Neuroendokrine Neoplasien: Zwei Familien mit sehr unterschiedlichen Charakteristika vereint in einer Klassifikation

All neuroendocrine neoplasms (NENs) are characterized by the expression of synaptophysin and chromogranin A (or B). Yet, they are not a homogeneous group of tumors. Paradigmatic for these tumors are the NENs of the gastroenteropancreatic (GEP) system. Two NEN families can be distinguished: predominantly well differentiated and low-proliferative NENs, called neuroendocrine tumors (NET), and poorly differentiated and high-proliferative NENs, called neuroendocrine carcinomas (NECs). Based on their proliferative activity, GEP NETs are further classified into G1, G2, and G3 tumors. NECs are per definition G3 carcinomas. The morphological NEN dichotomy is supported by differences in epidemiology, genetics, clinics, and prognosis, and potentially has its cause originating from different progenitor cells. Genetically, NECs are distinguished by TP53 and RB1 alterations, which are lacking in NETs and are helpful in the distinction of NETs from NECs. Comparison of the GEP NEN WHO classification with extragastroenteropancreatic NEN classifications commonly reveal differences in terminology and categorization. In addition, they lack a grading system. However, common to all NEN classifications is the recognition of two tumor families differing in histological differentiation and prognosis. This allows the construction of a uniform classification frame for all NENs.