Pathology- Neoplasia Flashcards
Hallmarks of cancer:
evasion of apoptosis, growth signal self-sufficiency, anti-growth signal insensitivity, Warburg effect (shift of glucose metabolism away from mitochondria toward glycolysis), sustained angiogenesis, limitless replicative potential, tissue invasion, and metastasis.
neoplastic progression
- Normal cells
- Dysplasia
- Carcinoma in situ/preinvasive: irreversible dysplasia that involves the entire thickness of epithelium but does not penetrate the intact basement membrane.
- Invasive carcinoma: Cells have invaded basement membrane using collagenases and hydrolases (metalloproteinases). Cell-cell contacts lost by inactivation of E-cadherin.
Metastasis
Tumor nomenclature
Carcinoma implies epithelial origin, whereas sarcoma denotes mesenchymal origin. Both terms generally imply malignancy.
Benign tumors are usually well differentiated, well demarcated, low mitotic activity, no metastasis,
no necrosis.
Malignant tumors may show poor differentiation, erratic growth, local invasion, metastasis, and decrease apoptosis. Upregulation of telomerase prevents chromosome shortening and cell death.
Terms for non-neoplastic malformations include
hamartoma (disorganized overgrowth of tissues in
their native location, eg, Peutz-Jeghers polyps).
choristoma (normal tissue in a foreign location,
eg, gastric tissue located in distal ileum in Meckel diverticulum).
Cell type neoplasia
- Epithelium
- Mesenchyme
Benign: Adenoma, papilloma
Malign: Adenocarcinoma, papillary carcinoma.
Benign: Hemangioma, osteoma, fibroma, lipoma, leiomyoma, rhabdomyoma, nevos/mole
Malign: Angiosarcoma, osteosarcoma, fibrosarcoma, liposarcoma, leiomyosarcoma, rhabdomyosarcoma, melanoma.
Tumor grade vs stage
Grade: Degree of cellular differentiation and mitotic
activity on histology. Range from low grade to high grade.
Degree of localization/spread based on site and size of 1° lesion, spread to regional lymph nodes, presence of metastases. (TNM)
Tumor
- Diferentiation
- Anaplasia
degree to which a tumor resembles its tissue of origin.
complete lack of differentiation of cells in a malignant neoplasm.
Paraneoplastic syndromes
- Musculoskeletal and cutaneous
Dermatomyositis
Acanthosis nigricans
Sign of Leser-Trélat
Hypertrophic osteoarthropathy
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Paraneoplastic syndromes
- Endocrine
Hypercalcemia
Cushing syndrome
Hyponatremia (SIADH)
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Paraneoplastic syndromes
- Hematologic
Polycythemia Pure red cell aplasia Good syndrome Trousseau syndrome Nonbacterial thrombotic (marantic) endocarditis
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Paraneoplastic syndromes
- Neuromuscular
Anti-NMDA receptor encephalitis Opsoclonusmyoclonus ataxia syndrome Paraneoplastic cerebellar degeneration Paraneoplastic encephalomyelitis Lambert-Eaton myasthenic syndrome Myasthenia gravis
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Oncogenes
- ALK
- BCR-ABL
- BCL-2
- BRAF
- c-KIT
Receptor tyrosine Kinase. Lung Adenocarcinoma (Adenocarcinoma of the Lung Kinase)
Tyrosine kinase. CML, ALL
Antiapoptotic molecule (inhibits apoptosis). Follicular and diffuse large B cell lymphomas
Serine/threonine kinase. Melanoma, non-Hodgkin lymphoma, papillary thyroid carcinoma.
Cytokine receptor. Gastrointestinal stromal tumor (GIST)
Oncogenes
- c-MYC
- HER2/neu (c-erbB2)
- JAK2
- KRAS
- MYCL1
- N-myc (MYCN)
- RET
Transcription factor. Burkitt lymphoma
Receptor tyrosine kinase. Breast and gastric carcinomas
Tyrosine kinase. Chronic myeloproliferative disorders
GTPase. Colon cancer, lung cancer, pancreatic cancer
Transcription factor. Lung tumor
Transcription factor. Neuroblastoma
Receptor tyrosine kinase MEN 2A and 2B, papillary thyroid carcinoma
Tumor suppressor genes
- APC
- BRCA1/BRCA2
- CDKN2A
- DCC
- SMAD4 (DPC4)
Negative regulator of β-catenin/WNT pathway. Colorectal cancer (associated with FAP).
DNA repair protein. Breast, ovarian, and pancreatic cancer
p16, blocks G1, S phase. Melanoma, pancreatic cancer
DCC—Deleted in Colon Cancer
DPC—Deleted in Pancreatic Cancer
Tumor suppressor genes
- MEN1
- NF1
- NF2
- PTEN
- Rb
Menin. Multiple Endocrine Neoplasia 1
Neurofibromin (Ras GTPase activating protein). Neurofibromatosis type 1.
Merlin (schwannomin) protein. Neurofibromatosis type 2
Negatively regulates PI3k/AKT pathway. Breast, prostate, and endometrial cancer
Inhibits E2F; blocks G1 S phase. Retinoblastoma, osteosarcoma