Pulmonary large cell carcinomas with neuroendocrine features are high-grade neuroendocrine tumors

Background. In 1999, the World Health Organization (WHO) categorized large cell carcinoma with neuroendocrine features as variants of large cell carcinoma and reclassified neuroendocrine lung tumors, especially typical and atypical carcinoid tumors. However, to date, the clinical relationship between these categories of neuroendocrine lung tumors has not been clearly defined. Methods. We analyzed 133 cases of neuroendocrine tumors from primary lung carcinoma cases surgically resected. Using electron microscopy and immunohistochemical staining, we classified these cases as typical carcinoid (TC), atypical carcinoid (AC), large cell carcinoma with neuroendocrine features (LCNF), or small cell lung carcinoma (SCLC) based upon the WHO classification. Results. TC and AC tumors were not related to smoking (p < 0.001) and, unlike LCNF, were found in younger patients (p < 0.001) without a male predominance (p < 0.001). Multivariate analysis revealed that LCNF predicted poorer overall and disease-free survivals comparable with SCLC (overall survival, p = 0.019, hazards ratio, 6.34; disease-free survival, p = 0.007, hazards ratio, 8.19). Conclusions. The prognoses of LCNF are comparable with those of SCLC, and LCNF should be classified as high-grade neuroendocrine tumors.