Burkitt lymphoma (BL) is a highly aggressive mature B-cell non-Hodgkin lymphoma characterized by rapid cellular proliferation and a high tumour growth fraction. It is one of the fastest-growing human malignancies and constitutes a medical emergency requiring prompt diagnosis and initiation of treatment.

Burkitt lymphoma is strongly associated with translocations involving the MYC oncogene, most commonly t(8;14). The disease is highly sensitive to intensive multi-agent chemotherapy, and cure is achievable in a significant proportion of patients when treatment is initiated early.

Three major clinical variants are recognized:

• Endemic (African) Burkitt lymphoma

• Sporadic Burkitt lymphoma

• Immunodeficiency-associated Burkitt lymphoma

Epidemiology

Burkitt lymphoma occurs worldwide but shows distinct geographical patterns.

Epidemiological characteristics include:

• Common in children and young adults

• Male predominance

• Endemic form is common in equatorial Africa

• Strong association with Epstein-Barr virus (EBV) in endemic disease

• Increased incidence among HIV-infected individuals

• Represents one of the most aggressive B-cell lymphomas

Risk factors

Epstein-Barr virus infection

Strongly associated with endemic Burkitt lymphoma.

HIV infection

Increases the risk of Burkitt lymphoma significantly.

Immunodeficiency states

Including:

• Congenital immunodeficiency syndromes

• Post-transplant immunosuppression

• Acquired immunodeficiency

Genetic abnormalities

Particularly:

• MYC gene translocations

• Chromosomal instability

Male sex

More common among males than females.

Pathophysiology

Burkitt lymphoma arises from mature germinal-center B lymphocytes.

The hallmark molecular abnormality is activation of the MYC oncogene, resulting in:

• Uncontrolled cell proliferation

• Increased metabolic activity

• Rapid tumour growth

• High risk of tumour lysis syndrome

The tumour doubling time may be as short as 24–48 hours.

Common sites of involvement include:

• Jaw and facial bones (endemic form)

• Abdomen and ileocecal region

• Lymph nodes

• Bone marrow

• Central nervous system

Clinical presentation

Clinical manifestations depend on the site and extent of disease involvement.

The disease usually presents with rapidly enlarging masses and systemic symptoms.

Symptoms

Constitutional symptoms

• Fever

• Weight loss

• Night sweats

• Fatigue

Head and neck symptoms

Particularly in endemic disease:

• Jaw swelling

• Facial swelling

• Dental loosening

• Facial deformity

Abdominal symptoms

• Abdominal swelling

• Abdominal pain

• Abdominal mass

• Nausea

• Vomiting

• Intestinal obstruction

Bone marrow involvement

• Fatigue

• Recurrent infections

• Easy bruising

• Bleeding tendencies

Central nervous system involvement

• Headache

• Vomiting

• Cranial nerve deficits

• Altered consciousness

• Seizures

Clinical signs

General examination

• Cachexia

• Fever

• Weight loss

Lymphatic system

• Rapidly enlarging lymph nodes

• Cervical lymphadenopathy

• Generalized lymphadenopathy

Abdominal examination

• Palpable abdominal mass

• Hepatomegaly

• Splenomegaly

• Ascites

Head and neck examination

• Jaw masses

• Facial tumours

• Orbital involvement

Neurological findings

• Cranial nerve palsies

• Focal neurological deficits

• Signs of meningeal involvement

Differential diagnosis

• Diffuse large B-cell lymphoma

• Acute lymphoblastic leukemia

• Hodgkin lymphoma

• Tuberculous lymphadenitis

• Neuroblastoma

• Wilms tumour

• Chronic lymphocytic leukemia

• Metastatic malignancy

• Infectious mononucleosis

Diagnostic criteria

Burkitt lymphoma should be suspected in patients presenting with:

• Rapidly enlarging tumour masses

• Jaw or facial tumours

• Abdominal masses

• B symptoms

• Bone marrow involvement

• CNS manifestations

Definitive diagnosis requires:

• Histopathological examination of tissue biopsy

• Immunohistochemistry

• Cytogenetic or molecular confirmation of MYC rearrangement when available

Investigations

Laboratory investigations

Full blood count (FBC)

To assess:

• Anaemia

• Leukocytosis

• Cytopenias

Renal function tests

• Urea

• Creatinine

• Electrolytes

Liver function tests

• AST

• ALT

• Bilirubin

• Albumin

Lactate dehydrogenase (LDH)

Usually markedly elevated and reflects tumour burden.

Uric acid

Important for assessment of tumour lysis syndrome risk.

HIV testing

Recommended in all patients.

Hepatitis B and C screening

Required before immunochemotherapy.

Imaging investigations

Chest X-ray

For thoracic involvement.

CT scan of neck, chest, abdomen and pelvis

For disease staging.

PET/CT

Useful for:

• Staging

• Treatment response assessment

• Detection of residual disease

Bone marrow assessment

Bone marrow aspirate and trephine biopsy

Required to determine marrow involvement.

