Pathology
The diagnostic core
Pathology answers three questions: is the lesion neoplastic, what is it, and what is its biological behaviour. Malignant features include invasion, metastasis, pleomorphism, high nuclear-to-cytoplasmic ratio, frequent mitoses, necrosis and infiltrative borders. Report differentiation (resemblance to parent tissue) separately from grade (aggressiveness); they are not interchangeable.
Grading systems
Breast: Nottingham modification of Scarff-Bloom-Richardson, scoring tubule formation, nuclear pleomorphism and mitotic count. Prostate: Gleason pattern sum, now expressed as grade groups. Renal cell carcinoma: WHO/ISUP grade. GIST: mitotic index. Soft tissue sarcoma: FNCLCC.
Immunohistochemistry
Lineage markers include cytokeratins (carcinoma), vimentin (sarcoma), CD45 (lymphoma), S100/SOX10/Melan-A (melanoma), TTF-1, GATA3, PAX8 and CD30. Predictive markers include ER and PR, HER2 (with in-situ hybridisation for equivocal 2+ cases), PD-L1 and mismatch repair proteins. All depend on fixation quality in formalin-fixed paraffin-embedded tissue.
Staging pathology
pT depends on size and invasion; pN on involved regional nodes and extranodal extension. Margins are reported as R0 (no residual tumour), R1 (microscopic) or R2 (macroscopic). Lymphovascular and perineural invasion carry prognostic weight.
Traps
In-situ versus invasive disease, grade versus stage, and spindle-cell mimics that require immunohistochemistry. Frozen section is for margins and nodal status, not for definitive diagnosis of an indeterminate primary.
Rule of thumb
Grade describes how ugly the cell looks; stage describes how far it has travelled, and stage usually outranks grade for prognosis.