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S3.M2.Path3
Neoplasia5-9
78
Pathology
Professional
06/17/2010

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Term
what types of CANCERS have a declining death rate?
Definition
MALES-->lung, prostate and colon cancer, stomach
FEMALES-->breast and colorectal cancer, stomach
Term
what ENVIRONMENTAL FACTORS can lead to the following cancers:
BLADDER
MESOTHELIOMA
CANCER OF OROPHARYNX AND LUNG
Definition
BLADDER-->aniline dyes, smoking
MESOTHELIOMA-->asbestos
CANCER OF OROPHARYNX AND LUNG-->smoking, asbestos, radon (also arsenic and nickel)
Term
what chemical in PLASTICS are especially dangerous? what does this give rise to?
Definition
vinyl chloride-->angiosarcoma of the liver
Term
what affect does AGE of patients have on cancer?
Definition
usually more common in older patients, but some types of cancers are very prevalent and dangerous to younger populations (leukemia, lymphoma, retinoblastoma, rhabdomyosarcoma)
Term
what are some characteristics of DYSPLASIA?
Definition
-Loss of uniformity
-Loss of architecture
-Pleomorphism
-Hyperchromasia
-Abnormal located mitosis
*DIFFERENT TERMS USED IN GRADING OF CERVICAL DYSPLASIA (can be mild moderate or severe)
Term
what is the worst kind of DYSPLASIA?
Definition
“Carcinoma in situ”-->FULL THICKNESS dysplasia
BASEMENT MEMBRANE IS INTACT
Term
what is INVASION?
Definition
erosion of basement membrane, cells go into the vascular channel
Term
what cancers can the following findings lead to:
ORAL LEUKO-PLAKIA?
Definition
squamous cell carcinoma
Term
what cancers can the following findings lead to:
BARRAT'S ESOPHAGUS?
Definition
AdeoCA of the esophagus
Term
what cancers can the following findings lead to:
Chronic atrophic gastritis of pernicious anemia?
Definition
gastric adenocarcinoma
Term
what cancers can the following findings lead to:
CHRONIC ULCERATIVE COLITIS?
Definition
ADENOCARCINOMA OF THE COLON
Term
what cancers can the following findings lead to:
HEPATITIS B or C?
Definition
hepato-cellular carcinoma
Term
***what is the function of the BRCA genes?***
Definition
DNA repair--> mutation leads to breast and ovarian cancers-->involves HYPERMETHYLATION of the PROMOTER
Term
what cancers can the following findings lead to:
Solar keratosis of skin
Definition
skin cancer--> usually squamous cell carcinoma
Term
what are the MECHANISMS involved in the activation of an oncogene?
Definition
-point mutations
-chromosomal translocations
-gene amplification
Term
what type of mutations affect RAS? what type of cancers does this lead to?
Definition
point mutation, leads to colon or pancreatic cancer
Term
***Which are the important chromosomal translocations? ***
Definition
-C-ABL-->Chronic myelogenous leukemia (CML)
-APML or AML-M3-->Acute pro-myelocytic leukemia
-C-MYC-->Burkitt's lymphoma (8-14)
Term
what is the Rb gene? when it is functioning properly, what is it doing?
Definition
tumor supressor-->Regulates G1-S phase
normal function is to block E2F-->normally phosphorylated
Term
what type of cancer are seeing a RISE in DEATH RATE?
Definition
hepato-cellular cancer
Term
what are ASBESTOS BODIES?
Definition
asbestos that has entered the lung and has been engulfed by macrophages forming a brownish fibrous mass
Term
cancer GENE involvement: RB, APC, P53, NF1&2
Definition
*all are tumor suppressors
RB--> retinoblastoma
APC-->adenomatous polyposis colon cancer
p53--> Li Fraumeni (multiple cancers
NF1&2--> neurofibromatosis
Term
what condition should you think of with a history of multiple cancers of the SKIN? ENDOCRINE? UNRELATED CANCERS?
Definition
skin-->xeroderma pigmentosum
endocrine--> multiple endocrine neoplasia (MEN1&2)
unrelated cancer--> Li Fraumeni syndrome
Term
main GROWTH FACTOR mutation that can cause cancer (type)?
Definition
SIS (PDGFbeta)--> astrocytoma
Term
main GROWTH FACTOR RECEPTOR mutations that can cause cancer (type)?
Definition
-ERBB1&2 (HER2/NEU)-->Breast and ovarian cancer (poor prognosis)
*think of this if no FAMILY HISTORY of breast cancer
-RET--> multiple endocrine neoplasia (MEN)
Term
main SIGNAL TRANSDUCTION PROTEIN mutations that can cause cancer (type)?
