Clinical course <p>A 65-year-old female patient presented with a slowly progressive right-sided ptosis. A myasthenia was excluded and the medical history included Hashimoto’s thyroiditis and a previous pneumonia. After a successful transcutaneous levator resection a recurrence of ptosis developed 2 years later accompanied by a firm, yellowish swelling of the upper eyelid and involvement of the contralateral upper eyelid.</p> Diagnostics <p>The biopsy revealed lymphocytic infiltrates with lymph follicle formation, invasion into striated muscle, foam cells and Touton giant cells as well as mildly fibrotic and necrotic areas, consistent with an adult orbital xanthogranulomatous disease (AOXGD), subtype adult-onset asthma and periocular xanthogranuloma (AAPOX). A differentiation from necrobiotic xanthogranulomatosis and Erdheim-Chester disease was based on the absence of skin necrosis, minimal fibrosis and a lack of systemic involvement. Evidence of an immunoglobulin G4 (IgG4) association was noted clinically (Hashimoto’s thyroiditis, chronic sinusitis) and histologically (increased IgG4-positive plasma cells).</p> Treatment <p>Following renewed upper eyelid blepharoplasty and multiple triamcinolone injections, a short-term systemic corticosteroid therapy was administered due to insufficient improvement. In the absence of a BRAF mutation, steroid-sparing immunosuppressive treatment with methotrexate was initiated, leading to marked regression of the swelling.</p> Conclusion <p>This case highlights the diagnostic complexity and the importance of a combined histopathological, immunohistochemical and clinical evaluation in rare xanthogranulomatous eyelid lesions.</p>