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Semin Diagn Pathol. 1985 Nov;2(4):235-54.

Carcinomas of the lung with neuroendocrine differentiation.


While there are examples of each of the histologic types of bronchogenic carcinoma in which ectopic hormone production has been demonstrated, three groups of lung cancers manifest this type of differentiation with great regularity. These are the carcinoid, atypical carcinoid, and the small cell carcinoma, which have been called neuroendocrine carcinomas of the lung. The carcinoids are neoplasms with a heterogeneous array of histologic appearances that share relatively uniform nuclear features, the absence of both tumor necrosis and mitotic figures, and a good prognosis. Neuroendocrine differentiation is demonstrable with such regularity in carcinoids that the diagnosis is not considered tenable in the absence of at least one of the following features: argyrophilia, the demonstration of neuron-specific-enolase or neuropeptides by immunohistochemistry or other techniques, or the demonstration of numerous dense-core membrane-bound granules, usually 150 to 250 nm in diameter, by electron microscopy. The atypical carcinoids (well or moderately differentiated neuroendocrine carcinomas) share the neuroendocrine differentiation of the carcinoids and many of their histologic features, but are distinguished by the presence of tumor necrosis, more anaplastic large cell nuclei with numerous mitotic figures, and a distinctly worse prognosis. They are a heterogeneous lot with some similarities to carcinoids, small cell carcinomas, and large cell or adenocarcinomas. The demonstration of at least one of the neuroendocrine features listed above is considered necessary for this diagnosis. Small cell carcinoma is also a heterogeneous group of neoplasma primarily distinguished by their finely granular chromatin pattern which correlates with a much worse prognosis but a higher likelihood of response to chemotherapy and radiotherapy. Many small cell carcinomas share the neuroendocrine differentiation of the carcinoids or atypical carcinoids, but some do not and the demonstration of these features is not a requisite for inclusion in the small group. The morphologic demonstration of neuroendocrine differentiation may be more difficult in small cell carcinomas, but they more frequently produce clinically important amounts of ectopic neuropeptides. While the term neuroendocrine carcinoma of the lung includes several quite different entities and does not by itself convey histogenetic or prognostic implications, the demonstration of neuroendocrine differentiation in pulmonary neoplasms is an important procedure when combined with the recognition of other cytologic and histologic features.

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