57 | GENERALIZED PLANE XANTHOMA AND NECROBIOTIC XANTOGRANULOMA HERALDING PROGRESSION FROM MGUS TO MULTIPLE MYELOMA: COMPLETE CUTANEOUS RESOLUTION AFTER MYELOMA-DIRECTED THERAPY

M. Di Prete¹, V. Lora², C. Cota¹ | ¹Dermatopathology Research Unit, San Gallicano Dermatological Institute IRCCS, Rome, Italy; ²Clinical Dermatology, San Gallicano Dermatological Institute IRCCS, Rome, Italy

Introduction. Generalized plane xanthoma (gPX) and necrobiotic xanthogranuloma (NXG) are rare xanthomatous disorders. Emerging evidence suggests that normolipemic PX and NXG may represent different manifestations within the same clinicopathological spectrum of paraprotein-associated dermatoses. We describe a case in which the coexistence of gPX and NXG heralded the progression of longstanding monoclonal gammopathy of undetermined significance (MGUS) to overt multiple myeloma (MM).
Materials and Methods. An 80-year-old man with a 17-year history of IgG lambda MGUS presented with a 5-year history of progressively enlarging yellowish skin lesions. Initially, the lesions were superficial and localized but progressively became infiltrated and confluent, eventually involving the trunk and extremities with diffuse yellow discoloration (Figure 1A, C). Serum cholesterol levels and liver enzymes were within normal limits. Three skin biopsies were performed from the back, abdomen, and right arm.
Results. Histopathological examination of truncal lesions revealed a dermal-subcutaneous granulomatous infiltrate composed of foamy histiocytes and multinucleated giant cells, predominantly Touton-type and foreign body-type, consistent with NXG. The arm lesion showed a more superficial dermal infiltrate mainly composed of xanthomatized histiocytes, compatible with PX (Figure 1E, F, G). Given the well-recognized association between NXG and plasma cell dyscrasias, hematologic reassessment was undertaken and demonstrated progression from MGUS to overt MM. The patient started myeloma-directed therapy with daratumumab, lenalidomide, and dexamethasone. After seven treatment cycles, MM was controlled and complete resolution of all cutaneous lesions was achieved without specific dermatologic treatment (Figure 1B, D). Cutaneous remission persisted one year after treatment initiation, in parallel with sustained hematologic disease control.
Conclusions. The coexistence of gPX and NXG in our patient is consistent with the hypothesis that these entities may represent different paraneoplastic manifestations within a common paraprotein-associated xanthomatous spectrum. Their sudden appearance during a long-lasting MGUS course can signal progression to overt MM. Consequently, their recognition should prompt thorough hematologic reassessment in patients with monoclonal gammopathies. The complete remission of cutaneous lesions following myeloma-directed therapy further supports their paraneoplastic nature.