Central nervous system assessment

Lumbar puncture and CSF cytology

Recommended because of the high risk of CNS involvement.

Histopathological investigations

Excisional biopsy

Preferred for diagnosis.

Immunohistochemistry

Typically demonstrates:

• CD20 positivity

• CD10 positivity

• BCL6 positivity

• High Ki-67 proliferation index

Staging

Burkitt lymphoma may be staged using:

• Ann Arbor staging system

• Murphy/St. Jude staging system in children

Assessment should include:

• Bone marrow involvement

• CNS involvement

• Extranodal disease

Management

Burkitt lymphoma is a hematologic emergency.

Management should proceed as follows:

1. Confirm diagnosis rapidly

2. Assess tumour burden

3. Prevent tumour lysis syndrome

4. Initiate intensive multi-agent chemotherapy

5. Provide CNS prophylaxis or treatment when indicated

6. Monitor for treatment complications

Treatment should be undertaken in specialized oncology centres.

Non-pharmacological treatment

Supportive care

Tumour lysis syndrome prevention

Includes:

• Aggressive hydration

• Monitoring electrolytes

• Monitoring renal function

• Urine output monitoring

Blood product support

When indicated:

• Packed red blood cells

• Platelet transfusion

Infection prevention

• Neutropenic precautions

• Prompt treatment of infections

Nutritional support

Particularly in patients with bulky disease or treatment complications.

Pharmacological treatment

Burkitt lymphoma requires intensive multi-agent chemotherapy.

Recommended regimens include:

CODOX-M/IVAC (Magrath regimen)

Consists of:

• Cyclophosphamide

• Vincristine

• Doxorubicin

• Methotrexate

Alternating with:

• Ifosfamide

• Etoposide

• Cytarabine

Administered intravenously according to established protocol schedules.

CALGB 9251 regimen

Consists of:

• Cyclophosphamide

• Prednisolone

• Ifosfamide

• Mesna

• Methotrexate

• Leucovorin

• Vincristine

• Cytarabine

• Etoposide

• Dexamethasone

• Doxorubicin

Administered intravenously according to protocol schedules.

Hyper-CVAD regimen

Consists of:

• Cyclophosphamide

• Vincristine

• Doxorubicin

• Dexamethasone

Alternating with:

• Methotrexate

• Cytarabine

• Leucovorin

• Methylprednisolone

• 6-mercaptopurine

Administered intravenously according to protocol schedules.D

Dose-adjusted CHOP plus etoposide

Consists of:

• Cyclophosphamide

• Doxorubicin

• Vincristine

• Prednisolone

• Etoposide

Administered intravenously according to institutional protocols.

CNS-directed therapy

Patients with CNS involvement or high risk of CNS dissemination may require:

• Intrathecal methotrexate

• Intrathecal cytarabine

• Systemic CNS-penetrating chemotherapy

According to specialist oncology protocols.

Management according to disease presentation

Localized disease

Management includes:

• Intensive combination chemotherapy

• CNS prophylaxis

• Supportive care

Advanced disease

Management includes:

• Intensive multi-agent chemotherapy

• Tumour lysis syndrome prevention

• CNS-directed treatment when indicated

CNS involvement

Management includes:

• CNS-penetrating chemotherapy

• Intrathecal chemotherapy

• Specialized neuro-oncology management

Relapsed or refractory disease

Management should be individualized and may include:

• Salvage chemotherapy

• Stem cell transplantation where available

• Palliative care when appropriate

Referral

All patients with suspected or confirmed Burkitt lymphoma should be referred urgently to a specialized oncology or hematology centre.

Urgent referral indications

• Rapidly enlarging tumour mass

• Airway compromise

• Superior vena cava obstruction

• Tumour lysis syndrome

• CNS involvement

• Bone marrow failure

• Severe metabolic abnormalities

Complications

Disease-related complications

• Tumour lysis syndrome

• Intestinal obstruction

• Bone marrow failure

• CNS involvement

• Organ compression

• Superior vena cava obstruction

Treatment-related complications

• Severe neutropenia

• Febrile neutropenia

• Sepsis

• Mucositis

• Renal dysfunction

• Hepatotoxicity

• Cardiotoxicity

Prognosis

Burkitt lymphoma is highly aggressive but highly chemosensitive.

Prognosis depends on:

• Stage at diagnosis

• Tumour burden

• CNS involvement

• Bone marrow involvement

• Response to chemotherapy

• Performance status

With early diagnosis and appropriate intensive therapy, long-term cure is achievable in many patients.

Prevention

Primary prevention

• HIV prevention and treatment

• Early management of immunodeficiency conditions

• Reduction of factors associated with chronic immune suppression

Secondary prevention

• Early evaluation of rapidly enlarging lymph node masses

• Prompt biopsy of suspicious lesions

• Early referral to oncology services

Tertiary prevention

• Regular follow-up after treatment

• Monitoring for relapse

• Early management of treatment-related complications