Oberndorfer and His Successors: From Carcinoid to Neuroendocrine Carcinoma

The year 2007 the centenary of Siegfried Oberndorfer’s seminal description of special tumors of the small intestine which he called “Karzinoide Tumoren” (carcinoids). Their endocrine nature was suggested by Pierre Masson in 1914. The work of Friedrich Feyrter and later Anthony Pearse established the concept of a diffuse endocrine cell system. They suggested that there is a family of endocrine cells whose members originate at different sites in the organism and give rise to similar tumors, the carcinoids. Subsequent studies revealed that the individual members of the endocrine cell system are distinguished from each other by the expression of specific polypeptides (i.e., hormones). Common to all of these cells is the expression of general markers such as synaptophysin and chromogranin A. This led to the term neuroendocrine cell system and consequently neuroendocrine tumor. Although many tumors are similar in histological appearance, biologically they show heterogeneity, which has important implications for treatment. Therefore, efforts have been made to define the neuroendocrine neoplasms on the basis of features that discriminate the tumors with almost no risk/low risk of malignancy from low-grade and high-grade malignant tumors. For the gastroenteropancreatic neuroendocrine tumors, this resulted in a new World Health Organization classification that was recently followed by a tumor–nodes–metastasis classification.