

proto-oncogenes must be activated, these genes regulate normal cell growth, activation leads to uncontrolled cell growth

Front 47

a tumor supressor gene must be activated/ inactivated to cause cancer

Back 47

inactivated, tumor supressor genes limit cell growth, inactivation leads to unregulated growth

Front 48

antiapoptosis genes must be activated/ inactivated to cause cancer

Back 48

activated-inhibits the process of apotosis when necessary

Front 49

apoptosis genes must be activated/ inactivated to cause cancer

Back 49

inactivated, presents the activation of apoptosis when necessary

Front 50

define proto-oncogene

Back 50

genes involved in regulating normal cell growth, expression is under tight regulatory control, e.g. (growth factors, GF receptors, signal transducers, transcription factors, cell-cycle regulators)

Front 51

define oncogene

Back 51

a mutated proto-oncogene, leads to autonmous, unregulated cell proliferation, constituative expression

Front 52

How many alleles of a proto-oncogene must be mutated in order for  oncogene properties to occur

Back 52

one, expression of oncogenes is dominant (this is in contrast to mutation of a tumor supressor which has recessive expresison ,both copies must fail for effects to take place, do not confuse with inheritance)

Front 53

SIS gene-class, gene product, alteration, tumor

Back 53

SIS is a proto-oncogene that encodes B-PDGF, a growth factor. Damage to this gene results in overexpression of the growth factor leading to astrocytoma and osteosarcoma

Front 54

ERB B2 gene-class, gene product, alteration, tumor

Back 54

ERB B2 is a proto-oncogene that encoges a tyrosine kinase linked growth factor receptor. Alteration of the gene leads to abnormal constituative expression leading to breast and ovarian tumors

Front 55

Overexpression of the ERB B2 gene can lead to breast and ovarian cancers. What treatment is targeted as this?

Back 55

Tratuzumab (Herceptin) is an anti ERB-B2 antibody, targets host immune system to tumor cell

Front 56

C-kit-class, gene product, alteration, tumor

Back 56

C-kit is an oncogene that encodes a cytokine/ growth factor receptor. A point mutation in this gene leads to overexpression which leads to GIST.

Front 57

Overexpression of C-kit gene leads to overexresion of a growth factor receptor. What treatment is aimed at this

Back 57

Imatinib mesylate (Gleevec) a tyrosine kinase inhibitor

Front 58

Ras-class , gene product, alteration, tumor

Back 58

Ras is a proto-oncogene that encodes a G protein GTPase. A point mutation in RAS leads to a decrease in GTPase activity leading to abnormal signal transduction. This resuls in pancrease & colon (K-ras), Bladder and kidney (H-RAS) and lung cancers

Front 59

c-ABL gene class, product, alteration ,tumor

Back 59

c-ABL is a proto-oncogene that encodes a protien with tyrosine kinase activity (not receptor linked). A translocation of the gene creates a bcr-abl fusi product leading to constituative activity. THis leads to CML and ALL
(ABL=a bad leukemia)

Front 60

c-ABL mutations cause constituative tyrosine kinase activity in the gene product. What treatment is aimed at this

Back 60

Imatinib mesylate (Gleevec) a tyrosine kinase inhibitor

Front 61

Cancers that result from problems with which two genes can be treated with gleevec

Back 61

c-ABL-tyrosine kinase,CML, ALL
c-KIT-TK linked growth factor receptor, GIST

Front 62

MYC-class, gene product, alteration, tumor

Back 62

MYC is a proto-oncogene that encodes for a transcription factor. When the c-MYC gene is translocated to the IgG Gene, it is continuously expressed resulign in Burkitt lymhpoma. When then n-MYC gene  is translocated, it is amplified resulting in Neuroblastoma

