Burkitt's lymphoma is a
cancer
Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
of the
lymphatic system
The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphoid organs, lympha ...
, particularly
B lymphocytes found in the
germinal center. It is named after
Denis Parsons Burkitt, the Irish
surgeon
In medicine, a surgeon is a medical doctor who performs surgery. Even though there are different traditions in different times and places, a modern surgeon is a licensed physician and received the same medical training as physicians before spec ...
who first described the
disease
A disease is a particular abnormal condition that adversely affects the structure or function (biology), function of all or part of an organism and is not immediately due to any external injury. Diseases are often known to be medical condi ...
in 1958 while working in
equatorial Africa.
It is a highly aggressive form of cancer which often, but not always, manifests after a person develops
acquired immunodeficiency from infection with
Epstein-Barr Virus or
Human Immunodeficiency Virus (HIV).
The overall
cure rate for Burkitt's lymphoma in developed countries is about 90%. Burkitt's lymphoma is uncommon in adults, in whom it has a worse
prognosis
Prognosis ( Greek: πρόγνωσις "fore-knowing, foreseeing"; : prognoses) is a medical term for predicting the likelihood or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) ...
.
Classification
Burkitt lymphoma can be divided into three main clinical variants: the endemic, the
sporadic, and the
immunodeficiency
Immunodeficiency, also known as immunocompromise, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that aff ...
-associated variants.
By
morphology (i.e., microscopic appearance),
immunophenotype, and genetics, the variants of Burkitt lymphoma are alike.
* The endemic variant (also called "African variant") most commonly occurs in children living in regions where malaria is endemic (such as
equatorial Africa,
Brazil
Brazil, officially the Federative Republic of Brazil, is the largest country in South America. It is the world's List of countries and dependencies by area, fifth-largest country by area and the List of countries and dependencies by population ...
, and
Papua New Guinea
Papua New Guinea, officially the Independent State of Papua New Guinea, is an island country in Oceania that comprises the eastern half of the island of New Guinea and offshore islands in Melanesia, a region of the southwestern Pacific Ocean n ...
).
Epstein–Barr virus (EBV) infection is found in nearly all patients.
Chronic
malaria
Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...
is believed to reduce resistance to EBV, allowing EBV infection to occur. The disease characteristically involves the jaw or other
facial bone,
abdomen
The abdomen (colloquially called the gut, belly, tummy, midriff, tucky, or stomach) is the front part of the torso between the thorax (chest) and pelvis in humans and in other vertebrates. The area occupied by the abdomen is called the abdominal ...
,
cecum
The cecum ( caecum, ; plural ceca or caeca, ) is a pouch within the peritoneum that is considered to be the beginning of the large intestine. It is typically located on the right side of the body (the same side of the body as the appendix (a ...
, distal
ileum
The ileum () is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may ...
,
ovaries
The ovary () is a gonad in the female reproductive system that produces ova; when released, an ovum travels through the fallopian tube/oviduct into the uterus. There is an ovary on the left and the right side of the body. The ovaries are endocr ...
,
kidney
In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
, or
breast
The breasts are two prominences located on the upper ventral region of the torso among humans and other primates. Both sexes develop breasts from the same embryology, embryological tissues. The relative size and development of the breasts is ...
.
Less than 10% of cases present with central nervous system involvement, which usually manifest as
cranial nerve palsies or
spinal cord compression.
* The sporadic type of Burkitt lymphoma (also known as "non-African") is the most common variant found in places where malaria is not endemic such as North America and parts of Europe.
The median onset is 10 years of age, but there are also peaks at ages 40 and 75 years old.
Males are 3-4 times more likely to be affected as compared to females.
The tumor cells have a similar appearance to those of the classical endemic Burkitt lymphoma. Sporadic type Burkitt lymphomas are less commonly associated with the EBV virus as compared to the endemic variant; with 20-30% of cases being attributed to EBV (most commonly in adults older than 50).
The jaw is less commonly involved in this variant.
The abdominal region is the most common site of involvement, often at the right lower quadrant.
The bone marrow is involved in 30-35% of cases and the central nervous system is involved in approximately 20% of cases (usually affecting the
meninges
In anatomy, the meninges (; meninx ; ) are the three membranes that envelop the brain and spinal cord. In mammals, the meninges are the dura mater, the arachnoid mater, and the pia mater. Cerebrospinal fluid is located in the subarachnoid spac ...
, or the covering of the brain and spinal cord).
* Immunodeficiency-associated Burkitt lymphoma is usually associated with
HIV infection, but can also occur in the setting of post-transplant patients.
