Follow-up study of a Colombian family with a novel MEN1 variant and rare ACTH-producing pancreatic neuroendocrine carcinoma

Abstract

Purpose This article reports on a 12-year follow-up of a Colombian family with a novel MEN1 gene variant (c.698dup, p.Met233IlefsTer4), identified through cascade genetic screening. The index case involved a rare type of tumor, an ACTH-secreting pancreatic neuroendocrine carcinoma.Methods The index case underwent MEN1 testing after presenting with pancreatic neuroendocrine tumors and hyperparathyroidism. Cascade genetic screening of relatives revealed four additional carriers. Biochemical and imaging surveillance was conducted as per clinical guidelines.Results All affected family members first showed signs of primary hyperparathyroidism (PHPT) in their 20s to 50s. Notably, the index case developed a rare type of tumor known as ACTH-secreting pancreatic neuroendocrine carcinoma, which, to our knowledge, is the first instance reported in a MEN1-affected family. Due to proactive screening, pituitary neuroendocrine tumors (PitNETs) were identified as microadenomas in two carriers.Conclusion This study demonstrates the value of cascade screening for early diagnosis and tailored management in MEN1 families. It also reports a unique ACTH-producing pancreatic neuroendocrine carcinoma in MEN1. Systematic documentation of cases is critical to elucidating geographical and phenotypic variation and devising genotype-based management approaches.