Lung Cancer Histological Types and Clinical Presentations
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Direct answer
Lung cancer histology divides tumours into small cell carcinoma and non-small cell carcinoma, and the non-small cell group into adenocarcinoma, squamous cell carcinoma and large cell carcinoma. Each type has a typical location, paraneoplastic syndrome and presentation, such as hypercalcaemia in squamous tumours and hyponatraemia in small cell carcinoma. Histology decides treatment, including targeted drugs for adenocarcinoma with driver mutations.
What you must remember
- Adenocarcinoma: the commonest lung cancer overall, usually peripheral, the most frequent type in never-smokers and the group carrying EGFR and ALK drivers.
- Squamous cell carcinoma: central or hilar, strongly linked to smoking, prone to cavitation, and the classic cause of PTHrP-mediated hypercalcaemia.
- Large cell carcinoma: peripheral and poorly differentiated, a diagnosis of exclusion with a poorer outlook than adenocarcinoma.
- Small cell carcinoma: central and bulky, neuroendocrine, rapidly growing and often metastatic at presentation.
- Small cell paraneoplastic features: SIADH with hyponatraemia, ectopic ACTH causing Cushing syndrome, and Lambert-Eaton myasthenic syndrome.
- Pancoast tumour: apical tumour invading the lower brachial plexus and sympathetic chain, causing shoulder pain, ulnar-sided arm symptoms and Horner syndrome.
- Clubbing: digital clubbing and hypertrophic pulmonary osteoarthropathy are typical of non-small cell tumours, particularly adenocarcinoma.
- Immunostaining: TTF-1 favours adenocarcinoma or small cell carcinoma, while p40 favours squamous cell carcinoma.
Matching the type to the location and clue
A 64-year-old man with a 40 pack-year smoking history presents with haemoptysis and weight loss, and his chest radiograph shows a central hilar mass. The clinical clues narrow the histology before biopsy.
| Type | Typical location | Classic clue |
|---|---|---|
| Adenocarcinoma | Peripheral | Clubbing, never-smoker, EGFR or ALK drivers |
| Squamous cell | Central or hilar | Cavitation, hypercalcaemia |
| Large cell | Peripheral | Poorly differentiated, diagnosis of exclusion |
| Small cell | Central, bulky | Hyponatraemia, Cushing features, rapid growth |
A central mass with hypercalcaemia points to squamous cell carcinoma, while a peripheral nodule in a never-smoking woman points to adenocarcinoma. Small cell carcinoma also lies centrally, which is why hilar masses in smokers need immunostaining before a surgical pathway is chosen.
Where the exam tries to catch you
Histology questions are won by matching the paraneoplastic clue to the right cell type.
- Trap: assuming every hilar mass in a smoker is squamous cell Correct: small cell carcinoma is also central, and early surgery is not the default because it is treated mainly with chemotherapy and radiotherapy.
- Trap: pairing hyponatraemia with squamous cell carcinoma Correct: hyponatraemia from SIADH is the classic small cell paraneoplastic effect, while squamous tumours cause hypercalcaemia.
- Trap: placing a Pancoast tumour among central hilar masses Correct: it is apical and presents with shoulder pain and Horner syndrome, and histology is still needed to plan treatment.
Frequently asked questions
Which lung cancer type is most common in never-smokers?
Adenocarcinoma is the lung cancer type most common in never-smokers. It usually arises in the periphery and is the group most often carrying EGFR mutations and ALK rearrangements.
Which lung cancer causes hypercalcaemia?
Squamous cell carcinoma is the classic lung cancer causing hypercalcaemia, through secretion of parathyroid hormone-related protein. Other tumours can cause it too, but squamous histology is the standard exam association.
Which lung cancer is linked with SIADH?
Small cell lung cancer is the classic lung cancer linked with SIADH, causing hyponatraemia with concentrated urine. Ectopic ACTH and Lambert-Eaton syndrome are the other typical paraneoplastic features of this histology.
What are the features of a Pancoast tumour?
A Pancoast tumour is an apical lung tumour that invades the brachial plexus and sympathetic chain, causing shoulder and arm pain. Horner syndrome, with ptosis, miosis and anhidrosis, is the classic combination, and it is most often a non-small cell tumour.