plasmablastic lymphoma (pbl); and primary effusion lymphoma (pel) (also termed pleural effusion lymphoma). (pel cases are infected not only with hiv and in most cases ebv but also kaposi's sarcoma-associated herpesvirus (hhv8) in all cases.) these lpd are b cell diseases which the world health organization (2016) divides into those occurring in: 1) immune-competent, hiv-negative individuals; 2) hiv+ individuals; and 3) individuals with other immunodeficiency disorders. the lpd occurring in immune-competent, hiv-negative individuals are detailed in the above section entitled ebv+ b cell lymphoproliferative diseases. the lpd occurring predominantly in hiv-positive individuals are detailed in the following table which gives the percentage of the lpd that are ebv+, the latency phase of the virus in each lpd, and some factors expressed by the hosts malignant cells which promote the development, growth, and/or survival of the malignant cells in each lpd. lpd typepercent ebv+latency phaselatent ebv genes expressedfactors promoting the development, growth and/or survival of malignant cells dlbl30–40%iiiallmutations or changes in the expression of tnfaip3, myc, and/or bcl6 genes. pcnsl90–100%iiiallmutations in myd88 and cd79b genes and copy number gains at the programmed death ligand 1 and programmed death ligand 2 gene loci on chromosome 9. bl30–40%ieberstranslocations and/or mutations in the myc and/or tp53 genes. hl100%iilmp1, lmp2, lmp2a, ebna1, ebersthe products proteins of some of these viral genes stimulate the nfkb cell signaling pathway. pbl70–80%possible i/iiebers, rarely lmp1translocations, amplifications, and other causes (e.g. mutations in the prdm1 gene) lead to the overexpression of the myc gene. pel90%possible i/iiebna1, lmp2a, ebersconcurrent infection with hhv8 and this virus's expression of its transforming proteins (e.g. lana1) appears responsible for the disorder. further findings and the treatment of ebv-related and hiv-related lpd are given in the "ebv+ b cell lymphoproliferative diseases" section. except for the possible exclusion of pel, these treatments should include continuance or, in individuals who have not yet been treated for aids, the institution of anti-hiv combination drug regimens. in the category of ebv+ lpd occurring in individuals who are immunodeficient due to other causes than hiv infection, the other causes for immune-incompetency include: 1) immune deficiency diseases such as common variable immunodeficiency, x-linked agammaglobulinemia, hypogammaglobulinemia, the wiskott–aldrich syndrome, ataxia telangiectasia, the radiosensitive forms of severe combined immunodeficiency disease (scid), the autoimmune lymphoproliferative syndrome, and the whim syndrome. 2) immunosuppressive drug therapy, particularly methotrexate and regimens including methotrexate. 3) genetic defects in the expression of genes for xiap encoding the x-linked inhibitor of apoptosis protein, iak encoding interleukin-2 inducible t cell kinase, cd27 encoding a receptor in the tumor necrosis factor receptor superfamily, stk4 encoding serine/threonine-protein kinase 4, 1ctps1 encoding ctp sythetase, coro1a encoding coronin 1a, apds encoding activated phosphatidylinositide 3-kinase, cd16 encoding fcγriii, gata2 encoding gata-binding factor 2 (a transcription factor), and mcm4 encoding the dna replication licensing factor, mcm4. 4) inflammatory/autoimmune diseases such as chronic hepatitis, ulcerative colitis, retroperitoneal fibrosis, and primary biliary cholangitis. 5) chronic autoimmune and inflammatory diseases such as rheumatoid arthritis, graves' disease, giant-cell arteritis, sarcoidosis, and severe psoriasis), particularly in individuals receiving immunosuppressive drugs for these diseases. treatment of these diseases generally follows that for the lpd occurring in immune-competent individuals but include discontinuing or reducing the dosages of immunosuppressive drugs and addressing the underlying disease causing immunodeficiency. post-transplant lymphoproliferative disorders main article: post-transplant lymphoproliferative disorder post-transplant lymphoproliferative disorders (ptld) are a group of lpd that occur following solid organ or hematopoietic stem cell transplantation. it is due to the immunosuppressive drug regimens that accompany these transplantations. ebv-positivity occurs in 60–80% of these cases and, unlike ebv-negative cases, ebv+ cases develop more often within the first year after transplantation. the 2026 who classification divides these disorders into: 1) non-destructive ptld: this disorder is characterized by hyperplasia of plasma cells, florid hyperplasia of lymph node follicles, and infectious mononucleosis. all three of these are non-malignant disorders that involve lesions admixed with non-destructive proliferations of plasma which are usually ebv-negative, ebv-negative b cells, and rare ebv-positive t cells. 