Lung Cancer Histologic and Immunohistochemical Heterogeneity in the Era of Molecular Therapies Analysis of 172 Consecutive Surgically Resected, Entirely Sampled Pulmonary Carcinomas

On the basis of seminal studies in the 1980s, appreciable histologic heterogeneity, ranging from 45% to 70% of cases, may be encountered in lung cancer. However, the epidemiologic and histologic landscape of lung cancer in the last 3 decades has radically changed. In this study, 172 consecutive surgically resected primary lung carcinomas evaluated from 2010 to 2012 were entirely sampled and examined according to current histologic classifications. In 129 cases, a positive preoperative biopsy was also available. Major histologic heterogeneity (a single tumor showing at least 2 different histologic types) and minor histologic heterogeneity (a single tumor showing just 1 histologic type but at least 2 different growth patterns) were evaluated in all cases. Immunohistochemical heterogeneity (ie, "aberrant" staining) was also assessed using a panel of markers of adenocarcinoma (TTF-1, napsin, and CK7), squamous cell carcinoma (p63, CK5/6), and neuroendocrine differentiation (chromogranin and synaptophysin), both on positive biopsies and surgical specimens. Overall, major and minor histologic heterogeneity on resections were disclosed in 4% (7 cases) and 50.6% (87 cases), respectively, whereas just 1 case of minor heterogeneity (pleomorphic carcinoma) was observed on biopsies. Minor heterogeneity was limited to adenocarcinomas (82.6%, 81/98 cases) and sarcomatoid carcinomas (6 pleomorphic types among 8 sarcomatoid carcinomas). Immunohistochemical heterogeneity was recorded in 22.6% of the cases, with expression of p63 and CK5/6 in a subset of adenocarcinomas (25 cases, 25.5%), CK7 in 17.4% of squamous cell carcinomas, and synaptophysin in 6 cases of non-neuroendocrine tumors (4%, 6/155). The high rate of adenocarcinomas, accounting for 57% (98 cases) of 172 consecutively resected lung cancers, reflects the new scenario of thoracic oncology and may explain the significant lower rate of major histologic heterogeneity (4%) and the higher frequency of different architectural patterns (minor heterogeneity) that we found in lung cancer compared with previous studies.