Large Cell Carcinoma of the Lung

Abstract

This study aims to evaluate large cell carcinomas (LCC) of the lung with a panel of immunohistochemical markers in an attempt to identify tumors belonging to other categories. We analyzed a tissue microarray platform of 101 LCC with a panel of 31 monoclonal antibodies. The tumors were 82 (81.3%) classic LCC, 7 (6.9%) neuroendocrine LCC, 6 (5.9%) lymphoepithelioma-like LCC, 3 (2.9%) basaloid LCC, 2 (2%) clear cell LCC, and 1 (1%) LCC with rhabdoid phenotype. Characteristic classic LCC immunophenotype was loss of staining with CK5/6, CK14 positive in most squamous cell carcinoma (SCC), lack of MOC 31 positive in most adenocarcinomas, and positive immunoreactivity to EGFR, PDGFR-alpha and c-kit. 27 of 82 classic LCC (32.9%) were re-classified as adenocarcinomas, because they coexpressed TTF-1, CK7, and CK19, and were negative for p63. 31 (37.8%) of 82 classic LCC were reclassified as poorly differentiated SCC, based on their immunoreactivity with 34betaE12, p63, thrombomodulin, and CD44v6. 16 (19.5%) of 82 classic LCC correspond to undifferentiated adenosquamous carcinomas, since they displayed conflicting immunostaining for markers of both SCC and adenocarcinomas. The use of 7 immunohistochemical markers, consisting of TTF-1, CK7, CK19, p63, 34betaE12, thrombomodulin, and CD44v6, markedly reduces dramatically to less than 10%, the number of classic LCC by readily identifying cases of poorly differentiated SCCs, adenosquamous carcinoma and adenocarcinomas.

Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens

“…7 Several recent studies showed that immunostains (and previously electron microscopy 42 ) can reveal the line of differentiation as adenocarcinoma vs squamous cell carcinoma in the majority of large cell carcinomas. 26,36,43,44 The proposed TTF-1/p63 algorithm could be used to determine biological identity within the large cell carcinoma, but this needs further study.…”

Utility of Immunohistochemistry in the Diagnosis of Pleuropulmonary and Mediastinal Cancers: A Review and Update

“…21 With additional immunostaining using common SCC and ADC IHC markers, about 34% and 25% of LCCs can be further subclassified as ADC and SCC, respectively. 41,42 In a small-sample setting, IHC analysis for p40, p63, CK5/6, CK5, desmocollin 3, TTF1, or napsin A is used as a predictive tool when the tumor shows no morphologic evidence of differentiation (NSCLCnot otherwise specified); predictive accuracy is around 80% to 85% in most unselected studies. 3,6,7,[11][12][13][14][15][16] A subset of cases may even focally express neuroendocrine markers, including chromogranin (9%) and synaptophysin (15%).…”

Clinicopathological features and prognosis of primary pulmonary lymphoepithelioma-like carcinoma

“…Lymphoepithelioma-like carcinoma (LELC) is one of the rare histological types of lung cancer, classified into one subtype of large cell carcinoma (LCC) (1), with the incidence of 1.15% to 5.90% of total LCC (2,3). It was reported that LELC was commonly found in the relatively young non-smoking Asian population, without a distinctive difference with respect to gender; more than half the patients were at an early stage (stage I and II) and were treated by complete resection (4).…”