Ch 3 Pathoma - Neoplasia Flashcards by Jenny Schreiber

Neoplasia is new tissue growth that is ____, ______, and ______; these features distinguish it from hyperplasia and repair

unregulated, irreversible, monoclonal

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______ 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

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In addition to G6PD, clonality can also be determined by _________ isoforms (also present on x chromosome)

androgen receptor

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Clonality of B lymphocytes is determined by __________.

Immunoglobulin (Ig) light chain phenotype

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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

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Changes in the normal ratio of G6PD isoforms or kappa:lambda light chains means there is ______.

Monoclonal proliferation = neoplasia

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Most common cancers by incidence in adults are:

(1) breast/prostate
(2) lung
(3) colorectal

not including skin cancer

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Most common cancers by morality in adults:

(1) lung
(2) breast/prostate
(3) colorectal

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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)

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Screening seeks to catch ____ before it becomes carcinoma or carcinoma before ______.

dysplasia (precancerous change); clinical symptoms arise

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Carcinogens are agents that ______, increasing risk for cancer. Important carcinogens include these three categories.

damage DNA; chemicals, oncogenic viruses, radiation

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Aflatoxins are derived from _______. The associated cancer that develops is _____.

Aspergillus; hepatocellular carcinoma.

Aspergillum can contaminate stored rice and grains

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______ agents in chemotherapy can cause leukemia/lymphoma as a side effect

Alkylating

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Alcohol can predispose you for these types of cancer (4)

squamous cell carcinoma of oropharynx and upper esophagus; hepatocellular carcinoma; and pancreatic carcinoma

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______ 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

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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

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______ are found in smoked foods and increase risk of stomach cancer (intestinal type)

Nitrosamines

responsible for high rates of stomach carcinoma in Japan

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______ increases risk of urothelial carcinoma of bladder

Napthylamine (derived from cigarette smoke)

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Vinyl chloride increases your risk of _______. Can occur due to occupational exposure. It’s used to make PVC pipes

angiosarcoma of liver

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These four chemical agents increase your risk for lung carcinoma and exposure is often occupational.

Nickel, chromium, beryllium, silica

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EBV increases your risk for these cancers (3)

Nasopharyngeal carcinoma (chinese male or african person), Burkitt lymphoma, and CNS lymphoma (in AIDS)

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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)

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______ 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