Tutorial 10: Introduction to Neoplasia

A neoplasm is an abnormal mass of tissue whose growth is uncoordinated with that of normal tissue and persists in an excessive manner after cessation of the stimuli that evoked the change. Benign neoplasms grow slowly, remain localised, and are composed of well-differentiated cells resembling their cell of origin. Malignant neoplasms (cancers) grow rapidly, invade adjacent tissues, and metastasise to distant sites.

Cancer is fundamentally a genetic disease: it arises from the accumulation of somatic mutations in genes controlling cell proliferation, differentiation, and survival. Two broad classes of genes are affected. Proto-oncogenes, when mutated to oncogenes, provide gain-of-function proliferative signals. Examples: RAS (GTPase in MAPK signalling pathway; mutated in ~25% of all cancers, ~90% of pancreatic cancer), EGFR (growth factor receptor; mutated/amplified in lung and breast cancers), HER2/ERBB2 (amplified in ~20% of breast cancers), MYC (transcription factor amplified in Burkitt lymphoma). Oncogene mutations are dominant — one mutant allele is sufficient to alter cell behaviour.

Tumour suppressor genes (TSGs) normally inhibit cell proliferation or promote apoptosis; their loss-of-function drives cancer. Mutations are recessive at the cellular level — both alleles must be inactivated (Knudson's two-hit hypothesis). Key TSGs: RB1 (retinoblastoma protein — master regulator of G1→S cell cycle transition; inactivated in retinoblastoma, osteosarcoma, lung, breast cancers), TP53 (p53 — "guardian of the genome"; detects DNA damage and triggers cell cycle arrest or apoptosis; mutated in >50% of all cancers), APC (Wnt pathway inhibitor; mutated in >80% of colorectal cancers), BRCA1/2 (DNA repair; germline mutations predispose to breast and ovarian cancer).

Carcinogenesis is a multistep process. Each mutational event confers a selective growth advantage (clonal expansion); subsequent mutations further increase proliferative capacity, invasiveness, and ability to evade immune surveillance. This stepwise accumulation — tumour progression — explains why most cancers arise in middle age or later.

Tumour nomenclature: benign tumours are named by cell type + "-oma" (fibroma, lipoma, adenoma). Malignant epithelial tumours = carcinomas (squamous cell carcinoma — from squamous epithelium; adenocarcinoma — from glandular/columnar epithelium). Malignant mesenchymal tumours = sarcomas (osteosarcoma, liposarcoma). Exceptions: melanoma, lymphoma, leukaemia, myeloma (all malignant despite "-oma" suffix or specific names).

Dysplasia is disordered cellular growth — cells show abnormal morphology (pleomorphism, increased nuclear:cytoplasmic ratio, abnormal mitoses) without invasion. Carcinoma in situ (CIS) is full-thickness dysplasia of an epithelial surface without breaching the basement membrane. Both are premalignant. Invasive carcinoma breaches the basement membrane and can access lymphatics and blood vessels.

Staging (TNM system) assesses tumour size and local extent (T), lymph node involvement (N), and distant metastasis (M). Metastasis routes: carcinomas preferentially spread via lymphatics to regional lymph nodes first, then haematogenously; sarcomas spread haematogenously from the outset. Common haematogenous metastatic sites: lung (pulmonary arterial filtration), liver (portal venous drainage from GI tract), bone (marrow blood flow), brain (systemic arterial).