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Burkitt Lymphoma

Burkitt lymphoma is a variant of non-Hodgkin lymphoma that targets B cells and is associated with Epstein Barr Virus infection.


Presentation

Burkitt lymphoma presents acutely, with the patients exhibiting the majority of symptoms in the space of a few weeks. This is caused by the rapid division of the lymphoma cells, which may also eventually lead to widespread dissemination upon diagnosis.
Burkitt lymphoma can present in a range of symptoms. Lymph node swelling is probably the most common initial manifestation and may not be restricted to a particular region of the body.

Nonspecific symptoms such as chills, night sweats, fatigue, fever, weight loss, limited appetite and flu-like symptoms can also be significant. Other symptoms include abdominal pain, diarrhea, abdominal swelling and ascites, bowel obstruction, hematochezia and melena because of involvement of the gastrointestinal system. Organs other than lymph nodes can be affected, particularly the kidneys, breasts, ovaries and the liver

Shortness of breath and fatigue as well as easy bruising may result from anemia and a decrease in platelets. Involvement of the central nervous system eventually leads to the development of seizures, decreased focusing ability, headaches and altered mental status. African Burkitt lymphoma is particularly distinguished by a propensity to affect the jaw, especially where permanent teeth are in the formation stage. Jaw involvement is rarely seen in sporadic, Western Burkitt lymphoma.

