Search

Neuroendocrine neoplasms (NENs) are made by transformed cells producing hormone/mediators and characterized by the shared expression of some neural-specific antigens. NENs may arise in nerve structures, endocrine organs, and in the diffuse neuroendocrine system at various organs and apparata. The rarity, complexity, and diversity of NENs impaired the development of shared definition and classification. Organ-specific classifications have been historically developed and are in use and formalized under the World Health Organization authority. Common classification themes however do exist including common morphology features for most well-differentiated low-grade tumors and for high-grade, poorly differentiated carcinomas, though with diverse prevalence at different anatomical sites. Common features and specific classifications schemes are briefly discussed here.

The cancer classification reflects the current status of the knowledge on the type of tumor for which it is built. In the case of neuroendocrine neoplasms, the current classification here detailed is the latest produced by the World Health Organization (WHO) in 2010. The WHO 2010 classification, besides the usual morphological ground on which is based, utilizes the instruments of grading and staging to formally define the malignancy of neuroendocrine neoplasm. Grading is based on proliferation as defined by mitotic count and Ki67 in a three-tier system with G1 (mitotic count 20; Ki67 >20 %). The rules of application require the count of mitoses in areas of highest mitoses presence and for Ki67 in areas of highest nuclear labeling, counting mitoses in at least 50 HPF and then normalizing to 10 HPF, and for Ki67 counting the % of labeled cells in 400–2,000 cells. The grading tool proved to be an effective prognostic instrument separating patients for progressive death risk in three statistically significant different groups. The staging tool is based on current staging parameters including tumor (T), lymph node (N), and metastasis (M). However, two staging systems are currently available: the one endorsed by major agencies including the International Union for Cancer Control (Union Internationale Contre le Cancer, UICC), the American Joint Committee on Cancer (AJCC), and the WHO, which is the very same as the one adopted for the pancreatic adenocarcinoma, and the other proposed by the European Neuroendocrine Tumor Society (ENETS). Both systems are equally effective, though at direct comparison the ENETS system better described the neuroendocrine neoplasm disease.