CHILDHOOD MALIGNANCIES: BURKITT’S LYMPHOMA

Introduction:

Burkitt's lymphoma (BL) is a rare, aggressive form of non-Hodgkin's lymphoma that is named after the
British surgeon Denis Burkitt, who first described the disease in 1958. It is characterized by a
characteristic translocation involving the MYC gene. It has been classified into three subtypes based on
clinical and epidemiological features:

1. Endemic
2. Sporadic, and
3. Immunodeficiency-associated BL.

This note will provide an overview of Burkitt's lymphoma, including it’s

― Causes
― Epidemiology
― Molecular pathogenesis
― Symptoms
― Clinical presentation
― Staging
― Diagnosis, and
― Treatment options

I. Causes:

Burkitt's lymphoma (BL) is a B-cell malignancy characterized by a translocation involving the MYC gene.
The exact causes of BL are not fully understood, but several factors have been implicated in its
development.

1. Genetic Factors: BL is associated with genetic abnormalities that affect B-cell differentiation and
activation. The characteristic translocation involving the MYC gene is the most common genetic
abnormality seen in BL. Other genetic factors, such as dysregulation of BCL2 and BCL6 genes,
have also been implicated in the pathogenesis of BL.
2. Infectious Agents: The endemic form of BL, which is most common in sub-Saharan Africa, is
strongly associated with Epstein-Barr virus (EBV) infection. EBV infection leads to the
dysregulation of B-cell differentiation and activation, and is thought to be an important
contributing factor in the development of BL.
3. Environmental Factors: Exposure to certain environmental factors, such as malaria or other
infectious diseases, has been associated with an increased risk of developing BL. Additionally,
studies have suggested that exposure to toxins, such as insecticides or other chemicals, may also
play a role in the development of BL.
4. Immune System Dysfunction: BL is more common in individuals with immune system
dysfunction, such as those with HIV/AIDS or other immunodeficiencies. Immune system
dysfunction can lead to dysregulation of B-cell differentiation and activation, which may
contribute to the development of BL.

Overall, the causes of BL are complex and likely involve a combination of genetic, infectious,
environmental, and immune system factors.
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II. Epidemiology:

Burkitt's lymphoma is rare in most parts of the world, with an incidence of approximately 1-2 cases per
million people per year. However, in endemic regions, such as sub-Saharan Africa, the incidence can be
as high as 5-10 cases per 100,000 people per year. Burkitt's lymphoma is more common in males than
females, and it is most frequently diagnosed in children and young adults, with a peak incidence
between the ages of 5 and 14 years.

III. Molecular pathogenesis

The most common molecular abnormality in BL is a chromosomal translocation involving the c-MYC
oncogene on chromosome 8 and one of the immunoglobulin (Ig) gene loci on chromosome 14, 2, or 22.
This translocation results in the constitutive activation of the c-MYC gene, which drives the uncontrolled
proliferation of B-cells.

IV. Symptoms:

Burkitt's lymphoma (BL) can affect multiple organs and tissues in the body. The symptoms of BL can vary
depending on the location and extent of the tumor, and may be similar to those of other types of
lymphoma or cancer.

A. Systemic Symptoms: Systemic symptoms of BL are related to the effects of the tumor on the body as
a whole. These may include:

1. Fever: Fever is a common symptom of BL and is thought to be related to the release of cytokines
by the tumor cells.
2. Night sweats: Night sweats are another common symptom of BL and may be related to the fever
or to the effects of the tumor on the body's metabolism.
3. Fatigue: Fatigue is a common symptom of many types of cancer, including BL, and is related to
the body's response to the tumor and its treatments.
4. Weight loss: Weight loss is another common symptom of cancer and may be related to the
effects of the tumor on the body's metabolism.

B. Localized Symptoms: Localized symptoms of BL are related to the effects of the tumor on specific
organs or tissues in the body. These may include:

1. Enlarged lymph nodes: Enlarged lymph nodes are a common symptom of BL, particularly in the
neck, groin, and armpit areas.
2. Abdominal pain: BL can affect the organs in the abdomen, leading to pain, swelling, or other
symptoms.
3. Jaw or facial swelling: Endemic BL, which is associated with Epstein-Barr virus (EBV) infection
and is most commonly seen in sub-Saharan Africa, often presents with jaw or facial bone
involvement.
4. Neurological symptoms: BL can affect the central nervous system, leading to symptoms such as
headache, seizures, or weakness.

V. Clinical Presentation:
 CHILDHOOD MALIGNANCIES: BURKITT’S LYMPHOMA
The clinical presentation of BL can vary depending on the subtype and the location and extent of the
tumor.

 Endemic BL, which is associated with Epstein-Barr virus (EBV) infection and is most commonly
seen in sub-Saharan Africa, typically presents with jaw or facial bone involvement, while
 Sporadic BL, which is not associated with EBV, is most commonly seen in North America and
Europe and may present with lymph node, abdominal, or other extranodal involvement.
 Immunodeficiency-associated BL, which is seen in individuals with HIV/AIDS or other
immunodeficiencies, may also present with extranodal involvement and may be more
aggressive than other subtypes.

VI. Staging

Staging of BL is a critical step in determining the extent of the disease and in guiding treatment
decisions. he Ann Arbor staging system is commonly used, which classifies the disease into four stages (I-
IV) based on the number and location of lymph node groups involved, as well as the presence or
absence of extranodal disease.

Stage I:

BL is limited to a single lymph node region or a single extralymphatic site.

