Burkitt Lymphoma: A Comprehensive Overview

Introduction

Burkitt lymphoma (BL) is a highly aggressive form of non-Hodgkin lymphoma (NHL) that has garnered significant attention in the fields of haematology and oncology due to its unique clinical features, rapid disease progression, and distinctive pathobiological characteristics. First described by Dr. Denis Burkitt in the 1950s in equatorial Africa, the disease has since become a subject of global research and clinical focus. Understanding BL is crucial for medical students and healthcare professionals, as early recognition and prompt intervention can significantly improve patient outcomes.

Definition

Burkitt lymphoma is a mature B-cell neoplasm characterised by the translocation and deregulation of the MYC gene on chromosome 8, resulting in uncontrolled cellular proliferation. It is classified as a high-grade, rapidly growing lymphoma with a doubling time of approximately 24–48 hours, making it one of the fastest-growing human tumours. BL is distinct from other lymphomas due to its unique clinical presentation, pathological features, and molecular profile.

Types of Burkitt Lymphoma

Based on clinical and epidemiological features, BL is broadly classified into three main subtypes:

1. Endemic Burkitt Lymphoma: Predominantly seen in equatorial Africa and Papua New Guinea, this type commonly affects children and is closely associated with Epstein-Barr virus (EBV) infection. It frequently involves the jaw or facial bones.
2. Sporadic Burkitt Lymphoma: Occurring worldwide, especially in Europe and North America, the sporadic form is less frequently associated with EBV. It often presents with abdominal tumours, particularly involving the ileocaecal region.
3. Immunodeficiency-Associated Burkitt Lymphoma: This subtype arises in individuals with underlying immunodeficiency, most notably those with HIV/AIDS or post-transplant immunosuppression. The clinical presentation is variable, with frequent nodal and extranodal involvement.

Epidemiology

Global Distribution

The incidence and distribution of Burkitt lymphoma vary significantly across different regions, influenced by environmental, genetic, and infectious factors.

• Endemic BL: Endemic BL accounts for the majority of childhood cancers in equatorial Africa, with an incidence as high as 3–6 cases per 1 lakh children annually. It is relatively rare in other parts of the world.
• Sporadic BL: The sporadic form has an incidence of approximately 2–3 cases per 1 crore population per year in Europe and North America.
• Immunodeficiency-Associated BL: The incidence has increased with the HIV pandemic, with BL representing about 30–40% of NHL cases in HIV-positive individuals.

Age and Gender Distribution

Burkitt lymphoma predominantly affects children and young adults, with a peak incidence between ages 4 and 7 years in endemic regions. In contrast, sporadic BL is more common in adolescents and young adults, but can occur at any age. The disease exhibits a marked male preponderance, with a male-to-female ratio of approximately 3–4:1.

Risk Factors

• Epstein-Barr Virus (EBV) Infection: Nearly all cases of endemic BL are associated with EBV infection, whereas only 20–30% of sporadic cases are EBV-positive.
• Malaria: Chronic Plasmodium falciparum infection in endemic regions is believed to contribute to immune dysregulation and increased risk of BL.
• Immunodeficiency: Individuals with HIV/AIDS, congenital immunodeficiencies, or those undergoing immunosuppressive therapy are at higher risk.
• Genetic Susceptibility: Certain genetic factors may predispose individuals to BL, although the precise mechanisms remain under investigation.

Pathophysiology

Cellular Origin

BL arises from germinal centre B-cells, typically at the stage of centroblasts or immunoblasts. These cells undergo malignant transformation due to genetic alterations that disrupt normal cell cycle regulation.

Genetic Mutations and Molecular Pathways

The hallmark of BL is the translocation involving the MYC gene on chromosome 8. The most common translocation is t(8;14)(q24;q32), where the MYC gene is juxtaposed to the immunoglobulin heavy chain locus, resulting in uncontrolled MYC expression. Less frequently, translocations may involve the kappa or lambda light chain loci, t(2;8)(p12;q24) and t(8;22)(q24;q11), respectively.

MYC overexpression leads to increased cellular proliferation, impaired differentiation, and inhibition of apoptosis. Secondary genetic alterations, such as mutations in TP53 and CDKN2A, may further contribute to tumourigenesis.

Role of Epstein-Barr Virus (EBV)

EBV infection is strongly implicated in the pathogenesis of endemic BL. The virus infects B-cells and promotes their proliferation through the expression of viral proteins such as latent membrane protein 1 (LMP1) and EBV nuclear antigen 1 (EBNA1). These proteins can inhibit apoptosis and facilitate the accumulation of genetic mutations.

In regions with high malaria prevalence, chronic immune stimulation by Plasmodium falciparum may impair T-cell surveillance, allowing EBV-infected B-cells to escape immune control and undergo malignant transformation.

