Large Cell Carcinoma: A Revised Concept
J Pardo, JJ Sola, A Martinez-Penuela, A Panizo, G Aisa, JM Martinez-Penuela, MD Lozano. Clinica Universitaria, University of Navarra, Pamplona, Navarra, Spain; Hospital de Navarra, Pamplona, Navarra, Spain
Background: Large cell carcinoma (LCC) accounts for 15.7% of lung cancer. Althought LCC includes some specific entities such as neuroendocrine LCC, basaloid LCC, lymphoepithelioma-like LCC, clear cell LCC, and LCC with rhabdoid features, most cases correspond to classic LCC, which is a diagnosis of exclusion, since it probable represents the end point of differentiation of various lung tumors This study aims to evaluate a panel of immunohistochemical markers in an attempt to reduce the number of LLCs by the identification of tumors belonging to other categories.
Design: We analyzed two tissue microarray platforms consisting of 121 LLC. 15 pulmonary squamous cell carcinomas and 22 adenocarcinomas were used as controls. A panel consisting of 31 monoclonal antibodies was evaluated.
Results: The tumors were classified as follows: 96 (79.2%) were classic LCC, 10 (8.1 %) were neuroendocrine LCC, 7 (5.5 %) were lymphoepithelioma-like LCC, 3 (2.7%) were basaloid LCC, 3 (2.7%) were clear cell LCC, and 2 (2.4%) was a LCC with rhabdoid phenotype. Characteristic classic LCC immunophenotype was loss of staining with CK5/6 and CK14, loss of MOC 31 expression, and the immunoreactivity to EGFR, PDGFR and c-kit. 37 of 96 classic LCC (38.5%) were re-classified as adenocarcinomas, because they coexpressed TTF-1, CK7, and CK19, and were negative for p63. 42 (43.7%) of 82 classic LCC were reclassified as poorly differentiated squamous cell carcinoma, based on their immunoreactivity with 34betaE12, p63, thrombomodulin, and CD44v6. All neuroendocrine LCC were positive for AE3AE1, MOC-31, NSE, and PGP 9.5, and, at least, two additional neuroendocrine markers. Basaloid carcinomas were positive for AE3AE1, EGFR, CK5/CK6, CK19, Ber-EP4, and p63. Lymphoepithelioma-like carcinomas were positive for AE3AE1, MOC31, NSE, and PGP9.5.
Conclusions: The use of seven immunohistochemical markers, consisting of TTF-1, CK7, CK19, p63, 34betaE12, thrombomodulin and CD44v6, markedly reduces the number of classic LCC by readily identifying cases of poorly differentiated squamous cell carcinomas and adenocarcinomas. Routine use of such an immunohistochemical approach in LCC will conduce to change the distribution of each type of lung cancer and will facilitate a more specific prognosis and treatment of each lung tumor.
Monday, March 9, 2009 1:00 PM
Poster Session II # 222, Monday Afternoon