Neuroendocrine neoplasms comprise a group of tumors derived from a diffuse system of neuroendocrine cells in various tissues and organs. A common feature of these tumors is the existence of neuroendocrine secretory vesicles within the tumor cells. Neuroendocrine neoplasms form a spectrum ranging from well-differentiated neuroendocrine tumors (NET), traditionally known as carcinoids, to poorly differentiated neuroendocrine carcinomas (NEC), such as small or large cell carcinomas. The cause of most neuroendocrine neoplasms is unknown and they may be associated with inherited syndromes such as Multiple endocrine neoplasia type 1 and 2 (MEN1, MEN2), von Hippel-Lindau syndrome, neurofibromatosis type 1, or tuberous sclerosis.
Neuroendocrine neoplasms show variable expression of different endocrine markers and clinical symptoms vary depending on the levels and composition of secreted proteins (hormones). Several NETs are endocrinologically silent.
The most common locations for NETs are the gastrointestinal tract (55%) and lungs (25%). NETs growing in the gastrointestinal tract are sub-classified according to anatomic location into gastric, duodenal, small intestine, jejunoileal, appendiceal, colonic, and rectal NENs, all displaying differences in secreted proteins, symptoms, and aggressiveness.
Microscopically, classical NETs are characterized by the formation of well-defined nests of tumor cells separated by thin fibrovascular septa and populations of tumor cells with a homogeneous appearance. The tumor cells are relatively small and round with abundant lightly eosinophilic and granular cytoplasm, and small nucleoli (described as “salt and pepper chromatin”). Mitotic figures are often absent or rare and are used for tumor grading together with immunohistochemical marker Ki-67. Necrosis can be punctate in higher grade NETs (atypical carcinoids) or extensive in carcinomas which also have a higher degree of cellular atypia and mitosis.
Immunohistochemistry has played an important role to define NENs. Commonly used antibodies include anti-chromogranin A (CHGA) and anti-synaptophysin (SYP) to determine neuroendocrine differentiation and various antibodies towards the different hormones and peptides that are produced and secreted by the tumor cells.
All NENs have a metastatic potential but higher grade NETs and NECs show a greater tendency for aggressive growth and metastatic spread. Treatment and prognosis vary among NENs and depend on the anatomic location, histological grade, and the stage of the disease. Rectal NETs have the best prognosis among all gastrointestinal NETs.