Ectopic Insulin-Derived Amyloidosis Arising in the Inguinal Region Distant From Injection Sites

Abstract

Insulin-derived amyloidosis typically develops at sites of repeated insulin injections, presenting as localized subcutaneous masses known as “insulin balls.” We report a highly unusual case of an ectopic insulin-derived amyloidoma presenting as a 35 × 20-mm subcutaneous nodule in the right inguinal region of a man in his 50s with type 1 diabetes. He had no history of insulin injection around the lesion but had undergone two surgeries for epidermoid cysts in the same area. Histopathology of the subcutaneous nodule revealed degenerated tissue containing amorphous, eosinophilic material embedded in a fibrofatty background, which was confirmed to be Congo red-positive amyloid deposits. While immunohistochemistry for major amyloid types was negative, liquid chromatography–tandem mass spectrometry (LC–MS/MS) identified peptides derived from both endogenous human insulin and the synthetic analog insulin aspart, confirming a diagnosis of insulin-derived amyloidosis. We suggest that circulating insulin may have been deposited in the inguinal region, potentially facilitated by a microenvironment disrupted by previous surgical trauma, including altered lymphatic drainage. This case highlights that insulin-derived amyloidosis should be considered in diabetic patients even at non-injection sites and emphasizes the utility of proteomic analysis in amyloid typing.