Neoplasia: Carcinogenesis, Tumour Biology, Invasion, and Metastasis
Nomenclature and behaviour
Benign tumours are well circumscribed, non-invasive, and do not metastasise; malignant tumours invade and metastasise. Know exceptions: some benign tumours are dangerous by location (meningioma, pituitary adenoma). Suffix conventions matter: -oma is usually benign (lipoma), but lymphoma, melanoma, and seminoma are malignant. Carcinoma arises from epithelium; sarcoma from mesenchyme.
Carcinogenesis
Multi-step carcinogenesis involves initiation (irreversible DNA damage), promotion (clonal expansion), and progression. Key oncogenes (RAS, MYC, HER2, ABL) are activated by mutation, amplification, or translocation; tumour suppressor genes (TP53, RB, APC, BRCA1/2) follow the two-hit hypothesis. Know the hallmarks: self-sufficiency in growth signals, insensitivity to growth inhibition, evasion of apoptosis, limitless replicative potential (telomerase), sustained angiogenesis, invasion and metastasis, genomic instability, and immune evasion. Chemical, radiation, and viral carcinogens (HPV E6/E7, EBV, HBV, HTLV-1) are commonly tested.
Tumour biology and metastasis
Grading describes differentiation; staging describes anatomical spread and is the stronger prognosticator. Metastasis requires detachment (loss of E-cadherin), basement membrane degradation (matrix metalloproteinases), vascular intravasation, survival in circulation, extravasation, and colonisation. Common routes: carcinomas via lymphatics, sarcomas via blood; follicular thyroid and hepatocellular carcinoma are haematogenous exceptions.
Traps
Do not equate grade with stage. Dysplasia versus carcinoma in situ: in situ has full-thickness atypia but intact basement membrane. Paraneoplastic syndromes (SIADH, Cushing, hypercalcaemia, Trousseau syndrome) may be the presenting feature. Cachexia is not explained by caloric intake alone.
Rule of thumb
If a stem asks which feature best predicts prognosis, choose stage over grade; if it asks about metastatic mechanism, choose loss of E-cadherin and MMP activity.