Neoplasia, Oncology

Definitions

• Neoplasia: a disorder of cell growth triggered by a series of acquired mutations affecting a single cell and its clonal prodigy. The new growth produced by these mutations is called a neoplasm. 
• grade: degree of differentiation of the cells
• stage: clinical system to help determine the prognosis of a patient with a neoplasm
• Tumor (T): how large is the primary tumor?
• Node (N): has the tumor spread to regional lymph nodes?
• Metastasis (M): is there distant spread (metastasis) of the tumor?
• Oncology: the study of tumors or neoplasms
• Tumor: 1. the swelling caused by inflammation, 2. new growth (i.e. neoplasm)
• Desmoplasia: when parenchymal cells stimulate the stroma (connective tissue, blood vessels, adaptive immune cells) become abundant and collagenous. 
• Angiogenesis: formation of new blood vessels to allow the tumor to grow larger. 
• Benign tumors: localized, can be removed with surgery, and the gross and microscopic appearance is not worrying; usually grow slow 
• capsule: rim of compressed fibrous tissue surrounding benign tumors; consists of extracellular matrix. As the benign tumor expands it exerts pressure on surrounding tissue resulting in hypoxic damage which activates fibroblasts which deposit the extracellular matrix that makes the capsule. The encapsulated tumor is moveable, palpable and easily removed with surgery. 
• Metaplasia: reversible replacement of a differentiated cell type with another cell type; often an adaptive response to stress
• Dysplasia: reversible, growth of cells in a disordered fashion with loss of normal cell shape, size, and orientation. 
• Malignant tumors: invasion, infiltration into surrounding tissues and spread to distant sites; not localized; poor demarcation between healthy tissue and tumor making surgery difficult; fast disordered growth
• seeding body cavities: malignant tumor penetrates into a body cavity e.g. pleural, pericardial, subarachnoid, joint spaces
• metastatic: spread of tumor to distant sites e.g. lymphatic spread, hematogenous spread
• sentinel lymph node: the first lymph node that receives lymphatic flow from the tumor in a specific region. 
• Anaplasia: lack of differentiation that is irreversible 
• Pleomorphism: variation is size and shape
• Loss of polarity: tumor cells growth is disorganized, their orientation is disturbed
• gliomas: malignant tumor of glial cells in the central nervous system
• pseudomyxoma peritonei: gelatinous neoplastic mass in the peritoneal cavity made by a mucus-secreting carcinoma of the appendix or ovaries. 
• Proto-oncogene: code for proteins that can cause neoplasia but these genes are not usually expressed. 
• Oncogene: mutated form of a normal gene that is expressed; this mutated gene is dominant meaning having one active mutated allele is enough to cause neoplasia
• Tumor suppressor gene: codes for proteins that suppress cell proliferation i.e. tumors. Mutations in tumor suppressor genes are recessive because the mutation must be in both alleles to cause complete loss of the encoded proteins e.g. loss of one tumor suppressor gene means loss of 1/2 the tumor suppressing proteins but not all.
• Loss of heterozygosity: when the second tumor suppressor gene is mutated, so that both alleles have a mutation leading to cancer
• Two-hit theory: there is a germ-line mutation of one tumor suppressor gene allele (first hit) followed by a mutation of the second allele in early adulthood (second hit). This is seen usually in familial cancer syndromes. 
• Retinoblastoma (RB) protein: a tumor suppressor protein that binds to (thus inhibiting) transcription factor E2F. The E2F transcription factor when active allows cells to progress from G1 to S phase of the cell cycle by binding additional proteins. The active (hypophosphorylated) form of Rb has this tumor suppressing function (ability to bind E2F). In healthy cells, during G1 to S phase, levels of cyclins (CDK4, CDK6) increase and these cyclins inactivate the Rb protein by phosphorylating it. 
• p53 protein: a tumor suppressor protein that in response to DNA damage, (a) activates DNA repair genes, (b) promotes apoptosis in cells that can not be repaired. It is encoded by the TP53 gene which is the most commonly mutated gene in human cancers. 
• b) p53 activates CDK inhibitor p21 which prevents phosphorylation (inactivation) of RB protein preventing progression from G1 to S phase of the cell cycle
• RB
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More definitions:

• Fibroma: benign tumor arising from fibrous tissue
• Chondroma: benign cartilaginous tumor
• Adenoma: benign epithelial tumor derived from glands
• Papilloma: benign epithelial tumors producing finger-like projections
• Linitis plastica: adenocarcinoma has spread to the submucosa of the stomach causing it to become rigid and atonic 
• Virchow's node: left supraclavicular lymphadenopathy
• Sister Mary Joseph nodule: umbilical nodule
• Krukeberg tumor: ovarian tumors that can sometimes be palpated during pelvic exam

Risk factors for the development of Cancers

• Smoking
• Alcohol
• Obesity: 
• HPV 16, 18 and 31: express oncogenic proteins, E6 and E7. The E6 protein binds to and mediates the breakdown of p53, a tumor suppressor, and it also stimulates TERT, the catalytic subunit of telomerase, allowing the cells to gain a kind of immortality. The E7 protein binds to the retinoblastoma (RB)  protein displacing E2F transcription factors, and allowing the cell to progress through the G1-S checkpoint. The E7 protein also activates cyclins E and A. 
• HPV vaccines: give before onset of sexual activity and avoid conception until 30 days after last dose. 
• Gardasil -- covers HPV 6, 11, 16 and 18. Approved or females 9-45 and males 9-26. Given intramuscularly 0, 2, and 6 months
• Gardasil-9 -- covers HPV 6, 11, 16, 18, 31, 33, 4, 52, and 58. Used to prevent cervical and other HPV-related cancer and also for genital warts. 
• Cervarix -- covers HPV 16 and 18. Approved for females age 10-25 and given intramuscularly 0, 1 and 6 months.

References:

Robbins and Cotran Pathologic Basis of Disease, ch 7