New Histologic Finding of Amyloid Insulin Bodies at an Insulin Injection Site in a Patient With Diabetes

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Abstract

Amyloidosis is a heterogeneous group of protein deposition diseases with more than 40 known clinical presentations. Localized amyloidosis occurs when the protein deposits exist in a singular location. Patients with diabetes mellitus who inject insulin at the same site can develop localized insulin-derived amyloidosis (AIns) at the injection site, which can be confused clinically with lipoma, lipohyperplasia, lipoatrophy, and fat necrosis. Histologic examination is performed to confirm localized AIns. We report a case of a patient with a long history of type 2 diabetes who presented with a subcutaneous mass in the abdomen at a preferred insulin injection site. Examination by light microscopy revealed diffuse deposition of eosinophilic material. Two of the tissue fragments contained numerous 30–40 μm spherical bodies within the eosinophilic material. The bodies had dark centers with peripheral eosinophilic material. Polarized sections stained with Congo red showed apple green birefringence, a characteristic of amyloid. Immunohistochemistry was positive for insulin antibodies in the dark spherules and the surrounding matrix. Proteomic analysis by mass spectrometry showed that the Congo red–positive material was insulin. Electron microscopy showed a background matrix consisting of nonbranching protein fibrils measuring 8.8–16.1 nm, consistent with amyloid; the spherules contained dark globular proteins in the center surrounded by nonbranching fibrillary proteins. Because these spherules were positive for insulin by immunohistochemistry and showed amyloid ultrastructurally, we refer to them as amyloid insulin bodies. The identification of AIns, specifically with amyloid insulin bodies, is important for diagnosis and treatment and may further our understanding of amyloidogenesis.

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