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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2Castro CY, Ostrowski ML, Barrios R, et al. Relationship between Epstein-Barr virus and lymphoepithelioma-like carcinoma of the lung: a clinicopathologic study of 6 cases and review of the literature. Hum Pathol 2001; 32:863-72

3Cavazza A, Colby TV, Tsokos M, et al. Lung tumors with a rhabdoid phenotype. Am J Clin Pathol 1996; 105:182-8

4Chan JK, Hui PK, Tsang WY, et al. Primary lymphoepithelioma-like carcinoma of the lung. A clinicopathologic study of 11 cases. Cancer 1995; 76:413-22

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

6Chang YL, Wu CT, Shih JY, et al. New aspects in clinicopathologic and oncogene studies of 23 pulmonary lymphoepithelioma-like carcinomas. Am J Surg Pathol 2002; 26:715-23

7Chen FF, Yan JJ, Lai WW, et al. Epstein-Barr virus-associated nonsmall cell lung carcinoma: undifferentiated "lymphoepithelioma-like" carcinoma as a distinct entity with better prognosis. Cancer 1998; 82:2334-42

8Demirer T, Ravits J,Aboulafia D Myasthenic (Eaton-Lambert) syndrome associated with pulmonary large-cell neuroendocrine carcinoma. South Med J 1994; 87:1186-9

9Gajra A, Tatum AH, Newman N, et al. The predictive value of neuroendocrine markers and p53 for response to chemotherapy and survival in patients with advanced non-small cell lung cancer. Lung Cancer 2002; 36:159-65

10Graziano SL, Mazid R, Newman N, et al. The use of neuroendocrine immunoperoxidase markers to predict chemotherapy response in patients with non-small-cell lung cancer. J Clin Oncol 1989; 7:1398-406

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13Matsui K, Kitagawa M, Wakaki K, et al. Lung carcinoma mimicking malignant lymphoma: report of three cases. Acta Pathol Jpn 1993; 43:608-14

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15Moro D, Brichon PY, Brambilla E, et al. Basaloid bronchial carcinoma. A histologic group with a poor prognosis. Cancer 1994; 73:2734-9

16Ruffini E, Rena O, Oliaro A, et al. Lung tumors with mixed histologic pattern. Clinico-pathologic characteristics and prognostic significance. Eur J Cardiothorac Surg 2002; 22:701-7

17Shimazaki H, Aida S, Sato M, et al. Lung carcinoma with rhabdoid cells: a clinicopathological study and survival analysis of 14 cases. Histopathology 2001; 38:425-34.

18Takei 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

19Travis WD, Linnoila RI, Tsokos MG, et al. Neuroendocrine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma. An ultrastructural, immunohistochemical, and flow cytometric study of 35 cases. Am J Surg Pathol 1991; 15:529-53

20Wong MP, Chung LP, Yuen ST, et al. In situ detection of Epstein-Barr virus in non-small cell lung carcinomas. J Pathol 1995; 177:233-40

21Zacharias J, Nicholson AG, Ladas GP, et al. Large cell neuroendocrine carcinoma and large cell carcinomas with neuroendocrine morphology of the lung: prognosis after complete resection and systematic nodal dissection. Ann Thorac Surg 2003; 75:348-52

22 Eymin B, Gazzeri S, Brambilla C, et al. Distinct pattern of E2F1 expression in human lung tumours: E2F1 is upregulated in small cell lung carcinoma. Oncogene 2001; 20:1678-87

This page last revised 29.3.2005.

©SMUHT/PW Bishop