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Large cell neuroendocrine carcinoma (LCNEC) is part of the neuroendocrine spectrum of lung cancer. LCNEC of the lung displays morphologic and immunohistochemistry characteristics common to neuroendocrine tumors and morphologic features of large cell carcinoma.

Large cell neuroendocrine carcinoma is composedof cells with moderate amounts of cytoplasm and nuclei that show peripheral clumping of chromatin, a prominent nucleolus, and much mitosis activity and extensive necrosis, as seen in any large cell carcinoma. However, the tumor cells are arranged in well-demarcated groups or cords with peripheral palisading. This feature is reminiscent of a carcinoid pattern, and the relationship to carcinoid is strengthened by shared immunocytochemistry and ultrastructural features of neuroendocrine differentiation such as the presence of neural cell adhesion molecule (CD56), chromogranin A, synaptophysin, and scanty dense-core granules. Certain squamous cell carcinomas also show these neuroendocrine features – these have been termed nonsmall-cell carcinoma with neuroendocrine features.

Neuroendocrine differentiation can be demonstrated by electron microscopy or immunohistochemistry in 10–15% of non-small-cell carcinomas of the lung despite an absence of morphological neuroendocrine features. Differential diagnosis of large cell neuroendocrine carcinoma includes atypical carcinoid tumor but the organoid pattern of that tumor is not so well developed and the degree of atypia, mitotic activity, and necrosis all far exceed those seen in an atypical carcinoid (which has between 2 and 10 mitoses per 2 mm square [ј10 high power fields]). In general, large cell neuroendocrine carcinomas are tumors of middle-aged or elderly cigarette smokers that arise in the central bronchi. Despite the morphological evidence of neuroendocrine differentiation, ectopic hormone secretion is not a feature. Patients with large cell neuroendocrine carcinomas have a significantly worse survival after resection than patients with large cell carcinomas, even in stage I disease. Accurate differentiation of large cell neuroendocrine carcinoma from large cell carcinoma is important because it identifies those patients at highest risk for the development of recurrent lung cancer. The clinical significance of these tumors has yet to be fully evaluated but their recognition is of potential therapeutic significance for their undoubted neuroendocrine nature links them to classic small cell carcinoma and it would be important if their metastases were similarly sensitive to chemotherapy.

However, reports available to date regarding their chemosensitivity are contradictory and as yet there have been no large-scale, prospective, controlled trials of small cell chemotherapy for this subgroup of large cell carcinomas or for other non-small-cell carcinomas showing neuroendocrine differentiation. Furthermore, the clinical importance of neuroendocrine differentiation may diminish if a current trend toward treating all inoperable lung carcinomas with aggressive chemotherapy continues.





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