Two novel multiple endocrine neoplasia type 1 variants caused thymic neuroendocrine tumor: a case report

Multiple endocrine neoplasia type 1 (MEN1), or Wermer’s syndrome, is a rare autosomal dominant genetic disorder caused by MEN1 mutations, which rarely result in thymic tumors. However, effective therapies or standard treatments are still lacking for patients with MEN1-associated tumors. Some patients with MEN1-associated tumors, such as parathyroid carcinoma and insulinoma, have both germline and somatic MEN1 mutations, consistent with Knudson’s two-hit hypothesis. However, this hypothesis has seldom been reported in connection with MEN1-associated thymic tumors. Herein, we observed a family carrying the MEN1 p.L105Sfs*14 mutation in which two males were diagnosed with MEN1-associated thymic neuroendocrine tumors (NETs). The proband was diagnosed with a left adrenal cortical adenoma and underwent surgery at 49 years of age. After two years, he underwent another surgery for thymic NET. The proband’s son underwent robot-assisted resection at the age of 29 years. Whole exome sequencing (WES) and 425 cancer-related gene panel sequencing revealed that they both had the same germline MEN1 p.L105Sfs*14 mutation and that the son carried the somatic MEN1 p.Q96* mutation. We present a case of two novel MEN1 variants (p.L105Sfs*14 and p.Q96*) in thymic NET. These mutations have not been previously reported in patients with MEN1-associated thymic NET; they resulted in the production of a truncated menin protein. The two-hit of MEN1 germline and somatic mutations occurred in the thymic tumor of the proband’s son. This may partially be the reason for early tumor onset and is consistent with the “two-hit hypothesis”.