This paper briefly illustrates the basis, rules of application, and present outcome of the current World Health Organization (WHO) classification for neuroendocrine neoplasms. Established in 2010 upon the proposal from the European Neuroendocrine Tumor Society (ENETS), the WHO 2010 fostered some definitional changes (most notably the use of neuroendocrine tumor (NET) instead of carcinoid) and indicated the tools of grading and staging. Specific rules for its application were also defined. The data generated from the use of WHO 2010 classification substantially endorsed its rules and prognostic efficacy. In addition, the application demonstrated some issues, among which are the possible re-definition of the cutoff for grading G1 vs G2, as well as the possible identification of cases with somewhat different clinical behavior within the G3 neuroendocrine cancer class. Overall, since the recent introduction of WHO 2010 grading and staging, it appears wise to keep the current descriptors to avoid unnecessary confusion and to generate comparable data. Homogenous data on large series are ultimately needed to solve such issues.
Tumors of the disseminated/diffuse neuroendocrine system (NET) are characterized by a common phenotype. However, the biology varies according to histomorphology, endocrine symptoms and organ of origin. The WHO classification takes these differences into account and uses a common framework, where the parameters size and extent of invasion vary according to the organ of origin. In order to achieve a further standardization of reporting the European Neuroendocrine Tumor Society (ENETS) recently proposed a tumor-node-metastasis (TNM) staging and grading system for gastro-entero-pancreatic NET.
During the last 5 years the European Neuroendocrine Tumor Society (ENETS) has developed basic recommendations for a standardized pathological diagnosis and classification of neuroendocrine neoplasms (NEN) of the gastroenteropancreatic system. These were included in the novel classification of tumors of the digestive system by the World Health Organization (WHO 2010) and the TNM classification of the union for international cancer control (2009). This review presents the pathology diagnosis regarding (1) basic diagnosis, (2) clinically relevant optional diagnosis, (3) proliferation-based grading, (4) nomenclature and (5) TNM classification. It is emphasized that a standardized diagnosis of NEN, together with clinical and radiological findings, is crucial for prognostic stratification and optimal therapy of patients with NEN. Therefore a close interdisciplinary collaboration is essential.