The median age of onset of the immunodeficiency-associated variant is between 40-45 years of age and it is equally prevalent in males and females.
It makes up 40% of the HIV associated lymphomas, and it usually occurs in those with normal
CD4+ T cell counts.
EBV is detected in 25-40% of cases and common areas of involvement include GI tract, lymph nodes and bone marrow with 20-30% of affected people having central nervous system involvement.
Burkitt lymphoma is commonly associated with the infection of
B cell
B cells, also known as B lymphocytes, are a type of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasm ...
lymphocytes with the
EBV and in these cases is considered to be one form of the
Epstein–Barr virus-associated lymphoproliferative diseases.
The endemic variant of Burkitt lymphoma is in almost all cases associated with EBV infection.
The fact that some Burkitt lymphoma cases do not involve EBV allows that many cases of the disease are not caused and/or promoted by EBV, i.e. the virus may be an innocent
passenger virus in these cases. However, the almost ubiquitous presence of the virus in the endemic variant of Burkitt lymphoma suggests that it contributes to the development and/or progression of this variant.
The mutational landscape in Burkitt lymphoma has recently been found to differ between tumors with and without EBV infection, further strengthening the role of the virus in disease origin.
Pathophysiology
Genetics
Almost all cases of Burkitt lymphoma are characterized by dysregulation of the ''
c-myc'' gene by one of three
chromosomal translocation
In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes "balanced" and "unbalanced" translocation, with three main types: "reciprocal", "nonreciprocal" and "Robertsonian" transloc ...
s which place the myc gene under the control of an immunoglobulin gene enhancer.
The MYC gene is found at
8q24.
* The most common variant is t(8;14)(q24;q32), which accounts for about 70 to 80% of cases of cases.
This involves
c-myc oncogene translocation from chromosome 8 to the
Ig heavy chain region of chromosome 14. A variant of this, a three-way translocation, t(8;14;18), has also been identified.
* Another variant is t(2;8)(p12;q24).
This involves the myc oncogene being translocated from chromosome 8 to the
Ig kappa locus on chromosome 2. This type of translocation is seen in 15% of cases of Burkitt lymphoma.
* A rare variant is t(8;22)(q24;q11).
This type involves myc oncogene translocation from chromosome 8 to the
Ig lambda locus on chromosome 22. This type of translocation is involved in about 5% of cases of Burkitt lympohoma.
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.
Expression of the c-myc gene results in the synthesis of
transcriptional factors that increase the expression of other genes involved in
aerobic glycolysis.
Ultimately, an increase in aerobic glycolysis plays a role in providing the necessary energy for cellular growth to occur.
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.
Overall, this translocation leads to increased cellular proliferation that is found in Burkitt lymphoma.
Point mutations can also be present in the translocated c-myc gene resulting in the expressed c-myc protein being overactive.
Bcl-2 translocations, which are frequently seen in
follicular lymphomas and other B-cell Non-Hodgkin Lymphomas, do not occur in Burkitt lymphomas.
One of the above described translocations of MYC is seen in 90% of cases of Burkitt lymphoma, but these oncogenic translocations are not usually sufficient to cause lymphoma; other mutations must also be present.
These additional mutations include mutations of the tumor suppressor
TP53
p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...
, which interacts with the tumor suppressor
p53 (which usually causes apoptosis in B cells carrying the disordered MYC oncoprotein). But with TP53 and p53 mutated, apoptosis is blocked, and the oncogenic B-cells are allowed to proliferate unchecked.
The tumor suppressors
ARF and
USP7 are also frequently mutated in Burkitt lymphoma leading to
MDM2 inhibition of the tumor suppressor p53 which then leads to enhanced oncogenesis.
SIN3A, a regulator of MYC, that acts to inhibit MYC by
deacetylating it, is often inactivated in Burkitt lymphoma.
Also, sequential mutations of the RNA helicases (involved in RNA synthesis)
DDX3X (found on the
x chromosome) and
DDX3Y (found on the
y chromosome
The Y chromosome is one of two sex chromosomes in therian mammals and other organisms. Along with the X chromosome, it is part of the XY sex-determination system, in which the Y is the sex-determining chromosome because the presence of the ...
) lead to MYC oncogenesis in Burkitt lymphoma.
Early in the pathogenesis process, DDX3X mutations limit translation (protein synthesis) allowing lymphoma cells to escape MYC induced proteotoxic stress and apoptosis, then later, DDX3Y mutations restore high level protein synthesis (by producing the
translational machinery) and leading to increased proliferation of tumor cells.