Clinical Features

Symptoms

The clinical presentation of Burkitt lymphoma varies by subtype and anatomical site of involvement. However, common features include:

• Endemic BL: Rapidly growing jaw or facial mass, often involving the maxilla or mandible. Other sites may include the orbit, kidneys, gastrointestinal tract, and central nervous system (CNS).
• Sporadic BL: Predominantly presents as an abdominal mass, with symptoms such as pain, distension, nausea, vomiting, or bowel obstruction. The ileocaecal region is frequently affected.
• Immunodeficiency-Associated BL: Presents with nodal or extranodal disease, including involvement of the bone marrow, CNS, or gastrointestinal tract.

Disease Progression

BL is characterised by its extremely rapid growth, with a tumour doubling time of 1–2 days. Patients may present with advanced disease, including:

• B symptoms: fever, night sweats, and weight loss
• Lymphadenopathy: swelling of peripheral or deep lymph nodes
• Extranodal involvement: central nervous system, bone marrow, liver, spleen, kidneys, and gonads
• Tumour lysis syndrome: a potentially life-threatening complication due to rapid cell turnover, leading to electrolyte imbalances and renal dysfunction

Organ Involvement

• In endemic BL, jaw and facial bones are most commonly affected, but the disease may also involve the kidneys, gastrointestinal tract, ovaries, and CNS.
• In sporadic BL, the abdomen (particularly the ileocaecal region), kidneys, and ovaries are frequent sites.
• CNS involvement occurs in approximately 10–30% of cases at diagnosis and is more common in immunodeficiency-associated BL.

Diagnosis

Laboratory Tests

• Haematological Tests: Complete blood count (CBC) may reveal anaemia, leukocytosis, or thrombocytopenia in advanced disease. Elevated lactate dehydrogenase (LDH) and uric acid levels are common due to high tumour burden.
• Biochemistry: Renal function tests and electrolyte panels are essential, especially to monitor for tumour lysis syndrome.
• Viral Serology: Testing for HIV and EBV is recommended in relevant clinical settings.

Imaging Studies

• Ultrasound and CT Scan: Useful for detecting abdominal masses, organomegaly, and lymphadenopathy.
• Magnetic Resonance Imaging (MRI): Particularly valuable for assessing CNS and soft tissue involvement.
• Positron Emission Tomography (PET): Assists in staging and assessing response to therapy.

Histopathology

Definitive diagnosis requires a tissue biopsy. Histological examination reveals a characteristic “starry sky” appearance due to numerous tangible body macrophages scattered among a background of medium-sized, basophilic lymphoid cells with high mitotic activity.

Immunophenotyping by flow cytometry or immunohistochemistry demonstrates expression of B-cell markers (CD19, CD20, CD22, CD79a), germinal centre markers (CD10, BCL6), and strong surface immunoglobulin expression. The tumour cells are typically negative for BCL2.

Cytogenetic analysis confirms MYC gene rearrangement in virtually all cases.

Differential Diagnosis

The differential diagnosis of BL includes other high-grade B-cell lymphomas (e.g., diffuse large B-cell lymphoma), lymphoblastic lymphoma, acute lymphoblastic leukaemia, and other small round blue cell tumours in children. Accurate diagnosis is essential for appropriate management.

Treatment

Chemotherapy Regimens

The mainstay of BL treatment is intensive, short-duration, multiagent chemotherapy. Due to the tumour’s rapid growth and high chemosensitivity, prompt initiation of therapy is critical.

• CODOX-M/IVAC: A commonly used regimen combining cyclophosphamide, vincristine, doxorubicin, methotrexate (CODOX-M), alternating with ifosfamide, etoposide, and cytarabine (IVAC).
• Hyper-CVAD: Consists of hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternated with high-dose methotrexate and cytarabine.
• CHOP-based Regimens: Less commonly used due to inferior outcomes in BL.

For paediatric patients, risk-adapted regimens such as the LMB protocol (developed by the French-American-British [FAB] group) are frequently employed.

Supportive Care

• Tumour Lysis Syndrome Prophylaxis: Aggressive hydration, allopurinol or rasburicase, and close monitoring of electrolytes and renal function.
• Infection Prevention: Prophylactic antibiotics, antifungals, and antivirals may be indicated, especially in immunocompromised patients.
• Transfusion Support: Blood products as required for anaemia or thrombocytopenia.

Novel and Targeted Therapies

The addition of rituximab, a monoclonal antibody targeting CD20, to chemotherapy regimens has improved outcomes, particularly in adults. Other targeted agents under investigation include inhibitors of the PI3K/AKT/mTOR pathway, MYC inhibitors, and immunotherapy approaches such as chimeric antigen receptor (CAR) T-cell therapy.

Central nervous system prophylaxis with intrathecal methotrexate or cytarabine is recommended due to the high risk of CNS involvement.

Treatment in Special Populations

In HIV-positive individuals, antiretroviral therapy (ART) should be optimised, and dose modifications may be necessary to minimise toxicity. Post-transplant BL requires careful immunosuppression management.

