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64 Cards in this Set
- Front
- Back
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The definition of cancer
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an uncontrolled proliferation of cells that express varying degrees of fidelity to their precursors
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Describe benign tumors
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-do not invade adjacent tissue borders
-do not spread (metastasize) to distant sites -typically more differentiated, closely resembling their tissue of origin |
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Describe malignant tumors
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-invade adjacent tissue borders
-spread (metastasize) to distant sites -typically composed of less differentiated cells with less fidelity to their precursors than benign tumors |
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Chondroma -->
Epithelioma --> Papilloma --> Adenoma --> |
THESE ARE BENIGN.
Resemble chondrocytes Squamous Epithelium Squamous Epithelium (branched and exophytic-grows outwards) Glandular Epithelium (such as in the colon or the endocrine glands) |
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Define teratoma.
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Benign tumor that arises from germ cells and is derived from different germ layers.
Occur in the gonads and sometimes in the mediastinum. |
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Define hamartoma
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Disorganized (abnormal) tissues in a normal location.
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Define choristoma.
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Well-organized (normal) tissues in an abnormal location.
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Carcinoma
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A malignant tumor of epithelial origin.
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Gastric adenocarcinoma -->
Squamous cell carcinoma --> Transitional cell carcinoma --> |
Stomach
Skin or mucosa Bladder |
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Sarcoma
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Malignant tumor of mesenchymal origin
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Chondrosarcoma-->
Osteosarcoma --> Fibrosarcoma --> |
cartilage
bone fibrous connective tissue |
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Papillary:
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frond-like structure
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Medullary:
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soft, cellular tumor with little connective tissue
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Scirrhouse or Desmoplastic:
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dense, fibrous stroma
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Comedocarcinoma
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Interductal neoplasm in which necrotic material can be expressed from ducts.
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Colloid or mucinous:
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secretion of abundant mucus
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Serous:
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production of serous fluid.
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Historical terms:
Hepatoma- Melanoma- Seminoma- |
(malignant neoplasms)
liver neuroectoderm of skin testis |
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Historical terms:
Lymphoma- Leukemia- Myeloma- |
(malignant neoplasms)
lymphocytes hematopoietic cells plasma cells |
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Histologic Diagnosis of Malignancy
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Anaplasia or cellular atypia
Mitotic activity Invasion Metastasis Tumor markers |
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Describe anaplasia or cellular atypia.
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-refers to lack of differentiated features in cells
-degree often correlates with aggressiveness (1) Variation in size and shape of cells and cell nuclei (pleomorphism) (2) Enlarged and hyperchromatic nuclei with coarsely clumped chromatin & prominent nucleoli (3) Atypical mitoses (4) Bizarre cells, including tumor giant cells |
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Invasion
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Malignancy is supported by the demonstration of invasion, particularly of blood vessels and lymphatics
For SCCa: local invasion is sufficient for the diagnosis |
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Describe Tumor Markers
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Products of malignant neoplasms in cells or in body fluids
Useful in identifying the origin of poorly differentiated tumors |
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Tumor Markers:
Cytokeratins PSA Carcinoembryonic antigen |
Carcinomas
Prostate cancer (prostate-specific antigen) colon cancer |
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Tumor Markers:
Chromogranin- S-100- LCA |
Neuroendocrine tumors
Melanomas, neural tumors Lymphomas (Leukocyte common antigen) |
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2 unique properties of cancer cells.
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The ability to invade locally and the capacity to metastasize to distant sites
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Direct Extension
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-Localized growth confined to epithelium: carcinoma in situ (dysplastic changes involving the full thickness of the epithelium)
-Extension through basement membrane: superficially infiltrating carcinoma which evolves into full-blown carcinoma -Growth within tissue of origin -Enlargement and infiltration into surrounding normal structures and organs -Spread inside serous cavities (e.g. peritoneum or pleura) |
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Metastasis
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transfer of malignant cells from one site to another not directly connected with it via vascular and lymphatic channels
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Hematogenous Metastases
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-cancer cells commonly invade capillaries and venules
-tumors must lodge in vascular bed of metastatic site -liver (portal system) & lung (vena cava) are common sites |
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Lymphatic Metastases
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lymph nodes bearing metastatic deposits may be enlarged
cut surface of lymph node usually resembles that of the primary tumor in color and consistency regional lymphatic pattern is exemplified by breast cancer lateral aspect nodes of axilla medial aspect mammary lymph nodes of thorax |
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Biology of Invasion and Metastasis
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Invasion of basement membrane
Movement through extracellular matrix Penetration of vascular or lymphatic channels Survival and arrest within circulating vascular or lymphatic system Exit from circulation into new tissue site Survival and growth as a metastasis |
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3 parts of invasion
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-binding to ECM
-Degradation of ECM -Movment through interstitial space |
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3 parts of metastasis
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-invasion of the circulation
-escape from the circulation -angiogenesis and local growth |
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Cancer Grading
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Cytologic/histologic grading is based on the degree of anaplasia and the number of proliferating cells (3-4 grades)
Degree of anaplasia shape and regularity of cells presence of distinct differentiation features Rate of growth number of mitoses, atypical mitoses, nuclear pleomorphism, and tumor giant cells |
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Cancer Staging
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Based on the extent of spread (Size of primary lesion, Spread to regional lymph nodes, Metastasis to distant sites)
Influences treatment more than cytologic/histologic grading Most cancer survival statistics based on staging Independent of cytologic/histologic grading |
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paraneoplastic syndromes
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remote effects of cancer that are not attributable to tumor invasion or metastasis (fever, anorexia, endocrine syndromes, gonadotropic syndromes, hypoglycemia)
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Mechanism of chemical carcinogenesis
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Initation: mutations in a single cell
Promotion: clonal expansion of the initiated cell- cells are depedent on the continued presence of the promoting stimulus. Progression: growth becomes autnomous and is independent of the carcinogen or promoter. Cancer: cells acquire the capactiy to invade and metastasize. |
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List viruses implicated in the development of human neoplasms
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RNA retrovirus HTLV-I and human T-cel lleukemia/plymphoma
Hyman papillomavirus (DNA) and squamous carcinoma of the cervix. Hep B and C and primary hepatocellular carcinoma EBV= epstein barr virus Human herpesvirus 8 and kaposi sarcoma. |
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molecules capable of stimulating angiogenesis
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FGF0 fibroblast growth factor
TGF - transforming grwoth factor TNF VEGF - vascular endothelial growth factor EGFL epidermal growth factor |
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Inhibitors of angiogenesis
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angiostatin, endostatin
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Define oncogenes.
