Large cell carcinoma of the lung

Definition

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

Epidemiology

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.

Radiology

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

Histopathology

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

Variants:

Immunohistochemistry

See immunohistochemistry of malignant epithelial tumours of lung.

Large cell neuroendocrine carcinoma:

 

CD56

usually positive

 

Chromogranin

usually positive

Synaptophysin

usually positive

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

TTF-1

50% of cases

CK14

negative

CK20

negative

Transcription factor E2F1

5/1022

   

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

Prognosis

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.

 

References

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

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This page last revised 29.3.2005.

©SMUHT/PW Bishop