What is Burkitt Lymphoma?
Burkitt lymphoma is a fast-growing type of lymphoma, a cancer that affects the white blood cells. This disease is connected to the Epstein Barr virus (EBV), which causes mononucleosis or ‘mono’, the human immunodeficiency virus (HIV), and certain gene changes that lead to an overproduction of a gene known as C-MYC.
The World Health Organization (WHO) has divided Burkitt lymphoma into three categories: endemic, sporadic, and immunodeficiency-related. The ‘endemic’ type is commonly found in areas with a high occurrence of malaria and the Epstein Barr virus. The ‘immunodeficiency-related’ type is typically seen in people with HIV or in those who have had an organ transplant.
While intense chemotherapy treatment can lead to positive results in children, the prognosis is generally less favorable in adults. It’s important to note that the treatment and outcome can vary depending on the individual and specific medical circumstances.
What Causes Burkitt Lymphoma?
Burkitt lymphoma, a type of cancer, is linked with the Epstein-Barr virus (EBV), a common virus that can lead to mononucleosis, more commonly known as mono. The exact way in which EBV helps in the development of this cancer is not fully understood. There is a protein related to the virus, called EBNA1, found in cases of Burkitt lymphoma. Removal of the EBNA2 gene from the virus results in the formation of a few other genes (EBNA3A-C), making the cancer cells more difficult to kill off. This could mean that the EBNA2 gene might help cancer cells survive.
It’s also been found that Burkitt lymphoman is more common in areas with high rates of malaria, such as Brazil, Papua New Guinea, and parts of Africa situated along the equator. Research has revealed a connection between the likelihood of getting Burkitt Lymphoma and increased antibodies to Plasmodium falciparum, which is a parasite causing the most severe form of malaria.
Interestingly, Burkitt lymphoma is also associated with HIV. Oddly enough, the risk of this type of lymphoma seems to be higher in HIV positive individuals with a CD4 count over 200 and no other opportunistic infections present. CD4 count refers to a test that measures the number of CD4 T lymphocytes (white blood cells that fight infection) in the blood.
Despite these findings, the link and mechanism between HIV and Burkitt lymphoma is not fully understood.
Risk Factors and Frequency for Burkitt Lymphoma
Burkitt lymphoma, making up about 1% to 5% of all non-Hodgkin lymphomas, is more often found in Caucasians than in people of African or Asian descent. It usually affects males more than females, with around three to four males affected for every female. The areas where this condition is most common are places in Africa and Papua New Guinea where malaria and the Epstein Barr virus are common.
- In children under 18, the yearly occurrence of Burkitt lymphoma is between 3 and 6 cases per 100,000 children.
- On average, children are diagnosed at 6 years of age.
- The variant of Burkitt lymphoma most often seen in North America and Europe affects 4 per 1 million children under the age of 16 and 2.5 per 1 million adults each year, with the typical age of diagnosis being 45.
- Patients diagnosed as children are usually between 3 and 12 years of age.
- For those with weakened immune systems, the incidence of Burkitt lymphoma is 22 per 100,000 people in the United States.
Signs and Symptoms of Burkitt Lymphoma
Burkitt’s lymphoma is often recognized by a rapidly growing lump, accompanied by increased levels of lactate dehydrogenase (LDH) and uric acid due to the fast growth of the tumor. This condition commonly shows up in the abdomen, but can also affect the head and neck. People usually experience belly-related discomfort like abdominal pain, belly bloating, nausea, and vomiting. Sometimes, this can result in gastrointestinal bleeding.
Adults with this condition often experience systemic symptoms like fever, weight loss, and night sweats. On rare occasions, the disease may impact the jaw or bone marrow. It’s important to note that it is unusual for this condition to affect the chest area, brain, testicles, skin, thyroid gland, or breast.
The endemic form of this disease often manifests as a growing jaw lump, swelling around the eyes, or issues with the urinary system. Children are particularly prone to jaw involvement. People with this condition are often malnourished at the time of diagnosis.
When the disease involves more than 25% of the bone marrow, it is categorized as Burkitt leukemia. However, it’s rare for it only to present as leukemia.
Testing for Burkitt Lymphoma
Getting enough tissue sample is a must for proper diagnosis. Fine-needle aspiration, a procedure that uses a thin needle to remove cells from your body, might not gather enough tissue to definitely identify the disease. That’s why doctors usually prefer excisional biopsy, a procedure where an entire lump or suspicious area is removed for further testing. Superficial lymph node or fluid from the lining of the lungs can also be taken for diagnosis.
In developed countries, the suspicion of Burkitt lymphoma, a type of fast-growing cancer, usually arises from microscopy or flow cytometry, two techniques for examining and measuring cells. Confirmation of the disease typically comes from specific tests like immunohistochemistry and cytogenetics, which detect proteins and genetic alterations, respectively, in the cells. In areas where these kinds of tests aren’t available, the diagnosis may be made using fine-needle aspiration and other clinical observations.