Definition
KRAS-->PANCREATIC and colon cancer (POINT MUTATION)
ABL-->chronic myeloid leukemia (translocation 9-22)
Term
main NUCLEAR REGULATORY PROTEIN mutation that can cause cancer (type)?
Definition
C-MYC-->BURKITT'S LYMPHOMA (B cells) translocation 8-14 (growth in the jaw***)
N-MYC-->neuroblastoma (primitive neural crest cell proliferation) amplification in children
Term
what DRUG is used to treat AML? what mechanism is it affecting?
Definition
IMATINIB-->tyrosine kinase mutations
Term
what type of CANCER is caused by a BCL2 mutation?
Definition
follicular lymphoma--> BCL2 amplification (14:18 translocation) *MOST COMMON INDOLENT CANCER-->B cell lymphoma
Term
what cancers are associated with RB gene mutations?
Definition
retinoblastoma, osteosarcoma--> usually in children-->BOTH Rb genes must be lost
Term
what TUMOR SUPRESSOR gene is involved in kidney cell carcinoma?
Definition
VHL-->Von Hippel Lindau syndrome*
Term
what is the role of Viral proteins E6 and E7 in cancer?
Definition
bind to and inhibit functions of Rb and p53 tumor suppressors
Term
What is the importance of the INK4a /ARF gene?
Definition
familial MELANOMA involvement
Term
NF-1 affects what protein?
Definition
GAP--> GTPase activation protein)
Term
genes involved in HEREDITARY NON-POLYPOSIS COLON CANCER SYNDROME-
Definition
MSH2 (2p16)
MLH1(3p21)
Term
how is TELOMERASE tied in with cancer?
Definition
presence of telomerase in 90% of tumors--> Maintenance of telomere strength-->Prevention of cell cycle arrest and apoptosis
Term
how does INVASION of the extracellular matrix take place?
Definition
1-Detachment of tumor cells from each other (E cadherins not produced)
2-Attachment to matrix component (increase in laminin)
3-Degradation of ECM (protease action)
4-Migration of tumor cells
Term
Carcinogenesis is a multistep process-->Accumulation of successive mutations
Definition
Term
what is WT1&2?
Definition
WILM'S TUMOR--> supressor gene, aggressive childhood kidney tumors
Term
what is the Rb protein doing in the normal state?
Definition
normally HYPOphosphorylated--> inhibits E2F-->Cyclin D induced phosphorylation of Rb which causes E2F activation
Term
how does the APC protein function under normal circumstances?
Definition
APC acts to downregulate Beta catenin whose job is to drive cycle forward
Term
what is the WARBURG EFFECT?
Definition
cancer cells shift their ENERGY METABOLISM from AEROBIC to ANAEROBIC (glycolysis) in order to gain growth advantage-->occurs even if O2 is present--> detectable via PET scan
Term
what are CHEMICAL CARCINOGENS?
Definition
highly reactive electrophiles that remove electrons from DNA, RNA or proteins - Cause cell damage
*either DIRECT or INDIRECT acting
Term
what is an INDIRECT vs. a DIRECT carcinogen?
Definition
INDIRECT needs metabolic conversion whereas DIRECT doesn't
Term
what does SNUFF cause? what type of cancer did CHIMNEY SWEEPS get historically?
Definition
snuff-->nasal polyps
chimney sweeps--> scrotal cancer-->told to bathe after work, greatly reduced cancers
Term
***what is an AMES TEST?
Definition
test that determines if a substance is a CARCINOGEN or not
Term
what chemical in smoke and smoked meats is a carcinogen? what cancers does this cause?
Definition
polycylic aromatic hydrocarbons--> cause lung and bladder cancer
Term
what cancer do Aromatic Amines and Azo Dyes cause?
Definition
liver --> hepatocellular carcinomas
Term
what does β-naphthylamine (aniline dyes and rubber industry) cause?
Definition
bladder cancer
Term
what are examples of PROMOTERS?
Definition
phorbol esters and phenobarbital
Term
where is AFLOTOXIN B1 found? what is it?
Definition
NATURAL CARCINOGEN from FUNGUS found on improperly stored CORN
Term
PROMOTERS of chemical carcinogenesis:
Estrogen-
Diethyl Stilbesterol-
High dietary fat-
Definition
Estrogen- liver cancer
Diethyl Stilbesterol- endometrial cancer, vaginal caner in offspring
High dietary fat-colon cancer
Term
what type of UV is the most dangerous?
Definition
UV B--> can cause skin cancer, pyrimadine dimers
Term
radiation induced neoplasms:
atomic bombs-
x ray workers-
radium-
Definition
atomic bombs- leukemia
x ray workers- skin cancers
radium- osteosarcoma
Term
what is the EPSTEIN BARR VIRUS?
Definition
c myc, 8:14 translocation, Burkitt's lymphoma and Nasopharyngeal carcinoma
Term
how can BURKITT'S LYMPHOMA be identified histologically?
