Neuroendocrine neoplasms (NEN)

Neuroendocrine neoplasms (NEN) originate from the diffuse neuroendocrine system and therefore can arise in any part of the body. In two-thirds of cases, they originate from the gastroenteropancreatic (GEP) tract, and in the remaining cases from the thoracic, cutaneous, paraganglia, skin, etc. 

NEN are usually considered rare neoplasms when compared in terms of incidence with corresponding non-neuroendocrine neoplasms. However, their frequency has significantly increased in recent decades, as reported by epidemiological studies conducted on SEER registries in the United States, which report an increase from 1 to 5 new cases/100,000 inhabitants/year and a prevalence of 35 cases/100,000. Among the main prognostic factors of NEN that affect survival are: the site of the primary tumor (NEN of the ileum generally have a better prognosis than those of the pancreas), the stage according to TNM, the histopathological classification according to WHO, which expresses both the morphological aspect of the tumor and its proliferative activity in terms of the number of mitoses or proliferation index (Ki67). Additional prognostic factors include the expression of somatostatin receptors (which predicts a more favorable clinical behavior compared to non-expression), the spontaneous evolution rate of the tumor, and the patient's age. Clinically, NEN are commonly distinguished into functioning and non-functioning, in relation to the presence or absence of a clinical syndrome related to the production and release into the circulation of one or more hormonal substances. From a pathological anatomical point of view, they are generally divided into well-differentiated and poorly differentiated forms (the latter called neuroendocrine carcinoma or NEC). The former have a well-differentiated, "organoid" growth (in nests, trabeculae, or solid) with minimal atypia, while the latter usually have diffuse, solid growth, with extensive necrosis and marked cytological atypia. In NEC, two groups are recognized, respectively small and large cells, with morphology similar to their pulmonary counterparts, but with inverse frequency (unlike the lung, in GEP NEN up to 75% of cases are large cell NEC). It is also not uncommon to find coexisting associated neoplastic components (mixed forms of neuroendocrine carcinoma and adenocarcinoma, called MINEN), and this also includes the search for possible precancerous lesions in the peritumoral tissue. This is recommended especially in the stomach, where, in addition to the diagnosis of type I gastric carcinoid, foci of linear or nodular hyperplasia of enterochromaffin-like (ECL) cells may coexist in the context of chronic atrophic gastritis of the gastric body. Or in the thoracic district in the case of TUMORLET. NEN are rare neoplasms, due to their complexity and peculiarity, they should be framed by a panel of expert clinicians and pathologists within multidisciplinary diagnosis and care groups. 

Classification 

Neuroendocrine tumors of the esophagus, stomach, pancreas, biliary tract, colon, rectum, lung, thymus. Pheochromocytomas, paragangliomas, Merkel cell carcinomas, other neuroendocrine tumors.