Fever
  • He came at our attention for fever and weight loss suspected for parasitic cyst discharge and also for lymphoproliferative disorder. We performed US, which showed disseminated parasitic cysts.[ncbi.nlm.nih.gov]
  • Other frequent symptoms include fever, night sweats and weight loss.[symptoma.com]
  • Other general symptoms may include: Fever Night sweats Unexplained weight loss Chemotherapy is used to treat this type of cancer. If the cancer does not respond to chemotherapy alone, a bone marrow transplant may be done.[nlm.nih.gov]
  • Significant toxicities include fever/neutropenia in 16%, grade 4 neutropenia in 47% and grade 3/4 thrombocytopenia in 22% of cycles. There were no treatment related deaths and no tumor lysis syndrome.[bloodjournal.org]
Anemia
  • Autoimmune hemolytic anemia (AIHA) in childhood, including paroxysmal cold hemoglobinuria, is an uncommon, potentially life-threatening disorder.[ncbi.nlm.nih.gov]
  • Shortness of breath and fatigue as well as easy bruising may result from anemia and a decrease in platelets.[symptoma.com]
  • […] gastrointestinal (GI) tract may also be affected, causing abdominal pain, diarrhea, and nausea Other general symptoms may include: Fever Night sweats Fatigue Loss of appetite Weight loss If the cancer has reached the bone marrow, individuals may display anemia[dovemed.com]
Ankle Edema
  • He also had decreased air entry in both lungs and bilateral ankle edema. His CBC revealed WBC 28.4 10 9 /L, Hgb 109 g/L, and platelets 330 10 9 /L.[doi.org]
Inguinal Lymphadenopathy
  • CT scan revealed bilateral pleural effusions, splenomegaly, massive matted retroperitoneal lymphadenopathy and bilateral inguinal lymphadenopathy.[doi.org]
Inguinal Lymphadenopathy
  • CT scan revealed bilateral pleural effusions, splenomegaly, massive matted retroperitoneal lymphadenopathy and bilateral inguinal lymphadenopathy.[doi.org]
Abdominal Lymphadenopathy
  • CT scan revealed marked intra-abdominal lymphadenopathy. Bone marrow smear and flowcytometric analysis did not show overt involvement by BL, though focal involvement of the bone marrow was demonstrated on immunohistochemical study.[doi.org]
Cervical Lymphadenopathy
  • The patient was a 7-year-old boy with NS, who was included in the first series reporting the association between Noonan and RAF1, and who later presented with a 2-week history of asymptomatic unilateral tonsillar swelling and ipsilateral cervical lymphadenopathy[ncbi.nlm.nih.gov]
Axillary Lymphadenopathy
  • We describe a 57 year-old woman with newly diagnosed HIV infection who presented with unilateral localized axillary lymphadenopathy.[ncbi.nlm.nih.gov]
Abdominal Mass
  • Burkitt lymphoma has many forms of clinical presentations and, in children, it is usually discovered due to the presence of an abdominal mass.[ncbi.nlm.nih.gov]
  • It is commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. B-cell antigens are expressed on the immature cells that make up the tumor in virtually all cases of burkitt lymphoma.[icd9data.com]
  • Usually found in central Africa, but also reported from other areas, and manifested most often as a large osteolytic lesion in the jaw or as an abdominal mass; called also African lymphoma.[medical-dictionary.thefreedictionary.com]
  • 11 M Abdominal mass P P P N n.d.[doi.org]
Abdominal Pain
  • A man aged 17 years presented with a history of recurrent abdominal pain over the past 3 weeks. The abdomen was distended with diffuse tenderness, and bowel sounds were present.[ncbi.nlm.nih.gov]
  • Gastrointestinal involvement can lead to abdominal pain, ascites, abnormal bowel habits, as well as bleeding and bowel obstruction.[symptoma.com]
  • The most frequent clinical signs are abdominal pain, nausea, an alteration of general state and/or the appearance of lymph nodes and tumors.[orpha.net]
Diarrhea
  • Described herein is the case of a nine-year-old boy with abdominal pain, jaundice, emesis, weight loss, diarrhea, who developed hyperlipidemia and cholestasis. Pancreatitis was suspected due to high amylase and lipase.[ncbi.nlm.nih.gov]
  • Other symptoms include abdominal pain, diarrhea, abdominal swelling and ascites, bowel obstruction, hematochezia and melena because of involvement of the gastrointestinal system.[symptoma.com]
  • ., Taniwaki, M. (2005) Pseudomembranous colitis presenting as acute colonic obstruction without diarrhea in a patient with gastric Burkitt lymphoma.[scindeks.ceon.rs]
  • Due to this fluid collection, the gastrointestinal (GI) tract may also be affected, causing abdominal pain, diarrhea, and nausea Other general symptoms may include: Fever Night sweats Fatigue Loss of appetite Weight loss If the cancer has reached the[dovemed.com]
Abdominal Distension
  • A 15-year-old girl was referred to our department because of persistent constipation and abdominal distension.[ncbi.nlm.nih.gov]
Recurrent Abdominal Pain
  • A man aged 17 years presented with a history of recurrent abdominal pain over the past 3 weeks. The abdomen was distended with diffuse tenderness, and bowel sounds were present.[ncbi.nlm.nih.gov]
Jaw Mass
  • Burkitt lymphoma should be considered in the differential diagnosis of any rapidly expanding or swelling jaw masses in young patients.[ncbi.nlm.nih.gov]
  • There are many signs and symptoms associated with Burkitt's lymphoma ; most commonly, the symptoms include abdominal and/or jaw masses, nausea and vomiting, headaches, visual impairment, and possibly renal, gastrointestinal, and other central nervous[medicinenet.com]
Unilateral Ptosis
  • The authors present a case of unilateral ptosis secondary to Burkitt lymphoma metastasis to brain with excellent response to chemotherapy and complete resolution of ptosis in a man with human immunodeficiency virus.[ncbi.nlm.nih.gov]
Neck Mass
  • We report the case of a 70-year-old woman with a 9-year history of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia who presented with rapid enlargement of a left neck mass and pancytopenia, which was diagnosed as Burkitt lymphoma with extensive[ncbi.nlm.nih.gov]
Neck Mass
  • We report the case of a 70-year-old woman with a 9-year history of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia who presented with rapid enlargement of a left neck mass and pancytopenia, which was diagnosed as Burkitt lymphoma with extensive[ncbi.nlm.nih.gov]

Workup

Burkitt lymphoma is diagnosed after the performance of several laboratory and imaging tests. Biopsy is critical for definitive diagnosis, although bone marrow and cerebrospinal fluid analyses should be performed because the hematologic and central nervous systems are frequently affected by the disease. In case of ascites or the presence of pleural fluids, samples should be extracted and sent for cytology.

