Primary Effusion Lymphoma (PEL) and Solid Variant of PEL

Primary Effusion Lymphoma (PEL) and Solid Variant of PEL

Francisco Vega, MD, PhD

Cytospin of primary effusion lymphoma (PEL) showing medium- to large-sized lymphoid cells with abundant finely vacuolated cytoplasm and irregular nuclei. (Courtesy W. Chen, MD.)

Cell block of primary effusion lymphoma (PEL) showing that virtually all neoplastic cells strongly HHV8(+). The neoplastic cells were CD20(−). Detecting evidence of HHV8 infection is essential for the diagnosis of PEL.



  • Primary effusion lymphoma (PEL)


  • Body cavity-based lymphoma

  • Kaposi sarcoma-associated herpesvirus (KSHV)-associated lymphoma


  • Human herpes virus 8 (HHV8)-associated large B-cell neoplasm most often involving body cavities

    • Pleural, pericardial, or peritoneal cavity

  • HHV8(+) lymphomas indistinguishable from PEL rarely present as solid tumor mass

    • These tumors are designated as extracavitary or solid variants of PEL


Infectious Agents

  • PEL arises from HHV8-infected B cells that are frequently coinfected by Epstein-Barr virus (EBV)

  • HHV8 virus

    • γ herpes double-stranded DNA lymphotropic virus

    • Endemic in sub-Saharan Africa and Mediterranean region

    • In addition to PEL, HHV8 is associated with

      • Kaposi sarcoma

      • Multicentric Castleman disease (MCD)

      • MCD-associated plasmablastic lymphoma

    • Encodes number of homologues of cellular genes

      • Involved in cell proliferation and apoptosis

Clinical Associations

  • HIV infection or other severe acquired immunodeficiencies

    • Preexisting acquired immunodeficiency syndrome (AIDS) is very common

  • PEL also can occur in patients without immunodeficiency

    • Elderly patients in 8th to 9th decades in HHV8 endemic areas

      • Usually these tumors are EBV(−)

  • Rare cases of PEL are associated with hepatitis C &/or B


  • In PEL, B-cell differentiation program is blocked

    • In part due to overexpression of activated B-cell factor 1 (ABF-1) and inhibitor of differentiation 2 (ID2)

      • These molecules inhibit E2A (B-cell transcription factor)

      • E2A inhibition downregulates B-cell specific genes

    • Restoration of E2A activity in PEL induces apoptosis of tumor cells



  • Incidence

    • Rare

      • 0.3% of all aggressive lymphomas in HIV(−) patients

      • 4% of all HIV-related lymphomas


  • Lymphoma cells grow in pleural, peritoneal, &/or pericardial effusions

  • Usually no distinct extracavitary tumor masses &/or organomegaly

  • Frequent B symptoms

  • Symptoms commonly result from massive malignant effusion

    • Dyspnea is frequent (from pleural or pericardial disease)

    • Abdominal distension (from peritoneal disease)

  • Systemic dissemination can occur during course of disease

  • Associated with clinical and laboratory findings of severe immunosuppression

    • Marked depletion of CD4(+) T cells

  • Involvement of central nervous system and bone marrow is rare

  • Standard Ann Arbor staging is not useful as, by definition, all PEL cases are stage IV

  • Some patients have coexistent Kaposi sarcoma

  • HHV8(+) lymphomas can present as masses involving organs (extracavitary or solid variant of PEL)

    • Gastrointestinal tract most frequently involved

    • Lymph nodes can be involved

    • Patients with extracavitary mass often develop malignant effusion over disease course


  • Highly active antiretroviral therapy (HAART) improves prognosis

  • Intracavitary cidofovir (antiviral agent that inhibits replication of HHV8) with interferon-α

  • Traditional chemotherapy, usually cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)

  • Bortezomib, a proteosome inhibitor that inhibits NFkB pathway

  • Antivirals (valganciclovir)

  • Rituximab probably has no role in patients with PEL

    • CD20 is usually negative


  • Usually poor; median survival < 6 months


Radiographic Findings

  • Bilateral or unilateral pleural effusion

  • Pericardial effusion, peritoneal effusion

  • Slight thickening of parietal pleura, pericardium, or peritoneum

  • Absence of solid tumor masses, parenchymal abnormalities, or mediastinal enlargement


Histologic Features

  • Diagnosis is usually made on cytological preparations of involved effusion fluid

  • Biopsy specimens of cavity lining tissue also may show small number of neoplastic cells adherent to mesothelial surfaces

  • Large lymphoid cells with round to irregular nuclei, prominent nucleoli, and variable morphology

    • Immunoblastic

      • Round nuclei with centrally located nucleoli

    • Plasmablastic

      • Eccentric nuclei with abundant cytoplasm, sometimes with perinuclear hof

    • Anaplastic

      • Multinucleated and Reed-Sternberg-like cells

Cytologic Features

  • Medium- to large-sized atypical cells, many with irregular nuclear contours, prominent nucleoli, and abundant cytoplasm (± vacuolated)

  • Cytomorphologic appearances ranging from immunoblastic to anaplastic and exhibiting frequent plasmablastic differentiation



  • HHV8(+) is essential for diagnosis

  • Plasma cell-associated markers(+)

    • CD138, VS38c, IRF-4/MUM1

    • CD38, EMA

  • Cytoplasmic Ig λ light chain(+/−)

  • CD30(+), CD45/LCA(+/−)

  • Notch(+) in most cases

    • Nuclear and cytoplasmic pattern of expression

  • Pan-B-cell markers(−)

    • CD19, CD20, CD79a, pax-5

  • CD15(−), LMP-1(−)

  • CD10(−), Bcl-6(−)

Flow Cytometry

  • Similar immunophenotype to that observed by immunohistochemistry

  • Results

    • CD45/LCA(+), CD71(+)

    • HLA-DR(+); CD23(+) in ˜ 20%

    • Surface Ig light chain expression is rare

    • CD19(−), CD20(−), CD22(−)

      • ˜ 10% of cases have dim CD20 expression

    • CD10(−), FMC7(−)

    • Aberrant T-cell markers are positive in subset of cases

      • CD45RO (˜ 90%), CD7 (˜ 30%), CD4 (˜ 20%)

      • CD2(−), CD3(−), CD5(−), CD8(−)


  • Usually complex karyotype

  • No recurrent chromosomal abnormalities identified

In Situ Hybridization

  • EBER(+) in ˜ 80% of cases

Array CGH

  • Gains of Iq21-41, 4q28-35, 7q, 8q, 11, 12, 17q, 19p, 20q

  • Losses of 4q, 11q25, 14q32

    • Amplification of selectin-P ligand (12q24.11)

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Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Primary Effusion Lymphoma (PEL) and Solid Variant of PEL
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