Front 63

Cyclin D-1 class, gene product, alteration, tumor

Back 63

Cyclin D-1 is a proto-oncogene. The gene produc activates CDK4 and allows progression through the cell cycle (G1=>S). Translocation of the Cyclin D gene to the IgH gene results in overexpression of cyclin D1 and unregulated progression through the cell cycle. This can lead to mantle cell lymphoma and a small population of plasma cell myeloma and hairy cell lukemia

Front 64

what type of expresion pattern do tumor supressor genes exhibit

Back 64

recessive, mutations in both alleles are required for oncogenesis. examples inclue APC/B catenin (FAP), p53 (Li-Fraumeni), and BRCA 1/2 (breast, ovary)

Front 65

BCL-2 class, gene product, alteration, tumor

Back 65

BCL-2 is an protooncogene that encodes a protein that prevents apoptosis. Translocation to the IgH gene creates a fusion product that is over expressed, Results in follicular lymphoma

Front 66

define direct acting carcinogen

Back 66

highly reactive electrophillic compounds that can react with DNA, RNA, or protein, do not require enzymatic processing, e.g. alkylating agents

Front 67

define indirect acting carcinons

Back 67

metabolism by cytochrome P450 system creates a toxic product

Front 68

explain how P450 polymorphisms can contribute to carcinogenesis. Give two examples

Back 68

CYP1A1-metabolizes polycyclic aromatic hydrocarbons, 10% of caucasians have highly inducible form leading to increased carcinogens, Gluthathione-S-transfrease detoxes, PAH's, 50% of caucasians have deletion=increased carcinogens

Front 69

define initiator

Back 69

chemical that causes permanent DNA mutations, permanent, propagated damage

Front 70

define promoter

Back 70

nontumorigeneic! chemical that enhances the proliferation of cells that have been initiated (mutated), the effect is reversible

Front 71

How do initiators and promoters work together to leads to propagated mutations

Back 71

DNA+initiator=Mutated DNA +promoter=Replicated Mutated DNA

Front 72

Describe polycyclic aromatic hydrocarbons. Structure? Source? Cancers?

Back 72

among the most potent chemical carcinogens, function as initiators, structure= 3+ fused benezne rings, souces=coal, oil, iron and steel foundaries, tobacco smoking, Cancers=lung, bladder, laryngeal, oral cavity, pancrease, esophagous

Front 73

Give two general mechanisms by which oncogenic viruses can  lead to cancer

Back 73

1. Viral proteins distrupt host genes 2. Stimulation of host inflammatory response and subsequent regeneration

Front 74

what is the mechanism by which HPV causes cancer

Back 74

Integration of the viral genome leads to loss of regulation of E6 and E7. E6 affects p53, E7 affects RB and p53, distruption of these tumor supressor genes leads to  cancer

Front 75

What tpes of  cancer does HPV cause

Back 75

carcinoma in situ and squamous cell carcinoma of th eGU tract, anus, and lyarnx (note squamous cell papilloma, squamous dysplasia, and condyloma accumination as well)

Front 76

How does EBV cause cancer

Back 76

promotes polyclonal B-cell proliferation, increases risk for (8;14) translocation

Front 77

what type of cancers are associated with EBV

Back 77

Burkitt lymphoma, CNS lymphoma in AIDS, post transplant lyphoproliferative B cell disorder, NK/T cell lymphoma, nasal, nasopharyngeal carcinoma

Front 78

How does hepatitis cause cancer

Back 78

chronic liver injury leads to regeneration and icnreases the risk of mutation, Hep B also expresses HBx protein which activates growth genes and inhibits p53

Front 79

How does H. pylori cause cancer

Back 79

host inflammatory response leads to carcinogenesis, regeneration, metaplasia, dysplasia, carcinoma

Front 80

What type of cancers are associated with H. pylori

Back 80

gastric adenocarcinoma, MALToma

Front 81

How do host CD8 t cells provide an anti-tumor defense

Back 81

the products of the oncogene or mutated protein are presented by the tumor cells to the CD8 cell via MHC1