These sequential DDX3X and DDX3Y mutations are thought to partially explain why Burkitt lymphoma is more common in males as the DDX3Y RNA helicase is only found on the Y chromosome.
Mutations affecting the transcription factor
TCF3
Transcription factor 3 (E2A immunoglobulin enhancer-binding factors E12/E47), also known as TCF3, is a protein that in humans is encoded by the ''TCF3'' gene. TCF3 has been shown to directly enhance Hes1 (a well-known target of Notch signaling) e ...
and its negative regulator
ID3 are found in about 70% of cases of Burkitt lymphoma.
These mutations prevent ID3 from binding to and inhibiting TCF3; thus the hyperactive TCF3 then activates
B cell receptors which activate
PI3K and
mTOR, as well as Ig heavy and light chain genes, which contribute to oncogenesis.
TCF3 and ID3 mutations lead to continuously active B-cell receptors, explaining the high level of proliferation seen in Burkitt lymphoma.
Mutations of ID3 and TCF3 are rarely seen in other aggressive B-cell lymphomas; as a result, they can be used to direct further
diagnostic workup if identified.
The cell cycle regulators
Cyclin D3 and
p16
p16 (also known as p16INK4a, cyclin-dependent kinase inhibitor 2A, CDKN2A, multiple tumor suppressor 1 and numerous other synonyms), is a protein that slows cell division by slowing the progression of the cell cycle from the G1 phase to the ...
may also be activated and deactivated respectively in Burkitt lymphoma; leading to massive tumor cell proliferation.
Some epigenetic mechanisms have been found to play a role in the pathogenesis of Burkitt lymphoma.
FBXO11 is a chromatin regulator. By activating
ubiquitin ligase, FBXO11 causes ubiquitination of
BCL6
Bcl-6 (B-cell lymphoma 6) is a protein that in humans is encoded by the ''BCL6'' gene. BCL6 is a master transcription factor for regulation of T follicular helper cells (TFH cells) proliferation. BCL6 has three evolutionary conserved structural d ...
which causes it to be targeted for proteasome degradation.
BCL6 normally helps B cells mature in the germinal center and produce antibodies specific to encountered antigens. In Burkitt lymphoma, FBXO11 is deactivated, leading to increased BCL6 activation which then leads to increased proliferation and decreased maturation of germinal center B-cells, thus promoting lymphomagenesis.
EBV associated Burkitts has increased expressional activity of
activation-induced cytidine deaminase, which is a mutator, this leads to EBV associated Burkitt lymphomas having more mutations than non-EBV types. Non-EBV subtypes of Burkitt lymphoma more commonly have dysregulation of cyclin D3 and mutated, inactivated p53.
Virology
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
telomere
A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes (see #Sequences, Sequences). Telomeres are a widespread genetic feature most commonly found in eukaryotes. In ...
s, and genome instability.
Although the specific pathogenic mechanisms of EBV in Burkitt Lymphoma are unclear, there has been an interest in further elucidating these aspects, particularly with the rise of transcriptomics. BART miRNAs are encoded by the EBV genome and highly expressed in cells infected by EBV.
Due to their ability to bind complementary mRNA sequences and thereby prevent gene expression, BART miRNAs assist EBV-infected cells in avoiding detection by the immune system. BART miRNAs thus contribute to EBV-infected cell survival and proliferation.
BART miRNAs may prove to be a new therapeutic target or specific biomarker for Burkitt Lymphoma patients. However, there needs to be further research into BART miRNAs interact with intrinsic signaling pathways and contribute to malignancy before any further conclusions can be made.
B cell infection with EBV is latent, and the virus does not undergo replication.
Latently infected B cells can then go on to produce proteins that function to promote cellular growth through modification of normal signaling pathways.
EBV promotes the development of malignant B cells via proteins that limit
apoptosis
Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
in cells that had the c-myc translocation.
Apoptosis is limited by EBV through various means such as the
EBNA-1 protein, BHF1 protein,
EBER
Eber (; ; ) is an ancestor of the Ishmaelites and the Israelites according to the Generations of Noah in the Book of Genesis () and the Books of Chronicles ().
Lineage
Eber (Hebrew: Ever) was a great-grandson of Noah's son Shem and the father ...
transcripts, vIL-10 gene,
BZLF1, and
LMP1.
Malaria has been found to cause genomic instability in endemic Burkitt lymphoma.
Malaria
Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...
can lead to the reactivation of latent EBV and also MYC translocations via activation of the toll-like receptor 9.
Malaria also promotes B-cell proliferation by altering the regular immune response.
