Endocrine Abstracts

Introduction

Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) of the pancreas are composed of two morphologically different components, each representing at least 30% of the tumor: ductal or acinar adenocarcinoma and neuroendocrine neoplasm (NEN). They are extremely rare tumors whose etiopathogenesis and biological behavior are not fully understood. Given its rarity, we describe a case of insulinoma in the context of MiNEN.

Clinical case A 55-year-old woman with no relevant medical or family history was referred to our department due to symptomatic hypoglycemic episodes with one year of evolution. The episodes were more frequent in the morning, improved after ingestion of carbohydrates, and capillary blood glucose was between 38–55 mg/dL. She denied taking hypoglycemic agents. Physical examination showed BMI 30 kg/m² and was otherwise unremarkable. Laboratory evaluation with 12 h fasting was consistent with endogenous hyperinsulinism: glycemia 53 mg/dL, insulin 11.45 μUI/ml (3–25), C-peptide 3.62 ng/ml (0.93–3.73) and anti-insulin antibody was negative. Calcium metabolism and pituitary lab tests were normal. CT scan and MRI did not show neoformative lesions. Ultrasound endoscopy revealed a solid intrapancreatic formation in the body-caudal transition, hypoechogenic, with 8.8 mm, well-delimited and vascularized, with features suggestive of NEN. Given these results, a diagnosis of insulinoma was made and the patient underwent distal pancreatectomy. After the surgery, the hypoglycemia episodes resolved. Anatomopathological examination revealed a MiNEN of the pancreas with 1.5 cm, comprising a G1 NEN (~70%) and ductal adenocarcinoma (~30%) – staging (AJCC 8th edition): pT1aN0. In the remaining pancreatic parenchyma, a 0.3 cm neuroendocrine microadenoma was also identified. The patient is under surveillance at the Endocrinology and Medical Oncology outpatient clinic. One year after surgery, there is no clinical and laboratory evidence of hypoglycemia nor suspicious lesions on FDG-PET scan. Given the presence of two neuroendocrine pancreatic tumors, the patient underwent MEN1 genetic testing, however, results are still unknown.

Conclusion

The follow-up and prognosis of patients with MiNEN are not well understood. There are few cases of pancreatic MiNEN published in the literature, and their presentation is heterogeneous. However, in most of them, the neuroendocrine component is non-functional, and the diagnosis is made in the context of detection of incidental pancreatic lesion or mass effect. In this case, the neuroendocrine component was as insulinoma and the study of endogenous hyperinsulinism preceded the identification of the tumor. With this exceptionally rare case, we intend to contribute to the body of knowledge about MiNEN, whose approach remains challenging for clinicians.