STEPTRACKERRESPIRATORY + ONCOLOGY | PATHOLOGY | HIGH-YIELD REVIEW

Lung Cancer

The leading cause of cancer death: four main carcinomas, carcinoid, metastases — each with a location, a smoking link and a paraneoplastic signature.

FOCUS ON
Central tumors: squamous cell (PTHrP, cavitation) and small cell (ACTH, ADH, Lambert-Eaton; not surgical). Peripheral: adenocarcinoma (non-smokers, EGFR/ALK) and large cell. Know Pancoast/Horner, SVC syndrome, and that metastases are the most common lung malignancy.
TYPE
LOCATION · HISTOLOGY
ASSOCIATIONS
CLUE
Overview
Cough, hemoptysis, weight loss, post-obstructive pneumonia; spread to adrenals, brain, bone, liver.
Smoking (most), radon (2nd), asbestos, arsenic, radiation
Solitary coin lesion differential: granuloma, hamartoma, carcinoma
Adenocarcinoma
most common overall
Peripheral; glands, mucin, TTF-1⁺.
Most common in non-smokers and women; EGFR, ALK, ROS1, KRAS mutations
Clubbing / hypertrophic osteoarthropathy · targeted TKIs
Adenocarcinoma in situ
Lepidic growth along intact alveolar walls; no invasion.
Former "bronchioloalveolar carcinoma"
Consolidation that never clears; good prognosis
Squamous cell carcinoma
Central (hilar); keratin pearls, intercellular bridges; may cavitate.
Strongly smoking-related; men
PTHrP → hypercalcemia
Small cell carcinoma
Central; small blue neuroendocrine cells, scant cytoplasm, salt-and-pepper chromatin, crush artifact; chromogranin, synaptophysin, CD56 ⁺.
Almost always smokers; L-MYC amplification; early metastasis
ACTH, ADH, Lambert-Eaton, anti-Hu · chemo + radiation, not surgery
Large cell carcinoma
Peripheral; undifferentiated large cells.
Smoking; poor prognosis
Can secrete β-hCG → gynecomastia
Bronchial carcinoid
Nests of uniform neuroendocrine cells; often an endobronchial polyp; chromogranin ⁺.
Younger patients; not smoking-related; low grade
Obstruction, hemoptysis; carcinoid syndrome rare
Local complications
Pancoast (superior sulcus) tumor; SVC syndrome; nerve invasion; effusions.
Horner (sympathetic chain), C8–T1 arm pain/weakness · face/arm swelling (often small cell) · hoarseness (recurrent laryngeal) · raised hemidiaphragm (phrenic)
Pleural or pericardial effusion
Metastases to lung
most common lung malignancy
Multiple well-circumscribed "cannonball" nodules.
Breast, colon, prostate, kidney, sarcomas
Multiple nodules → think metastasis first

Mechanism — smoke to carcinoma

CarcinogensField effect
→
Squamous metaplasiaBronchi
→
Dysplasia → in situ
→
Central SCC / small cell
Peripheral alveoli
→
Atypical adenomatous hyperplasia
→
AIS → invasive
→
AdenocarcinomaEGFR/ALK/KRAS

Paraneoplastic and marker cheat sheet

TYPE
PARANEOPLASTIC
MARKER
Squamous cell
PTHrP → hypercalcemia
p40, keratin
Small cell
ACTH, ADH, Lambert-Eaton, anti-Hu, cerebellar degeneration
Chromogranin, synaptophysin, CD56
Adenocarcinoma
Hypertrophic osteoarthropathy, Trousseau
TTF-1, napsin A
Large cell
β-hCG (gynecomastia)
—
Carcinoid
Rarely carcinoid syndrome
Chromogranin

How it's tested

COMMON CONFUSIONSquamous cell and small cell are both central, smoking-linked tumors. Hypercalcemia points to squamous cell; hyponatremia or Cushing points to small cell.
THE TRAPA non-smoking young woman with a peripheral lung mass still has lung cancer on the differential. Adenocarcinoma with EGFR or ALK is the classic answer.
YOUR APPROACHLocation (central/peripheral) + smoking + paraneoplastic labs + histology/markers → type → treatment (surgery/TKI vs chemo-radiation).

If you see… think…

Non-smoking woman, peripheral TTF-1⁺ mass, EGFR mutation → adenocarcinoma — TKI
Smoker, central cavitating mass, Ca²⁺ 13 → squamous cell carcinoma
Smoker, central mass, Na⁺ 120 → small cell (SIADH)
Small blue cells with crush artifact, chromogranin⁺ → small cell carcinoma
Ptosis, miosis, anhidrosis + shoulder and ulnar-side pain → Pancoast tumor
Swollen face and arms, distended neck veins → SVC syndrome
Young non-smoker with an endobronchial polyp and hemoptysis → bronchial carcinoid
Consolidation that never clears with antibiotics → adenocarcinoma in situ
Multiple round nodules in both lungs → metastases
Second leading cause of lung cancer → radon