Thymic Carcinoid Tumor as Single Manifestation of Multiple Endocrine Neoplasia Type 1 : A Clue to Suspect a Germline MEN 1 Mutation ?

Multiple endocrine neoplasia type 1 (MEN1) is a familiar tumor syndrome of endocrine neoplasia involving parathyroid, anterior pituitary and enteropancreatic neuroendocrine tissues. Thymic carcinoid tumors are rare tumors that occur in 2-8.2% of patients with MEN1 and they exhibit a predilection for men over women. Published data of thymic carcinoid tumors in MEN1 are scarce and they seldom constitute the first manifestation in this syndrome. We present a case of a woman with a thymic carcinoid tumor diagnosed at a very young age with no other clinical features of MEN1, and apparently not significant family history (mother with breast cancer developed at the age of 35), which was genetically diagnosed of a splice site mutation in MEN1 gene. Although no classical MEN1 clinical or familial criteria were met, the age of presentation of thymic carcinoid in our subject gave us the main clue of our clinical suspicion. Since MEN1 syndrome has a variable expression and it may not be exclusively correlated with endocrine tumors, we suggest that MEN1 mutational analysis should also be considered in all patients with carcinoid thymic tumors, especially if it is presented at young age, independently of the absence of classical clinical or familial MEN1 criteria. Sergio Carrera1*, Intza Garin2, Aintzane Sancho1, Elena Beristain2, Eider Azkona1, Guillermo López-Vivanco1, Itziar Rubio1 and Cristina Martínez-Bouzas3 1Genetic Counseling Unit-Medical Oncology Department, University Hospital of Cruces, Spain 2Molecular Genetics Laboratory, University Hospital of Araba, Spain 3Molecular Genetics Laboratory, University Hospital of Cruces, Spain Sergio Carrera, et al., Annals of Clinical Case Reports Oncology Remedy Publications LLC. , | http://anncaserep.com/ 2017 | Volume 2 | Article 1293 2 are splice-site mutations and 20% are missense mutations, and 1% are whole o partial gene deletions [9]. The current guidelines recommend that MEN1 mutational analysis should be performed in: 1) an index case with two or more MEN1 typical associated endocrine tumors (parathyroid, pancreatic or pituitary tumors), 2) asymptomatic first degree relative of a known MEN1 mutation carrier, 3) a first degree relative of a MEN1 mutation carrier expressing familial MEN1 (having symptoms, signs, biochemical or radiological evidence for one or more MEN1 associated tumors) [10]. In addition MEN1 mutational analysis should be performed in patients with suspicious or atypical MEN1: parathyroid adenomas before the age of 30 years or multigland parathyroid disease, gastrinoma and multiple pancreatic islet cells tumors any age or individuals who have two or more MEN1 associated tumors, which are not part of the classical triad of parathyroid, pancreatic islet cell and anterior pituitary tumors [10]. Thymic carcinoids are rare neuroendocrine tumors. The prevalence of thymic carcinoid tumors in patient with MEN1 ranged from 2% to 8.2% in different series, and they exhibit a predilection for men over women, with a male/female ratio of 20:1 [11]. With scarce data reported in the literature of thymic carcinoids in patients with MEN1, all available information of these tumors is relevant. A retrospective study of MD Anderson Cancer Centre in 291 patients who fulfilled clinical, genetic and or familial criteria for diagnosis of MEN1 showed 9 cases (3.1%) of thymic carcinoids. The male/female ratio was 2:1 and the mean age of diagnosis was 38.6 years. Almost half of the patients already had distant metastases at the time of their diagnosis [12].