Histopathology Image of Large Cell Neuroendocrine Carcinoma 2

Patients with large cell neuroendocrine carcinoma (LCNEC) of the lung are considered to have poor prognosis. However, the benefit of adjuvant chemotherapy for these patients has not been established. In this study, we retrospectively evaluated the efficacy of perioperative chemotherapy for patients with completely resected LCNEC in a single-center setting. From 1999 through 2007, 45 patients with surgically resected LCNEC or mixed LCNEC containing at least one portion of the neuroendocrine differentiation or morphology in non-small cell lung carcinoma were enrolled as participants of this study. Survival rates were calculated by the Kaplan-Meier method. Differences between survival curves were computed with the log-rank test. For multivariate analysis, the Cox's proportional hazards regression model was used to evaluate variables that were significant predictors of survival. Of 1397 patients undergoing surgical resection for primary lung cancer from 1999 to 2007, 45 (3.2%) were classified as LCNEC. Thirty-six (80%) patients were men, and nine (20%) were women. Twenty-four (92%) of 26 patients were present or past smokers. Twenty-three (41%) of 45 patients received perioperative chemotherapy, including seven induction chemotherapies and 16 adjuvant chemotherapies. Survival of patients who underwent perioperative adjuvant chemotherapy was significantly higher than that of those who received surgery alone (P = 0.04). The 5-year survival rate of patients who underwent perioperative adjuvant chemotherapy was 87.5%, whereas that of patients who underwent surgery alone was 58.5%. Even in stage I cases, perioperative adjuvant chemotherapy still favors survival compared with surgery alone. In the Cox proportional hazard multivariate analysis, surgery with or without chemotherapy showed an independent prognostic influence on overall survival (P = 0.0457). Patients who received surgery alone were 9.5 times more likely to die than patients who underwent surgery plus chemotherapy. In conclusion, perioperative chemotherapy will be needed to improve survival in patients with LCNEC. As the population of LCNEC is small, it has been difficult to conduct randomized controlled trials to show the survival benefit of adjuvant chemotherapy. This should be, therefore, evaluated further in prospective multi-institutional phase II trials.

High-grade neuroendocrine carcinoma of the lung: comparative clinicopathological study of large cell neuroendocrine carcinoma and small cell lung carcinoma. Pathol Int. 2009 Aug;59(8):522-9.

Large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC) are high-grade neuroendocrine carcinomas. In order to clarify the similarities and differences between these cancers, 22 cases each of LCNEC and SCLC were collected and a comparative pathological study was carried out. First, their clinicopathological characteristics were confirmed, which were very similar to those previously reported. The 5 year survival rate of LCNEC and SCLC patients was 38.3% and 29.7%, respectively. The morphological characteristics of LCNEC and SCLC were then reviewed with regard to the morphology previously used to differentiate these cancers. As a result, many morphological indicators, such as tumor cell size, nuclear/cytoplasmic ratio, nuclear molding, rosette formation, prominent nucleoli and karyolysis were confirmed to be significant indicators for distinguishing LCNEC from SCLC. On comparative immunohistochemistry, LCNEC had significantly high staining scores for the expression of keratin 7 and 18, E- and P-cadherins, beta-catenin, villin 1, retinoblastoma protein (pRB), c-met and alpha-enolase. These results might reflect the differentiation or deviation of LCNEC toward an epithelial nature irrespective of neuroendocrine tumor lineage. In conclusion, the present comparative study of LCNEC and SCLC defined the similarities and differences between these cancers, and showed the biologically and clinicopathologically overlapping spectrum of the tumor lineage.

Comparison of chemotherapy for unresectable pulmonary high-grade non-small cell neuroendocrine carcinoma and small-cell lung cancer. Lung Cancer. 2009 Aug 20.

BACKGROUND: Pulmonary large cell neuroendocrine carcinoma (LCNEC) shares several features with small cell lung carcinoma (SCLC). Most histologic diagnoses of LCNEC are currently obtained by surgical specimens. While the diagnosis of LCNEC by biopsy specimens is challenging, a definitive diagnosis of this highly malignant tumor is critical in unresectable cases to determine the optimal therapeutic strategy. The objective of this study was to assess the efficacy of chemotherapy for unresectable high-grade non-small cell neuroendocrine carcinoma (HNSCNEC) called by us, which likely includes most LCNECs except for combined types, and to compare the efficacy of chemotherapy for HNSCNEC, with that for extended disease SCLC (ED-SCLC). METHODS: Between September 2002 and October 2007, we reviewed 14 patients with HNSCNEC, which was defined using biopsy specimens according to histological and immunohistological criteria proposed by us. We simultaneously evaluated the clinical response to the chemotherapy and survival time of the 14 HNSCNEC and 77 ED-SCLC patients. RESULTS: The chemotherapy regimens in the 14 patients with unresectable HNSCNEC were platinum-based combination regimens or irinotecan or vinorelbine or docetaxel alone. The chemotherapy regimens in the 77 patients with ED-SCLC were platinum-based combination regimens. We assessed an objective response rate, a one-year survival rate, and median survival time as 50% (7/14), 34% and 10 months, respectively, in the 14 HNSCNEC patients, and as 53% (41/77), 48% and 12.3 months, respectively, in the 77 ED-SCLC patients. CONCLUSION: The clinical efficacy of chemotherapy for unresectable HNSCNECs, including most LCNECs, is comparable to that for ED-SCLC.

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