Ch 3 Pathoma - Neoplasia Flashcards
Neoplasia is new tissue growth that is ____, ______, and ______; these features distinguish it from hyperplasia and repair
unregulated, irreversible, monoclonal
______ was historically determined by glucose-6-phosphate dehydrogenase enzyme isoforms, which is present on which chromosome?
clonality; x chromosome
only 1 isoform is present in neoplasia, which is monoclonal
In addition to G6PD, clonality can also be determined by _________ isoforms (also present on x chromosome)
androgen receptor
Clonality of B lymphocytes is determined by __________.
Immunoglobulin (Ig) light chain phenotype
Normal kappa to lambda light chain ratio of B cells is _____. Ratio can be either ____ or ____ in lymphoma, which is monoclonal
3:1; >6:1 or 1:3
Changes in the normal ratio of G6PD isoforms or kappa:lambda light chains means there is ______.
Monoclonal proliferation = neoplasia
Most common cancers by incidence in adults are:
(1) breast/prostate
(2) lung
(3) colorectal
not including skin cancer
Most common cancers by morality in adults:
(1) lung
(2) breast/prostate
(3) colorectal
Approximately how many divisions must occur before the earliest clinical symptoms of neoplasia arise?
30 divisions - each division results in increased mutations (explains why cancers that are detected later have a poorer prognosis)
Screening seeks to catch ____ before it becomes carcinoma or carcinoma before ______.
dysplasia (precancerous change); clinical symptoms arise
Carcinogens are agents that ______, increasing risk for cancer. Important carcinogens include these three categories.
damage DNA; chemicals, oncogenic viruses, radiation
Aflatoxins are derived from _______. The associated cancer that develops is _____.
Aspergillus; hepatocellular carcinoma.
Aspergillum can contaminate stored rice and grains
______ agents in chemotherapy can cause leukemia/lymphoma as a side effect
Alkylating
Alcohol can predispose you for these types of cancer (4)
squamous cell carcinoma of oropharynx and upper esophagus; hepatocellular carcinoma; and pancreatic carcinoma
______ causes squamous cell carcinoma of the skin, lung cancer, and angiosarcoma of the liver
Arsenic (present in cigarette smoke)
Women in the fields used to put arsenic on their skin since it made it paler, to hide their tan
Cigarette smoke increases risk of these 6 cancers. _______ found in cigarette smoke are particularly carcinogenic.
Carcinoma of the oropharynx, esophagus, lung, kidney, bladder, and pancreas
Polycyclic hydrocarbons
______ are found in smoked foods and increase risk of stomach cancer (intestinal type)
Nitrosamines
responsible for high rates of stomach carcinoma in Japan
______ increases risk of urothelial carcinoma of bladder
Napthylamine (derived from cigarette smoke)
Vinyl chloride increases your risk of _______. Can occur due to occupational exposure. It’s used to make PVC pipes
angiosarcoma of liver
These four chemical agents increase your risk for lung carcinoma and exposure is often occupational.
Nickel, chromium, beryllium, silica
EBV increases your risk for these cancers (3)
Nasopharyngeal carcinoma (chinese male or african person), Burkitt lymphoma, and CNS lymphoma (in AIDS)
Kaposi sarcoma is a tumor of ______. Caused by which virus? Clinical presentation and 3 groups predisposed.
endothelial cells; HHV-8;
purplish raised lesions on skin - seen in older european males (excise it) and AIDS pts (treat with antiretorvirals - aka tx the virus), and transplant pts (decrease their immunosuppression slightly)
______ increases risk of adult t cell leukemia/lymphoma.
HTLV-1 (human t cell leukemia virus)
High risk HPV (name 4 high risk subtypes) increases risk of these 5 cancers
16, 18, 31, 33
squamous cell carcinoma of vulva, vagina, anus, and cervix; and adenocarcinoma of cervix
Ionizing radiation increases risk of these three cancers. Exposure occurs from ______ and it generates hydroxyl free radicals
AML, CML, papillary carcinoma of the thyroid
nuclear reactor accidents and radiotherapy
Non-ionizing radiation increases risk of these three cancers. Exposure occurs from _____ which results in formation of _______ normally excised by _______.
Basal cell carcinoma, squamous cell carcinoma, melanoma of skin
UVB sunlight; pyrmidine dimers in DNA; restriction endonucleases (xeroderma pigmentosum has abnormal restriction endonucleases –> increased risk of skin cancer)
______ are essential for cell growth and differentiation. Mutations form oncogenes that lead to unregulated cell growth
proto-oncogenes
Name five categories of oncogenes
Growth factors, growth factor receptors, signal transducers, nuclear regulators, and cell cycle regulators
