EBV+ Diffuse Large B-cell Lymphoma of the Elderly

EBV+ Diffuse Large B-cell Lymphoma of the Elderly

Tarlq Muzzzafar, MBBS

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).



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


  • Senile EBV(+) B-cell lymphoproliferative disorder

  • Age-related EBV(+) lymphoproliferative disorder

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


  • 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


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



  • 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


  • 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


  • 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


  • 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


  • Median survival is 2 years

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


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

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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