Table 3.
Summary Table: HHV8/KSHV-Positive Lymphoproliferative Disorders and the Spectrum of Plasmablastic and Plasma Cell Neoplasms
| HHV8+ MCD |
| Castleman disease is classified according to the presence or absence of HHV8+ |
| HHV8+ MCD is a lymphoid, histiocytic, and plasma cell proliferation related to cytokine production, particularly viral interleukin 6 |
| Polyclonal plasmablasts with IgM λ light chain restriction are characteristically present in HHV8+ MCD |
| Some cases are associated with plasmablastic aggregates (previously called microlymphomas), which, despite light chain restriction, are poly- or oligoclonal |
| HHV8+ DLBCL |
| Usually but not always related to MCD |
| In some cases, there may be evolution from MCD with plasmablastic aggregates to sheets of plasmablasts with tissue destruction and monoclonal expression of light chains |
| Lymphomas express markers of terminal B-cell differentiation but are negative for EBV |
| HHV8+ GLPD |
| Occurs in immunocompetent patients, EBV+, and may be monotypic κ or λ but polyclonal or oligoclonal (compared with EC-PEL, which is clonal) |
| PEL and PEL/EC-PEL |
| PELs are negative for B-cell markers, but immunoglobulin gene rearrangements are positive, indicating a B-cell genotype |
| Usually but not always associated with HIV infection |
| Not all PELs present as effusions, and cases have been reported in the space surrounding breast implants, CSF, and peripheral blood |
| PELs are HHV8+ by definition, and EBV is present in about 75% of cases, particularly those associated with HIV |
| PELs express markers of terminal B-cell differentiation (MUM1, Blimp1) |
| Not all effusions are PELs, and other HHV8– lymphomas can present as effusions |
| Effusion-based DLBCL HHV8– |
| May be seen with longstanding chronic inflammation and associated with EBV as in cases of PAL |
| Similar lymphomas occur in patients with medical conditions leading to fluid overload such as liver disease and ascites |
| Unlike cases of PEL, most express B-cell markers |
| Plasma cell neoplasms associated with immunodeficiency |
| Spectrum ranges from marginal zone–like lymphoma to plasmacytoma to plasmablastic lymphoma and plasma cell leukemia, sometimes in the same patient |
| Plasmablastic lymphomas differ in different settings (immunocompetent vs HIV vs PTLD) |
| Clinical features are important in making the correct diagnosis |
| EBV and MYC are variably involved in different immunodeficiency settings |
| CD56, CD117, and myeloma FISH are helpful in separating blastic myeloma from plasmablastic lymphoma |
| PL in the immunodeficiency and nonimmunodeficiency setting |
| Phenotype is important for the definition, generally negative for CD20 and positive for CD138, CD38, and IRF4/MUM1 |
| Although the oral cavity is a common site of presentation, particularly in association with HIV, PL may occur at other sites |
| In the non-HIV population, plasmablastic lymphoma has a more variable appearance and clinical presentation |
| Cases with marked plasmacytic differentiation may resemble plasmablastic myeloma and be difficult to differentiate, even with clinical information |
| EBV is positive in most cases, particularly in patients with AIDS, and MYC translocations are seen in over 50% of cases |
CSF, cerebrospinal fluid; DLBCL, diffuse large B-cell lymphoma; EBV, Epstein-Barr virus; EC-PEL, extracavitary primary effusion lymphoma; FISH, fluorescence in situ hybridization; GLPD, germinotropic lymphoproliferative disorder; HHV8, human herpes virus 8; HIV, human immunodeficiency virus; IRF4, interferon regulatory factor 4; MCD, multicentric Castleman disease; PAL, pyothorax-associated lymphoma; PEL, primary effusion lymphoma; PL, plasmablastic lymphoma; PTLD, posttransplant lymphoproliferative disorder.