_______ overexpression leads to astrocytoma. It does this in an autocrine fashion.
platelet derived growth factor
growth factors induce cellular growth
Name three growth factor receptor oncogenes and the cancer they are associated with
1) ERBB2 (HER2/neu) = breast carcinoma
2) RET (neural GFR) = MEN2A/B and sporadic medullary carcinoma of the thyroid (MEN = multiple endocrine neoplasm
3) KIT (stem cell GFR) = GI stromal tumor
Name two signal transducer oncogenes and the cancer they are associated with
1) RAS (GTP- binding protein) = Carcinomas, melanoma, and lymphoma
2) ABL (tyrosine kinase - 9:22 translocation with BCR) = CML and adult ALL
Name three nuclear regulator oncogenes and the cancer they are associated with
1) c-MYC (t8:14 involving IgH) = Burkitt lymphoma
2) N-MYC = Neuroblastoma
3) L-MYC = Lung carcinoma (small cell)
They are all TF’s; IgH is normally overexposed so translocation causes oncogene in c-MYC
Name two cell cycle regulators (proteins that assist mvmt through the cell cycle) and the cancer they are associated with
1) CCND1 (cyclin D1) (t11:14 involving IgH) = mantle cell lymphoma
2) CDK4 (cyclin dependent kinase) = melanoma
____ is normally associated with GFRs in an inactive GDP bound state. Receptor binding causes GDP to be replaced with GTP activating it. Once it is activated, it sends growth signals to the nucleus. It inactivates itself by cleaving GTP to GDP, which is augmented by ____. Mutation of the first thing, inhibits activity of the second thing, prolonging the active state and increasing growth signals
RAS; GAP (GTPase activating protein)
____ and ____ regulate progression from G1 to S phase and are classic tumor suppressor genes
p53; Rb
In response to DNA damage, p53 slows the cell cycle and ______. If DNA repair is not possible, it induces apoptosis by up regulating _____, which disrupts Bcl2
upregulates DNA repair enzymes; BAX
p53 loss is seen in >50% of cancers
Knudson two hit hypothesis
both copies of a tumor suppressor gene must be knocked out for tumor formation
Li Fraumeni syndrome involves a _____ mutation in the ____ gene and is characterized by the propensity to develop multiple types of carcinomas and sarcomas
germline; p53
Rb holds the ___ transcription factor, which is necessary for transition to the S phase. It is released when Rb is phosphorylated by the _____.
E2F; cyclinD/cyclin-dependent kinase 4 (CDK4) complex
mutation in Rb leads to constitutively free E2F allowing progression through the cell cycle
Sporadic mutation (both hits are somatic) of Rb is characterized by ______. Germline mutation results in _______ (2nd hit is somatic) characterized by _____ and ____.
unilateral retinoblastoma; familial retinoblastoma; bilateral retinoblastoma; osteosarcoma
Bcl2 is overexpressed in ______. There is a t14;18 that moves Bcl2 to the Ig heavy chain locus (on 14) resulting in increased Bcl2, and prevention of apoptosis.
follicular lymphoma
B cells that normally undergo apoptosis during somatic hypermutation in the LN germinal center accumulate –> lymphoma
Other important features of tumor development - often you will see tumors with upregulated ____, which preserves telomeres; increased ___ and ___ which are needed for angiogenesis, and down regulation of _____ so tumor cells can evade immune surveillance
telomerase; FGF and VEGF (fibroblast FG and vascular endothelial GF); MHC class I
For tumor invasion/spread, tumor cells downregulate ______ (a cellular adhesion molecule) –> dissociation of cells –> cells attach to _____ and destroy the basement membrane via collagenase. Cells then attach to _____ in the ECM, and spread locally. Entrance into ____ or _____ allows for metastasis
E-cadherin (normally attaches epithelial tumor cells to one another); laminin; fibronectin; vascular or lymphatic spaces
_____ spread is characteristic of carcinomas and ____ spread is characteristic of sarcomas and some carcinomas (routes of metastasis)
Lymphatic; hematogenous
Name the classic four carcinomas that spread hematogenously
RCC (invades renal vein); HCC (invades hepatic vein), follicular carcinoma of the thyroid; choriocarcinoma (placental tissue cancer)
Seeding of body cavities is characteristic of ____, which often involves the peritoneum (omental caking)
ovarian carcinoma
Clinical characteristics of benign tumors (4)
slow growing, well circumscribed, distinct, mobile
Clinical characteristics of malignant tumors (4)
rapid growing, poorly circumscribed, infiltrative, fixed (to surrounding tissues and local structures)
Classic histological features of benign tumors (6)
1) Organized growth; 2) Uniform nuclei; 3) Low nuclear:cytoplasmic ratio (lots of cytoplasm); 4) Minimal mitotic activity; 5) Lack of invasion; 6) No metastatic potential
tend to be well differentiated
Classic histological features of malignant tumors (5)
1) disorganized growth (loss of polarity - poorly differntiated); 2) nuclear pleomorphism (many sizes) and hyperchromasia (dark blue nuclei); 3) high nuclear:cytoplasmic ratio (lots of nucleus); 4) high mitotic activity with atypical mitosis; 5) invasion (through BM or into local tissue)
_____ is used to characterize tumors that are difficult to classify on histology. It involves taking an antibody for a target, labeling it with a brown stain, and seeing if it binds to cells –> helps identify proteins that could help sub classify the cell type
Immunohistochemistry
Intermediate filament immunohistochemical stain. Name the tissue type based on the IF type. Keratin GFAP Neurofilament Desmin Vimentin
Epithelium Neuroglia Neurons Muscle Mesenchyme
Immunohistochemical stain. Name the tissue type based on the positive stained item listed below Chromogranin S-100 PSA ER Thyroglobulin
Neuroendocrine cell (small cell carcinoma of lung and carcinoid tumors)
Melanoma, Schwannoma and Langerhans cell histiocytosis
Prostatic epithelium
Breast epithelium (ER = estrogen receptor)
Thyroid follicular cells
Serum tumor markers are useful for these 3 things. Elevated levels require ____ for diagnosis of carcinoma
Screening, monitoring response to treatment, monitoring recurrence
tissue biopsy
______ (high/low grade) tumors resemble normal parent tissue and have a good/poor prognosis
well differentiated; low grade; good
______ (high/low grade) tumors do not resemble parent tissue and have a good/poor prognosis
poorly differentiated; high grade; poor
Staging of cancer is an assessment of both ___ and ___ of a cancer. The most important prognostic factor of TNM staging is ___.
size; spread; M - metastasis
