Burkitt's lymphoma

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Burkitt's lymphoma
Classification and external resources
Burkitt lymphoma, touch prep, Wright stain.jpg
Burkitt lymphoma, touch prep, Wright stain
ICD-10 C83.7
ICD-9 200.2
ICD-O: M9687/3
OMIM 113970
DiseasesDB 1784
MedlinePlus 001308
eMedicine med/256
Patient UK Burkitt's lymphoma
MeSH D002051
Seven-year-old Nigerian boy with a several month history of jaw swelling which had been treated with antibiotics. The tumor was ulcerated and draining.
Picture of a mouth of a patient with Burkitt's lymphoma showing disruption of teeth and partial obstruction of airway

Burkitt's lymphoma (Burkitt's tumor, Burkitt lymphoma, or malignant lymphoma, Burkitt's type) is a cancer of the lymphatic system, particularly B lymphocytes found in the germinal center. It is named after Denis Parsons Burkitt, a surgeon who first described the disease in 1958 while working in equatorial Africa.[1][2]

Classification[edit]

Currently Burkitt's lymphoma can be divided into three main clinical variants: the endemic, the sporadic, and the immunodeficiency-associated variants.[3]

  • The endemic variant (also called "African variant") most commonly occurs in children living in malaria endemic regions of the world (e.g., equatorial Africa, Brazil, and Papua New Guinea). Epstein-Barr Virus (EBV) infection is found in nearly all patients. It is believed that chronic malaria reduces resistance to EBV, allowing it to take hold. The disease characteristically involves the jaw or other facial bone, distal ileum, cecum, ovaries, kidney or the breast.
  • The sporadic type of Burkitt lymphoma (also known as "non-African") is the most common variant found in places where malaria is not holoendemic. The tumor cells have a similar appearance to the cancer cells of classical endemic Burkitt lymphoma. Sporadic lymphomas are rarely associated with the Epstein–Barr virus.[4] Non-Hodgkin lymphoma, which includes Burkitt's, accounts for 30–50% of childhood lymphoma. The jaw is less commonly involved, compared to the endemic variant. The ileocecal region is the common site of involvement.
  • Immunodeficiency-associated Burkitt lymphoma is usually associated with HIV infection[5] or occurs in the setting of post-transplant patients who are taking immunosuppressive drugs. Burkitt lymphoma can be one of the diseases associated with the initial manifestation of AIDS.

By morphology (i.e. microscopic appearance) or immunophenotype, it is almost impossible to differentiate these three clinical variants. Immunodeficiency-associated Burkitt lymphoma may demonstrate more plasmacytic appearance or more pleomorphism, but these features are not specific.

Epidemiology[edit]

Of all cancers involving the same class of blood cell, 2.3% of cases are Burkitt's lymphoma.[6]

Malignant B cell characteristics[edit]

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[edit]

The tumor consists of sheets of a monotonous (i.e. similar in size and morphology) population of medium size lymphoid cells with high proliferative activity and apoptotic activity. The "starry sky" appearance seen[7] under low power is due to scattered tingible body-laden macrophages (macrophages containing dead body of 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 amount of basophilic cytoplasm with three to four small nucleoli. The cellular outline usually appears squared off.

Immunohistochemistry[edit]

The tumor cells in Burkitt lymphoma generally strongly express markers of B cell differentiation (CD20, CD22, CD19) as well as CD10, and BCL6. The tumour 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.[8]

Genetics[edit]

All types of Burkitt's lymphoma are characterized by disregulation of the c-myc gene by one of three chromosomal translocations.[9] This gene is found at 8q24.

  • The most common variant is t(8;14)(q24;q32), which accounts for approximately 85%[9] of cases. This involves c-myc and IGH@. A variant of this, a three-way translocation, t(8;14;18), has also been identified.[10]
  • A rare variant is at t(2;8)(p12;q24).[11] This involves IGK@ and c-myc.
  • Another rare variant is t(8;22)(q24;q11).[11] 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.[9]

Gene targets[edit]

Unique genetic alterations promote cell survival in Burkitt lymphoma, distinct from other types of lymphoma.[12] These TCF3 and ID3 gene mutations in Burkitt correspond to a cell survival pathway that may be found to be amenable to targeted therapy.[13]

Treatment[edit]

Treatment may be dose-adjusted EPOCH with Rituxan (rituximab)[14] or the modified Magrath regimen (R-CODOX-M/IVAC).[15]

The effects of the chemotherapy, as with all cancers, depend on the time of diagnosis. With faster growing cancers, such as Burkitt's, 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.

Chemotherapy

Other treatments are immunotherapy, bone marrow transplants, stem cell transplant, surgery to remove the tumor, and radiotherapy.

