Endocrine Pathology

, Volume 27, Issue 4, pp 284–311 | Cite as

Mixed Neuroendocrine-Nonneuroendocrine Neoplasms (MiNENs): Unifying the Concept of a Heterogeneous Group of Neoplasms

  • Stefano La Rosa
  • Fausto Sessa
  • Silvia Uccella


The wide application of immunohistochemistry to the study of tumors has led to the recognition that epithelial neoplasms composed of both a neuroendocrine and nonneuroendocrine component are not as rare as traditionally believed. It has been recommended that mixed neuroendocrine-nonneuroendocrine epithelial neoplasms are classified as only those in which either component represents at least 30 % of the lesion but this cutoff has not been universally accepted. Moreover, since their pathogenetic and clinical features are still unclear, mixed neuroendocrine-nonneuroendocrine epithelial neoplasms are not included as a separate clinicopathological entity in most WHO classifications, although they have been observed in virtually all organs. In the WHO classification of digestive tumors, mixed neuroendocrine-nonneuroendocrine neoplasm is considered a specific type and is defined as mixed adenoneuroendocrine carcinoma, a definition that has not been accepted for other organs. In fact, this term does not adequately convey the morphological and biological heterogeneity of digestive mixed neoplasms and has created some misunderstanding among both pathologists and clinicians. In the present study, we have reviewed the literature on mixed neuroendocrine-nonneuroendocrine epithelial neoplasms reported in the pituitary, thyroid, nasal cavity, larynx, lung, digestive system, urinary system, male and female genital organs, and skin to give the reader an overview of the most important clinicopathological features and morphological criteria for diagnosing each entity. We also propose to use the term “mixed neuroendocrine-nonneuroendocrine neoplasm (MiNEN)” to define and to unify the concept of this heterogeneous group of neoplasms, which show different characteristics mainly depending on the type of neuroendocrine and nonneuroendocrine components.


Mixed neoplasm Neuroendocrine Mixed adenoneuroendocrine carcinoma Composite tumor Combined tumor Classification 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of PathologyOspedale di CircoloVareseItaly
  2. 2.Department of Surgical and Morphological SciencesUniversity of InsubriaVareseItaly

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