Long-Standing Bilateral Adult-Onset Orbital Xanthogranuloma With Unique Histologic Findings Uncovering the Diagnosis of Sitosterolemia.

Abstract: Sitosterolemia is a rare autosomal recessive lipid disorder characterized by markedly elevated plasma plant sterol levels, premature atherosclerosis, and cutaneous xanthomas. Adult-onset orbital xanthogranuloma (AOX) is an uncommon non-Langerhans cell histiocytosis marked by xanthogranulomatous infiltration of the orbital tissues. We report the case of a 49-year-old woman with bilateral periorbital tumors and tendinous xanthomas who remained undiagnosed for >2 decades. Histopathologic examination of multiple biopsies for a 15-year period revealed xanthogranulomatous infiltrates consistent with AOX, accompanied by intracytoplasmic eosinophilic bodies not previously described. Imaging revealed severe stenosis of both cardiac and cerebral vessels. Laboratory testing showed markedly elevated levels of β-sitosterol, campesterol, and stigmastanol. Genetic analysis identified a homozygous nonsense mutation in the ABCG5 gene, confirming the diagnosis of sitosterolemia. This represents only the third reported case of AOX associated with sitosterolemia. The significance of the eosinophilic bodies observed in this patient remains unclear. Our findings highlight AOX as a rare but potentially under-recognized cutaneous manifestation of sitosterolemia. Importantly, measurement of plant sterol levels and genetic testing should be considered in patients with unexplained xanthogranulomatous lesions, particularly when accompanied by vascular disease or atypical lipid profiles. Recognizing this association may lead to earlier diagnosis and targeted treatment, potentially reducing the risk of life-threatening complications associated with this treatable metabolic disorder.