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Altered version of normal genes (proto-oncogenes) that regulat normal cell grwoth and differentiation.
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Acute transforming viruses
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produces tumors in a few weeks.
Transduction- viruses have transduced viral genes called viral oncogenes (v-onc), which come from cellular genes called cellular oncogenes (c-onc) or proto-oncogenes. |
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Slow transforming viruses
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produce tumors in months.
Produce tumors by integrating the provirus at critical sites in the cell genome, deregulating a neighboring cellular oncogene. INSERTIONAL MUTAGENESIS. |
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Wat are the 2 mechanisms of activation of cellular oncogenes?
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mutation in the structure of the proto-oncogene results in an abnormal gene product.
increase in the expression of the proto-oncogene causes overproduction of a normal gene product. |
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Examples of physical carcinogenesis.
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UV radiation.
Asbestos Foreign body carcinogenesis (humans highly resistant) |
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What are the 4 DNA viruses?
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HPV (human papillomavirus)
EBV (epstein barr virus) Hep B Herpesvirus 8 |
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Define tumor suppressor genes
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normal genes whose products inhibit cellular proliferation.
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define mutator genes
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maintain the integrity of the genome and fidelity of DNA replication.
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Philadelphia chromosome
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Found in 95% of patients with chronic myelogneous leukemia.
The c-abl proto-oncogene on chromosome 9 is translocated to 22, where it is placed next to the breakpoint cluster region (bcr). This produces a hybrid oncogene that codes for an aberrant protein with very high tyrosine kinase activity. |
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Describe the chromosomal translocation of Burkitt Lymphoma.
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Removal of the c-myc proto-oncogene from its site on chromosome 8 to 14, where it is placed next to the genes that control transcription of the immunoglobulin heavy chains.
Stimulates overproduction of a normal gene product. |
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Name 3 chromosomal alterations that result in gene amplification.
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Homogeneous staining regions (HSR's)
Abnormal banding regions on chromosomes Double minutes (multiple paired cytoplasmic bodies) |
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Bcl-2
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Chromosomal translocation from 14-18; bcl-2 gene is brought under the transcriptional control of the immunoglobulin light-chain gene promoter, causing overexpression of bcl2.
Bcl-2 is an oncogene that INHIBITS APOPTOSIS of malignant B cells --> follicular B-cell lymphomas. |
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ras Oncogenes
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Loss of intrinsic GTPase activity, loss of sensitivty to the G-activating protein (GAP), increased exchange of GTP for GDP.
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Competence genes
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proto-oncogenes that are expressed early in the cell cycle render the cells competent to receive the final signals for mitosis.
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Name 5 chemical carcinogens.
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Polycyclic Aromatic hydrocarbons (cigarette smoke)
aflatoxin (fungus Aspergillus flacus) Aromatic amines and azo dyes--bladder and liver tumors respectively. nitrosamines metals (electrophilic and can react with macromolecules). |
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Difference between DNA viruses and retroviruses (RNA)
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Transforming genes of DNA vrisues exhibit NO HOMOLOGY with cellular genes.
Transforming genes of retroviruses are derived from and are homolous with their cellular counterparts (proto-oncogenes. |
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Factors that influence chemical carcinogenesis.
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metabolism of carcinogens: correlation between levels of mixed function oxidases and sensitivity to chemical carcinogens.
Sex and hormonal status (prengnacy - decreased incidence). Diet - low-protein diet--> decreased sensitivity to hepatocarcinogens. obesity is bad. dietary fiber is good for colorectal cancer? |
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HOw do DNA viruses cause human cancers?
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They have genes that encode protein products that bind to specific host proteins involved in regulation of cell proliferation.
THey decouple cell porliferation from inhibitory control and create the transformed phenotype of a cancer cell. |
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3 situations in which EBV is associated with development of human cancers.
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Burkitt Lymphoma
Polyclonal Lymphoproliferation in Immunodeficient States. Nasopharyngeal Carcinoma. |
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Name some tumor suppressor genes
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Retinoblastoma gene
p53 gene WT-1 gene APC gene NF-1 gene |
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Describe the hypercoagulable state.
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Venous thrombosis, commonly in deep veins of legs.
Disseminated Intravascular Coagulation Nonbacterial thrombotic endocarditis- left-sided heart valves |
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3 situations in which EBV is associated with development of human cancers.
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Burkitt Lymphoma
Polyclonal Lymphoproliferation in Immunodeficient States. Nasopharyngeal Carcinoma. |
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Name some tumor suppressor genes
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Retinoblastoma gene
p53 gene WT-1 gene APC gene NF-1 gene |
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Describe the hypercoagulable state.
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Venous thrombosis, commonly in deep veins of legs.
Disseminated Intravascular Coagulation Nonbacterial thrombotic endocarditis- left-sided heart valves |