Definition
"starry sky" appearance with MACROPHAGE accumulation
Term
what causes KAPOSI SARCOMA? what patients normally see this type of cancer?
Definition
herpes virus (HHP 8)--> seen in AIDS patients
Term
what does Human T-cell leukemia virus Type 1 (HTLV-1) cause?
Definition
T-cell leukemia/lymphomas
Term
How is Helicobacter pylori infection associated with neoplasia?
Definition
Gastric lymphoma
MALT lymphomas; marginal zone lymphomas
Gastric carcinoma
Term
how is HYPERCALCEMIA a symptom of para-neoplastic syndrome?
Definition
squamous cell carcinoma of the lung--> release of PTH RELATED peptide (NOT PTH!!!)--> hypercalcemia
Term
what is a PARA-NEOPLASTIC SYNDROME? examples
Definition
Distant effects of a tumor unrelated to primary tumor or metastasis-->HORMONE is overproduced
-endocrinopathies-->ACTH
-hyponatremia SIADH-->ADH
-carcinoid syndrome-serotonin
-acanthosis nigricans
Term
how is cancer diagnosed?
Definition
PHYSICAL EXAM->MORPHOLOGIC METHODS (biopsy, FNAC,etc)-->MOLECULAR METHODS (flow cytometry, DNA probe)-->BIOCHEMICAL ASSAY (tumor markers)
Term
How would you know that a tumor is EPITHELIAL in origin?
Definition
If the tumor is positive for CYTOKERATIN, keratin or epithelial membrane antigen (EMA), it indicates an epithelial origin
Term
What does VEMINTIN positivity indicate?
Definition
MESENCHYMAL origin
Term
what would Positive S-100, HMB-45 and melanin be a sign of?
Definition
MELANOMA
Term
Which IHC marker would you use if you suspected the tumor to be NEURO-ENDOCRINE in origin?
Definition
-Neuron-specific enolase (NSE)
-Chromogranin
-Bombesin
-Synaptophysin
Term
What is a TUMOR MARKER?
Definition
substance found in the blood, urine, or body tissues that can be elevated in cancer, among other tissue types
Term
the following TUMOR MARKERS are indications of what type of cancer?
CEA-
beta HCG-
PSA-
Definition
CEA-->Carcino-embryonic antigen-->colon cancer
Beta HCG--> choriocarcinoma
PSA-->prostate specific antigen-->prostate cancer
Term
What is carcinogenesis?
Definition
Transformation of normal to neoplastic cells--> caused by exogenous or endogenous factors
Term
What are Carcinogenic Agents?
Definition
Agents that cause genetic damage and induce neoplastic change-->chemical carcinogens, radiation, oncogenic viruses/microbes
Term
What are the steps involved in Chemical carcinogenesis?
Definition
INITIATION- agents that directly or indirectly cause permanent DNA damage
PROMOTION- passing on of damaged DNA trait to subsequent generations of cells--> leads to tumorigenesis
**INITIATION must be followed by PROMOTION
Term
what cancers do AMINES and NITROSAMINES lead to?
Definition
Gastric carcinoma--> converted to nitrites in the stomach by bacteria, common in JAPANESE population
Term
Which subtypes of HPV are associated with cancer?
Definition
-benign genital warts (6,11 low risk)
-cervical cancer (16,18,31 high risk)
-E6=p53 mutation
-E7=Rb mutation
Term
HORMONAL carcinogenesis:
ESTROGEN-
CONTRACEPTIVES-
ANABOLIC STEROIDS-
Definition
ESTROGEN-breast and cervical cancer
CONTRACEPTIVES- liver tumors
ANABOLIC STEROIDS- liver tumors
Term
What are the clinical features in a patient with a tumor?
Definition
-Local or hormonal effects
-Cancer cachexia
-Para-neoplastic syndromes
Term
When should you use IHC?
Definition
when you do not know the CELL OF ORIGIN of the tumor--> UNDIFFERENTIATED or POORLY DIFFERENTIATED tumors
Term
the following TUMOR MARKERS are indications of what type of cancer?
alpha FP-
CA-125-
NSE-
Definition
alpha FP-->alpha fetoprotein--> hepato-cellular carcinoma
CA-125-->ovarian carcinoma
NSE-small cell carcinoma of the lung
Term
the following TUMOR MARKERS are indications of what type of cancer?
calcitonin-
CA 19-9-
CA 15-3-
Definition
calcitonin-Medullary thyroid carcinoma
CA 19-9- Colon cancer, pancreatic cancer
CA 15-3-Breast carcinoma
Term
name some important EM findings in cancer-
Definition
-tonofilaments
-weibel palade bodies
-neuro-secretory granules
-melanosomes
-Birbeck granules
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