Management of a metastasized high grade insulinoma (G3) with refractory hypoglycemia: Case report and review of the literature

Abstract

Insulinomas represent the most common functional neuroendocrine tumor of the pancreas. They are usually solitary, benign, well differentiated (G1/G2) and curable by surgery. We describe the case of a 45 year old male Caucasian with a unique malignant, metastasized pancreatic insulinoma (Ki 67 of 70%, G3). To control excessive insulin production emanating in refractory hypoglycemia and growth of the highly proliferating tumor a multimodal therapeutic approach including the consecutive use of tumor debulking surgery, chemotherapy, TACE, SIRT, PRRT as well as a drug therapy with diazoxide, somatostatin analogs and everolimus was employed. Chemotherapy with carboplatin/etoposide plus everolimus provided the longest normoglycemic period. After progress chemotherapy with dacarbazine had the most positive effect, while debulking approaches such as surgery and liver directed therapies, as well as PRRT were less efficient with only transient success.

Introduction

Insulinomas are rare with an occurrence of approximately 4/1,000,000. The median age at diagnosis is around 47 with a slight female predominance [1]. Yet they are also the most common functioning neuroendocrine pancreatic tumor as well as the most common cause of hyperinsulinemic hypoglycemia in adults [2]. In general they are solitary and benign [3]. The proliferation rates reported in the literature range from Ki67 1–25% and grading usually corresponds to G1/2. To our knowledge only one case with a proliferation of 25% (G3) has been reported [4]. The present report describes a yet unreported case of a malignant, metastasized and functional active insulinoma with severe hypoglycemia and an unusually high proliferation rate with a Ki67 of 70%.