Burkitt Lymphoma: Understanding Your Pathology Report

by Rosemarie Tremblay-LeMay MD FRCPC
April 16, 2026

Burkitt lymphoma is a rapidly growing blood cancer that starts in B cells — the white blood cells that help the body fight infections. It is classified as a type of non-Hodgkin lymphoma and is defined by a specific genetic change in the MYC gene. This change causes the cancer cells to divide at an extraordinary rate — among the fastest of any cancer — which means tumors can grow very quickly and the disease can spread widely before symptoms are noticed. Despite its aggressive nature, Burkitt lymphoma is potentially curable in most patients when treated promptly with intensive chemotherapy. This article will help you understand the findings in your pathology report, what each term means, and why it matters for your care.

What are the symptoms of Burkitt lymphoma?

Because Burkitt lymphoma grows so rapidly, symptoms often develop and worsen over days to weeks rather than months. The specific symptoms depend on where in the body the lymphoma has developed. Unlike many other lymphomas, Burkitt lymphoma frequently arises outside the lymph nodes — at extranodal sites — and the most common locations vary by subtype.

In children and adolescents, common presentations include swelling or pain in the jaw or face from tumor growing in the facial bones, abdominal pain, bloating, or a palpable abdominal mass from intestinal or retroperitoneal involvement, and testicular swelling in boys. In adults, abdominal involvement is also frequent. General symptoms such as fever, drenching night sweats, and unintentional weight loss — sometimes called B symptoms — can occur but are not universal. Rapidly rising LDH (lactate dehydrogenase) blood levels, reflecting the fast pace of cell turnover, are a common laboratory finding that often prompts urgent investigation.

Spread to the central nervous system — the brain and spinal cord — occurs in approximately 10–30% of cases and can cause headache, confusion, visual changes, or neurological symptoms. Because CNS involvement requires specific treatment, it is routinely evaluated at diagnosis.

Where in the body is Burkitt lymphoma found?

Burkitt lymphoma most commonly develops at extranodal sites — organs and tissues outside the lymph nodes. Common sites include the abdomen (particularly the intestines and the area behind the abdominal organs called the retroperitoneum), the jaw and facial bones, the kidneys, the testes or ovaries, the breast, and the eye socket. The specific sites affected vary by subtype and are described further in the subtypes section below. Lymph node involvement does occur but is more typical of the immunodeficiency-associated subtype. In up to 20% of cases — particularly in immunodeficiency-associated disease — the lymphoma cells are also found in the bone marrow and blood, which represents leukemic spread.

What causes Burkitt lymphoma?

Burkitt lymphoma is caused by a specific type of genetic change called a translocation involving the MYC gene. A translocation is a rearrangement in which a segment of one chromosome breaks off and reattaches to a different chromosome, placing a gene in a new genetic neighborhood that can change how it behaves. In Burkitt lymphoma, the MYC gene moves next to one of the immunoglobulin genes — the genes that B cells use to make antibodies, which are permanently and highly active in B cells. Because MYC is now sitting next to a constantly active genetic switch, it becomes permanently turned on, driving the cancer cells to divide without stopping.

The most common translocation, found in approximately 80% of cases, is called t(8;14) — meaning a piece of chromosome 8 (where MYC lives) swaps with a piece of chromosome 14 (where the immunoglobulin heavy chain gene lives). Less common variant translocations involve chromosomes 2 or 22. Regardless of the specific translocation, the result is the same: MYC becomes constitutively active and drives relentless cell proliferation.

Three factors are known to increase the risk of developing Burkitt lymphoma. Epstein-Barr virus (EBV) — the virus that causes infectious mononucleosis — is found inside the lymphoma cells in a large proportion of cases, particularly in endemic disease in sub-Saharan Africa. EBV is thought to help set the stage for lymphoma development by allowing B cells to survive in an abnormal state before the MYC translocation occurs. Malaria (specifically Plasmodium falciparum infection) is closely linked to endemic Burkitt lymphoma in Africa; repeated malaria infection chronically stimulates B cells and activates an enzyme called AID (activation-induced cytidine deaminase), which is responsible for the DNA-editing errors that can generate the MYC translocation. Immune system weakness — from HIV infection, organ transplantation immunosuppression, or inherited immune deficiencies — also increases risk, in part because the immune system normally eliminates abnormal B cells before they can become lymphoma.

What are the subtypes of Burkitt lymphoma?

