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Pathology III — Neoplasia — USMLE Step 2 CK Notes
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Vocabulary
- Benign: well-differentiated, encapsulated, no invasion or metastasis; suffix -oma
- Malignant: anaplastic, invasive, metastasises; carcinoma (epithelial) or sarcoma (mesenchymal)
- Anaplasia: loss of differentiation, pleomorphism, high nuclear-to-cytoplasmic ratio, atypical mitoses
The two-hit logic
- Oncogenes — ONE activating hit, gain of function, dominant (RAS, MYC, HER2, ABL, RET)
- Tumour suppressors — TWO hits, loss of function (Knudson): TP53, RB, APC, BRCA, NF1/2, VHL, WT1
- TP53 (the 'guardian of the genome') is the most commonly mutated gene in human cancer; germline loss = Li-Fraumeni
Carcinogens and their cancers
- Aflatoxin → hepatocellular carcinoma (TP53) · vinyl chloride → hepatic angiosarcoma
- Aromatic amines → bladder · asbestos → mesothelioma and bronchogenic carcinoma
- Radiation → thyroid and leukaemia · alkylating agents → leukaemia
- HPV 16/18 → cervical (E6 degrades p53, E7 degrades Rb) · EBV → Burkitt, nasopharyngeal · HBV/HCV → hepatocellular
Tumour markers (for monitoring, not screening)
- AFP → hepatocellular, yolk sac · beta-hCG → choriocarcinoma, germ cell
- CEA → colorectal · CA-125 → ovarian · CA 19-9 → pancreatic · PSA → prostate
- Chromogranin → neuroendocrine · calcitonin → medullary thyroid
Paraneoplastic syndromes (small cell and squamous lead)
- Squamous cell lung → PTHrP → hypercalcaemia
- Small cell lung → ectopic ACTH (Cushing), ADH (SIADH), Lambert-Eaton
- Renal cell / hepatocellular → erythropoietin → polycythaemia
Metastasis and grade vs stage
- Carcinoma spreads via lymphatics; sarcoma via blood (haematogenous)
- Grade = differentiation; Stage = spread (TNM). Stage matters more for prognosis
- Commonest metastases to bone: prostate (blastic), breast (mixed), lung, kidney, thyroid
AI-authored Step 1 pathology · not editorially reviewed · study aid only.
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