Prognosis[edit]

Treatment with dose-adjusted EPOCH with Rituxan (rituximab) has shown an 8 year survival rate of 91% for low risk, 90% for low-intermediate risk, 67% for high-intermediate risk, and 31% for high risk cases with few of the side effects associated with Burkitt's lymphoma chemotherapy.[14]

References[edit]

  1. ^ synd/2511 at Who Named It?
  2. ^ Burkitt D (1958). "A sarcoma involving the jaws in African children". The British journal of surgery 46 (197): 218–23. doi:10.1002/bjs.18004619704. PMID 13628987. 
  3. ^ Molyneux E, Rochford R, Griffin B, Newton R, Jackson G, Menon G, Harrison C, Israels T, Bailey S (April 2012). "Burkitt's lymphoma". The Lancet 379 (9822): 1234–1244. doi:10.1016/S0140-6736(11)61177-X. PMC 1769902. PMID 22333947. 
  4. ^ Epstein–Barr virus and Burkitt lymphoma G Brady, G J MacArthur, and P J Farrell, Journal of Clinical Pathology, 2007 December; 60(12): 1397–1402
  5. ^ Bellan C, Lazzi S, De Falco G, Nyongo A, Giordano A, Leoncini L (March 2003). "Burkitt's lymphoma: new insights into molecular pathogenesis". J. Clin. Pathol. 56 (3): 188–92. doi:10.1136/jcp.56.3.188. PMC 1769902. PMID 12610094. 
  6. ^ Turgeon, Mary Louise (2005). Clinical hematology: theory and procedures. Hagerstown, MD: Lippincott Williams & Wilkins. p. 283. ISBN 0-7817-5007-5. "Frequency of lymphoid neoplasms. (Source: Modified from WHO Blue Book on Tumour of Hematopoietic and Lymphoid Tissues. 2001, p. 2001.)" 
  7. ^ Fujita S, Buziba N, Kumatori A, Senba M, Yamaguchi A, Toriyama K (May 2004). "Early stage of Epstein–Barr virus lytic infection leading to the "starry sky" pattern formation in endemic Burkitt lymphoma". Arch. Pathol. Lab. Med. 128 (5): 549–52. doi:10.1043/1543-2165(2004)128<549:ESOEVL>2.0.CO;2. PMID 15086279. 
  8. ^ . ISBN 978-92-832-2431-0.  Missing or empty |title= (help)
  9. ^ a b c Hoffman, Ronald (2009). Hematology : basic principles and practice (5th ed. ed.). Philadelphia, PA: Churchill Livingstone/Elsevier. pp. 1304–1305. ISBN 978-0-443-06715-0. 
  10. ^ Liu D, Shimonov J, Primanneni S, Lai Y, Ahmed T, Seiter K (2007). "t(8;14;18): a 3-way chromosome translocation in two patients with Burkitt's lymphoma/leukemia". Mol. Cancer 6: 35. doi:10.1186/1476-4598-6-35. PMC 1904237. PMID 17547754. 
  11. ^ a b Smardova J, Grochova D, Fabian P, et al. (October 2008). "An unusual p53 mutation detected in Burkitt's lymphoma: 30 bp duplication". Oncol. Rep. 20 (4): 773–8. doi:10.3892/or_00000073. PMID 18813817. 
  12. ^ "NIH study shows Burkitt lymphoma is molecularly distinct from other lymphomas". National Cancer Institute. 
  13. ^ Staudt L, et al. Burkitt Lymphoma Pathogenesis and Therapeutic Targets from Structural and Functional Genomics. Nature. August 12, 2012 doi:10.1038/nature11378
  14. ^ a b Wyndham H. Wilson, Kieron Dunleavy, Stefania Pittaluga, Upendra Hegde, Nicole Grant, Seth M. Steinberg, Mark Raffeld, Martin Gutierrez, Bruce A. Chabner, Louis Staudt, Elaine S. Jaffe, and John E. Janik (2008). "Phase II Study of Dose-Adjusted EPOCH-Rituximab in Untreated Diffuse Large B-cell Lymphoma with Analysis of Germinal Center and Post-Germinal Center Biomarkers". Journal of Clinical Oncology 26 (16): 2717–2714. doi:10.1200/JCO.2007.13.1391. PMC 2409217. PMID 18378569. 
  15. ^ http://annonc.oxfordjournals.org/content/early/2011/02/21/annonc.mdq677.full.pdf
  16. ^ Yustein JT, Dang CV (2007). "Biology and treatment of Burkitt's lymphoma". Curr. Opin. Hematol. 14 (4): 375–81. doi:10.1097/MOH.0b013e3281bccdee. PMID 17534164.