The immune system targets
antigen
In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.
...
s (e.g., EBNA2 and LMP-1) and eliminates most B cells infected with EBV.
Downregulation of antigens targeted by the immune system leads to the development of persistent B cells.
These B cells can then undergo further mutations (e.g., c-myc translocation) that promote cancer development.
Immunology
Burkitt Lymphoma cells express HLA class I molecules normally, as well as some HLA class II complexes; however, CD4+ T cells are not properly activated. Burkitt lymphoma cells only express EBNA 1, a poorly antigenic EBV-associated antigen, that is able to escape HLA class I presentation, thus evades an immune response. EBNA 1 can be presented via HLA class II molecules, however HLA Class II pathway is unable to activate the CD4+ T cells.
Diagnosis
Malignant B cell characteristics
Normal B cells of a
germinal center possess rearranged immunoglobulin heavy and light chain genes, and each isolated B cell possesses a unique IgH gene rearrangement. Since Burkitt lymphoma and other B-cell lymphomas are a clonal proliferative process, all tumor cells from one patient are supposed to possess identical IgH genes. When the DNA of tumor cells is analyzed using
electrophoresis, a clonal band can be demonstrated, since identical IgH genes will move to the same position. On the contrary, when a normal or reactive lymph node is analyzed using the same technique, a smear rather than a distinct band will be seen. This technique is useful since sometimes benign reactive processes (e.g. infectious mononucleosis) and malignant lymphoma can be difficult to distinguish.
Microscopy
The tumor consists of sheets of a monotonous (i.e., similar in size and morphology) population of medium-sized lymphoid cells with high proliferative and
apoptotic activity. The "starry sky" appearance seen
under low power is due to scattered
tingible body-laden
macrophage
Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
s (macrophages containing dead apoptotic tumor cells). The old descriptive term of "small non-cleaved cell" is misleading. The tumor cells are mostly medium in size (i.e., tumor nuclei size similar to that of
histiocytes or
endothelial cells). "Small non-cleaved cells" are compared to "large non-cleaved cells" of normal
germinal center lymphocytes. Tumor cells possess small amounts of basophilic cytoplasm with three to four small nucleoli. The cellular outline usually appears squared off.
Immunohistochemistry
The tumor cells in Burkitt lymphoma generally strongly express markers of B cell differentiation (CD20, CD22, CD19), as well as CD10 and BCL6. The tumor cells are generally negative for BCL2 and TdT. The high mitotic activity of Burkitt lymphoma is confirmed by nearly 100% of the cells staining positive for Ki67.
Treatment
In general, the first line of treatment for Burkitt lymphoma is
chemotherapy
Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
. A few of these regimens are: the GMALL-B-ALL/NHL2002 protocol, the modified Magrath regimen (R-CODOX-M/IVAC). COPADM, hyper-CVAD,
and the Cancer and Leukemia Group B (CALGB) 8811 regimen;
[ these can be associated with rituximab.][ In older patients, treatment may be dose-adjusted ]EPOCH
In chronology and periodization, an epoch or reference epoch is an instant in time chosen as the origin of a particular calendar era. The "epoch" serves as a reference point from which time is measured.
The moment of epoch is usually decided b ...
with rituximab
Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer. It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia (in children and ad ...
.
The effects of the chemotherapy, as with all cancers, depend on the time of diagnosis. With faster-growing cancers, such as Burkitt, the cancer actually responds faster than with slower-growing cancers. This rapid response to chemotherapy can be hazardous to the patient, as a phenomenon called " tumor lysis syndrome" could occur. Close monitoring of the patient and adequate hydration is essential during the process. Since Burkitt lymphoma has high propensity to spread to the central nervous system (lymphomatous meningitis), intrathecal chemotherapy with methotrexate and/or ARA-C and/or prednisolone is given along with systemic chemotherapy.
Chemotherapy
Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
* cyclophosphamide
* doxorubicin
* vincristine
Vincristine, also known as leurocristine and sold under the brand name Oncovin among others, is a chemotherapy medication used to treat a number of types of cancer. This includes acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin lym ...
* methotrexate
* cytarabine
* ifosfamide
* etoposide
Etoposide, sold under the brand name Vepesid among others, is a chemotherapy medication used for the treatments of a number of types of cancer including testicular cancer, lung cancer, lymphoma, leukemia, neuroblastoma, and ovarian cancer. It is ...
* rituximab
Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer. It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia (in children and ad ...
