OncologyTier 2Topic

Histopathology

Role

Histopathological examination of tumour tissue provides the definitive cancer diagnosis and the information that most directly drives treatment selection - tumour type, grade, margin status, and (increasingly) molecular/immunohistochemical markers
Remains the diagnostic gold standard despite advances in imaging and liquid biopsy - a tissue diagnosis is required before most oncological treatment decisions

Grade reflects how closely tumour cells resemble their tissue of origin (differentiation) and correlates with aggressiveness - distinct from stage, which reflects anatomical extent of spread; a tumour can be low-grade but high-stage, or vice versa
Margin status (following resection) - a positive margin (tumour at the cut edge) predicts local recurrence risk and often triggers adjuvant therapy or re-excision
Immunohistochemistry (IHC) identifies specific protein expression (e.g. oestrogen/progesterone receptor and HER2 in breast cancer, PD-L1 in various cancers) that directly determines eligibility for targeted/immunotherapy

Molecular/genomic testing (increasingly performed alongside standard histology) identifies actionable mutations (e.g. EGFR, ALK in lung cancer; BRAF in melanoma) that predict response to specific targeted therapies - histopathology has evolved from purely morphological to an integrated morphological-molecular discipline

Grade, margin status, and molecular markers together determine the adjuvant treatment plan following surgery, and predict which patients will benefit from specific targeted or immunotherapies

Breast cancer (ER/PR/HER2), lung cancer (EGFR/ALK/PD-L1), melanoma (BRAF), colorectal cancer (RAS/BRAF/MSI status)

The shift toward molecular classification means two tumours with identical conventional histology can now be treated very differently based on their underlying molecular profile - histopathology reporting has become substantially more complex and clinically consequential over the past decade

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