Principles of Neoplasia Flashcards
What is the normal ratio of kappa to lambda light chains for immunoglobulins? How is this used differentiate between neoplasia vs. hyperplasia?
Normal ratio is 3:1 for kappa:lambda.
In an individual who presents with enlarged lymph node, can be one of three differentials: metastasis, reactive hyperplasia (due to infection), or lymphoma. If a study was done to see that there was proliferation of cells, then either reactive hyperplasia or lymphoma.
If we run a test to look at the ratio of kappa:lambda and it deviates from the normal ratio, then that would be an indication of monoclonal proliferation (e.g. neoplasia) vs. a polyclonal proliferation (e.g. hyperplasia).
Pathoma, page 23
Provide the goal of each screening test:
1) Pap smear
2) Mammography
3) PSA and digital rectal exam
4) Hemoccult test and colonoscopy
1) Detect cervical dysplasia (CIN) before it becomes carcinoma/malignant
2) Detect in situ breast cancer (DCIS) before it invades/becomes invasive carcinoma before it becomes clinically palpable–look for calcifications!
3) Detects prostate carcinoma before it spreads
4) Detects colonic adenoma before it becomes colonic carcinoma or carcinoma before it spreads
Pathoma, page 24
Cancers associated with ionizing vs. non-ionizing radiation?
Ionizing radiation (e.g. nuclear reactor accidents, radiotherapy) generates hydroxyl free radicals from water in tissue –> damages DNA –> AML, CML, papillary carcinoma of thyroid
Non-ionizing radiation (e.g. UVB sunlight) generates pyrimidine dimers in DNA (normally excised by restriction endonucleases but can be overwhelmed with excessive exposure to UVB) –> BCC, SCC, melanoma
Pathoma, page 25
How are the ratios of glucose-6-phosphate dehydrogenase isoforms different between hyperplasia and neoplasia?
In normal physiological hyperplasia, normal ratio of active isoforms is 1:1 of any tissue (polyclonal, cells derived from multiple cells). In neoplasia, ratio of active isoforms deviate from 1:1, indicative of monoclonality (or derivation of cells from one single malignant cell).
Pathoma, page 23
How does p53 act as a tumor suppressor gene/in response to DNA damage?
p53 regulates progression of G1 to S phase.
In response to DNA damage, p53 slows cell cycle and upregulates DNA repair enzymes. If repair is not possible, p53 upregulates BAX, which disrupts Bcl2 to induce apoptosis (cyt c leaks to activate caspases).
Pathoma, page 27
What is the Knudson two-hit hypothesis in regards to p53? What is the Li-Fraumeni syndrome?
The two-hit hypothesis states that BOTH copies of p53 must be knocked out for tumor formation.
Li-Fraumeni syndrome is a condition in which there is an initial germline mutation and subsequent somatic mutation to knock out the second p53 copy, resulting in propensity to develop multiple types of carcinomas and sarcomas.
Pathoma, page 27
How does Rb regulate progression from G1 to S phase as a tumor suppressor gene?
Rb “holds” the E2F transcription factor, which is necessary to transition to S phase. E2F is released once RB is phosphorylated by cyclinD/cyclin-dependent kinase 4 (CDK4) complex.
Pathoma, page 27
Sporadic vs. germline mutations for retinoblastoma?
Sporadic mutation, where both “hits” are somatic, characterized by unilateral retinoblastoma. This is due to the nature of the unlikelihood of TWO sporadic mutation to occur in same cell.
Germline mutations, where first hit is germline and second is somatic to result in familial retinoblastoma, is characterized by BILATERAL retinoblastoma and osteosarcoma.
Pathoma, page 27
t(14;18) translocation?
Moves Bcl2 to IgH heavy chain locus, resulting in overexpression of Bcl2. This results in further stabilization of mitochondrial membrane and prohibition of apoptosis –> B cells that normally undergo apoptosis during somatic hypermutation in lymph node germinal center accumulate –> follicular lymphoma.
Pathoma, page 27
Progression of epithelial tumor cells –> invasion –> spread
Epithelial tumor cells normally attached to one another via cellular adhesion molecules E-cadherin. Downregulation results in dissociation of cells, which then attach to laminin and destroy basement membrane (type IV collagen) via collagenase.
Cells then break through basement membrane and attach to fibronectin of extracellular matrix and spread locally.
Entrance into vascular/lymphatic spaces allow for metastasis.
Pathoma, page 28
Routes of metastasis and associated cancers?
Lymphatic spread (initial spread to regional draining lymph node) characteristic of carcinomas.
Hematogenous spread characteristic of sarcomas and SOME carcinomas. Renal cell carcinoma through renal vein invasion. Hepatocellular carcinoma through hepatic vein invasion. Follicular carcinoma of thyroid and choriocarcinoma are also exceptions.
Seeding of body cavities characteristic of ovarian carcinomas, often involving peritoneum to result in “omental caking.”
Pathoma page 28
Hallmark of malignancy?
METASTATIC POTENTIAL–benign tumors NEVER metastasize!
Pathoma, page 29
What is the corresponding IHC stain ( specifically for the intermediate filament component) for each of the following tissue types?
Epithelium Mesenchyme Muscle Neuroglia Neurons
Epithelium - Keratin Mesenchyme - Vimentin Muscle - Desmin Neuroglia - GFAP Neurons - Neurofilament
Pathoma, page 29
What tissue types correspond with the following stains? Which cancers are you assessing for?
PSA ER Thyroglobulin Chromogranin S-100
PSA - prostatic epithelium
ER - breast epithelium
Thyroglobulin - Thyroid follicular cells
Chromogranin - Neuroendocrine cells (small cell carcinoma of lungs, carcinoid tumors)
S-100 - melanoma, Schwannoma, Langerhans cell histiocytosis
Pathoma, page 29