Stage II:

BL is present in two or more lymph node regions on the same side of the diaphragm or in one lymph
node region and a contiguous extralymphatic site.

Stage III:

BL is present on both sides of the diaphragm, including involvement of the spleen.

Stage IV:

BL has spread beyond the lymphatic system to involve one or more extranodal organs, such as the bone
marrow, liver, or lungs.

In addition to the stage of disease, the Ann Arbor system also includes two additional parameters:

B symptoms:

B symptoms include fever, night sweats, and unexplained weight loss. The presence of B symptoms can
indicate a more advanced stage of disease.

E designation:

The E designation is used to indicate involvement of a single extranodal site adjacent to a known nodal
site. For example, if BL is present in a lymph node and adjacent bone, it would be designated as stage II
E.
 CHILDHOOD MALIGNANCIES: BURKITT’S LYMPHOMA

Overall, the Ann Arbor staging system provides a standardized method for describing the location and
extent of disease involvement in Burkitt's lymphoma. This information is important for guiding
treatment decisions and predicting prognosis.

VII. Diagnosis:

a. Imaging Studies:

Imaging studies, such as computed tomography (CT) or magnetic resonance imaging (MRI), are
important for evaluating the extent and location of BL. CT or MRI scans of the chest, abdomen, and
pelvis can help to identify lymph node or organ involvement, while bone scans can help to detect bone
involvement. Positron emission tomography (PET) scans may also be used to evaluate the metabolic
activity of tumors.

b. Laboratory Tests:

Laboratory tests can provide important information for diagnosing BL and monitoring treatment
response.

 Full blood count (FBC) and lactate dehydrogenase (LDH) levels may be elevated in patients with
BL, and may be used to monitor disease activity.
 Flow cytometry can help to identify the B-cell lineage of the tumor cells, while
 Immunohistochemistry can be used to confirm the diagnosis and subtype of BL.

c. Pathological Studies:

Biopsy of an involved lymph node or other tissue is necessary for definitive diagnosis of BL. Pathological
evaluation of the biopsy specimen can help to confirm the diagnosis of BL and identify the subtype.
Histological examination typically shows a characteristic "starry sky" pattern, with numerous small
lymphocytes interspersed with large, rapidly dividing malignant cells.

Immunohistochemical staining for markers such as CD20, CD10, and Ki-67 can help to differentiate BL
from other lymphomas.

Molecular studies, such as fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR),
can be used to detect the characteristic translocation involving the MYC gene.

VIII. Treatment:

Treatment for Burkitt's lymphoma typically involves a combination of

1. Chemotherapy
2. Immunotherapy, and
3. Supportive care
 CHILDHOOD MALIGNANCIES: BURKITT’S LYMPHOMA
Chemotherapy is the primary treatment for Burkitt's lymphoma, and involves using powerful drugs to
kill cancer cells. Treatment for BL typically involves aggressive chemotherapy regimens, such as the
CODOX-M/IVAC or R-Hyper-CVAD regimens, which aim to achieve rapid tumor debulking and complete
remission. Radiation therapy may also be used in some cases, particularly for localized disease or
residual disease after chemotherapy.

 CODOX-M/IVAC: This regimen includes cyclophosphamide, doxorubicin, vincristine,

methotrexate, ifosfamide, etoposide, and cytarabine. It is the most commonly used regimen in
the United States.
 Hyper-CVAD regimen includes the drugs cyclophosphamide, vincristine sulfate, doxorubicin
hydrochloride (Adriamycin), and dexamethasone. R-Hyper-CVAD regimen is typically
administered in alternating cycles of high-dose chemotherapy (Hyper-CVAD) and rituximab (R).
 DA-EPOCH-R: This regimen includes dose-adjusted etoposide, prednisone, vincristine,
cyclophosphamide, doxorubicin, and rituximab. It is often used in Europe and other parts of the
world.

Note: the modified Zigler's regimen is a chemotherapy treatment option that has been used in the past
for Burkitt's lymphoma. The modified Zigler's regimen is a combination chemotherapy regimen that
includes the drugs cyclophosphamide, vincristine, methotrexate, and cytarabine. This regimen was
originally developed in the 1970s and was modified over time to improve its effectiveness and reduce
toxicity. However, the modified Zigler's regimen is no longer commonly used as a first-line treatment for
Burkitt's lymphoma due to the availability of newer and more effective combination chemotherapy
regimens, such as CODOX-M/IVAC and DA-EPOCH-R. These newer regimens have been shown to have
higher response rates and better long-term outcomes compared to the modified Zigler's regimen.
Nonetheless, the modified Zigler's regimen may still be considered as a treatment option for patients
who cannot tolerate or do not respond to other chemotherapy regimens.

Immunotherapy, which involves using the body's immune system to target cancer cells may also be
used in some cases. Immunotherapy, such as rituximab, may be used in combination with
chemotherapy.

Supportive care, such as pain management and nutritional support, is also an important part of
treatment for Burkitt's lymphoma. Infection prophylaxis and management of treatment-related
toxicities, is also an important aspect of treatment for BL.

IX. Prognosis:

The prognosis for Burkitt's lymphoma can vary depending on the location and extent of the cancer, as
well as the individual's overall health and response to treatment. The prognosis for BL is generally poor
without treatment, but with aggressive chemotherapy and supportive care, many patients can achieve
complete remission and long-term survival. However, relapse is common, particularly in high-risk
subgroups, such as those with immunodeficiency-associated BL or advanced disease at diagnosis.