Other treatments for Burkitt lymphoma include immunotherapy, bone marrow transplant
Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood, in order to replicate inside a patient and produce a ...
s, stem cell transplant, surgery
Surgery is a medical specialty that uses manual and instrumental techniques to diagnose or treat pathological conditions (e.g., trauma, disease, injury, malignancy), to alter bodily functions (e.g., malabsorption created by bariatric surgery s ...
to remove the tumor, and radiotherapy
Radiation therapy or radiotherapy (RT, RTx, or XRT) is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle ...
.
Prognosis
Burkitt lymphoma is a very aggressive cancer, which can quickly metastasize
Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...
and spread throughout the body if the cancer is not treated quickly. If the patient is left untreated, or if treatment is initiated too late, Burkitt lymphoma can be fatal. Burkitt lymphoma in children often has a better prognosis
Prognosis ( Greek: πρόγνωσις "fore-knowing, foreseeing"; : prognoses) is a medical term for predicting the likelihood or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) ...
than the same cancer in an adult.
The overall cure rate for ''sporadic'' Burkitt lymphoma in developed countries is about 90%.
Burkitt lymphoma is not common in adults, but has worse outcomes than in children. If treatment with an initial chemotherapy
Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
regimen of cyclophosphamide, vincristine
Vincristine, also known as leurocristine and sold under the brand name Oncovin among others, is a chemotherapy medication used to treat a number of types of cancer. This includes acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin lym ...
, prednisolone
Prednisolone is a corticosteroid, a steroid hormone used to treat certain types of allergies, inflammation, inflammatory conditions, autoimmune disorders, and cancers, Electrolyte imbalance, electrolyte imbalances and skin conditions. Some of ...
, and/or other drugs fails to produce meaningful remission or regression, this usually indicates a more severe outcome. Furthermore, failed initial treatment and return of Burkitt lymphoma after a six-month stint of time serve as a poor prognostic indicator. The adequate utilization of therapeutic drugs during initial treatment limits additional treatment options following the return of the disease. 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. Laboratory studies such as lactate dehydrogenase (LDH), CD4 count, and other cytogenetic studies are also prognostic indicators. Unsatisfactory outcomes have been associated with an LDH that is found to be two times above the upper limit of normal. Specifically, there is a poor prognosis associated with a CD4 count that is decreased in the immunodeficiency-associated variant of Burkitt lymphoma. Genetic mutations extending beyond the previously described MYC translocation may also serve as negative prognostic indicators. 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. The prognosis for Burkitt lymphoma can be better determined following staging utilizing imaging modalities such as positron emission tomography
Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, r ...
and computed tomography
A computed tomography scan (CT scan), formerly called computed axial tomography scan (CAT scan), is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers or ...
scans where tumor burden and invasion of the central nervous system have been found to indicate a poor prognosis.
Epidemiology
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. The endemic variant mainly impacts areas with an increased prevalence of malaria
Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...
and EBV in Africa and Papua New Guinea. For children less than 18 years of age from equatorial Africa, the annual incidence of Burkitt lymphoma is 4–5/100,000. 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. The peak incidence for endemic Burkitt lymphoma is from ages 4 to 7 with an average age of 6 years. 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. This variant is 3.5 times more commonly found in males compared to females and it is more frequent in younger individuals. 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. For adults, 45 years was the median age that the sporadic Burkitt lymphoma was diagnosed. The immunodeficiency-associated variant predominantly impacts the HIV-infected population. For those in the United States and with AIDS
The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...
, the incidence of this variant was found to be 22/100,000 person-years. 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.
EBV infection is associated with Burkitt lymphoma. EBV is found in virtually all instances of endemic Burkitt lymphoma. The sporadic variant of Burkitt lymphoma is associated with EBV in only 10–20% of cases. Approximately 30% of immunodeficiency-associated Burkitt lymphoma cases were associated with EBV.
Research
Gene targets
Unique genetic alterations promote cell survival in Burkitt lymphoma, distinct from other types of lymphoma.
These ''TCF3
Transcription factor 3 (E2A immunoglobulin enhancer-binding factors E12/E47), also known as TCF3, is a protein that in humans is encoded by the ''TCF3'' gene. TCF3 has been shown to directly enhance Hes1 (a well-known target of Notch signaling) e ...
'' and '' ID3'' gene mutations in Burkitt correspond to a cell survival pathway that may be found to be amenable to targeted therapy
Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy (oncology), hormonal therapy and cytotoxic chemotherapy. As a form of molecular medici ...
.
References
External links
{{Viral diseases
Non-Hodgkin lymphoma
Epstein–Barr virus–associated diseases
Infectious causes of cancer