Lymphoma & related disorders

Lymphoid proliferations and lymphomas associated with immune deficiency and dysregulation

Lymphomas arising in immune deficiency / dysregulation

Last author update: 1 January 2012
Last staff update: 20 July 2023 (update in progress)

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PubMed Search: Lymphomas [title] "HIV infection"

Dragos C. Luca, M.D.
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Cite this page: Luca DC. Lymphomas arising in immune deficiency / dysregulation. website. Accessed November 29th, 2023.
Definition / general
  • Lymphomas that develop in HIV+ patients (LHIV) are predominantly aggressive B cell lymphomas
  • Some are considered acquired immunodeficiency syndrome (AIDS); defining conditions and are the initial manifestation of AIDS
  • These disorders are heterogeneous and include lymphomas usually diagnosed in immunocompetent patients, as well as those seen much more often in the setting of HIV infection (WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue, IARC 2008)
  • Occur in 4 - 10% of AIDS patients, 100× expected rates of non-Hodgkin lymphoma (Hum Pathol 2002;33:392)
  • Overall 60 - 200× increase of all types of NHL in HIV+ patients
  • Conversely, 10% of non-Hodgkin lymphomas in US / Europe are AIDS related
  • Most common LHIV: Burkitt lymphoma, diffuse large B cell lymphoma (DLBCL), primary effusion lymphoma (PEL), plasmablastic lymphoma (ScientificWorldJournal 2011;11:687)
  • Burkitt Lymphoma in HIV patients is 1000× more common than in non HIV+ individuals
  • Three categories:
    1. More specific to HIV+ patients: primary effusion lymphoma, plasmablastic lymphoma, primary CNS lymphoma (Arch Neurol 2010;67:291)
    2. Common also in HIV- patients: Burkitt lymphoma, DLBCL, extranodal MZL, MALT, rare peripheral T cell lymphoma, classic Hodgkin lymphoma (Adv Hematol 2011;2011 Epub 2010 Sep 23)
    3. Occurring in other immunodeficient states: polymorphic B cell posttransplant lymphoproliferative disease
  • Before highly active antiretroviral therapy (HAART), primary CNS lymphoma & Burkitt lymphoma had a 1000× increase in HIV+ patients; since HAART, risk of NHL declined dramatically from 53 to 23 standardized incidence ratio
  • Considerable risk decrease in 1996, stable thereafter
  • Decreased incidence of AIDS associated NHL after HAART also consistent with improved CD4 counts
  • HAART associated with enhanced survival (75% decrease in mortality)
  • Unexpected increase in the incidence of classic Hodgkin lymphoma (CHL) since HAART may be related to improved CD4 counts (CHL incidence lower in patients with severe immunosuppression)
  • Usually extranodal: GI, CNS, liver, bone marrow
  • Rare peripheral blood involvement (occasional Burkitt lymphoma presenting as acute leukemia)
  • Unusual sites frequently involved: oral cavity, jaw, body cavities
  • Other possible extranodal sites: lung, skin, testis, heart, breast
  • Lymph node involvement: 1/3 of patients, since HAART – 1/2
  • Heterogeneous, with several pathogenetic mechanisms: chronic antigen stimulation, genetic abnormalities, cytokine dysregulation, EBV and HHV8
  • EBV+ lymphomas have decreased in the HAART era
  • Generally monoclonal but some are polyclonal / oligoclonal suggesting multistep lymphomagenesis
  • Chronic antigen stimulation reflected by: B cell stimulation, hypergammaglobulinemia, persistent generalized lymphadenopathy
  • Cytokine dysregulation: high levels of IL6 and IL10 (LHIV associated with EBV or HHV8)
  • EBV positivity: overall ~40% of LHIV, 80 - 100% of primary CNS lymphomas & PEL, 80% of DLBCL with immunoblastic features, 30 - 50% of Burkitt lymphoma, virtually 100% of CHL
  • HHV8 specifically associated with PEL, usually in the context of profound immunosuppression (late stage disease)
  • HIV is NOT directly involved in the malignant transformation of B cells (no HIV sequences detected in lymphoma cells)
Clinical features
  • Frequent presentation with advanced clinical stage, bulky disease and high tumor burden
  • LDH markedly elevated
  • Significant relationship between lymphoma type and HIV disease status:
    • DLBCL: long standing AIDS, lower CD4 counts (mean < 100×106/L), higher rate of opportunistic infections
    • Burkitt lymphoma: less immunodeficient patients, higher CD4 counts ( > 200×106/L), shorter mean interval between the diagnosis of HIV seropositivity and lymphoma
  • Aggressive, poor outcome
  • Before HAART:
    • ~50% rate of complete remission for most histological subtypes
    • 2 year survival significantly lower for DLBCL than Burkitt lymphoma
    • International Prognostic Index (IPI): reliable indicator, also correlated with the degree of immunosuppression
    • Other adverse prognostic indicators: age > 35 years, IV drug use, Stage III / IV, CD4 count < 100×106/L
    • Outcome closely related to the severity of immunodeficiency (despite dose adjustment)
  • Since HAART:
    • Improved overall survival of patients with DLBCL approaching that of patients with de novo lymphoma
    • Most important prognostic factor for time of survival – achievement of complete remission
  • Long-term survival in ~1/3 of patients with favorable prognostic features
  • PEL – usually low complete remission rate and very poor prognosis
Microscopic (histologic) description
  • Diffuse, pleomorphic, high grade B cells; frequent mitotic figures, increased cellular debris, necrosis common
  • Some aggressive B cell lymphomas are common with HIV negative patients, some are more specific for AIDS patients
Immunohistochemistry & special stains
  • Usually B cell, occasionally CHL, rarely T cell
Molecular / cytogenetics description
  • Consistently monoclonal
  • Abnormalities involving MYC, BCL6 and tumor suppressor genes
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