Front 82

WHat is the mechanism of Rituxan

Back 82

monoclonal antibody agaist CD20, used to reat B cell lymphoma, non-Hodgkin lymphoma

Front 83

How do tumors evade host CD8 response

Back 83

imunosupress the host, down regulate/ alter MHC, failure to produce tumor antigen, inhibition of T cell activation

Front 84

describe cachexia

Back 84

wasting disease, progressive loss of body fat and lean body mass, profound weakness and anorexia, cytokine mediated by TNF, IL-1, IFN-gamma

Front 85

Describe the hematologic abnormalities associated with cancer

Back 85

1. Anemia (of chronic disease, secondary blood less, nutritional, infiltrative process) 2. Hypercoagulability (DIC b/c of relese of thromboplastin from tumor)

Front 86

what are paraneoplastic syndromes

Back 86

non-hormonal or hormonal effects of a tumor, unreleated to local spread or metastasis, 10% of cancer pts.

Front 87

describe cushing syndrome in terms of paraneoplastic disease. WHich cancers is it characteristic of?

Back 87

excess cortisol because tumor causes release of ACTH or ACTH like substance, characteristic of small cell lung CA, pancreatic CA, and neuronal tumors

Front 88

Describe hypercalcemia in terms of paraneoplastic disease. which cancers?

Back 88

production of parathyorid hormone related protein leads to hypercalcemia, most common PNPS, esp. squamous cell carcinoma of the lung, breast, kidney and ovarain CA

Front 89

describe the paraneoplastic syndromes associated with renal cell CA

Back 89

"Great mimicker" polycythemia, hpercalcemia, hypertension, cushing syndrome, femini/masculi nization, eosinophilia

Front 90

Describe the paraneoplastic syndromes assocated with lung CA

Back 90

1-10% of all lung CA, hyponatremia secondary to ADH, cushing syndrome, Hyper/hypo calcemia, gynecomastia,

Front 91

lifetime risk or breast CA

Back 91

12.1%, 1 in 8, most common cancer in US women, 2nd most common cause of cancer death

Front 92

Risk factors for breast CA

Back 92

strong-female, inherited mutation, affected relativies, prior breast CA, atypical hyperplasia;

Moderate-1 first degree relative, chest radition, high bone density;

minor-first preg >30, early menarche, late menopause, no babies/ breastfeeding, oral contraceptives, HRT, obesity;

other=physical inactivity, alochol, hieght, high SES, shift work

Front 93

Next steps after clinical suspicion of breast CA

Back 93

core needle biopsy for typing and grade, fine needle aspiration of axillary lymph node

Front 94

What type of cancers are most breast CA's

Back 94

adenocarcinomas, aprox 2/3 are invasive ductal carcinoma, 5-15% are invasive lobular carcinoma

Front 95

describe the prognostic indicators used in breast CA

Back 95

1. morphologic (size, lymph nodes, type, grade, vascular/ lymphatic invasion) 2. ER/PR status 3. HER2 status 4. oncotype

Front 96

describe breast CA survial by stage

Back 96

0,1=100% 2= 86%, 3=57%, 4=20%

Front 97

define tumor grade

Back 97

extent to which tumor cells morphologicall and functionally resemble the normal tissue counterpart

Front 98

which receptors are tested for in most breast cancers

Back 98

1. ER/PR  (steroid hormone receptors) 2. Her-2 (EGFR family)

Front 99

Give some examples of disease that lead to a heritable risk for breast cancer

Back 99

1. BRCA 1/2 mutations 2. Li-Fraumeni syndrome (p53) 3. Cowden syndrome (PTEN gene mutation) 4. Peutz-Jeghers syndrome 5. ataxia telangectasia

Front 100

what % of breast CA are due to BRCA 1/2 mutations, what is the risk for female carriers

Back 100

3% of breast CAs, 60-80% lifetime risk, develop 20 yrs younger tend to be high grade ER/PR negative