Gl-NETs—Uniform But Also Diverse

In the 100 years since the term Karzinoid was first coined by Siegfried Oberndorfer to describe gastrointestinal tumors that resembled carcinomas but pursued a relatively indolent course, these tumors have captured the attention, not only of internists, surgeons, endocrinologists, and pathologists but of biochemists, physiologists, geneticists, and molecular biologists as well. Initially thought to be limited to the gut, these tumors were soon found to arise in a variety of other organs as well. With the gradual evolution of the concept of a dispersed neuroendocrine cell system and the recognition that it was made up of a galaxy of at least 20 or so functionally distinct cell types (each of which could potentially give rise to a specific type of tumor, each of which could in turn be endocrinologically functional or silent), came the realization that carcinoids should perhaps be considered as a family of neoplasms that, despite sharing certain commonalities, can however, show significant heterogeneity among themselves in some of their other features. While it may seem that our knowledge of this fascinating group of tumors has improved significantly, a closer look reveals that we may have just begun to scratch the surface.