After a tissue diagnosis is made, tests to check for the spread of the disease are generally performed. These include a bone marrow aspiration and biopsy, which involve taking a sample of bone marrow for testing, and checking the fluid around the brain and spinal cord. Computerized Tomography (CT) scans, which use X-rays to make detailed images of parts of your body, are performed to get images of your chest, abdomen, and pelvis. Whole body Positron Emission Tomography (PET)/CT scans, which allow your doctors to check for diseases in your body, should be done, although they shouldn’t delay the start of therapy. Necessary lab tests include complete blood count, erythrocyte sedimentation rate (ESR), complete metabolic panel, prothrombin time (PT), partial thromboplastin time (PTT) and other tests to measure chemicals and substances in your blood.
In areas with limited resources, ultrasonography, a test that uses sound waves to create images of the inside of your body, can assist in determining the stage of the disease.
Treatment Options for Burkitt Lymphoma
Burkitt lymphoma, a type of cancer affecting the lymphatic system, enjoys a high cure rate of roughly 90% in children and young adults in developed countries. Treatment differs based on the age of the patient and how far the disease has progressed. After completely removing the cancerous cells through surgery, children usually undergo two rounds of moderate-intensity chemotherapy, which uses drugs like cyclophosphamide, vincristine, prednisolone, and doxorubicin.
In more advanced stages of the disease, such as stage III or if it spreads to the brain or bone marrow, children may need more intensive chemotherapy treatments. Treatments could range from four to eight rounds, sometimes coupled with other chemotherapy drugs like methotrexate, cytarabine, and etoposide. Alongside this, a therapy method called intrathecal therapy, which directly targets the brain and spinal cord, is used.
The treatment approaches for adults are somewhat different. Traditional chemotherapy methods such as those used in children might not be as efficient. Organizations recommend more complex, multi-agent therapies, which include a mix of several drugs. It’s also common to safeguard the brain against possible spread of the disease through CNS prophylaxis.
Adding immunotherapy, a type of treatment that uses the body’s immune system to fight cancer, can improve the patient’s chances for recovery. Drugs like rituximab, which target specific types of cells involved in the immune response, have proven effective. Researchers are investigating newer drugs similar to rituximab, as well as others that can help churn the growth of cancer cells or help the immune system better recognize and attack them.
In the care of patients with the HIV virus, who may have immunodeficiency-related Burkitt lymphoma, high-dose chemotherapy is made possible through anti-retroviral therapy (HARRT). It’s important, however, to use less toxic chemotherapy because HIV patients are more susceptible to organ failure and infections.
The disease’s return, or relapse, typically presents a poor outlook. However, treatment options will depend on each patient’s particular condition. Newer, more effective chemotherapy drugs are improving outcomes for patients, and other intensive salvage therapies may be considered. In elderly patients, who may not be strong enough to withstand intense drug treatment, palliative care that aims to provide relief from symptoms and improve quality of life is often recommended.
What else can Burkitt Lymphoma be?
When trying to diagnose Burkitt Lymphoma (BL), doctors must also consider other illnesses that may look similar. Those are:
- Diffuse large B-cell lymphoma (DLBCL)
- High-grade follicular lymphoma
- B-cell acute lymphoblastic leukemia/lymphoma (B-ALL)
Both DLBCL and high-grade follicular lymphoma usually have bigger cells and a wider range of shapes than usually seen in BL. If BCL2 is present and the cell multiplication index is below 90%, it’s more likely to be another diagnosis than BL. Even though finding an MYC gene rearrangement might seem like a clue, it doesn’t confirm BL, as around 10% of DLBCL cases have this alteration. B-ALL might look like BL in terms of cell size, but usually has a finer chromatin, a substance within a cell’s nucleus. Also, B-ALL typically shows signs of immaturity like CD34 and/or TdT when tested.
Also, there are some other less common diseases that should be considered. Cases that look like BL but don’t show the MYC rearrangement should be tested for specific changes on chromosome 11q – this could indicate a “Burkitt-like lymphoma with 11q aberration.” The outlook for this newly defined disease appears to be similar to BL.
What to expect with Burkitt Lymphoma
The patient’s condition prognosis largely depends on the stage of the illness and the spread of the disease. Generally, younger patients tend to have a better outcome, possibly due to their ability to withstand intense treatments like chemotherapy.
A poor patient response to drugs like cyclophosphamide, prednisolone, and vincristine can lead to a worse prognosis. Additionally, if the central nervous system (brain and spinal cord) is affected at the time of diagnosis, this can also lead to a poor prognosis. Higher than normal levels of the enzyme lactose dehydrogenase in the patient’s body can suggest poor outcomes. Certain genetic changes beyond the regular ones can also suggest a worse prognosis.
Furthermore, patients who are malnourished, particularly in low-income countries, are at a higher risk of developing neutropenia, which is a low number of a specific type of white blood cells due to chemotherapy. For patients with immunodeficiency-related BL, a low count of a type of white blood cell called CD4 is a poor marker for survival. If the disease returns within 6 months of completing treatment, chances of survival are reduced because most treatment options would have been exhausted during initial therapy.
In developing countries, doctors use the stage of the illness and imaging techniques such as abdominal ultrasound, to predict how the patient will do. They also use techniques such as fluorodeoxyglucose positron emission tomography (PET), a type of scan to check for leftover or recurring disease. Whether early PET or CT scans help predict the disease’s outcome is under investigation. There is ongoing research to find out if minimal leftover disease (MRD) is a risk factor for a worse prognosis in Burkitt lymphoma. Polymerase chain reaction (PCR), a type of lab test, can be used to detect MRD by picking up specific genetic changes.
