Large cell carcinoma of the lung


An undifferentiated carcinoma lacking squamous, glandular or small cell features.


Large cell carcinoma accounts for about 9% of primary lung carcinomas, of which about one third are large cell neuroendocrine carcinomas. All subtypes occur predominantly in smokers, except for lymphoepithelioma-like carcinoma7, which is most common in among the Chinese2,4,6.

Clinical features

A case associated with Eaton-Lambert syndrome has been reported8.


Apart from basaloid carcinoma, most large cell carcinomas occur peripherally within the lung4.


These tumours are poorly differentiated and lack squamous, glandular or small cell components.



See immunohistochemistry of malignant epithelial tumours of lung.

Large cell neuroendocrine carcinoma:



usually positive



usually positive


usually positive

Definite positivity with one neuroendocrine marker is sufficient to establish the diagnosis of LCNEC


50% of cases





Transcription factor E2F1



Basaloid carcinoma: Neuroendocrine markers are negative (in 10% of cases, one marker is positive in less than 20% of tumour cells). TTF-1 is negative.

Large cell carcinoma with rhabdoid phenotype: the cytoplasmic globules are positive for vimentin and cytokeratin3.

Differential diagnosis


As for other non-small cell carcinomas of lung, dependent on performance status and TNM staging. The prognosis is worse than for other non small cell carcinomas18. Lymphoepithelioma-like carcinoma has a better prognosis7. Basaloid carcinoma is reported to have a prognosis inferior to that of poorly differentiated squamous cell carcinoma15.

The prognostic significance of neuroendocrine differentiation remains uncertain9,10. It has been proposed that large cell neuroendocrine carcinoma 14 or large cell carcinoma with large cell neuroendocrine features11 are more aggressive than is classical large cell carcinoma. Accurately staged stage I large cell carcinoma with neuroendocrine differentiation may have a relatively good prognosis21. Combined small cell carcinoma / large cell carcinoma has an inferior survival compared to pure large cell carcinoma16.

Lung tumours with a rhabdoid phenotype show aggressive behaviour and poor prognosis5, particularly if the proportion of rhabdoid cells exceeds 10%17.



0Tumours of the Lung, Pleura, Thymus and Heart. WHO Classification of Tumours. IARC Press 2004.

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5 Chetty R, Bhana B, Batitang S, et al. Lung carcinomas composed of rhabdoid cells. Eur J Surg Oncol 1997; 23:432-4

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18 Takei H, Asamura H, Maeshima A, et al. Large cell neuroendocrine carcinoma of the lung: a clinicopathologic study of eighty-seven cases. J Thorac Cardiovasc Surg 2002; 124:285-92

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This page last revised 29.3.2005.

©SMUHT/PW Bishop