non-small cell lung cancer

NSCLC comprises three major histologic subtypes: (1) Adenocarcinoma - most common overall and in non-smokers, typically peripheral location, associated with mutations in EGFR, ALK, ROS1, KRAS; glandular pattern with mucin production; often stains positive for TTF-1 and napsin A. (2) Squamous cell carcinoma - centrally located, strongly linked to smoking, associated with cavitation, hypercalcemia (PTHrP secretion), keratin pearls and intercellular bridges histologically, p40/p63 positive. (3) Large cell carcinoma - undifferentiated, poor prognosis, diagnosis of exclusion.

Unlike small cell lung cancer, NSCLC is less associated with paraneoplastic syndromes (except SCC-hypercalcemia) and lacks the aggressive neuroendocrine features and rapid doubling time of SCLC. NSCLC is generally less responsive to standard chemotherapy but more amenable to surgical resection when localized (stages I-IIIA), unlike SCLC which is almost always treated with chemoradiation given its propensity for early metastasis.

Molecular testing is essential for adenocarcinoma to identify targetable mutations (EGFR, ALK, ROS1, BRAF, KRAS G12C) for treatment with tyrosine kinase inhibitors. Immunotherapy (PD-1/PD-L1 inhibitors) has become important in NSCLC treatment, particularly for PD-L1-high tumors.

Staging follows TNM classification, guiding treatment: early-stage disease is treated with surgical resection ± adjuvant chemotherapy, locally advanced disease with chemoradiation, and metastatic disease with systemic therapy (chemotherapy, targeted therapy, or immunotherapy based on molecular/PD-L1 status).

Risk factors include smoking (especially SCC), radon exposure, asbestos (mesothelioma more specifically), and family history. Presentation may include cough, hemoptysis, weight loss, dyspnea, or be found incidentally on imaging. Pancoast tumors (superior sulcus tumors) can cause Horner syndrome and brachial plexopathy.