Burkitt lymphoma is traditionally described using three clinical subtypes based on geography and immune status. These are still commonly used in clinical settings and may appear in your pathology report or treatment discussion. However, the current WHO classification also recognizes a biologically more meaningful division into EBV-positive and EBV-negative subtypes, which reflects genuine differences in how the lymphoma develops. Both classification approaches are described below.

Traditional subtypes

Endemic Burkitt lymphoma is most common in equatorial Africa and Papua New Guinea, where malaria is widespread. It primarily affects children between the ages of 4 and 7 and has a strong association with EBV — the virus is found in more than 90% of endemic cases. It most often involves the jaw, facial bones, and orbit (the bony socket around the eye), though abdominal presentations are also frequent. Endemic Burkitt lymphoma is the most common childhood cancer in many parts of sub-Saharan Africa.

Sporadic Burkitt lymphoma occurs worldwide outside of endemic regions. It affects both children and adults, with a bimodal age distribution peaking at ages 10 and 60. In North America and Europe, it most commonly involves the abdomen — particularly the ileocecal region where the small intestine meets the large intestine — along with other abdominal organs and soft tissues. EBV is found in only about 20% of sporadic cases, though the rate increases with age in some populations.

Immunodeficiency-associated Burkitt lymphoma occurs in people with weakened immune systems, most commonly those with HIV infection. It is often the first cancer to develop in people with HIV, even before the immune system is severely depleted, and it tends to involve lymph nodes more than the other subtypes. The association with EBV varies in this group. Advances in HIV treatment have improved outcomes for this subtype substantially.

EBV-positive and EBV-negative subtypes

Regardless of geographic subtype, Burkitt lymphoma can be classified based on whether Epstein-Barr virus (EBV) is present inside the lymphoma cells. This distinction is increasingly recognized as biologically important because EBV-positive and EBV-negative Burkitt lymphoma develop through somewhat different molecular pathways, even though they look similar under the microscope and are treated in the same way. Your pathology report will typically state whether EBV was detected. EBV-positive Burkitt lymphoma tends to have fewer additional gene mutations (because EBV itself provides some of the molecular changes needed for lymphoma development), while EBV-negative Burkitt lymphoma tends to carry more mutations in genes controlling cell survival and proliferation. EBV status does not currently change the treatment approach in most patients.

How is the diagnosis made?

The diagnosis of Burkitt lymphoma is made by examining tissue under the microscope and using a panel of specialized tests. A biopsy — removal of a piece of the tumor — is required, and in many cases, the disease has already spread widely by the time of diagnosis, so biopsy of the most accessible site is preferred to avoid delaying treatment. Because Burkitt lymphoma can resemble several other aggressive lymphomas, the pathologist uses the microscopic appearance, along with immunohistochemistry, flow cytometry, and FISH, to confirm the diagnosis. The diagnosis requires demonstrating the characteristic cell appearance and immunophenotype — and in adults in particular, confirming the MYC rearrangement while excluding concurrent BCL2 and BCL6 rearrangements (which would change the diagnosis to high-grade B cell lymphoma with MYC and BCL2 rearrangements). EBV status is determined using a special test called EBER in situ hybridization, which detects small genetic molecules produced by EBV inside infected cells. Once the diagnosis is confirmed, PET/CT imaging, blood tests, bone marrow biopsy, and lumbar puncture (to check the fluid around the brain and spinal cord for lymphoma cells) are used to determine the extent of disease.

What does Burkitt lymphoma look like under the microscope?

Under the microscope, Burkitt lymphoma has a distinctive appearance. The tumor is composed of medium-sized B cells that all look very similar — they are described as monomorphic, meaning uniform in appearance. Each cell has a round nucleus (the DNA-containing compartment) with several small but prominent nucleoli (dense dots inside the nucleus) and a relatively small rim of deeply blue-staining cytoplasm (the body of the cell surrounding the nucleus). This dark, basophilic cytoplasm is a recognizable feature of Burkitt lymphoma cells.

The cells divide at an extraordinary rate — virtually every cell is in some stage of division or dying — so both mitotic figures (cells caught mid-division) and apoptotic bodies (the remnants of cells that have died) are abundant throughout the tumor. Many dying cells are engulfed and cleared by large immune cells called macrophages. Because macrophages are pale-staining and the surrounding lymphoma cells are very dark, the scattered pale macrophages within a sea of dark blue cancer cells create a characteristic visual pattern called the “starry sky” appearance — the pale macrophages resemble stars against the dark background. While this pattern is often described as a classic feature of Burkitt lymphoma, it is not unique to this disease and can be seen in other rapidly growing lymphomas; the combination of all microscopic, immunohistochemical, and molecular features is needed to confirm the diagnosis.

