Burkitt's lymphoma pathophysiology: Difference between revisions
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In 2014, it was described that short non-coding RNAs named [[microRNAs]] (miRNAs) have important functions in lymphoma biology. In malignant B cells miRNAs participate in pathways fundamental to B cell development like B cell receptor (BCR) signalling, B cell migration/adhesion, cell-cell interactions in immune niches, and the production and class-switching of [[immunoglobulins]].<ref name="pmid25541152">{{Cite journal | pmid = 25541152| year = 2014| author1 = Musilova| first1 = K| title = MicroRNAs in B cell lymphomas: How a complex biology gets more complex| journal = Leukemia| last2 = Mraz| first2 = M| doi = 10.1038/leu.2014.351}}</ref> MiRNAs influence B cell maturation, generation of marginal zone, follicular, plasma, and memory B cells.<ref name="pmid25541152"/> | In 2014, it was described that short non-coding RNAs named [[microRNAs]] (miRNAs) have important functions in lymphoma biology. In malignant B cells miRNAs participate in pathways fundamental to B cell development like B cell receptor (BCR) signalling, B cell migration/adhesion, cell-cell interactions in immune niches, and the production and class-switching of [[immunoglobulins]].<ref name="pmid25541152">{{Cite journal | pmid = 25541152| year = 2014| author1 = Musilova| first1 = K| title = MicroRNAs in B cell lymphomas: How a complex biology gets more complex| journal = Leukemia| last2 = Mraz| first2 = M| doi = 10.1038/leu.2014.351}}</ref> MiRNAs influence B cell maturation, generation of marginal zone, follicular, plasma, and memory B cells.<ref name="pmid25541152"/> | ||
===Immunohistochemistry=== | ===Immunohistochemistry=== | ||
The tumor cells in Burkitt lymphoma generally strongly express markers of B cell differentiation ([[CD19]], [[CD20]], [[CD22]]), [[CD10]], and BCL6. The tumor cells are generally negative for BCL2 and TdT. The high [[mitotic]] activity of Burkitt's lymphoma is confirmed by nearly 100% of the cells staining positive for Ki67.<ref>{{cite book | isbn=978-92-832-2431-0}}</ref> | The tumor cells in Burkitt lymphoma generally strongly express markers of B cell differentiation ([[CD19]], [[CD20]], [[CD22]]), [[CD10]], and BCL6. The tumor cells are generally negative for BCL2 and TdT. The high [[mitotic]] activity of Burkitt's lymphoma is confirmed by nearly 100% of the cells staining positive for Ki67.<ref>{{cite book | isbn=978-92-832-2431-0|title=WHO classification of tumours of haematopoietic and lymphoid tissues|year=2008|author= Steven H Swerdlow|publisher= Lyon, France : International Agency for Research on Cancer|series=World Health Organization classification of tumours}}</ref> | ||
===Malignant B cell characteristics=== | ===Malignant B cell characteristics=== | ||
Malignant B cells have identical [[DNA]] recombinations of the V(D)J region of the [[immunoglobin]] genes. This means that no increase in specificity of [[antibody]] molecules is occurring in the malignant cells. These malignant cells are thus clonal populations and can be assayed for by using [[DNA]] probes specific for the regions where recombination is expected. Normal DNA will be characterized by two high concentration of identical germ line DNA V(D)J regions and endless, likely undetectable, non-germline Ig V(D)J DNA. Lymphoma cells have an additional high concentration of V(D)J DNA that is unlike the germ line, indicating clonal populations of B Cells that are not undifferentiated B cells (germ line DNA cells). Assays typically use the process of [[electrophoresis]] and [[southern blot]] analysis to determine the existence of these characteristics. | Malignant B cells have identical [[DNA]] recombinations of the V(D)J region of the [[immunoglobin]] genes. This means that no increase in specificity of [[antibody]] molecules is occurring in the malignant cells. These malignant cells are thus clonal populations and can be assayed for by using [[DNA]] probes specific for the regions where recombination is expected. Normal DNA will be characterized by two high concentration of identical germ line DNA V(D)J regions and endless, likely undetectable, non-germline Ig V(D)J DNA. Lymphoma cells have an additional high concentration of V(D)J DNA that is unlike the germ line, indicating clonal populations of B Cells that are not undifferentiated B cells (germ line DNA cells). Assays typically use the process of [[electrophoresis]] and [[southern blot]] analysis to determine the existence of these characteristics. | ||
Revision as of 18:50, 8 October 2015
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Burkitt's lymphoma Microchapters |
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Burkitt's lymphoma pathophysiology On the Web |
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Risk calculators and risk factors for Burkitt's lymphoma pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Shivali Marketkar, M.B.B.S. [2] Sowminya Arikapudi, M.B,B.S. [3]
Overview
The c-myc gene is involved in the pathogenesis of Burkitt's lymphoma. On gross pathology, ulceration and discharge are characteristic findings of Burkitt's lymphoma. On microscopic histopathological analysis, "starry sky" appearance is a characteristic finding of Burkitt's lymphoma.
