Necrobiotic Xanthogranuloma Associated With IgG Kappa Smoldering Myeloma Presenting as Vision-Threatening Orbital Disease: Clinical Response to Plasma Cell-Directed Therapy.

Necrobiotic xanthogranuloma (NXG) is a rare chronic non-Langerhans cell histiocytosis characterized by xanthomatous granulomatous lesions and a strong association with monoclonal gammopathies, particularly IgG-kappa paraproteinemia. Periorbital involvement is common and may lead to orbital mass effect, visual compromise, and significant morbidity. We report the case of a 68-year-old woman who presented with progressive visual decline, choroidal folding, orbital compression, and ulcerative periorbital lesions. Biopsies of the right upper eyelid and lower extremity confirmed NXG. Evaluation demonstrated an IgG-kappa monoclonal gammopathy with bone marrow findings consistent with smoldering multiple myeloma. Given vision-threatening orbital disease, plasma cell-directed therapy was initiated despite the absence of myeloma-defining events. The patient received sequential treatment with daratumumab-bortezomib-dexamethasone, cyclophosphamide-lenalidomide-dexamethasone, cyclophosphamide-dexamethasone, and later isatuximab-carfilzomib-dexamethasone. Although the best hematologic response achieved was partial remission, she experienced near-complete resolution of cutaneous and periorbital lesions with stabilization of ocular symptoms. This case supports the concept of NXG as a monoclonal gammopathy of clinical significance and highlights that plasma cell-directed therapy may produce substantial clinical benefit even without deep hematologic remission.