Novel association of thymic carcinoid with a germline mutation in a kindred with multiple endocrine neoplasia 1 (MEN1)

Multiple endocrine neoplasia 1 (MEN1) is an autosomal dominant syndrome characterized by a triad of endocrine (parathyroid, enteropancreatic and pituitary) tumors. Familial MEN1 is defined by one first-degree relative having at least one of these 3 main tumors, and is associated with germline mutations in the MEN1 gene on 11q13 in a large proportion of cases. MEN1 patients may also develop non-endocrine tumors, notably thymic carcinoid. These are rare tumors found predominantly in men, and are a major cause of death in MEN1 due to their insidious nature, lack of effective treatment and unpredictable recurrence. Prophylactic thymectomy has been advocated for prevention but continued surveillance for recurrence is necessary. Although genotype-phenotype correlation in MEN1-related thymic carcinoid is inconsistent, there is a high prevalence of truncating mutations in this condition. We describe a father and son with MEN1, associated with thymic carcinoid (father) and the truncating mutation R29X (son), which was not previously reported in MEN1-related thymic carcinoid, and review the literature about thymic carcinoids in MEN1. Our cases illustrate the importance of a high index of suspicion for early diagnosis and lifelong surveillance in MEN1, and the utility of genetic analysis in defining surveillance for MEN1-related thymic carcinoid.