PA25.6 | Tumours of the Lung & Pleura — Summary & Reflection

KEY TAKEAWAYS

Core take-home messages from this module:

1. Smoking causes ~85% of lung cancers via DNA-adduct formation; dose-response relationship; radon and asbestos are key cofactors.

1. The SCLC vs NSCLC split is the first and most important classification step — it determines whether surgery is even considered. SCLC = neuroendocrine, central, oat cells, early metastasis, chemo only, TP53+RB1. NSCLC = surgery-eligible if localised.

3. NSCLC subtypes by location and histology:
• SCC = central, keratin pearls, PTHrP-mediated hypercalcaemia.
• Adenocarcinoma = peripheral, glands/lepidic, TTF-1+, EGFR/ALK targetable.
• Large cell = exclusion diagnosis.

1. Spread: Local (SVCO, Pancoast-Horner, pericardial), lymphatic, haematogenous (brain-adrenal-liver-bone). TNM staging guides resectability.

1. Paraneoplastic syndromes by type: SCLC → SIADH, ectopic ACTH, LEMS. SCC → hypercalcaemia (PTHrP). NSCLC → HPOA/clubbing.

1. Mesothelioma: asbestos (amphiboles), 25–45 year latency, encases lung, epithelioid/sarcomatoid/biphasic. Diagnosed by IHC: calretinin+/WT-1+/D2-40+ (meso) vs TTF-1+/CEA+ (adeno).

1. Pleural mets are commoner than mesothelioma — always exclude secondary malignancy before diagnosing primary pleural tumour.

REFLECT

Return to the hook scenario: a 58-year-old smoker with SVC syndrome and a hilar mass.

1. Based on location (central, hilar) and the presence of SVC obstruction, which two subtypes top your differential — and what single IHC or clinical feature would help you choose between them?

1. If the biopsy confirms SCLC and the patient is found to have hyponatraemia (Na+ 118 mEq/L) with concentrated urine, which paraneoplastic syndrome explains this — and what is the ectopic substance?

1. Now imagine a second patient: a peripheral nodule in a 45-year-old non-smoking South Indian woman. The pathologist reports adenocarcinoma. What molecular test would you request, and why does the answer alter treatment?

Write your answers before reviewing the module summary.