(13.09) Gastrointestinal Stromal Tumor (GIST) in a Patient with Multiple Endocrine Neoplasia -1 (MEN-1); A Rare Presentation

Multiple endocrine neoplasia type 1 (MEN-1) is a rare autosomal dominant, highly penetrant endocrine tumor syndrome, characterized by the inactivation of the Menin gene, a tumor suppressor, located on chromosome 13 (13q11). MEN-1 syndrome is associated with pituitary, parathyroid, and pancreatic islet tumors. Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors constituting 1% of all sarcomas and 3-5% of gastrointestinal tumors, with an estimated prevalence of 10-15 per million population. Co-occurrence of GISTs and MEN-1 syndrome is very rare with only 5 cases reported in the literature. Herein, we report a case of a large GIST tumor diagnosed incidentally in a patient with MEN-1.

Case(s) Description :

A 47-year-old woman establishes care in the endocrinology clinic for a known diagnosis of MEN-1. She had recently had a parathyroidectomy for primary hyperparathyroidism. Work-up revealed a nonfunctional pituitary microadenoma while a CT scan done for screening for pancreatic tumors showed a small 0.6 cm pancreatic cyst. Incidentally, on the CT scan it also showed a 7.0 x 7.3 x 9.1 cm complex cystic-solid mass above the uterus, suspicious for ovarian origin. She was then urgently referred to the Gynecologic Oncology service and subsequently underwent exploratory laparotomy, total abdominal hysterectomy, and small bowel resection. Pathological examination confirmed the mass to be GIST, originating from and confined to the small intestine. Genetic analysis of the GIST was positive for somatic mutations of MEN-1 and NF1 genes. Further germline testing conducted for KIT, MAX, NF1, PDGFRA, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127, VHL were negative. She is currently in remission and remains under close surveillance for GIST while also following endocrinology for MEN-1.

Discussion :

The mechanism of coexistence of GIST and MEN-1 remains unclear. In our patient, genome analysis revealed no known inherited genetic factors. Therefore, it may be a sporadic occurrence. However, it is plausible that the role of genetic mechanisms in MEN-1 e.g., methylation of promoters and/or regulatory intronic sequence, could also contribute to the development of GIST. While one prior study found no evidence of loss of the wild‑type MEN-1 allele in GISTs, future research in understanding the pathomechanism leading to both GIST and MEN-1 syndrome is needed. If indeed there is a correlation, a sensitive screening tool could aid in early diagnosis of GIST in people with MEN-1 syndrome, thus likely improving overall prognosis.