Mixed endocrine
tumors are
tumors composed of at least two distinct
tumor populations, one of which is endocrine. Because of their rarity and unusual presentation, endocrine mixed
tumors raise many problems of diagnosis, management and
therapy. Three main types of endocrine mixed
tumors are recognized: The existence of these various types has been confirmed by recent molecular studies, even if the same studies have also shown that the histogenesis of a mixed endocrine
tumor cannot be predicted from its histological features. Composite
tumors are the less rare mixed
tumors. The recent WHO classification recommends to restrict the term of composite endocrine
tumor to the epithelial
tumors containing at least 30% of obviously tumoral endocrine cells; some authors recommend to use higher thresholds, of at least 50%, in order to avoid overdiagnosis. The endocrine component is usually well differentiated, easily identified by its suggestive histological features; the endocrine nature of
tumor cells is confirmed by the immunodetection of specific endocrine and neuro-endocrine markers (such as
chromogranin A and
synaptophysin). In some cases, the endocrine component is poorly differentiated: the demonstration of neuro-endocrine markers is necessary to confirm the diagnosis. Mixed
tumors can occur in every anatomical site; they are more frequent in organs containing endocrine cells in the normal state (especially the digestive tract and the pancreas), but they can also be observed in organs devoid of endocrine cells (such as the mammary gland). The management of mixed endocrine
tumors must take into account the more aggressive component. Mixed
tumors containing a well differentiated endocrine component and an adenocarcinomatous component are to be treated like
adenocarcinomas. Mixed
tumors containing a poorly differentiated endocrine component must be considered as poorly differentiated endocrine
carcinomas.