On the other hand, Burkitt lymphoma is staged after the performance of a number of imaging tests that include a chest x-ray, CT, MRI and positron emission tomography (PET). Minimal residual disease (MRD) technology that consists of flow cytometry and PCR (polymerase chain reaction) can also be employed for diagnosis and staging purposes.

Treatment

Sensitivity to chemotherapy varies considerably depending on the subtype of Burkitt lymphoma. Sporadic variants and those associated with immunodeficiency are generally more resistant to chemotherapy. Treatment is recommended to be brief and intensive, particularly in children and results in a very elevated cure rate. The same treatment is employed in adults but usually in combination with rituximab, a monoclonal antibody.

Chemotherapy is generally administered as a combination of vincristine, doxorubicin, methotrexate, ifosfamide, cytarabine, etoposide and cyclophosphamide. Chemotherapeutic agents may also be injected intrathecally to prevent any spread to the central nervous system. Intensive treatment in stages I-III of Burkitt lymphoma can be replaced by a non-intensive chemotherapeutic protocol that consists of cyclophosphamide and methotrexate. This is usually done in underdeveloped countries with poor resources.

Other treatment modalities can be utilized to address potential complications. Allopurinol is particularly useful in cases of tumor lysis syndrome and should be initiated with alkalinization and hydration, in addition to electrolyte monitoring. Resistant cases of tumor lysis syndrome may ultimately require kidney dialysis. In addition, surgery may be needed in cases of bowel obstruction or small resectable abdominal tumors. If malignancy is relapsing or extensive despite chemotherapeutic treatment, bone marrow or stem cell transplantation may be necessary, followed by radiotherapy and high-dose chemotherapy.

Prognosis

Prognosis depends on the stage of the disease when it was first diagnosed. Outcomes are excellent when tumors remain localized and survival rate can top 90%. Children and adolescents typically have a brighter prognosis than adults diagnosed after the age of 40, although treatment advances have also improved outcomes for adult patients.

HIV patients should generally expect a poor prognosis, as the disease is usually disseminated at the time of diagnosis. Furthermore, Burkitt lymphoma can develop into a leukemia in rare cases.

Etiology

African Burkitt lymphoma has been strongly associated with an Epstein-Barr virus (EBV) infection, that is also known to cause glandular fever. Burkitt lymphoma that is characteristically related to Great Britain is however less strongly linked with EBV.

EBV infection is very common. Studies indicate that up to 90% of British adults have been infected at one time with EBV. The causes underlying the development of lymphoma in only a subset of patients infected with the virus are still unclear.

Individuals with a weakened immune system are generally more susceptible to develop Burkitt lymphoma after infection with the EBV virus. Patients with HIV (human immunodeficiency virus) are particularly at risk, although the majority of individuals with Burkitt lymphoma do not have HIV. It is recommended that all patients diagnosed with the disorder be tested for HIV.

Despite the fact that Burkitt lymphoma is strongly related with EBV infection, it cannot spread from person to person. It also cannot be transmitted genetically from parents.

Epidemiology

Burkitt lymphoma targets adults as well as children. It represents the most common form of B-cell lymphomas occurring in childhood and less than 10% of all adult diffuse lymphomas. Burkitt lymphoma is particularly prevalent in sub-Saharan African, where it is estimated to represents 50% of all childhood malignancies [7]. The disease is more common in males, with incidence being highest among children between 5 and 8 years of age. In addition to sub-Saharan Africa, Burkitt lymphoma is particularly prevalent in South America, the Middle East, North Africa and Papua New Guinea.

Burkitt lymphoma can be either sporadic or endemic, with both forms associated with EBV infection. Nonetheless, the EBV association is stronger for endemic Burkitt lymphoma. Sporadic Burkitt lymphoma is found infrequently in the developed world and may be accounted for in 20% of the cases by EBV infection.

Other infections in addition to EBV that can increase the risk of acquiring Burkitt lymphoma include malaria and arboviruses, with the latter being transmitted through insects. Plant extracts that are used as herbal remedies can also act as cofactors. They are thought to promote tumor generation.

