Co-existence of two different types of pancreatic neuroendocrine tumors in a patient with multiple endocrine neoplasia type-1

Abstract

Pancreatic neuroendocrine tumors (PNETs) are rare forms of pancreatic malignancies which are classified according to functionality. Coexistence of two functional PNETs is extremely rare, but case reports are encountered in the literature. We present a 23-year-old male patient who was referred for recurrent hypoglycemic symptoms while investigating for pituitary adenoma. In addition to overt hypoglycemia, the patient's laboratory examination was compatible with primary hyperparathyroidism, hyperprolactinemia and acromegaly. Prolonged fasting test revealed hypoglycemia due to endogenous hyperinsulinism. Multiple hypodense mass lesions in the tail and body of pancreas were detected on the computed tomography scan. After surgical excision of these lesions, histopathologic examination of the specimens showed a grade 1 NET, which was positive for glucagon and chromogranin, negative for insulin. Histopathologic and immunostaining evaluation suggested that there were two pancreatic NETs with different characteristics. The patient was diagnosed as multiple endocrine neoplasia type-1 (MEN-1) syndrome due to clinical coexistence of the all 3 components, family history and genetic confirmation (frameshift mutation in MEN1 gene due to pathogenic deletion). After the operation, hypoglycemic symptoms were ameliorated. After 9 years of lost to follow-up period, the patient admitted to the emergency Department with complaints of nausea, vomiting and abdominal pain. In the evaluation of patient, recurrences of hyperparathyroidism, pituitary adenoma and PNET were observed. Coexistence of insulinoma and glucagonoma is a rare condition and the underlying physiopathological mechanisms have not been fully understood. However, it is important to note that two simultaneous functional tumors may coexist in PNETs associated with MEN-1 syndrome.