Immunodeficiency-Associated Lymphoproliferative Disorders.

S24 The incidence of lymphoproliferative disorders is significantly higher in individuals who have congenital, acquired, or iatrogenically induced immunodeficiency. The incidence of post-transplantation lymphoproliferative disorders (PT-LPDs) varies according to the organ transplanted and the type and degree of immunosuppression. Multiparametric analysis suggests that PT-LPDs are divisible into three categories as follows: Plasmacytic hyperplasia: benign histopathology, nearly always polyclonal, usually multiclonal or clonal EBV, and lack molecular genetic alterations; polymorphic lymphoproliferative disorders: polymorphic histopathology, monoclonal B cell, clonal EBV, and lack molecular genetic alterations; malignant lymphoma/multiple myeloma: monomorphic malignant cytopathology, monoclonal B cell, clonal EBV, and exhibit molecular genetic alterations. Plasmacytic hyperplasias usually regress following removal of immunosuppression while malignant lymphomas/multiple myelomas usually progress despite therapeutic intervention. The behavior of the polymorphic lymphoproliferative disorders ranges from spontaneous regression to progression. Bcl-6 gene mutations predict lack of regression following reduction of immunosuppression and shortened survival. AIDS related non-Hodgkin's lymphomas (NHL) are divisible into three broad categories according to their anatomic site of origin: systemic (nodal or extranodal) 80%, primary central nervous system 20%, and body cavity-based (primary effusion) lymphomas. <5%. Virtually all AIDS-NHLs are monoclonal B cell tumors divisible into three histopathologic categories: Burkitt's lymphoma (BL), large cell lymphoma (LCL), and immunoblastic lymphoma (IBL). Approximately 50% contain EBV and they exhibit a variety of molecular genetic alterations including bcl-6, c-myc, and p53 gene mutations that vary somewhat according to histopathologic category. A small number of AIDS-related lymphoproliferative disorders resemble the polymorphic PT-LPDs morphologically and molecularly. Their malignant nature, biological significance and relationship to monomorphic AIDS-NHLs is unclear. Finally, we described a rare and unusual subset of AIDS-NHLs that grow exclusively or principally in the body cavities as lymphomatous effusions and contain the Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8 (KSHV/HHV-8). These occur predominantly in HIV-infected homosexual men, present as an effusion in the absence of a contiguous tumor mass, remain localized to the body cavity of origin, exhibit cytomorphologic features that bridge immunoblastic lymphoma and anaplastic large cell lymphoma, express CD45 and one or more activation-associated antigens in the frequent absence of B cell lineage-associated antigens, exhibit clonal immunoglobulin gene rearrangements, consistently contain KSHV, nearly always contain EBV, lack c-myc gene rearrangements and lack bcl-2, bcl-6, ras, and p53 gene mutations. These KSHV-containing primary effusion lymphomas represent a distinct clinicopathologic and biologic entity. In summary, the immunodeficiency-associated lymphoproliferative disorders represent a significant clinical problem but they also represent an important biological model for studying the development and progression of lymphoid neoplasia in immune deficiency.