Historical background and natural history of carcinoids

Historically, carcinoids are a morphologically distinct class of rare intestinal tumors that behave less aggressively than the more common intestinal adenocarcinomas. Their endocrine nature was recognized much later. Some authors restrict the term carcinoid to intestinal endocrine tumors, and others include a large variety of neuroendocrine tumors. In this review the following definition is given: Carcinoids are tumors of the diffuse endocrine system which are either benign or neoplasms with a more favorable prognosis than carcinomas; they are characterized by a typical growth pattern, silver affinity and positive immunohistochemical reaction with neuron-specific markers, and can express different peptides and biogenic amines. Neuroendocrine tumors originating from the endocrine glands (pituitary, thyroid, adrenals, pancreas) are excluded from the carcinoid group of neoplasms and therefore are highly malignant neuroendocrine carcinomas. For the natural history of carcinoid tumors, several independent predictive parameters can be defined: size, site of origin, growth pattern, and hormone dependence. The number of neuropeptides and amines expressed by a carcinoid or the amount of biologically active neurohormones secreted (and eventually producing a clinical syndrome) are of no prognostic significance regarding malignancy. Only the association of an endocrine tumor with an inappropriate endocrine syndrome seems to be predictive of malignancy.