Areas of necrosis — patches of dead tissue — are common, given the rapid tumor growth. In some EBV-positive cases, especially those with limited-stage disease, a prominent inflammatory reaction with granulomas (small clusters of immune cells) may partially obscure the lymphoma cells; these cases can have an especially favorable outcome.

Immunohistochemistry results

Immunohistochemistry (IHC) is essential for confirming the diagnosis and distinguishing Burkitt lymphoma from other aggressive B cell lymphomas. The characteristic protein profile is described below.

CD20 — Positive. Confirms B cell origin. Also the target of rituximab, the antibody included in treatment.
PAX5 — Positive. Confirms B cell lineage.
CD10 — Positive (characteristically strong). A marker of germinal center B cells — the type of B cell from which Burkitt lymphoma arises.
BCL6 — Positive. Another germinal center marker, expressed in most cases.
MYC protein — Positive in greater than 80% of cells in almost all cases, reflecting the effect of the MYC gene rearrangement driving continuous protein production.
BCL2 — Negative in most cases, or only weakly positive. This is one of the most important distinguishing features of Burkitt lymphoma. BCL2 negativity (or weak expression) helps separate Burkitt lymphoma from high-grade B cell lymphoma with MYC and BCL2 rearrangements, in which BCL2 is strongly expressed. Strong BCL2 positivity makes a diagnosis of Burkitt lymphoma much less likely and should prompt testing for BCL2 gene rearrangement to exclude the double-hit diagnosis.
CD5 — Negative. CD23 — Negative. Help exclude other B cell lymphomas.
TdT — Negative. TdT is a marker of immature lymphoid cells; its absence helps exclude B-lymphoblastic lymphoma, which can look similar but requires completely different treatment.
Ki-67 — Greater than 95% in virtually all cases. The Ki-67 index measures what proportion of cells are actively dividing; a result close to or at 100% is characteristic of Burkitt lymphoma and reflects its extraordinarily rapid growth rate. A Ki-67 below 95% should raise doubt about the diagnosis.

EBV testing

Testing for Epstein-Barr virus is performed on all Burkitt lymphoma biopsies using EBER in situ hybridization — a technique that detects small RNA molecules produced by EBV inside infected cells. When EBER is positive, EBV is present within the lymphoma cells, identifying the case as EBV-positive Burkitt lymphoma. When EBER is negative, EBV is absent, and the case is EBV-negative Burkitt lymphoma.

EBV status does not currently change the treatment approach in most patients. However, it provides important biological information and contributes to understanding the disease subtype. In resource-limited settings where genetic testing (FISH) is unavailable, strong EBV positivity alongside the typical cell appearance and immunophenotype can support the diagnosis.

FISH testing for MYC rearrangement

FISH testing is used to confirm the MYC gene rearrangement that defines Burkitt lymphoma. FISH uses fluorescent probes to detect whether MYC has moved from its normal position on chromosome 8 — a finding that confirms the translocation characteristic of this disease. In most cases the translocation is t(8;14), though variant translocations t(8;22) and t(2;8) also occur and are equally diagnostic.

In adults particularly, FISH must also be performed for BCL2 and BCL6 rearrangements. If both MYC and BCL2 gene rearrangements are detected simultaneously, the diagnosis changes from Burkitt lymphoma to high-grade B cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma) — a distinct disease that requires different treatment. Confirming that BCL2 is not rearranged is therefore an essential part of establishing the diagnosis of Burkitt lymphoma. Cases with both MYC and BCL6 rearrangements but without BCL2 rearrangement remain classified as a subtype of diffuse large B cell lymphoma rather than Burkitt lymphoma.

Staging

Burkitt lymphoma is staged using the Murphy staging system (revised 2015) in children, which was designed specifically for lymphomas that commonly arise outside the lymph nodes. In adults, the Lugano classification (a modification of the Ann Arbor system) is typically used. Staging is based on PET/CT imaging, bone marrow biopsy, and lumbar puncture to evaluate cerebrospinal fluid.

