All types of Burkitt lymphoma are characterized by dysregulation of the c-myc gene by one of three chromosomal translocations.^[11] This gene is found at 8q24.

• The most common variant is t(8;14)(q24;q32), which accounts for about 85%^[11] of cases. This involves c-myc and IGH@. A variant of this, a three-way translocation, t(8;14;18), has also been identified.^[12]
• A rare variant is at t(2;8)(p12;q24).^[13] This involves IGK@ and c-myc.
• Another rare variant is t(8;22)(q24;q11).^[13] This involves IGL@ and c-myc.

Combined, the two less-common translocations, t(2;8)(p12;q24) and t(8;22)(q24;q11), account for the remaining 15% of cases not due to the t(8;14)(q24;q32) translocation.^[11]

The c-myc gene found on chromosome 8 is part of the Myc family of genes that serve as regulators of cellular transcription and is associated with Burkitt lymphoma.^[14][15] Expression of the c-myc gene results in the synthesis of transcriptional factors that increase the expression of other genes involved in aerobic glycolysis.^[14] Ultimately, an increase in aerobic glycolysis plays a role in providing the necessary energy for cellular growth to occur.^[14] The translocation of the c-myc gene to the IGH, IGK, or IGL region moves the gene to a location in the genome near immunoglobulin enhancers which increases the expression of the c-myc gene.^[14] Overall, this translocation leads to increased cellular proliferation that is found in Burkitt lymphoma.^[14] Point mutations can also be present in the translocated c-myc gene resulting in the expressed c-myc protein being overactive.^[14] Other mutations found include the TCF transcription factor mutation, which increases cellular proliferation via the increased expression of other genes.^[14] Along with mutations that support cell proliferation, Burkitt lymphoma has been found to also harbor mutations in the TP53 gene that is a tumor suppressor and would normally function to limit cellular growth.^[15]

The complete role of EBV in the pathogenesis of endemic Burkitt lymphoma is not completely elucidated, but it has been shown to cause DNA damage, dysfunction of telomeres, and genome instability.^[16][15] B cell infection with EBV is latent, and the virus does not undergo replication.^[16] These latently infected B cells can then go on to produce proteins that function to promote cellular growth through modification of normal signaling pathways.^[16] EBV promotes the development of malignant B cells via proteins that limit apoptosis in cells that had the c-myc translocation.^[15] Apoptosis is limited by EBV through various means such as the EBNA-1 protein, BHF1 protein, EBER transcripts, vIL-10 gene, BZLF1, and LMP1.^[15] Malaria has been found to cause genomic instability in endemic Burkitt lymphoma.^[17] Malaria can lead to the reactivation of latent EBV and also MYC translocations via activation of the toll-like receptor 9.^[15] Malaria also promotes B-cell proliferation by altering the regular immune response.^[16] The immune system targets antigens (e.g., EBNA2 and LMP-1) and eliminates most B cells infected with EBV.^[15] Downregulation of antigens targeted by the immune system leads to the development of persistent B cells.^[15] These B cells can then undergo further mutations (e.g., c-myc translocation) that promote cancer development.^[15]

Furthermore, failed initial treatment and return of Burkitt lymphoma after a six-month stint of time serve as a poor prognostic indicator.[15] The adequate utilization of therapeutic drugs during initial treatment limits additional treatment options following the return of the disease.[15] Notably, in areas of the world where the initial treatment of Burkitt lymphoma is inadequate further treatment options may remain for cases when the disease returns.[15] Laboratory studies such as lactate dehydrogenase (LDH), CD4 count, and other cytogenetic studies are also prognostic indicators.[15] Unsatisfactory outcomes have been associated with an LDH that is found to be two times above the upper limit of normal.[15] Specifically, there is a poor prognosis associated with a CD4 count that is decreased in the immunodeficiency-associated variant of Burkitt lymphoma.[15] Genetic mutations extending beyond the previously described MYC translocation may also serve as negative prognostic indicators.[15] Some notable genetic findings that may be associated with poor outcomes include: 13q deletion, 7q gain, ID3 and CCND3 double-hit mutations, and 18q21 CN-LOH mutations.[15] The prognosis for Burkitt lymphoma can be better determined following staging utilizing imaging modalities such as positron emission tomography and computed tomography scans where tumor burden and invasion of the central nervous system have been found to indicate a poor prognosis.[27][15]

As a non-Hodgkin lymphoma (NHL), Burkitt lymphoma makes up 1-5% of cases, and it is more common in males than females with a 3–4 to 1 ratio.^[15] The endemic variant mainly impacts areas with an increased prevalence of malaria and EBV in Africa and Papua New Guinea.^[15][28] For children less than 18 years of age from equatorial Africa, the annual incidence of Burkitt lymphoma is 4–5/100,000.^[28] Additionally, in equatorial Africa, 50% of tumors that are diagnosed during childhood as well as 90% of lymphoma cases can be attributed to Burkitt lymphoma.^[28] The peak incidence for endemic Burkitt lymphoma is from ages 4 to 7 with an average age of 6 years.^[15][28] The sporadic variant with an annual incidence 2-3/million is more commonly found in North America and Europe comprising 1-2% of adult lymphomas and 30–40% of NHL cases.^[15][28] This variant is 3.5 times more commonly found in males compared to females and it is more frequent in younger individuals.^[28] The sporadic variant has a peak incidence at 11 years of age in children, and diagnosis typically occurs from 3–12 years of age on average.^[15][28] For adults, 45 years was the median age that the sporadic Burkitt lymphoma was diagnosed.^[15] The immunodeficiency-associated variant predominantly impacts the HIV-infected population.^[28] For those in the United States and with AIDS, the incidence of this variant was found to be 22/100,000 person-years.^[15][28] There is also an increased risk of developing this variant of Burkitt lymphoma for individuals that have received an organ transplant after 4–5 years.^[28]