Reproducibility of Histopathological Diagnosis in Poorly Differentiated NSCLC: An International Multiobserver Study

The 2004 World Health Organization classification of lung cancer contained three major forms of non–small-cell lung cancer: squamous cell carcinoma (SqCC), adenocarcinoma (AdC), and large cell carcinoma. The goal of this study was first, to assess the reproducibility of a set of histopathological features for SqCC in relation to other poorly differentiated non–small-cell lung cancers and second, to assess the value of immunohistochemistry in improving the diagnosis. Resection specimens (n = 37) with SqCC, large cell carcinoma, basaloid carcinoma, sarcomatoid carcinoma, lymphoepithelial-like carcinoma, and solid AdC, were contributed by the participating pathologists. Hematoxylin and eosin (H&E) stained slides were digitized. The diagnoses were evaluated in two ways. First, the histological criteria were evaluated and the (differential) diagnosis on H&E alone was scored. Second, the added value of additional stains to make an integrated diagnosis was examined. The histologic criteria defining SqCC were consistently used, but in poorly differentiated cases they were infrequently present, rendering the diagnosis more difficult. Kappa scores on H&E alone were for SqCC 0.46, large cell carcinoma 0.25, basaloid carcinoma 0.27, sarcomatoid carcinoma 0.52, lymphoepithelial-like carcinoma 0.56, and solid AdC 0.21. The κ score improved with the use of additional stains for SqCC (combined with basaloid carcinoma) to 0.57, for solid AdC to 0.63. The histologic criteria that may be used in the differential diagnosis of poorly differentiated lung cancer were more precisely refined. Furthermore, additional stains improved the reproducibility of histological diagnosis of SqCC and AdC, uncovering information that was not present in routine H&E stained slides.