A Long Way to Find a Small Tumor: The Hunt for an Insulinoma

Abstract

We report a case of a 35-year-old woman with recurrent episodes of hypoglycemia. Biochemical investigation was suggestive of hyperinsulinemic hypoglycemia, and hence a provisional diagnosis of insulinoma was made. Despite extensive investigation using magnetic resonance imaging, endoscopic ultrasound, and ⁶⁸Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) scanning, the tumor could not be localized. Long-distance travel allowed her to undergo a ⁶⁸Ga-Exendin-4 PET/CT scan that identified a lesion in the uncinate process of the pancreas, subsequently confirmed by intraoperative ultrasound. Enucleation of the 1.5-cm lesion was performed, and histopathology confirmed a well-differentiated pancreatic neuroendocrine tumor. Postoperatively, the patient has remained free of hypoglycemic episodes and has shown normalization of glucose levels. This case underscores the efficacy of ⁶⁸Ga-Exendin-4 PET/CT in the localization of an occult insulinoma, facilitating timely and curative surgical intervention, and the importance of patients having access to such a facility when not locally available.

Keywords: 68Ga-DOTATATE PET/CT; 68Ga-Exendin-4 PET/CT; hyperinsulinemic hypoglycemia; hypoglycemia; insulinoma; occult insulinoma; pNET.

Figure 1.

Maximum intensity projection (MIP) image of regional ⁶⁸Ga-exendin PET (A) showing focal tracer uptake in the region of the uncinate process of pancreas with mild diffuse uptake in the rest of the pancreas. Axial fused PET/CT image (B) showing focal tracer uptake (SUVmax 21.8) in the uncinate process of the pancreas with an inapparent lesion on corresponding CT image (C). Mild diffuse uptake was seen in the rest of the pancreas (D and E).

Figure 2.

Hematoxylin and eosin (H&E)-stained sections (magnification: 40×) showing circumscribed tumors arranged in nests and trabeculae, with individual tumor cells are monomorphic with round nuclei, stippled chromatin, inconspicuous nucleoli, and moderate granular eosinophilic cytoplasm. Neuroendocrine tumor grade I. Immunohistochemistry (IHC) studies show cytoplasmic positivity by tumor cells for synaptophysin (B) and insulin (C) with Ki67 proliferation index of 1% (D). IHC for SSTR2 (E) shows 2+ intensity cytoplasmic positivity in 60% tumor cells, whereas it is negative for SSTR5 (F).