Sex distribution
Age distribution

Pathophysiology

The underlying pathophysiological mechanisms of Burkitt lymphoma remain unknown. Nonetheless, several theories have been suggested to explain the development of the disease. These include infection with EBV and malaria and c-myc oncogene activation.

Almost all patients with endemic Burkitt lymphoma show evidence of infection with EBV. On the other hand, only 20% of patients with sporadic Burkitt lymphoma have been infected by EBV. It is thought that EBV infection targets particularly B cells, which eventually manage to evade cellular immune defenses. EBV infected B cells enter the germinal centers, where they subsequently become neoplastic and undergo rapid proliferation. This process is further amplified by a concomitant infection with malaria that results in the inhibition of the immune response against EBV. Nonetheless, scientists do not yet understand the direct mechanisms relating EBV and lymphomagenesis. It is thought that mRNA derived from both viruses and cellular microRNA disrupts gene expression and translation.

Another leading explanatory theory involves the activation of the c-myc oncogene. This is caused by a translocation of the c-myc oncogene that is normally present on chromosome 8 into the heavy chain gene present on chromosome 14. This ultimately leads to the activation of c-myc gene with subsequent cellular proliferation. Around 80% of all cases of Burkitt lymphoma share the t(8;14) translocation, and the remaining 20% also show c-myc activation following translocations of the proto-oncogene near to the light chain gene of immunoglobulins on chromosome 2 or 22 (kappa light chain [t(8:2)] and lambda light chain [t(8:22)] respectively) [8] [9] [10].

Prevention

There are no current preventive strategies for Burkitt lymphoma, although potential avenues include vaccination for both EBV and malaria.

Summary

Burkitt lymphoma is a type of non-Hodgkin lymphoma that results from unrestricted proliferation of B cells [1]. It is strongly associated with an infection of Epstein Barr Virus (EBV) and is particularly endemic to sub-Saharan Africa [2]. The underlying pathophysiological mechanisms are still poorly understood but it is thought that infection with EBV, malaria and c-myc oncogene activation result in the development of the disease. B cells infected with EBV can successfully evade the cell mediated immune response lead by T cells, and eventually lead to the unrestricted proliferation of B cells in germinal centers [3]. It is suggested that B cell mRNA and cellular microRNA work together to disrupt gene translation and transcription, resulting in abnormal cellular growth and proliferation. On the other hand, the disease has been also strongly correlated with translocation of the c-myc proto-oncogene, particularly in a translocation from chromosome 8 into chromosome 14, near the gene of the heavy chain of immunoglobulins. Other chromosomal translocations also associated with the disease involve c-myc and genes that code for the light chain of immunoglobulins [4].

Burkitt lymphoma has a wide presentation, but it most commonly manifests initially with lymph node swelling, in addition to nonspecific signs and symptoms such as weight loss, fever and night sweat. More specific symptoms may result from involvement of particular organ systems. Gastrointestinal involvement can lead to abdominal pain, ascites, abnormal bowel habits, as well as bleeding and bowel obstruction. On the other hand, central nervous system involvement leads to seizures, an inability to concentrate, headaches and altered mental status. Other organs that can be targeted include the kidneys, the liver, the ovaries and the breast. Anemia and easy bruising may result due to defects in platelets and RBC function. Furthermore, African Burkitt lymphoma is particularly distinguished by involvement of the jaw [5].

Diagnosis is established with biopsy, although examinations of the cerebral spinal fluid and a bone marrow sample may be necessary to rule out involvement of the hematologic and central nervous systems. Staging is critical in the management process, and is usually done after performance of imaging procedures with MRI, CT, x-ray, positron emission tomography and minimal residual disease technology. The latter is a new addition to the diagnosis and monitoring armory and consists of a combination of flow cytometry and polymerase chain reaction (PCR) [6].

Treatment consists of chemotherapy in children, and a combination of chemotherapy and monoclonal antibody administration in adults. Chemotherapy is generally intensive and has a very high success rate among children. A less intensive protocol may be followed in underdeveloped countries with poor resources. Allopurinol is generally employed in tumor lysis syndrome, although more severe cases may necessitate kidney dialysis. Relapsing or unresponsive disease can be treated with stem cell or bone marrow transplantation.