Prognosis

Survival Rates

With current intensive chemotherapy protocols, the prognosis for BL has improved markedly, especially in paediatric populations. Reported 5-year survival rates are:

• Children: 80–90%
• Adults: 60–80%
• HIV-positive patients: 40–60% (variable, depending on ART and comorbidities)

Factors Affecting Outcomes

• Stage at Diagnosis: Early-stage disease is associated with better outcomes.
• Age: Younger patients have better prognosis.
• Performance Status: Poor functional status is linked to unfavourable outcomes.
• CNS or Bone Marrow Involvement: Associated with higher risk of relapse and lower survival.
• HIV Status: Immunodeficiency and co-infections can complicate management.

Nursing Care of Patients with Burkitt Lymphoma

Assessment and Initial Care

• Comprehensive Assessment: Conduct a thorough assessment of the patient’s medical history, presenting symptoms (like swelling, pain, fever, night sweats, and weight loss), and risk factors. Monitor for signs of tumour lysis syndrome and organ dysfunction.
• Baseline Investigations: Ensure all baseline laboratory investigations are completed, including complete blood count, renal and liver function tests, uric acid, electrolytes, and imaging as prescribed.
• Psychosocial Assessment: Assess the patient’s mental and emotional status, as a diagnosis of cancer can cause significant distress. Evaluate family support systems.

Symptom Management

• Pain Management: Administer prescribed analgesics and non-pharmacological pain relief methods. Regularly assess pain levels using appropriate scales.
• Fever and Infection Control: Monitor temperature frequently. Educate patient and family about infection prevention, as immunosuppression is common due to chemotherapy.
• Management of Tumour Lysis Syndrome: Monitor for symptoms such as nausea, vomiting, diarrhoea, muscle cramps, and arrhythmias. Ensure adequate hydration and administer medications like allopurinol or rasburicase as prescribed.

Nutritional Support

• Dietary Assessment: Assess nutritional status and encourage a high-protein, high-calorie diet to support healing and maintain strength.
• Manage Side Effects: Provide interventions for chemotherapy-induced nausea, vomiting, or oral mucositis. Suggest small, frequent meals and oral care routines.

Administration of Chemotherapy

• Preparation and Education: Prepare patients and caregivers for chemotherapy by explaining the process, potential side effects, and the importance of adherence to the treatment schedule.
• Safe Handling: Follow protocols for safe preparation and administration of cytotoxic drugs. Use personal protective equipment (PPE) as required.
• Monitoring: Observe for adverse reactions during and after chemotherapy infusions. Monitor blood counts and organ function as per protocol.

Prevention and Management of Complications

• Infection Prevention: Maintain strict aseptic techniques during procedures. Educate the patient and family about hand hygiene and avoiding crowds or sick contacts.
• Bleeding Precautions: Monitor for signs of bleeding (bruises, petechiae, gum bleeding) due to thrombocytopenia. Avoid invasive procedures unless necessary and use soft toothbrushes.
• Psychosocial Support: Provide emotional support, encourage expression of feelings, and involve counsellors or support groups as needed.

Patient and Family Education

• Disease and Treatment: Educate about Burkitt lymphoma, treatment options, potential side effects, and the importance of follow-up appointments.
• Home Care: Instruct on medication adherence, signs of complications, and when to seek immediate medical attention.
• Support Resources: Provide information about financial assistance, community resources, and cancer support organisations.

End-of-Life Care

For patients with advanced disease or poor prognosis, provide palliative care focused on comfort, symptom management, and supporting the patient and family through the process. Respect cultural and spiritual preferences in end-of-life care planning.

REFERENCES

1. Adeyinka A, Bashir K. Tumor Lysis Syndrom. https://www.ncbi.nlm.nih.gov/books/NBK518985/. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.
2. Naing PT, Kaur A, Lynch DT. Burkitt Lymphoma. [Updated 2025 Feb 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538148/
3. American Cancer Society. Surgery for Non-Hodgkin Lymphoma in Children. https://www.cancer.org/cancer/types/childhood-non-hodgkin-lymphoma/treating/surgery.html. Last reviewed 8/10/2021.
4. Cancer Research UK. Burkitt Lymphom. https://www.cancerresearchuk.org/about-cancer/non-hodgkin-lymphoma/types/burkitt-lymphoma. Last reviewed 3/13/2024.
5. Graham BS, Lynch DT. Burkitt Lymphoma. https://www.ncbi.nlm.nih.gov/books/NBK538148/. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.
6. Lymphoma Research Foundation. Burkitt Lymphoma. https://lymphoma.org/understanding-lymphoma/aboutlymphoma/nhl/burkitt/.
7. Mukhtar F, Boffetta P, Risch HA, et al. Survival predictors of Burkitt’s lymphoma in children, adults and elderly in the United States during 2000-2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6919213/. Int J Cancer. 2017 Apr 1;140(7):1494-1502.
8. Pereira RF, Mauro GP, Medici CTM, Casimiro LC, Weltman E. Radiotherapy in Adult Burkitt Lymphoma: A Retrospective Analysis in a Large University Center. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9209630. Indian J Hematol Blood Transfus. 2022 Jul;38(3):508-515.
9. Fang H, et al. Burkitt lymphoma. Human Pathology. 2024; doi:10.1016/j.humpath.2024.105703.

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