Post-transplant lymphoproliferative disorder (PTLD) of the Burkitt lymphoma (BL) type
Posttransplant lymphoproliferative disorder (PTLD) is a wide encompassing group of disorders ranging from atypical lymphoid or plasmacytoid proliferations to malignant lymphomas that are the direct result of immunosuppression in a transplant patient of a solid organ, bone marrow, or stem cell allograft. Pediatric transplant recipients are at increased risk of developing a PTLD because many of them are Epstein-Barr virus (EBV) seronegative at the time of transplantation, which makes them vulnerable to developing a primary, active EBV infection while on potent immunosuppressive medications (1,2,3).
The histological features of PTLDs can range from early EBV-associated infectious mononucleosis-like proliferations to malignant lymphoma (4). The majority of monomorphic PTLDs (M-PTLD) are composed of transformed B-cells that fit the criteria of a non-Hodgkin Lymphoma (NHL), predominately of the diffuse large B-cell type (DLBCL), and rarely of a Burkitt lymphoma (BL) type. However, newer data are emerging to suggest that many PTLDs are distinct from their NHL/B-cell lymphoma counterparts and share a molecular profile with memory or activated B cells of post-germinal center origin, with the possible exception of those PTLDs retaining a germinal center profile, such as BL (5).
BL is an aggressive, mature B-cell lymphoma, composed of a monomorphic population of small to intermediate-sized, noncleaved lymphoid cells with high mitotic and proliferation rate, and a characteristic "starry-sky" appearance imparted by the scattered tingible body macrophages engulfing apoptotic debris of the tumor. Ancillary studies with immunophenotyping and cytogenetic analysis confirm the diagnosis, separating it from a diffuse large B-cell lymphoma (DLBCL). While the c-MYC translocation is nonspecific and can be seen in up to 10% of DLBCL, the expression profile of near 100% Ki-67/MIB-1 proliferation index, positive CD10 and bcl-6, and negative bcl-2, with the morphologic "starry-sky" pattern is diagnostic for BL. Three main clinical variants of BL have a varying propensity to express EBV (4). The highest expression is seen in the endemic type of equatorial Africa (>95% of cases), while the North American sporadic type (20-30%) and immunodeficiency-associated/HIV type (25-40%) have a lower association with EBV expression (6,7). However, previous case reports of BL occurring in the post-transplant setting have a higher incidence of EBV expression (>70%), greater than that is reported for immunodeficiency-associated BL, and more akin to the endemic type and other PTLDs (8-12).
As a PTLD, BL type is a rare form of M-PTLD with distinct clinical and pathologic features. It also has features distinguishing it from its lymphoma counterpart in the non-transplant setting. While BL-PTLD is a rare entity with little in-depth investigation in the literature, it appears to be a distinct form of PTLD, with a high EBV expression; however, there are unique clinical and pathologic features that separate it from the other M-PTLDs. BL in the post-transplant setting is a more aggressive type of PTLD. Furthermore, BL-PTLD does not respond to decreased immunosuppression alone, and requires immediate therapeutic regimens with alkylating chemotherapy (13). The current patient was treated with chemotherapeutic agents along with decreased immunosuppression and is alive without disease 168 months after original diagnosis.
We have preliminary data on 11 cases at our institution which show a high incidence of EBV expression in the majority of the BL-PTLD cases, suggest that this is an aggressive and distinct PTLD, and separate from sporadic and immunodeficiency-associated BL.
Contributed by Jennifer Picarsic, MD anf Miguel Reyes-Mugica, MD