Primary neuroendocrine carcinomas of the mediastinum: review of current criteria for histopathologic diagnosis and classification

Primary neuroendocrine neoplasms occurring in the mediastinum are rare. The spectrum of such tumors can range from low- to high-grade neoplasms. The histogenesis of these tumors is varied, and some of them may originate from ectopic tissues in the mediastinum whereas others represent tumors native to the thymus. Primary thymic neuroendocrine carcinomas therefore need to be separated from other neuroendocrine neoplasms of the mediastinum, namely ectopic parathyroid tumors and paragangliomas. The histopathologic classification of primary neuroendocrine carcinomas of the mediastinum is still under debate and continues to be controversial, as is attested to by the different publications on the topic. Some authors continue to use old terms such as “carcinoid” and “atypical carcinoid” to designate these lesions, whereas others favor the use of a more unifying nomenclature that acknowledges the malignant nature of these lesions, namely that of neuroendocrine carcinoma. However, one aspect that all agree on is that, when they occur in the thymic region, these tumors should be considered as aggressive neoplasms capable of local recurrence and distant metastasis. This review will center on the morphologic spectrum of neuroendocrine carcinomas of the thymus, with special emphasis on diagnostic features and criteria for classification.