Lung Carcinoma
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Direct answer
Lung carcinoma is the leading cause of cancer death worldwide, overwhelmingly linked to cigarette smoking, and splits into non-small cell types and the neuroendocrine small cell carcinoma. Adenocarcinoma is now the commonest subtype overall — peripheral, gland-forming, TTF-1 positive, enriched in non-smokers, women and the young, and the subtype carrying EGFR mutations and ALK rearrangements that guide targeted therapy. Squamous cell carcinoma arises centrally in smoking-damaged airways with keratinisation and cavitates, while small cell carcinoma — central, densely cellular, chromogranin and synaptophysin positive — secretes ACTH and ADH-like peptides and is usually metastatic and non-surgical at diagnosis.
What you must remember
- Adenocarcinoma: commonest overall; peripheral location; lepidic, acinar, papillary and solid patterns; TTF-1 positive; precursor is atypical adenomatous hyperplasia and in-situ (lepidic) growth; targetable EGFR mutation and ALK rearrangement enrichments.
- Squamous cell carcinoma: central, through squamous metaplasia and dysplasia; keratin pearls, intercellular bridges, p40 positive; cavitates; produces parathyroid hormone-related peptide causing hypercalcaemia.
- Small cell carcinoma: central, poorly differentiated "oat" cells with scant cytoplasm, high mitotic rate and extensive necrosis; positive for neuroendocrine markers (chromogranin, synaptophysin, CD56); chemoradiation and immunotherapy per current guidance, but prognosis remains poor.
- Paraneoplastic syndromes: small cell — Cushing syndrome from ACTH, syndrome of inappropriate ADH secretion, Lambert-Eaton myasthenic syndrome from anti-voltage-gated calcium channel antibodies; squamous — hypercalcaemia; any — hypertrophic pulmonary osteoarthropathy with clubbing and gynaecomastia from human chorionic gonadotropin.
- Local spread effects: hoarseness from recurrent laryngeal nerve palsy, superior vena cava syndrome, Horner syndrome with a Pancoast tumour of the apex (usually squamous), dysphagia and sympathetic chain involvement.
- Metastases and the reverse: lung metastases outnumber primary tumours — deposits from breast, colon, kidney and bone appear as cannon-ball nodules; primaries spread to adrenals, brain, liver and bone.
- Typical carcinoid: a low-grade neuroendocrine tumour of younger non-smokers, central and well-differentiated, with carcinoid syndrome only when hepatic metastases release serotonin into the systemic circulation.
Common confusion
Small cell carcinoma versus carcinoid tumour — both neuroendocrine — differ in grade: small cell is high-grade with necrosis and high mitoses, carcinoid low-grade and indolent. Squamous versus adenocarcinoma sorts by site and marker: central with keratin versus peripheral with mucin and TTF-1. Do not forget that adenocarcinoma has overtaken squamous carcinoma as the commonest subtype, a favourite "which is most common" trap, and that Pancoast tumour produces arm pain with Horner syndrome, not isolated apical opacity.
Exam-focused takeaway
Stems are vignette-plus-microscopy: a smoker with a cavitating central mass and keratin pearls, a young non-smoking woman with a peripheral TTF-1 positive adenocarcinoma on EGFR-targeted therapy, or a man with hyponatraemia, proximal weakness and a central small cell tumour. Questions test marker panels, paraneoplastic hormone matching, and the non-operative status of small cell disease. Repeat the grid — site, histology, marker, hormone, treatment — for each subtype.
Frequently asked questions
Which lung carcinoma subtype is now most common?
Adenocarcinoma — peripheral and TTF-1 positive, commonest in women, non-smokers and the young, often with targetable driver mutations.
Which markers identify small cell carcinoma?
Neuroendocrine markers chromogranin, synaptophysin and CD56, plus the dense cellular "oat cell" morphology with high mitotic count.
What paraneoplastic syndromes does small cell carcinoma cause?
Cushing syndrome from ACTH, hyponatraemia from inappropriate ADH secretion and Lambert-Eaton myasthenic syndrome from calcium-channel antibodies.
What is a Pancoast tumour?
An apical (superior sulcus) carcinoma, usually squamous, invading the sympathetic chain and brachial plexus to cause Horner syndrome with arm pain.
How do typical carcinoid and small cell carcinoma differ?
Carcinoid is a low-grade neuroendocrine tumour of young non-smokers with indolent behaviour; small cell carcinoma is high-grade, necrotic, mitosis-rich and rapidly lethal.