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.


TERMINOLOGY


Abbreviations



  • Plasmablastic lymphoma (PBL)


Definitions



  • 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(−)


ETIOLOGY/PATHOGENESIS


Infectious Agents



  • EBV positive


  • Strongly associated with HIV infection


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



    • Example: Post-transplantation


CLINICAL ISSUES


Epidemiology



  • 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


Presentation



  • 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


Treatment



  • 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


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


IMAGE FINDINGS


Radiographic Findings



  • PBL is PET scan positive


  • PET or CT scan can show widespread bone involvement


MICROSCOPIC PATHOLOGY


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


ANCILLARY TESTS


Immunohistochemistry



  • 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


Cytogenetics



  • 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[-])


PCR



  • 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


DIFFERENTIAL DIAGNOSIS


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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