Large cell neuroendocrine carcinoma (LCNEC) is a rare pulmonary tumor, diagnosed based on high-grade features (>10 mitotic figures in 2 mm2 of viable tumor), and the presence of both neuroendocrine morphology as well as immunohistochemical evidence of neuroendocrine markers. However, application of the latter requirement to cytologic specimens and small biopsies, as opposed to resected tumors, is problematic [1-3]. LCNECs do not meet the criteria for the three better recognized neuroendocrine tumors (carcinoid, atypical carcinoid, and small cell carcinoma). (See "Pathology of lung malignancies", section on 'Large cell neuroendocrine carcinoma'.)
The clinical presentation and natural history of LCNEC appear similar to the other high-grade neuroendocrine pulmonary tumor, small cell lung carcinoma (SCLC), with two exceptions: primary LCNECs tend to be located peripherally rather than centrally and presentation of LCNECs with early stage (I-II) disease is more common than for SCLC (approximately 25 percent versus less than 5 percent). Thus, patients with LCNEC more commonly undergo resection. Further, because LCNEC can be a difficult diagnosis based on needle aspirate or small biopsy, the diagnosis is frequently made post-resection.
Most studies indicate that survival is worse for LCNEC compared to non-small cell carcinoma and other large cell carcinomas, and similar to that of SCLC [1,3]. In a surveillance epidemiology and end results (SEER) database study of 1444 early stage patients who underwent resection only (no radiation therapy and no information regarding chemotherapy), a numerically worse four-year survival rate was observed in patients with SCLC, compared to LCNEC and other large cell carcinomas . However multivariate analysis demonstrated no significant difference in overall or lung cancer-specific survival between LCNEC and SCLC, nor between LCNEC and other large cell carcinomas. These data should not alter the general impression that LCNEC carries a relatively poor prognosis given the limitations of this analysis . (See "Overview of the risk factors, pathology, and clinical manifestations of lung cancer" and "Overview of the initial evaluation, treatment and prognosis of lung cancer".)
Because of the rarity of LCNEC, there are no clinical trials that define the optimal treatment approach for either localized or advanced disease . Treatment recommendations are based upon extrapolation from the approach to patients with non-small cell lung cancer and small cell lung cancer and the established literature, which is primarily retrospective in nature. Because of the worse prognosis compared with other forms of non-small cell lung cancer, adjuvant chemotherapy may offer the best chance to improve survival. Data supporting this are summarized in a comprehensive review and small prospective studies. [1,5-7].