Well-Differentiated Neuroendocrine Carcinomas: The Spectrum of Histologic Subtypes and Various Clinical Behaviors

The term “well-differentiated neuroendocrine carcinoma” was coined to describe a variety of demonstrably neuroendocrine tumors which were more aggressive (both with respect to their histologic appearance and their clinical course) than (typical) bronchial carcinoids but were also clearly distinguishable from small cell neuroendocrine carcinomas. This umbrella term encompasses a variety of tumors previously described by a variety of terms including “atypical” carcinoids, “malignant tumorlets,” peripheral stage I small-cell carcinoma, as well as neoplasms described simply as “undifferentiated carcinoma” (prior to the recognition of their neuroendocrine properties). As such, this term is a broad term and is not simply synonymous with “atypical carcinoid.” Over time, at least 3 subtypes have been identified based upon their histologic appearance and mitotic index, with correspondingly aggressive clinical courses.