Case Report: Giant insulinoma, a very rare tumor causing hypoglycemia

Abstract

Insulinomas, with an incidence of 4 cases per million individuals per year, remain amongst the most frequent functional neuroendocrine tumors. The usual diameter of insulinomas usually remains under 3 cm of major axis. However, 44 exceptional cases of "giant insulinomas", have been reported worldwide, generally exceeding 9 cm in major axis. In this article, we report the case of a 38-year-old woman whom suffered from chronic hypoglycemia despite treatment with diazoxide. Abdominal CT-scan revealed a 88 x 73 mm mass located at the tail of the pancreas. Following surgical excision, histopathological analysis confirmed G1 neuroendocrine tumor, with focal cytoplasmic expression of insulin in tumor cells. After a 16-month follow-up period, the patient didn't address any specific complaint, and no disease recurrence and/or metastasis were observed. A ⁶⁸Ga-DOTATATE-PET scan was performed 6 months after surgery, which came back normal. Genetic evaluation has not been performed in our patient. The physiopathology of giant insulinomas remain unexplained, however with possible relationship with type 1 multiple endocrine neoplasia, sporadic somatic YY1 mutations and possible transformation of bulky non-functional pancreatic neuroendocrine tumors to a functional phenotype, with slow insulin secretion. While giant insulinomas remain rare in the literature, multicentric genetic analysis of tumor samples might reveal unique features of this rare subtype of neuroendocrine pancreatic tumors. Insulinomas of large size tend to have greater malignancy and higher rates of invasiveness. Careful follow-up, especially for liver and lymph node metastases, must be performed using functional imaging techniques to avoid disease relapse.

Keywords: giant insulinoma; hypoglycemia; neuroendocrine tumors; pancreas; pathology.

Figure 1

Abdominal injected CT-scan of a giant insulinoma in a 38-year-old female patient suffering from severe hypoglycemia. (A) Plain Computed Tomography scan (CT-scan); horizontal cut: the 88 mm-wide mass was observed in the left hypochondrium, without invasion of adjacent structures (dashed lines). (B) Plain Computed Tomography scan (CT-scan); tridimensional reconstruction: The absence of organ invasion was confirmed using three-dimensional reconstruction for computed tomography (arrow).

Figure 2

Gross description and histopathological analysis of a giant insulinoma in a 38-year-old female patient suffering from severe hypoglycemia. Positive detection of antibodies is indicated by brown staining. (A) (Photography – horizontal cut-section): Gross examination of the tumor following surgical resection and formalin fixation during 48 hours. The encapsulated tumor of approximately 80 mm of diameter shows well-defined borders and a homogenous whitish-grey appearance at cut-section with several hemorrhagic foci. (B) (HES, x 200): Histopathological analysis shows a monophasic proliferation of nests and cords of basophilic cells, organized around numerous vascular slits and inside a moderately thick fibrous capsule (arrow). No atypia, necrosis or capsular invasion were noted. The mitotic index was estimated at approximately 1 mitosis/10 hpf. (C) (HES, x 400): Endocrine cells were also surrounded by a hyaline stroma (arrow). (D) (Congo Red, x400) The hyaline stroma was negative for Congo Red staining (arrow). (E) (CD56, x 400): Tumor cells showed intense diffuse cytoplasmic staining. (F) (Synaptophysin, x 400): Tumor cells showed intense diffuse cytoplasmic staining. (G) (Chromogranin A, x 400): Tumor cells showed intense heterogeneous cytoplasmic staining. (H) (Neuron-Specific Enolase, x 400): Tumor cells showed weak diffuse cytoplasmic staining. (I) (Ki-67, x 400): The Ki-67 proliferation index was estimated around 1%. (J) (Insulin, x 400): Few scattered cells were positive for insulin immunostaining (arrow).