Neoplasia

"new growth"; lack of responsiveness to normal growth controls

remains localized, amenable to surgical removal and patient survival

"cancer"; potential to invade and destroy adjacent normal tissue and spread to distant anatomic sites (metastisis). may cause death.

transformed or neoplastic cells; determines biologic behavior of the particular neoplasm

supporting tissue of the tumor: non-neoplastic blood vessels and CT

"-oma", ex. Chondroma: benign tumor of cartilaginous origin.

"-sarcoma"; ex. Osteosarcoma: malignancy of osseous tissue.

"carcinoma"; ex. Squamous cell carcinoma or adenocarcinoma (malignancy of glandular epithelial origin)

Lymphoma and Melanoma (both are malignant instead of benign)

degree parenchmyal tissue of a neoplasm resembles the parent tissue, functionally and morphologically

What is anaplastic---correct for $200!!

altered growth pattern that may become cancerous eventually

carcinoma-in-situ. contains microscopic features of cancer but the atypical cells have not invaded the host yet

• benign: grow slowly
• malignant: most grow rapidly

what is a "capsule"

hemangioma and neurofibroma

process of portions of a malignancy breaking free and traveling to distant sites to form new tumor masses

osteosarcoma and melanoma

basal cell carcinoma

30%

greater anaplasia = greater tendency to metastasize

• 1. seeding within body cavities
• 2. lymphatic spread
• 3. hematogenous spread (by blood)

hematogenous

lung and liver. the lungs act to filter the blood above the diaphram while the liver filters blood below the diaphram

• 1. inherited cancer syndromes (autosomal dominant like retinoblastoma)
• 2. familial cancers (breast, ovarian, colon)
• 3. defective DNA repair syndromes (xeroderma pigmentosum)

cancer arising from disorder within the life of the patient (not inherited or environmental necessarily)

• 1. persistent regenerative cell replication
• 2. hyperplastic and dysplastic proliferations
• 3. leukoplakia of oral mucosa/vulva/penis
• 4. villous adenomas of the colon

nonlethal genetic damage. most cancers are clonal proliferations that arise from one genetically altered cell.

• 1. protooncogenes (growth promoting)
• 2. cancer suppressor genes (growth inhibiting)
• 3. apoptosis regulatory genes

if DNA repair genes are disabled, increased frequency of mutations and increased rate of neoplastic transformation

• 1. growth factors
• 2. growth factor receptors
• 3. signal-transducing proteins
• 4. nuclear transcription factors
• 5. CDKs (cyclin-dependent kinases)

• 1. platelet-derived growth factor (glioblastoma)
• 2. TGF-a (sarcomas)

• 1. ERBB-1: overexpressed in 80% of squamous cell carcinomas of the lungs
• 2. ERBB-2: amplified in some breast cancers leading to poorer prognosis

RAS. Mutated RAS binds to GAPs but GTPase activity is not accentuated. cell continues to receive signals to divide as a result.

MYC: overexpression causes continuous cell proliferation

CDKs are responsible for determining if a cell will start the cell cycle or not. Dysregulation/overexpression favors cell proliferation.

Retinoblastoma gene

in order for retinoblastoma to develop, both Rb alleles must be disabled or mutated ("hit"). Children inherit one defective Rb gene and the second "hit" is very likely to occur as a somatic mutation resulting in tumor formation

TP53

• 1. slows down DNA replication when mutations have affected the DNA
• 2. activates the transcription of DNA repair enzymes. if DNA cannot be repaired TP53 activates apoptosis

BCL2

defective nucleotide excision repair system. risk for skin cancer from UV light

hypersensitivity to DNA damage

BRCA1 and 2

• 1. balanced translocations
• 2. deletions
• 3. gene amplifications

occurs in chronic myelogenous leukemia: it is a translocation between chromosome 22 and 9. as a result 22 is shortened.

17p, 5q, 18q

3p, 9p, 17p

electrophiles

8-12 years from exposure

RNA and DNA oncogenic viruses

Human T-cell leukemia virus Type 1 (HTLV-I)

HPV, EBV, HBV

MAGE-1 (melanoma-associated antigen)

prostate-specific antigen. expressed in a normal state but levels are elevated in a neoplastic state

• 1. CD8 T cells
• 2. NK cells
• 3. Macrophages
• 4. Humoral mechanisms

• 1. selective outgrowth of antigen-negative subclones (antigenic subclones are attacked and killed by immune system leaving tumor cells that are essential invisible to the immune system)
• 2. lost or reduced expression of MHC antigens
• 3. lack of co-stimulation for t-cell response
• 4. immunosuppression from a carcinogenic agent

• 1. location: a benign tumor next to the pituitary can compress it and cause damage
• 2. hormone production: common in well-differentiated benign tumors. adenomas and carcinomas from beta cells in the pancreas can produce hyperinsulinism
• 3. ulceration (breaking through epithelial surface)
• 4. cachexia (progressive loss of body fat and lean body mass)
• 5. paraneoplastic syndrome (A set of symptoms that is associated with cancer but is not directly caused by the cancer)

attempt to assess the aggressiveness of a malignancy based on degree of differentiation of the tumor cells and number of mitoses

assessment of the size of the primary lesion, presence or absence of lymph node involvement and presence or absence of metastatic lesions involving other distant tissues. Stage I: most localized, Stage IV: most disseminated. Staging is more valuble than grading for determining prognosis

• T: primary tumor diameter
• N: lymph node involvement
• M: metastases