Lymphoma & related disorders
HHV8 associated lymphoproliferative disorders
HHV8 related germinotropic lymphoproliferative disorder
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Last author update: 9 August 2021
Last staff update: 10 August 2021
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PubMed Search: HHV8 germinotropic lymphoproliferative disorder
Table of Contents
Definition / general | Essential features | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Prognostic factors | Case reports | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1Cite this page: Venkateswaran J, Teruya-Feldstein J. HHV8 related germinotropic lymphoproliferative disorder. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomaHHV8germinotropicLPD.html. Accessed November 28th, 2024.
Definition / general
- Monotypic HHV8 positive lymphoproliferative lesion occurring characteristically in HIV negative patients
Essential features
- Coinfection of HHV8 and EBV
- Immunocompetent patients
- Localized lymphadenopathy
- Aggregates or single plasmablasts / immunoblasts in the germinal centers
- Good prognosis
Epidemiology
- No known epidemiological association
- Usually seen in HIV negative, immunocompetent patients
- Occasional cases seen in HIV positive patients
Sites
- Involves lymph nodes
Pathophysiology
- Uncertain contribution of EBV in pathogenesis
- Occasional EBV negative cases
- Elusive role of vIL6
- Activation of IL6 receptor signaling through vIL6 and human IL6 may play a role in differentiation of Kaposi sarcoma associated herpesvirus infected B cells into plasmablasts and development of lymphoproliferative lesions (Am J Surg Pathol 2017;41:795)
Etiology
- Unclear origin of the plasmablasts; possible theories include:
- Migration of neoplastic B lymphocytes into germinal centers by ecotaxis / homing (Am J Surg Pathol 2017;41:795)
- Somatic hypermutation and intraclonal variation, favoring a germinal center derivation (Am J Surg Pathol 2017;41:795)
Clinical features
- Localized, sometimes multifocal lymphadenopathy in otherwise healthy individuals
Diagnosis
- Lymph node biopsy
- Morphology and immunohistochemistry
- Immunophenotype and molecular studies
Radiology description
- Very few descriptions of radiological features reported so far
Prognostic factors
- Overall favorable response to chemotherapy and radiation
- Rare reported cases progressed to high grade HHV8+ EBV+ lymphoma (Am J Clin Pathol 2017;147:171, Am J Surg Pathol 2017;41:795)
Case reports
- 20 year old woman with localized lymphadenopathy (BMJ Case Reports CP 2020;13:e231640)
- 49 year old patient with lymphadenopathy (Ann Pathol 2014;34:373)
- 75 year old man with an incidentally discovered neck mass (Int J Hematol 2012;95:107)
Treatment
- Treatment approach is variable; some cases have not been treated, while others have been treated with surgery alone or with chemotherapy and radiation
- Potential therapeutic role of PD1 / PDL1 immunotherapy has been suggested due to the PDL1 expression and it requires additional research
Microscopic (histologic) description
- Small aggregates of or single plasmablasts / immunoblasts confined to the germinal center (Ann Hematol 2020;99:2243)
- These are large atypical cells with anaplastic features (Int J Surg Pathol 2020;28:804)
- Coinfected by HHV8 and EBV
- Atrophic and hyalinized follicles with vascular proliferation resembling Castleman disease
Microscopic (histologic) images
Contributed by Julie Teruya-Feldstein, M.D.
Follicles of varying sizes
Hyalinization in some follicles
Plasmablasts
EBER1
Plasmablasts positive for MUM1
Plasmablasts negative for CD30
Plasmablasts negative for BCL6
Plasmablasts negative for CD10
Plasmablasts negative for CD79a
Positive stains
- Plasmablasts are positive for cytoplasmic monotypic light chain (kappa or lambda), IgA, CD38, MUM1 / IRF4, vIL6, HHV8 / LANA and EBER (Mod Pathol 2020;33:18)
- More than 70% positive for HHV8 / LANA / vIL6 favors diagnosis of germinotropic lymphoproliferative disorder over plasmablastic multicentric Castleman disease (Mediterr J Hematol Infect Dis 2018;10:e2018061)
- Cells are positive for cytoplasmic monotypic immunoglobulin heavy chain
Negative stains
- Negative for LMP, EBNA2 and BZLF1 expression, i.e latency type 1 (Mod Pathol 2020;33:18)
- Plasmablasts are usually negative for CD20, CD79a, PAX5, BCL6, CD10 and CD30
- T cell markers may occasionally be positive (Mod Pathol 2020;33:18)
Molecular / cytogenetics description
- Plasmablasts are polyclonal or oligoclonal
Sample pathology report
- Lymph node, excision / core needle biopsy:
- HHV8 related germinotropic lymphoproliferative disorder
Differential diagnosis
Board review style question #1
Which of the following is true about HHV8 related germinotropic lymphoproliferative disorder?
- There is coinfection of EBV and HHV8
- Usually seen in HIV positive patients
- Positive for LMP1, EBNA2 and BZLF1 expression and negative for cytoplasmic monotypic immunoglobulin heavy chain
- Unfavorable response to chemotherapy and radiation
Board review style answer #1
A. There is coinfection of EBV and HHV8
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