2) monomorphic ptld: this disorder is a b- or t cell lymphoma. it includes only aggressive lymphomas while excluding all indolent forms of lpd except for the inclusion of ebv-positive mucocutaneous ulcer the ebv+ positivity of cells involved in these ptld are similar to those occurring in immune-competent individuals. in ebv-positive mucocutaneous ulcer, lesions commonly include ebv-positive plasma cells. 3) classic hodgkin lymphoma: this hd malignancy is characterized by have ebv+ cells its lesions. these lesions are otherwise similar to those occurring in immune competent individuals. the virus in the three ptld are in latency phase iii and express most if not all of their latency genes including, in particular, lmp1 and lmp2a. the latter two ebv latency proteins are thought to promote the development and progression these ptld by activating the nfkb pathway in and thereby stimulating the proliferation and survival of the infected host cells. ebv-associated histiocytic-dendritic disorders inflammatory pseudotumor-like follicular/fibroblastic dendritic cell sarcoma main article: follicular dendritic cell sarcoma inflammatory pseudotumor-like follicular/fibroblastic dendritic cell sarcoma is a variant of follicular dendritic cell sarcoma (fdcs). fdcs is a rare malignancy of follicular dendritic cells (fd cells). these myofibroblast-like cells are derived from the stroma (i.e. connective tissue) of lymph nodes and other lymphatic tissue and therefore are not lymphocytes. fd cells express several markers expressed by lymphocytes; occupy the germinal centers of lymphoid tissues; and attract, stimulate the differentiation and proliferation of, and present foreign antigens to b-cells. the fd cells in fdcs may derive from follicular lymphoma cells by the process of transdifferentiation. fdcs affects primarily young to middle-aged adults of both sexes. affected individuals commonly present with painless, slowly progressive swelling of cervical lymph nodes. about 33% of cases exhibit (with or without cervical lymph node swelling) tumors of skin, mediastinum, tonsils, gastrointestinal tract, and/or soft tissues. some 10–20% of all cases are associated with precedent or contemporary castleman disease, a benign lymphoproliferative disorder. there are two histopathological forms of fdcs, conventional and inflammatory. conventional fdcs exhibits spindle-shaped fd cells in a background of small lymphocytes; inflammatory fdcs exhibits relatively rare spindle-shaped cells in a background of plasma cells, middle- to large-sized lymphocytes, and reed–sternberg-like cells. ebv is associated only with the inflammatory form of fdcs. in these cases, the fd cells express fd-cell markers (e.g. cd21, cd23, cd35, clusterin, podoplanin, gamma-synuclein) and in >90% of cases products of the virus's eber and lmlp1 genes. these cells are infected with ebv in latency ii or iii phases while the background cells are ebv-negative and not malignant. in one study, two of five individuals with ebv+ fdcs had an activating mutation in braf. while a role for ebv in fdcs remains unproven, lmp1 is able to transform rat fibroblasts into malignant-like behavior in vitro. the expression of lmp1 by fd cells might contribute to the malignancy of these cells in fdcs. overall, patients with fdcs have local recurrence rates of 40–50 and a long term mortality rates due to the disease of ~20%. however, fdsc, particularly in cases with only lymph node involvement, usually has an indolent course with a low rate (~10%) of metastasis. in these cases, surgical removal appears to be the treatment of choice; the role of radiation and chemotherapy here is not well-defined. cases with extranodal involvement, especially those with abdominal tumors, have a higher metastatic rate (~20%). chemotherapy regimens remain the mainstay for treating disseminated fdcs. however, these regimens (e.g. chop, ice, and abvd) have produced variable results. too few individuals have been treated with allogeneic hematopoietic stem cell transplantation to determine its role in treating fdsc. further studies on the usefulness of radiation, chemotherapy, bone marrow transplantation, and newer non-chemotherapy drugs such as the braf oncogene inhibitor, vemurafenib, (for individuals with the braf oncogene), are needed. treatment on 13 october 2022, the committee for medicinal products for human use (chmp) of the european medicines agency (ema) recommended the granting of a marketing authorization under exceptional circumstances for tabelecleucel.