Stage I — A single tumor or a single group of lymph nodes in one area, without involvement of the abdomen or chest.
Stage II — A single tumor with involvement of nearby lymph nodes on the same side of the diaphragm, or two or more tumors on the same side of the diaphragm, or a tumor in the gastrointestinal tract (with or without nearby lymph node involvement).
Stage III — Tumors on both sides of the diaphragm, or extensive abdominal disease, or any chest involvement, or tumors around the spine.
Stage IV — Any of the above with involvement of the bone marrow or central nervous system.

Most patients present with advanced-stage (stage III or IV) disease because of how rapidly the tumor grows before symptoms appear. Bone marrow involvement is found in up to 20% of cases at diagnosis. CNS involvement, found in 10–30% of cases, significantly affects prognosis and requires specific treatment.

What is the prognosis?

Despite its aggressive nature, Burkitt lymphoma is one of the most curable aggressive lymphomas when diagnosed promptly and treated with intensive chemotherapy. In high-resource settings, overall survival rates are excellent: more than 90% of children and approximately 80% of adults achieve long-term remission with modern chemoimmunotherapy.

Doctors use a scoring system called the Burkitt Lymphoma International Prognostic Index (BL-IPI) to estimate the likelihood of long-term remission for individual patients. The BL-IPI assigns points based on age, performance status (ability to carry out daily activities), LDH level, and CNS involvement, dividing patients into three risk groups:

Low risk — Approximately 96% long-term survival.
Intermediate risk — Approximately 76% long-term survival.
High risk — Approximately 59% long-term survival.

Patients with HIV-associated Burkitt lymphoma who receive appropriate antiretroviral therapy alongside chemotherapy also achieve good outcomes with modern treatment. CNS involvement at diagnosis is the single strongest adverse prognostic factor and drives the need for CNS-directed treatment as part of induction.

In resource-limited settings, outcomes have historically been less favorable due to delays in diagnosis, limited access to intensive chemotherapy, and inadequate supportive care infrastructure. Outcomes have improved as more intensive regimens have been introduced in sub-Saharan Africa, but Burkitt lymphoma continues to place a significant burden on healthcare systems where it is most common.

What happens after the diagnosis?

Because Burkitt lymphoma grows so rapidly, treatment must begin quickly — ideally within days of diagnosis. Patients are typically referred to a hematologist or lymphoma oncologist with experience treating aggressive lymphomas. The treatment goal is cure.

Standard treatment uses intensive, short-duration chemoimmunotherapy regimens that include rituximab (an anti-CD20 antibody) combined with multi-drug chemotherapy. The most commonly used regimens in North America and Europe include R-CODOX-M/IVAC (rituximab, cyclophosphamide, doxorubicin, vincristine, and methotrexate alternating with ifosfamide, etoposide, and cytarabine) and DA-EPOCH-R. These regimens differ from those used for standard diffuse large B cell lymphoma (such as R-CHOP), which are not intensive enough for Burkitt lymphoma. The choice of regimen depends on the patient’s age, overall health, risk group, and whether CNS involvement is present.

CNS-directed treatment — delivered as intrathecal chemotherapy (medication injected directly into the spinal fluid) or high-dose systemic methotrexate (which penetrates the brain) — is a routine part of most Burkitt lymphoma treatment regimens, because preventing CNS relapse is essential for cure. In patients with confirmed CNS involvement at diagnosis, treatment is intensified accordingly.

Because these regimens are intensive and require hospitalization for administration and monitoring of side effects, most patients are treated in hospital, at least for the initial cycles. Response is assessed by PET/CT imaging. Most patients who achieve a complete metabolic response after treatment are considered cured and do not require stem cell transplantation. Autologous stem cell transplantation may be considered for selected patients with relapsed disease.

Questions to ask your doctor

Was a MYC gene rearrangement confirmed by FISH testing, and was BCL2 rearrangement excluded?
Which subtype of Burkitt lymphoma do I have — endemic, sporadic, or immunodeficiency-associated — and was EBV found in my tumor?
What is my stage, and has the cancer been found in my bone marrow or central nervous system?
What is my BL-IPI risk group, and what does it mean for my expected outcome with treatment?
Which chemotherapy regimen are you recommending — R-CODOX-M/IVAC, DA-EPOCH-R, or another — and why?
Will I need CNS-directed treatment, and in what form?
How quickly does treatment need to start, and will I need to be admitted to hospital?
Will my HIV status or other immune condition affect my treatment plan?
How will you know if treatment is working — when will I have a PET/CT scan?
What are the most important side effects I should watch for during treatment?
What happens if the lymphoma does not respond or comes back after treatment?
Are there clinical trials I should consider?