Pulmonary Large Cell Neuroendocrine Carcinoma: Its Place in the Spectrum of Pulmonary Carcinoma⁎

In 1999, the World Health Organization categorized large cell neuroendocrine carcinoma (LCNEC) as a variant of large cell carcinoma. The World Health Organization categorization not only classified histologic types of large cell carcinomas of the lung in detail, but also revealed that histologic subtypes of lung carcinomas were closely related to the prognosis of patients with those carcinomas. Large cell neuroendocrine carcinomas are common tumors that are now more frequently diagnosed by pathologists as recognition of LCNEC improves. Since the first report of LCNEC in 1991, many authors have reported that LCNECs are aggressive tumors and that patients with LCNECs have a very poor prognosis. Although LCNEC is categorized as a variant of large cell carcinoma, the biological behaviors of LCNEC tumors resemble those of small cell lung carcinomas, and LCNEC reveals the feature of a high-grade neuroendocrine tumor. Because patients with LCNEC have a poor prognosis, surgery alone is not sufficient. Multimodality therapies (including adjuvant chemotherapy) appear to be promising for the improvement of the prognosis in patients with LCNEC, even if the pathologic stage is IA, and should be evaluated further in larger multi-institutional trials.