EBV-associated malignancies

EBV Essentials - The Cancer-Causing Kiss

• Epstein-Barr virus (HHV-4) primarily infects B-lymphocytes via the CD21 receptor, establishing a latent infection.
• Viral proteins (e.g., LMP1, EBNA-2) promote cell proliferation and inhibit apoptosis, contributing to oncogenesis.

⭐ Burkitt lymphoma is classically associated with a t(8;14) translocation, placing the c-myc oncogene under the control of the highly active immunoglobulin heavy chain enhancer.

Viral Oncogenesis - Hijacking Host Cells

• Primary Targets: B-lymphocytes (via CD21 receptor) and nasopharyngeal epithelial cells.
• Mechanism: EBV establishes latency, expressing oncoproteins that drive cell proliferation and survival.
• Key Viral Oncoproteins:
  • LMP-1 (Latent Membrane Protein 1): Mimics a constitutively active CD40 receptor. It activates NF-κB and JAK/STAT pathways, upregulating survival proteins like BCL-2 and preventing apoptosis.
  • EBNA-2 (EBV Nuclear Antigen 2): A potent transactivator that turns on host genes, including Cyclin D and the MYC proto-oncogene, promoting cell cycle progression.

⭐ In Burkitt Lymphoma, a t(8;14) translocation places the MYC oncogene under the control of the highly active immunoglobulin heavy chain (IgH) promoter, leading to massive overexpression.

Malignancy Spectrum - The Usual Suspects

• Burkitt Lymphoma

  • Caused by translocation of the c-myc gene, t(8;14).
  • Histology: Classic "starry sky" appearance from macrophages phagocytosing apoptotic tumor cells.
  • Forms: Endemic (African, jaw mass) vs. Sporadic (abdominal mass).

• Nasopharyngeal Carcinoma

  • Undifferentiated carcinoma with lymphoid stroma (lymphoepithelioma).
  • Presents with nasal obstruction, epistaxis, or metastatic neck mass.

  ⭐ Strongly associated with Southern Chinese ancestry.

• Hodgkin Lymphoma

  • Most commonly the mixed cellularity subtype.
  • EBV is found in the diagnostic Reed-Sternberg cells in about 40-50% of cases.

• Primary CNS Lymphoma

  • Occurs almost exclusively in severely immunocompromised patients (e.g., HIV/AIDS with CD4 < 50).
  • Presents as ring-enhancing lesions on brain MRI, often solitary.

Clinical Toolkit - Diagnosis & Management

• Diagnosis
  • Serology: Anti-VCA (IgM, IgG), anti-EBNA establishes exposure.
  • Histopathology (Biopsy): Definitive. Look for characteristic cells (e.g., Reed-Sternberg in Hodgkin).
  • Molecular: PCR for EBV DNA in plasma or tissue; FISH for translocations.
• Management
  • Tailored to the specific cancer.
  • Chemotherapy: Standard for lymphomas (e.g., R-CHOP for Burkitt, ABVD for Hodgkin).
  • Radiation: Primary modality for nasopharyngeal carcinoma (NPC), often combined with chemotherapy.

⭐ Burkitt Lymphoma shows a classic t(8;14) translocation, overactivating the c-myc oncogene.

High‑Yield Points - ⚡ Biggest Takeaways

• EBV infects B-cells, where it establishes latency, driven by the oncogene LMP-1.
• LMP-1 mimics a constitutively active CD40 receptor, promoting B-cell proliferation and upregulating BCL-2 to prevent apoptosis.
• Strongly associated with endemic Burkitt lymphoma (t(8;14); c-myc), nasopharyngeal carcinoma, and mixed-cellularity Hodgkin lymphoma.
• The cause of primary CNS lymphoma in immunocompromised patients, especially in the context of HIV/AIDS.
• Diagnosis confirmed by detecting EBV DNA or EBNA-1 in tumor cells.