Lung carcinoma: histologic types
- Lesion
Four main types: adenocarcinoma is peripheral and glandular, squamous is central and keratinising, small cell is aggressive and neuroendocrine.
What it is
Lung carcinoma is the leading cause of cancer death worldwide. It is divided into small cell carcinoma and non-small cell carcinoma, the latter mainly adenocarcinoma and squamous cell carcinoma. The type decides molecular testing and treatment, so the pathologist confirms it with morphology and a small immunohistochemistry panel. Mixtures of types occur in the same tumour.
Structure
- Gross: grey-white, firm to hard mass, sometimes with necrosis or hemorrhage; squamous tumours may cavitate.
- Adenocarcinoma: acinar, papillary, micropapillary, solid or lepidic patterns; mucinous variants spread through the airspaces and form satellite nodules.
- Squamous: sheets of cells with abundant eosinophilic cytoplasm, keratinisation and intercellular bridges; adjacent squamous dysplasia and carcinoma in situ.
- Small cell: sheets of small round to fusiform cells, frequent mitoses, extensive necrosis, crush artefact and the Azzopardi effect (DNA on vessel walls); neurosecretory granules on EM.
- Large cell: sheets of large cells with vesicular nuclei and prominent nucleoli.
Step by step
- Carcinogens hit a wide field of bronchial and alveolar epithelium (field effect).
- Central airways exposed to heavy smoke develop squamous metaplasia, dysplasia and squamous carcinoma.
- Peripheral alveolar and bronchiolar cells progress through atypical adenomatous hyperplasia and adenocarcinoma in situ to adenocarcinoma.
- Neuroendocrine precursor cells with loss of TP53 and RB1 give small cell carcinoma, which spreads early.
- Tumours invade the bronchial wall, nodes, pleura and vessels and metastasise.
The main types of lung carcinoma
| Type | Share | Location | Histology | IHC |
|---|---|---|---|---|
| Adenocarcinoma | About 50% | Peripheral | Glands, mucin, lepidic edge | TTF-1, napsin A |
| Squamous cell carcinoma | About 20% | Central | Keratin pearls, intercellular bridges | p40, p63, CK5/6 |
| Small cell carcinoma | About 15% | Central | Small cells, moulding, necrosis | Chromogranin, synaptophysin, CD56, TTF-1 |
| Large cell carcinoma | Few percent | Any | Undifferentiated large cells | No specific lineage markers |
Markers
- TTF-1
- Napsin A
- p40
- p63
- Chromogranin
- Synaptophysin
- CD56
- Ki-67
Clinical notes
- Cough, weight loss, chest pain, dyspnoea and hemoptysis; many tumours are found late or on imaging of a nodule.
- Small cell carcinoma has usually spread at diagnosis and is treated with chemotherapy and radiotherapy; non-small cell tumours are resected when possible.
- Adenocarcinomas are tested for targetable alterations (EGFR, ALK, ROS1 and others) and PD-L1.
Test yourself
Think of the answer, then tap the question to see it.
Which lung cancer type is most common in never-smokers?
Adenocarcinoma.
Which immunohistochemical markers separate adenocarcinoma from squamous cell carcinoma?
Adenocarcinoma is TTF-1 and napsin A positive; squamous cell carcinoma is p40 (and p63) positive.
What are the cytologic features of small cell carcinoma?
Small cells with scant cytoplasm, finely granular salt-and-pepper chromatin, inconspicuous nucleoli, nuclear moulding, many mitoses and necrosis.
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Non–Small Cell Lung Cancer (StatPearls (NCBI Bookshelf), 2025); Small Cell Lung Cancer (StatPearls (NCBI Bookshelf), 2025); Lung Cancer (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.