Burkitt Lymphoma: Classification, Pathology and Treatment

Burkitt lymphoma (BL) is an aggressive, high-grade B-cell non-Hodgkin lymphoma (NHL) marked by rapid proliferation and characterized by chromosomal translocations involving the C-MYC proto-oncogene on chromosome 8. The most common translocation is t(8;14)(q24;q32), leading to overexpression of the MYC oncogene and uncontrolled cell proliferation.

C-MYC Proto-oncogene

• Located on chromosome 8q24.
• Regulates cell cycle progression, apoptosis, and metabolism.
• When dysregulated (as in BL), promotes oncogenesis by driving rapid cell division and inhibiting differentiation.

Epidemiology

• Burkitt lymphoma accounts for 30–50% of pediatric NHLs.
• More common in males (M:F = 3:1).
• Three clinical variants:
  1. Endemic (African) – most common in equatorial Africa; strongly associated with EBV.
  2. Sporadic (non-endemic) – seen worldwide, especially in the U.S. and Europe.
  3. Immunodeficiency-associated – occurs in individuals with HIV/AIDS, post-transplantation, or congenital immunodeficiencies.

Pathophysiology

• BL is a monoclonal B-cell tumor arising from germinal center B lymphocytes.
• Characterized by:
  • High mitotic index.
  • “Starry-sky” appearance on histology: tangible body macrophages with apoptotic debris scattered among uniform tumor cells.
• Common genetic abnormalities:
  • t(8;14) – C-MYC and IgH (heavy chain).
  • t(8;22) – C-MYC and Igλ (light chain).
  • t(8;2) – C-MYC and Igκ (light chain).
• Epstein-Barr Virus (EBV) is implicated in >95% of endemic cases and ~20–30% of sporadic cases.
  • In endemic regions, co-infections (e.g., malaria) impair immune control over EBV.

Clinical Manifestations

Presentation varies by subtype:

Endemic Form

• Jaw or facial bone tumors (mandible or maxilla).
• Tooth loosening or facial asymmetry.

Sporadic Form

• Abdominal masses (commonly ileocecal region).
• Symptoms of bowel obstruction or intussusception.
• Hepatosplenomegaly, ascites.

Immunodeficiency-associated Form

• Generalized lymphadenopathy.
• CNS and bone marrow involvement more frequent.

Other Signs and Symptoms

• B-symptoms: fever, night sweats, weight loss.
• Painless lymphadenopathy.
• CNS symptoms: headaches, seizures, altered mental status.
• Bone marrow failure: anemia, thrombocytopenia, leukopenia.
• Tumor lysis syndrome (TLS): electrolyte abnormalities, acute kidney injury.

Staging

Ann Arbor Staging (Adults)

• Stage I: Single lymph node region or a single extralymphatic organ.
• Stage II: ≥2 lymph node regions on the same side of the diaphragm ± nearby extralymphatic involvement.
• Stage III: Lymph node regions on both sides of the diaphragm ± spleen or extralymphatic organ.
• Stage IV: Diffuse involvement of ≥1 extralymphatic organs ± lymph nodes.

Suffixes:

• A: No systemic symptoms.
• B: Presence of B-symptoms.
• E: Extranodal involvement.
• H: Hepatic involvement.
• D: Cutaneous involvement.

St. Jude/Murphy Staging (Pediatric)

• Stage I: Single tumor or lymph node group outside the abdomen or mediastinum.
• Stage II: Multiple tumors or nodes on one side of the diaphragm.
• Stage III: Involvement on both sides of the diaphragm or large abdominal/chest tumors.
• Stage IV: CNS and/or bone marrow involvement.

Diagnostic Workup

Laboratory Investigations

• Complete blood count (CBC) with differential.
• Serum LDH – marker of tumor burden.
• Uric acid, creatinine, BUN – assess for tumor lysis syndrome.
• Liver function tests (LFTs).
• HIV serology.
• CSF analysis (cytology, flow cytometry).
• Bone marrow biopsy.

Imaging Studies

• Chest X-ray and CT.
• Abdominal ultrasound or CT scan.
• MRI or CT of the brain/spinal cord if CNS symptoms are present.
• PET-CT scan for staging and treatment monitoring.

Tissue Diagnosis

• Excisional lymph node biopsy is gold standard.
• Fine needle aspiration (FNA) may be adjunctive.
• Immunophenotyping: CD20+, CD10+, BCL6+, Ki-67 >95%.
• Cytogenetics/FISH: confirms MYC translocation.

Treatment

Supportive Management

• Tumor Lysis Syndrome Prophylaxis:
  • IV hydration, allopurinol or rasburicase.
  • Monitor electrolytes, renal function.
• Transfusions for anemia or thrombocytopenia.
• Antibiotics for infection.
• Antipyretics, antiemetics during chemotherapy.

Definitive Treatment

• High-intensity, short-duration chemotherapy regimens (CODOX-M/IVAC, HyperCVAD).
• Agents include:
  • Cyclophosphamide, Vincristine, Doxorubicin, Methotrexate.
  • Cytarabine, Ifosfamide, Etoposide.
  • Rituximab (anti-CD20 monoclonal antibody).
• CNS prophylaxis with intrathecal methotrexate and/or cytarabine is essential.

Note: Surgery is typically not indicated except for diagnostic biopsy or management of complications like obstruction.

Prognosis

• High cure rate (>85%) in children with early-stage disease.
• Prognosis depends on:
  • Disease stage.
  • Age and performance status.
  • CNS or bone marrow involvement.
  • LDH level at diagnosis.

Key Points for NCLEX & USMLE

• Burkitt lymphoma = fast-growing B-cell lymphoma with MYC translocation.
• Classic histologic finding = “starry sky” appearance.
• Endemic variant = jaw mass, EBV-associated.
• Sporadic variant = abdominal mass, often ileocecal.
• Evaluate and prevent tumor lysis syndrome.
• CNS prophylaxis is critical due to high risk of CNS dissemination.
• Treatment = aggressive combination chemotherapy + Rituximab.

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