Gastrinomas and non-functioning pancreatic endocrine tumors in multiple endocrine neoplasia syndrome type-1 (MEN-1)

Multiple endocrine neoplasia type-1 (MEN-1) is a rare hereditary autosomal dominant syndrome due to frameshift and non-sense mutations in the MEN-1 tumor suppressor gene localized on the long arm of chromosome 11 [1]. Also known as Wermer syndrome, it has a prevalence of 2–20/100,000 individuals who may develop multiple neoplastic lesions arising in the parathyroid (90–95%) as well as the pituitary glands (40–50%), the pancreatic islet cells (50–60%) and the duodenal wall (35–40%) [2]. While the most common clinical onset of patients affected by MEN-1 is due to primary hyperparathyroidism [3], pancreatic endocrine tumors (PNETs) represent the main cause of cancer-related death, which is most commonly due to non-functioning (NF) subtypes [4]. Indeed, these tend to have a more aggressive behavior compared to their sporadic counterparts with a malignant potential reported to be size-related with a cut-off value set at 2 cm [5,6,7]. Hence, active surveillance with endoscopic ultrasonography (EUS) combined with either contrast-enhanced multi-detector-CT (MDCT) [8] or magnetic resonance imaging [9] is strongly recommended in patients with MEN-1 syndrome. As far as contrast-enhanced MDCT is concerned, recent advances suggest that contrast-enhancement patterns of PNETs may be indeed predictive of tumor grading defined as the rate of expression of the proliferation index Ki-67 [10]. As most G1 (Ki-67 <3%) tumors usually appear as hypervascular lesions, G2 (Ki-67 3–20%) or G3 (Ki-67 >20%) tumors typically manifest as hypovascular lesions [11,12,13]. However, as PNETs in MEN-1 syndrome are usually multifocal [14], the co-existence of lesions with different contrast-enhancement patterns and different biological behavior may indeed occur in clinical practice. Herein, we describe a case of 48-year-old male with a genetic diagnosis of MEN-1 syndrome who had a Zollinger–Ellison syndrome due to duodenal gastrinomas shown by an EUS and confirmed by contrast-enhanced MDCT, which also depicted loco-regional adenopathies and three other NF-PNETs with different contrast-enhancement patterns and biological behavior.