Overview of Classification Systems for Posttransplant Lymphoproliferative Disorders
(updated April 19, 2005)
Links to Individual Classification Systems:
Prior to 1981, lymphoid tumors in transplant patients were uniformly referred to as immunoblastic sarcomas. In that year Simmons, Hanto and colleagues launched a series of studies, centered on the renal transplant population at the University of Minnesota, that established the relationship between the Epstein-Barr virus and posttransplant lymphoproliferations. Frizzera and colleagues examined tumors from a small number of renal transplant recipients. They observed several forms of lymphoproliferation which had not been previously described and applied the term "polymorphic" to emphasize the heterogeneity in size and shape of the tumor cells. Ancillary studies showed the tumors to be comprised of B lymphocytes. In the classification system of Frizzera et al., polymorphic diffuse B cell hyperplasia and polymorphic B cell lymphoma were distinguished from reactive lymphoid hyperplasia and from immunoblastic sarcoma. The authors stressed that the behavior of posttransplant lymphoproliferations could not be reliably predicted by pathologic studies alone.
In 1984 Starzl et al. introduced reduction of immunosuppression as a primary maneuver to induce regression of posttransplant lymphoproliferations based on their experience at the University of Colorado and the University of Pittsburgh. Nalesnik and colleagues reported their experience with PTLDs observed in the University of Pittsburgh transplant population. They also were unable to discern any significant difference in the clinical behavior of the two types of polymorphic lesions and combined them under the heading of polymorphic PTLDs. In contrast, lesions which resembled typical non-Hodgkin's lymphomas also occurred and behaved, as a group, in a more aggressive fashion. In the classification system of Nalesnik et al., the term monomorphic PTLD was introduced to distinguish these lesions from polymorphic PTLDs. In a followup study in 1989, Locker and Nalesnik described several categories of PTLDs based on combined pathologic and molecular features. The most recalcitrant tumors had a monomorphic histology, were monoclonal, and contained rearrangements of the c-myc proto-oncogene.
In 1995, Knowles and his collaborators evaluated posttransplant lymphoproliferations in a series of heart transplant patients from Columbia-Presbyterian Medical Center. By combining morphologic appearance with molecular genetic analysis they were able to distinguish three separate categories of lesions. In the classification system of Knowles et al., the first category consisted of reactive hyperplasia of plasma cells. The second comprised the lesions of polymorphic hyperplasia and polymorphic lymphoma, both of which were monoclonal, but both of which were recognized to behave similarly. The third category was considered to represent true lymphomas and hematopoietic neoplasms which were monoclonal and could contain alterations in proto-oncogenes and/or tumor suppressor genes.
A Society for Hematopathology Workshop held in Duarte, California, in October 1995 led to discussions which expanded the spectrum of recognized posttransplant lymphoproliferations. However, the spectrum of categories continued to include reactive or early lesions, polymorphic PTLDs, and lesions which appeared to represent lymphomas or hematopoietic neoplasms. The Society for Hematopathology Workshop Classification includes additional lesions such as plasmacytomas, T cell rich B-cell lymphomas, and T cell lymphomas under the umbrella term of PTLD.
Harris, Swerdlow, Frizzera and Knowles updated this classification for the 2001 World Health Organization Classification of Tumours. The WHO Classification represents the system in widest use at present (2005).
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