Posttransplant lymphoproliferative disorder: EBV⁻ plasma cell myeloma with large multinucleated plasma cells

A 67-year-old man, 15 years post–living related kidney transplant developed a cutaneous squamous cell carcinoma (SCC). Surveillance positron emission tomography/computed tomography scan for SCC identified an ischial bone lesion. Immunoglobulin A λ paraproteins were found on serum protein electrophoresis/urine protein electrophoresis. Bone marrow biopsy and aspirate were normocellular, but displayed multifocal clusters of large binucleated and multinucleated plasma cells with variable histiocytoid or Hodgkin/Reed-Sternberg cell–like cytomorphology (panel A [hematoxylin and eosin stain, original magnification ×1000]; panels B-C [Wright-Giemsa stain, original magnification ×500]), ∼20% of marrow cellularity, and immunophenotype: CD45⁻, CD138⁺ (panel D; CD138 stain, original magnification ×500), CD19⁻, CD20⁻, CD117⁻, CD27⁺, CD28⁺, CD56(weak)⁺ (panel E; CD56 stain, original magnification ×500), cyclin D1⁻ and CD30⁻, with λ light-chain restriction (panel F; in situ hybridization for lambda mRNA stain, original magnification ×500). Epstein-Barr virus (EBV)-encoded RNA–in situ hybridization was negative. Fluorescence in situ hybridization analysis revealed monosomy 13, loss of 1 copy of the immunoglobulin heavy chain gene, and 1q21 (CKS1B) gain; subclones showed monosomy 17 and 1p32 (CDKN2C) deletion.

This case represents a monomorphic posttransplant lymphoproliferative disorder (PTLD)–plasma cell myeloma (PCM), which accounts for ∼5% of all PTLD (prevalence ∼1/1000 solid organ transplant recipients). Posttransplant (PT)-PCM usually occurs late after transplantation, in older individuals (median age, 60 years), recipients of deceased donor allografts, and in those having received antithymocyte globulin therapy. Most are EBV⁻ and cytogenetic abnormalities are similar to immunocompetent multiple myeloma. Reduction of immunosuppression is not efficacious in PT-PCM, but use of modern myeloma therapeutic regimens has led to significantly improved outcomes.