Plasmablastic Lymphoma

Plasmablastic Lymphoma

Francisco Vega, MD, PhD

This case of plasmablastic lymphoma (PBL) is characterized by diffuse infiltrate of large atypical lymphoid cells with a “starry sky” pattern.

PET scan shows widespread metastatic PBL image. The patient was HIV positive and initially presented with PBL of the left jaw.



  • Plasmablastic lymphoma (PBL)


  • PBL was initially described as rare variant of diffuse large B-cell lymphoma (DLBCL) involving oral cavity

    • 15 of 16 patients were immunodeficient as a result of human immunodeficiency virus (HIV) infection

  • PBL is currently defined as diffuse proliferation of large neoplastic cells

    • Immunoblastic or plasmablastic cytologic features

    • Plasma cell immunophenotype: CD38(+), CD138(+), CD20(−)


Infectious Agents

  • EBV positive

  • Strongly associated with HIV infection

  • Has been reported in patients with immunodeficiency due to other causes

    • Example: Post-transplantation



  • Incidence

    • Unknown

      • Frequency: PBL represents < 1% of all non-Hodgkin lymphomas

  • Age

    • Depends on clinical setting

      • HIV(+) patients: Median age = 40 years

      • HIV(−) patients: Children or elderly

  • Gender

    • Male predominance: 7:1

      • Related to HIV(+) population affected


  • PBL most often originates in mucosal extranodal sites

    • 2 general groups: Oral and nonoral sites

    • Rapidly growing and often painful mass

  • Oral cavity is most common site

    • 90% of patients are HIV(+)

      • Patients have very low CD4(+) counts

    • Mean duration of HIV(+) prior to PBL: 5 years

    • 60% have localized disease (stage I) at diagnosis

    • PBL frequently arises near mucosa

      • Often involves gingiva

      • Frequently infiltrates adjacent bone

  • Nonoral type PBL

    • Less frequently HIV(+)

    • 60% are disseminated disease (stage IV) at diagnosis

    • Most common nonoral sites

      • Maxillary sinus, nasopharynx, gastrointestinal tract

    • Less common nonoral sites

      • Orbit, skin, lung, gastrointestinal tract, soft tissues

    • Rare sites of PBL (case reports)

      • Mediastinum, vulva, bone marrow

  • PBL uncommonly involves lymph nodes

  • PBL can widely disseminate during course of disease

  • International prognostic Index (IPI): Usually intermediate or high score

  • Some cases are reported in patients with history of myeloma or lymphoma

    • Better considered as plasmablastic transformation of underlying neoplasm


  • CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)

    • Some regimens have included rituximab &/or radiotherapy

  • More aggressive chemotherapy regimens have been employed without benefit

  • Addition of antiretroviral therapy (HAART) improves prognosis


  • Poor prognosis

  • Most patients die within 1st year after diagnosis

  • In large review, prognosis did not correlate with

    • Age, sex, CD4(+) count, HIV load

    • Stage, anatomic site of PBL, EBV status

    • Use of CHOP chemotherapy


Radiographic Findings

  • PBL is PET scan positive

  • PET or CT scan can show widespread bone involvement


Histologic Features

  • Diffuse growth pattern

  • Frequent “starry sky” pattern with tingible body macrophages

  • Apoptotic bodies and mitoses are usually numerous

  • Confluent areas of necrosis are common

Cytologic Features

  • Monotonous proliferation of large neoplastic cells in histologic sections

    • More cytologic variability in smear/imprint preparations

  • PBL cases can exhibit cytologic spectrum

    • Immunoblastic

      • Cells have prominent central nucleoli

      • More common in oral cavity and in HIV(+) patients

    • Plasmablastic

      • Cells have more abundant cytoplasm and eccentrically located nuclei

      • More common in nonoral sites

  • Binucleation or multinucleation is common in PBL

  • Cytoplasm of PBL cells is usually deeply basophilic

    • Dutcher and Russell bodies are usually absent in PBL



  • Immunophenotype is essential to establish diagnosis of PBL

  • Common pan-B-cell markers commonly absent

    • CD20, CD22, and pax-5

    • Weak expression reported in small subset of cases

    • CD79a is more often positive; also often weak intensity

  • Strong positivity for plasma cell-associated markers

    • IRF-4/MUM1(+), CD38(+), CD138/syndecan-1(+), VS38/p63(+)

    • PRMD1/BLIMP1(+), XBP1(+)

  • Ki-67 is high: > 70% in most cases

  • Monotypic cytoplasmic light chain positive in 50-70% of cases

  • EMA is often positive; CD30(+) in subset

  • Aberrant expression of T-cell markers in some cases

    • CD3, CD4, CD43, CD7

  • Germinal center B-cell antigens positive in subset of PBL

    • Bcl-6 uncommon; CD10 (+ in ˜ 50%)

  • CD56 can be positive in cases with plasmablastic cytologic features

    • Must exclude plasma cell myeloma

  • Bcl-2 is usually negative

  • CD45/LCA is negative or weakly positive in subset of cases

  • ALK1(−), CD117(−), Cyclin-D1(−)

  • HHV8(−)

  • EBV-LMP 1 and 2 are not expressed

    • Consistent with restricted latency

    • In contrast to AIDS-related immunoblastic lymphomas that usually express EBV-LMP 1

  • No significant differences in frequency of expression of any immunohistochemical marker between PBL and plasmablastic plasma cell myeloma


  • t(8;14)(q24;q32) or MYC-IgH fusion identified in subset of PBL

    • HIV(+) patients

In Situ Hybridization

  • EBV small encoded RNA (EBER) is positive in ˜ 75% of cases

    • EBER useful for distinguishing PBL from plasmablastic plasma cell myeloma (EBER[-])


  • Monoclonal IgH gene rearrangements

  • T-cell receptor genes usually in germline configuration

  • Single case reports showing both IgH and TCR gene rearrangements

  • IgH genes commonly show somatic mutations of IgH variable regions


Diffuse Large B-cell Lymphoma, Not Otherwise Specified (DLBCL)

  • DLBCL often has centroblastic cytologic features

    • Plasmacytoid differentiation is uncommon

  • Immunophenotype of DLBCL is distinct from PBL

    • CD19(+), CD20(+), CD22(+), pax-5(+)

    • CD45/LCA is usually positive

    • Large subset is strongly positive for CD10 &/or Bcl-6

Diffuse Large B-cell Lymphoma, Immunoblastic Variant (DLBCL-IB)

  • Morphologic overlap between DLBCL-IB and PBL

    • Immunophenotype is needed to make this distinction

    • DLBCL-IB is usually CD20(+) &/or pax-5(+)

    • CD45/LCA often positive

    • CD10(+/−), Bcl-6(+/−)

    • CD4(+) is extremely rare in DLBCL-IB

  • By contrast, PBL is CD20(−), CD38(+), CD138/syndecan-1(+), and VS38/p63(+)

    • CD4 or CD56 can be positive

Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Plasmablastic Lymphoma
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