Poorly Differentiated Gastroenteropancreatic Neuroendocrine Carcinoma Associated with X-Linked Hyperimmunoglobulin M Syndrome (Case Report) (Disease/Disorder Overview‪)‬

Neuroendocrine tumors (NETs) arise from the cells of the disseminated neuroendocrine system, which is widely distributed in the body. These are a rare and heterogeneous group of neoplasms characterized by differences in embryologic, biologic, and histopathologic aspects. (1) Gastroenteropancreatic NETs constitute about 2% to 3% of all gastrointestinal malignancies. In 2000, a new World Health Organization classification was established for gastroenteropancreatic NETs. These are now classified according to the classic structural criteria combined with proliferation index (measured by Ki-67) into well-differentiated NETs (proliferation index, 2%), well-differentiated neuroendocrine carcinoma (proliferation index, 2% but 15%), poorly differentiated neuroendocrine carcinoma (15%), mixed exocrine-endocrine tumors, and tumorlike lesions. (2) Hyperimmunoglobulin M (hyper-IgM) syndrome encompasses a family of congenital immunodeficiency states characterized by frequent infections and markedly low serum levels of IgG, IgA, and IgE but normal or elevated level of IgM. (3) The major defect shared by all forms of the hyper-IgM syndrome is failure of immunoglobulin isotype switching. Mutations affecting at least 5 different genes have been identified to cause this immunodeficiency disorder. (4,5) These genes are involved directly or indirectly in B-cell signaling via CD40 and are required for class switching and somatic hypermutation. The most common form of hyper-IgM syndrome is X-linked and is due to mutation of the CD40 ligand (CD40L) gene. (5) Most of these patients present with severe recurrent infections in early childhood. These patients are also at a higher risk for developing malignancies, particularly adenocarcinoma of the gastrointestinal tract and lymphoma. (3) In this case study, we describe association of poorly differentiated gastroenteropancreatic neuroendocrine carcinoma in a patient with X-linked immunodeficiency with hyper-IgM (XHIGM).