Lymphoproliferative diseases EBV-induced

The Epstein-Barr virus (EBV) is a ubiquitous virus that infects almost everyone in the world. EBV target cells include the naso-pharyngeal epithelia and B lymphocytes, which carry the CD21 antigen as "EBV receptors". Most EBV-infected B lymphocytes are quickly destroyed and eliminated if the immune system is intact.

However, a small residual population of surviving B lymphocytes can cause lifelong persistence. EBV-associated lymphoproliferative diseases comprise a heterogeneous spectrum of diseases ranging from benign, self-limiting infections to aggressive lymphomas. The diseases mainly affect B-cell proliferates, but also proliferates in which T cells and/or NK cells dominate. In addition, immunosuppression or certain genetic constellations increase the risk of malignant progression. Diagnosis is based on a combination of clinical symptoms, histopathology and immunohistopathology, as well as specific EBV diagnostics (EBV-PCR, EBV-EBER in situ hybridization).

Acute lymphoproliferative diseases EBV-induced

• Acute Epstein-Barr virus infection/infectious mononucleosis (glandular form (50%, exanthematic form 3% of cases)
• Hemophagocytic lymphohistiocytosis (secondary) (EBV-HLH)

Chronic lymphoproliferative diseases, EBV-induced

• Lymphoproliferative syndrome X-linked inherited (Purtilo syndrome)
• Post-transplant lymphoproliferative disease (PTLD)
• Hodgkin's lymphoma (HL )
• Burkitt's lymphoma
  • Burkitt's lymphoma sporadic (in 20% EBV-associated)
  • Burkitt's lymphoma endemic (mainly in Africa; EBV-associated in approx. 95%)
• Diffuse large B-cell lymphoma/DLBCL(partly EBV-associated)

Chronic EBV viral infections with associated T-cell and NK-cell lymphoproliferations

• EBV-associated lymphoproliferative cutaneous diseases, with photosensitivity
  • Hydroa-vacciniform (HV), classic form
  • Hydroa-vacciniforme-like lymphoproliferative disease (HV-LPD)
  • Hydroa-vacciniform-like cutaneous lymphoma
• Various cutaneous entities of EBV-associated lymphoproliferative diseases
  • Severe insect bite hypersensitivity (SMBA)
  • Cutaneous methotrexate-related lymphoproliferative disease (MTX-LPD)
  • Miliaria-like reactive lymphoproliferative disease (UV-induced, non-systemic lymphoproliferative disease, EBV induction not proven)
  • Lymphomatoid papulosis (EBV-associated variant/rare form)
  • Mucocutaneous ulcer, EBV-associated
  • Hydroa vacciniforme-like T-cell lymphoma, EBV-associated (HV-CTCL)
• Other EBV-associated NK/T-cell lymphomas
  • Extranodal NK-/T-cell lymphoma, nasal type /ENKTL (highly aggressive lymphoma, common in Asia and Latin America, usually affects the nasal cavity and upper respiratory tract).
  • Aggressive NK-cell leukemia/ANKL (highly aggressive, often fatal, mainly Asian populations)

1. Hooper MJ et al. (2023) Epstein-Barr Virus-Associated Lymphomatoid Papules: A Sign of Immunosuppression Resembling Lymphomatoid Papulosis. Am J Dermatopathol 45: 789-800.
2. Hue SS et al. (2020) Epstein-Barr virus-associated T- and NK-cell lymphoproliferative diseases: an update and diagnostic approach. Pathology 52:111-127.
3. Lindsay J et al. (2020) Epstein-Barr virus related post-transplant lymphoproliferative disorder prevention strategies in allogeneic hematopoietic stem cell transplantation. Rev Med Virol 30:e2108.
4. Quintanilla-Martinez L et al. (2023) New concepts in EBV-associated B, T, and NK cell lymphoproliferative disorders. Virchows Arch 482:227-244.