[Current WHO classification (2022) of neuroendocrine neoplasms]

After the first description of the "carcinoid tumors" by the pathologist Siegfried Oberndorfer in Munich, the classification system of neuroendocrine neoplasms (NENs) is still a challenge and an evolving concept.

The new WHO classification system proposed a framework for universal classification.

The new WHO classification system recognizes two distinct families distinguished by genetic, morphology and clinical behaviour: Well differentiated NENs are defined as neuroendocrine tumor (NET G1, G2, G3), while poorly differentiated ones are defined as neuroendocrine carcinoma (NEC, G3) and further subdivided into small and large cell carcinoma. All NENs are characterized by the expression of synaptophysin and chromogranin A, Ki-67 and morphology.

The morphological NEN dichotomy is supported by genetic alterations. NECs show TP53 and RB1 alterations that are absent in NETs and are therefore useful for differentiating between NETs and NECs.

All NENs are divided into well-differentiated neuroendocrine tumor (NET G1, G2, G3) or poorly differentiated neuroendocrine carcinoma (NEC, G3). They are categorized by morphology, mitotic count and immunohistochemistry with synaptophysin, chromogranin and Ki-67.