Neuroendocrine Differentiation in Thymic Carcinomas: A Diagnostic Pitfall

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Objectives: Neuroendocrine differentiation in carcinomas of the nonneuroendocrine type has been observed in various organ systems. Awareness of this phenomenon is important since such tumors need to be separated from true neuroendocrine neoplasms because of therapeutic and prognostic consequences. To investigate this occurrence in thymic carcinomas, 27 cases of different histologies were analyzed using neuroendocrine immunohistochemical markers.

Methods: Twenty-seven conventional thymic carcinomas from thymectomies were studied immunohistochemically with antibodies directed against synaptophysin, chromogranin A, and CD56 in addition to the standard markers for these tumors.

Results: Focal expression of at least one neuroendocrine marker was identified in a total of 12 (44%) cases. Chromogranin A was positive in five (19%) cases, synaptophysin in eight (30%), and CD56 in 10 (37%). All three markers were coexpressed in four (15%) cases.

Conclusions: Neuroendocrine differentiation in conventional thymic carcinomas is a common occurrence. It is imperative to separate these tumors from true neuroendocrine neoplasms of the thymus—especially large cell neuroendocrine carcinoma—since both entities require different treatment modalities and likely show different biologic behavior. Contrary to prior suggestions, neuroendocrine differentiation should not be used to distinguish thymic carcinomas from thymomas, and these tumors should not be regarded as “mixed carcinomas.”

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