Prognosis is excellent in children, with up to 90% of all patients achieving full remission.

Patient Information

Burkitt lymphoma is a form of malignancy that targets cells within the lymph nodes. It is associated with an infection with a virus called the Epstein Barr Virus (EBV) and is especially endemic in sub-Saharan Africa. The exact processes underlying the development of the disease are still unknown, but it is thought that infection with the virus weakens the immune system and results in unrestricted proliferation and growth of the B cells within the lymph nodes. The disease targets especially children and is more common in males than females.

Patients present symptoms in a relatively acute fashion, usually with swelling and enlargement of the lymph nodes. Other frequent symptoms include fever, night sweats and weight loss. The tumor may also grow within the nervous and digestive systems and lead to various signs and systems such as diarrhea, bowel obstruction, abdominal pain and swelling, seizures, headaches, confusion and decreased concentration ability. It may also result in anemia and a tendency to bruise easily due to platelet involvement.

Diagnosis is established after taking a sample of the lymph nodes for pathology analyses. These may reveal abnormal neoplastic cells. It is also important to take a sample of the cerebrospinal fluid and the bone marrow to detect any involvement of the nervous or blood systems. Imaging tests with MRI, CT, PET and x-ray may be necessary to accurately stage the disease for correct treatment.

Burkitt lymphoma is treated with a high intensity regimen of chemotherapy. Adult patients may also receive doses of an antibody that particularly targets cancer cells. Patients who do not respond to the chemotherapy treatment may be cured with a bone marrow or stem cell transplantation.

Prognosis of Burkitt lymphoma is excellent in children with more than 90% of patients establishing complete cure.

References

Article

  1. Leoncini L, Raphael M, Stein H, Harris NL, Jaffe ES, Kluin PM. Burkitt Lymphoma. Swerdlow SH, Campo E, Harris NL, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC Press; 2008; 262-4.
  2. Boerma EG, van Imhoff GW, Appel IM, Veeger NJ, Kluin PM, Kluin-Nelemans JC. Gender and age-related differences in Burkitt lymphoma--epidemiological and clinical data from The Netherlands. Eur J Cancer. 2004 Dec; 40(18):2781-7. 
  3. Gong JZ, Stenzel TT, Bennett ER, et al. Burkitt lymphoma arising in organ transplant recipients: a clinicopathologic study of five cases. Am J Surg Pathol. 2003 Jun; 27(6):818-27.
  4. Husain M, Grunebaum E, Naqvi A, et al. Burkitt's lymphoma in a patient with adenosine deaminase deficiency-severe combined immunodeficiency treated with polyethylene glycol-adenosine deaminase. J Pediatr. 2007 Jul; 151(1):93-5. 
  5. Ferry JA. Burkitt's lymphoma: clinicopathologic features and differential diagnosis. Oncologist. 2006 Apr; 11(4):375-83. 
  6. Blum KA, Lozanski G, Byrd JC. Adult Burkitt leukemia and lymphoma. Blood. 2004 Nov 15; 104(10):3009-20. 
  7. Phillips JA. Is Burkitt's lymphoma sexy enough? Lancet. 2006 Dec 23;368(9554):2251-2.
  8. Preudhomme C, Dervite I, Wattel E, et al. Clinical significance of p53 mutations in newly diagnosed Burkitt's lymphoma and acute lymphoblastic leukemia: a report of 48 cases. J Clin Oncol. 1995 Apr; 13(4):812-20.
  9. Gaidano G, Ballerini P, Gong JZ, et al. p53 mutations in human lymphoid malignancies: association with Burkitt lymphoma and chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 1991 Jun 15; 88(12):5413-7. 
  10. Coller HA, Grandori C, Tamayo P, et al. Expression analysis with oligonucleotide microarrays reveals that MYC regulates genes involved in growth, cell cycle, signaling, and adhesion. Proc Natl Acad Sci U S A. 2000 Mar 28; 97(7):3260-5.

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Last updated: 2019-07-11 21:47