Familial Angiolipomatosis: A Report of Two Cases and Review of Clinicopathologic Features, Diagnostic Considerations, and Management Challenges in an Underserved Population

Angiolipomas are benign mesenchymal tumors composed of mature adipose tissue with proliferative capillary vessels. Most cases are sporadic, presenting shortly after puberty as one or two small, painful “lumps” under the skin, followed by the appearance of two or three more each year, for several years. However, familial forms are rare and occur during the third through fifth decades of life on the trunk and extremities, with the forearms representing a common site of involvement. These lipomas generally affect consecutive generations, suggesting an autosomal dominant mode of inheritance, and are characterized by multiple, well-encapsulated, oval-to-round subcutaneous rubbery lipomas that range from a few millimeters to 25 centimeters in size and can often be misdiagnosed as neurofibromas. We report cases of two patients who presented with multiple painful angiolipomas that involved the arms, with lesions ranging up to 5 cm in size, and multiple smaller lesions were present as well. Both patients reported pain and physical discomfort, leading to functional impairment. Excision and biopsy were performed, and histopathologic examination confirmed features consistent with angiolipoma, including vascular proliferation, mature adipocytes, and fibrin microthrombi, along with a family history supporting an autosomal dominant influence. This case report aims to highlight that familial multiple angiolipomatosis remains a poorly characterized condition, with limited data on its geographic distribution and population prevalence. Appalachia is an underrepresented region in rare disease literature and is characterized by unique demographic and healthcare access factors that may contribute to delayed diagnosis or underrecognition. This case report provides regional context and serves as a hypothesis-generating contribution toward understanding potential geographic patterns of this rare disorder. Early recognition is important in avoiding misdiagnosis, facilitating appropriate counseling, and guiding management.