EBV-Positive Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue in the Post-Transplant Setting: A Distinct Type of Monomorphic Post-Transplant Lymphoproliferative Disorder?
Sarah E Gibson, Steven H Swerdlow, Fiona E Craig, Urvashi Surti, James R Cook, Michael A Nalesnik, Chris Lowe, Katrina M Wood, Chris M Bacon. Virginia Commonwealth University School of Medicine, Richmond; University of Pittsburgh School of Medicine, PA; Cleveland Clinic, OH; Newcastle upon Tyne Hospitals NHS Foundation Trust, United Kingdom
Background: The 2008 WHO classification defines monomorphic post-transplant lymphoproliferative disorders (M-PTLD) as lymphoid or plasmacytic proliferations that fulfill the criteria for one of the B-cell or T/NK-cell neoplasms recognized in immunocompetent patients. However, indolent B-cell lymphoid neoplasms are specifically excluded from this category.
Design: Four cases fulfilling the 2008 WHO classification criteria for MALT lymphoma that were EBER+ and arose in 4 patients who had previously received a solid organ transplant were identified. The clinicopathologic features were reviewed and additional immunophenotypic, molecular and cytogenetic FISH studies were performed.
Results: The 4 patients (age 12-71 years) received a solid organ transplant (2 heart, 1 kidney, 1 kidney/pancreas) at a median of 116 months prior to presentation and had been maintained on varying immunosuppressive regimens that included cyclosporine, azathioprine, tacrolimus, and sirolimus. Three of the 4 patients presented with solitary subcutaneous masses, and one presented with a solitary orbital soft tissue mass. All 4 cases were morphologically typical for MALT lymphoma, demonstrated plasmacytic differentiation with IgA heavy chain-restriction (3 κ+, 1 λ+), and were diffusely EBER+ with occasional cells EBV-LMP1+. All cases appeared EBNA2-. The small B-cells and plasma cells were positive for CXCR3 in all 4 cases. Genotypic studies demonstrated clonal IGH and IGK gene rearrangements in all cases, and FISH studies were negative for MALT1, BCL2, BCL6, BCL10, IGH, and MYC gene rearrangements. Patients were followed for a median of 44.9 months (range 10.5-92.9 months) and all achieved a complete response following various regimens that included reduced immunosuppression with or without antiviral therapy, local surgical excision, rituximab, or local radiation therapy.
Conclusions: The uniform EBV positivity and response to immune reconstitution in some cases suggest that EBV+ MALT lymphomas arising in the post-transplant setting should be included among the PTLD. Whether their distinctive subcutaneous/soft tissue localization and IgA positivity are uniform features will require identification of additional cases.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 173, Wednesday Morning