An Uncommon Presentation of Non-Hodgkin’s Lymphoma in a Renal Transplant Recipient

Abstract

Dear Sirs, Primary cutaneous posttransplantation B-cell lymphoproliferative disorder is rare. Posttransplantation lymphoproliferative disorders (PTLDs) are usually of non-Hodgkin’s lymphoma (NHL), accounting for 93% of lymphomas in the transplant population versus 65% in the general population. We present a rare case of cutaneous manifestation of a NHL in a renal transplant recipient. A 44-year-old woman was referred to our department due to skin lesion recognized on the right arm (level of deltoid muscle) (Fig. 1). She had undergone renal transplantation from a living donor 7 years ago due to end-stage renal disease attributed to immunoglobulin A nephropathy. Her immunosuppressive regimen included azathioprine, corticosteroids, and cyclosporine. Clinically, skin lesion resembled a soft-tissue sarcoma or a squamous cell carcinoma. Skin biopsy demonstrated diffuse large non-Hodgkin’s B-cell lymphoma (DLBCL; centroblastic cells with appearance of medium- to large-sized lymphocytes with scanty cytoplasm). On immunohistochemistry, cells of DLBCL expressed B-cell–associated antigens (CD19, CD20, and CD22). Serologic analysis for Epstein-Barr Virus (EBV) was positive (seroconversion of a previously seronegative patient) and in situ hybridization techniques identified EBV sequences in the nuclei of lymphoid cells within the lesion. Computed tomography scan applied for staging the disease showed large lung, mesothoracic, and inguinal lymph-node blocks. She was diagnosed with EBV-related PTLD. Immunosuppression reduction, chemotherapy with CHOP-R regimen, was administrated, which induced complete remission of the tumor. No surgical intervention was applied. However, the patient succumbed to recurrent disease 18 months later.FIGURE 1: Skin lesion on the right arm (level of deltoid muscle).DISCUSSION Solid organ transplant recipients have elevated cancer risk due to immunosuppression and oncogenic viral infections. Among transplant recipients, NHL represents one extreme of EBV-driven proliferative disease acknowledged as PTLD, which ranges from benign hyperplasia and infectious mononucleosis to lymphoid malignancy (1 ). The most common NHL subtype among transplant recipients is DLBCL and most cases are EBV positive (2 ). In situ hybridization techniques using the EBV-encoded RNA probe for EBV messenger RNA are used to identify EBV sequences in the nuclei of lymphoid cells within the lesion (1 ). A diagnosis of presumed PTLD was based on documentation of EBV seroconversion of a previously seronegative patient or reactivation of immunoglobulin M against EBV viral capsid antigen, along with symptoms such as fever, fatigue, and anorexia and the detection of pulmonary nodules or extrapulmonary masses or both on radiologic evaluation (1 ). PTLD presenting with skin involvement rarely manifests as lesions and such lesions develop slowly, when they occur. Intensity of immunosuppressive therapies also influences the risk for PTLD. The use of EBV viral load monitoring facilitates the diagnosis and management of EBV/PTLD as well as being used to inform preemptive therapy with reduction of immunosuppression, the most effective intervention for prevention of and treatment for PTLD (3, 4 ). Other therapies, including rituximab (anti-CD20 monoclonal antibody) and traditional chemotherapy, are also useful in the treatment of established PTLD (3). These lesions regress after dose reduction or cessation of treatment (4 ). Future perspectives on treatment of PTLD may include adoptive immunotherapy, intravenous immunoglobulin, mammalian target of rapamycin inhibitors, monoclonal antibodies to interleukin-6 and galectin-1, and even EBV vaccination (5). Demetrios Moris 1,3 Spiridon Vernadakis2,3 Vasileios Zavvos1 Georgios Zavos3 1 1st Department of Surgery Athens University School of Medicine “Laikon” General Hospital Athens, Greece 2 Department of General, Visceral and Transplantation Surgery University Hospital Essen Essen, Germany 3 Transplantation Unit “Laikon” General Hospital Athens, Greece