EBV+ Diffuse Large B-cell Lymphoma of the Elderly



EBV+ Diffuse Large B-cell Lymphoma of the Elderly


Tarlq Muzzzafar, MBBS





Key Facts


Terminology



  • DLBCL infected by EBV occurring in patients > 50 years old without history of immunodeficiency or lymphoma


Clinical Issues



  • Median age: ˜ 70 years (range: 45-92 years)


  • Affected patients are relatively healthy prior to diagnosis


  • Extranodal mass ± lymphadenopathy in ˜ 70%



    • Only lymphadenopathy in ˜ 30%


  • Median survival is 2 years


Microscopic Pathology



  • EBV(+) DLBCL-E effaces architecture of extranodal site &/or lymph node


  • 2 subtypes: Polymorphous and large cell lymphoma (monomorphous)



    • Represent a morphologic spectrum


    • No clinical or prognostic relevance


  • Sheets of necrosis; often with geographic pattern


Ancillary Tests



  • CD20(+), CD22(+), CD79α(+), pax-5(+)


  • IRF-4/MUM1(+), CD30(+/-)


  • Ki-67 (MIB1) shows high proliferation index


  • Lymphoma cells have EBV type III latency pattern


  • EBV present in monoclonal episomal form


Top Differential Diagnoses



  • DLBCL, not otherwise specified


  • Plasmablastic lymphoma


  • Classical Hodgkin lymphoma







EBV(+) diffuse large B-cell lymphoma of the elderly (EBV[+] DLBCL-E) involving needle biopsy of thigh mass. This neoplasm is the monomorphous subtype and is composed of sheets of lymphoma cells.






EBV(+) DLBCL-E, monomorphous subtype involving needle biopsy of thigh mass. In situ hybridization analysis shows that the lymphoma cells are strongly positive for EBV small encoded RNA (EBER).


TERMINOLOGY


Abbreviations



  • Epstein-Barr virus(EBV) diffuse large B-cell lymphoma of the elderly (DLBCL-E)


Synonyms



  • Senile EBV(+) B-cell lymphoproliferative disorder


  • Age-related EBV(+) lymphoproliferative disorder


  • EBV-associated B-cell lymphoproliferative disorder of the elderly


Definitions



  • DLBCL infected by EBV occurring in patients > 50 years old without history of immunodeficiency or lymphoma


  • These tumors exhibit a broad morphologic spectrum from polymorphous and Hodgkin-like lesions to monotonous DLBCL


ETIOLOGY/PATHOGENESIS


Epstein-Barr Virus (EBV) Drives B-cell Transformation and Lymphoproliferation



  • EBV: γ-herpes virus ubiquitous in humans


  • > 90% of humans are infected



    • Most have lifelong asymptomatic infection


  • EBV can infect B, T, and NK cells as well as epithelial cells


  • Increased risk for EBV-associated lymphomas in patients with



    • Congenital immunodeficiency


    • Acquired immunodeficiency



      • Human immunodeficiency virus infection


      • Iatrogenic causes


    • Elderly adults in apparent good health recently identified as at-risk group



      • Impaired immunity associated with aging is implicated


      • In particular, impaired host T-cell surveillance


  • When EBV infects B cells, the virus will



    • Upregulate and activate multiple cell signaling pathways and antiapoptotic proteins


    • Induce B-cell proliferation and transformation


  • In EBV(+) DLBCL-E, virus shows type III EBV latency pattern



    • All EBV nuclear antigens (EBNAs), EBER, and latent membrane proteins (LMPs) are expressed


CLINICAL ISSUES


Epidemiology



  • Incidence



    • In Asian countries, EBV(+) DLBCL-E represents up to 10% of all DLBCL cases in patients without apparent immunodeficiency


    • Apparently less common in Western nations; little data available


  • Age



    • Median: ˜ 70 years (range: 45-92 years)


    • ˜ 25% of patients ≥ 90 years


  • Gender



    • M:F = 1.4:1


Site



  • Extranodal sites involved in 70% of patients



    • Skin, lung, tonsil, and stomach most common


    • Bone marrow or blood involved in ˜ 10% of patients


  • Lymph nodes


Presentation



  • Affected patients are relatively healthy prior to diagnosis


  • Extranodal mass ± lymphadenopathy in ˜ 70% of patients



    • Only lymphadenopathy in ˜ 30% of patients



  • B symptoms in ˜ 60% of patients


  • High International Prognostic Index (IPI) score in ˜ 60% of patients


  • Ann Arbor stage III-IV in ˜ 60% of patients


Laboratory Tests



  • ˜ 50% of patients have elevated lactate dehydrogenase (LDH) level


Treatment



  • Drugs



    • Consensus for specific chemotherapy regimen has not been established


    • Cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) regimen has been used


    • Clinical remission achieved in 63%



      • Response worse than in patients with EBV(-) DLBCL


    • Role of rituximab has not been determined


Prognosis



  • Median survival is 2 years


  • Presence of B symptoms and age > 70 years indicate worse prognosis


MICROSCOPIC PATHOLOGY


Histologic Features



  • EBV(+) DLBCL-E effaces architecture of extranodal site &/or lymph node


  • 2 subtypes: Polymorphous and large cell lymphoma (monomorphous)



    • Represent a morphologic spectrum


    • Distinguishing these subtypes histologically can be arbitrary in some cases


    • No clinical or prognostic relevance


  • Both types demonstrate



    • Large lymphoma cells and Hodgkin and Reed-Sternberg (HRS)-like cells


    • Increased mitotic activity


    • Sheets of necrosis; often with geographic pattern


  • Polymorphous subtype



    • Broad spectrum of B-cell maturation


    • Polymorphous reactive infiltrate in background: Small lymphocytes, plasma cells, and histiocytes


  • Monomorphous subtype



    • Sheets of large monomorphous cells resembling DLBCL


Cytologic Features



  • Large lymphoma cells can be centroblastic, immunoblastic, or plasmablastic


ANCILLARY TESTS


Immunohistochemistry

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Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on EBV+ Diffuse Large B-cell Lymphoma of the Elderly

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