Pathology
Burkitt's lymphoma is an aggressive and rapidly growing tumor.[1] It can present in a wide variety of locations which include:
- Head and neck (facial bones and Waldeyer's ring)
- Pleural space (~70%)
- Gastrointestinal tract, especially ileocaecal region
- Mesentery, peritoneum, and retroperitoneum
- Kidneys
- Gonads (~75%)
Genetics
Translocation of chromosome 8 myc locus with 3 possible partners (accounting for 90% of translocations):[2]
- The Ig heavy chain region on chromosome 14: t(8;14)
- The kappa light chain locus on chromosome 2: t(2;8)
- The lambda light chain locus on chromosome 22: t(8;22)
- WHO committees suggest the following:
- If morphologic features are intermediate, diagnosis of Burkitt's should only be made if the Ki-67 fraction of viable cells is at least 99 percent
- If morphologic features suggest diffuse large B cell lymphoma, but have with a high proliferation fraction or t(8;14), they should be classified as diffuse large B cell lymphoma
Gene targets
Unique genetic alterations promote cell survival in Burkitt's lymphoma, distinct from other types of lymphoma.[3] These TCF3 and ID3 gene mutations in Burkitt's correspond to a cell survival pathway that may be found to be amenable to targeted therapy.[4]
MicroRNA expression
In 2014, it was described that short non-coding RNAs named microRNAs (miRNAs) have important functions in lymphoma biology. In malignant B cells miRNAs participate in pathways fundamental to B cell development like B cell receptor (BCR) signalling, B cell migration/adhesion, cell-cell interactions in immune niches, and the production and class-switching of immunoglobulins.[5] MiRNAs influence B cell maturation, generation of marginal zone, follicular, plasma, and memory B cells.[5]
Immunohistochemistry
The tumor cells in Burkitt lymphoma generally strongly express markers of B cell differentiation (CD19, CD20, CD22), CD10, and BCL6. The tumor cells are generally negative for BCL2 and TdT. The high mitotic activity of Burkitt's lymphoma is confirmed by nearly 100% of the cells staining positive for Ki67.[6]
Malignant B cell characteristics
Malignant B cells have identical DNA recombinations of the V(D)J region of the immunoglobin genes. This means that no increase in specificity of antibody molecules is occurring in the malignant cells. These malignant cells are thus clonal populations and can be assayed for by using DNA probes specific for the regions where recombination is expected. Normal DNA will be characterized by two high concentration of identical germ line DNA V(D)J regions and endless, likely undetectable, non-germline Ig V(D)J DNA. Lymphoma cells have an additional high concentration of V(D)J DNA that is unlike the germ line, indicating clonal populations of B Cells that are not undifferentiated B cells (germ line DNA cells). Assays typically use the process of electrophoresis and southern blot analysis to determine the existence of these characteristics.
Gross Pathology
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Burkitt lymphoma: bilateral eye involvement
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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
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Picture of a mouth of a patient with Burkitt lymphoma showing disruption of teeth and partial obstruction of airway
Microscopic Pathology
- On microscopic histopathological analysis, characteristic findings of Burkitt's lymphoma include:
- "Starry-sky pattern":
- The stars in the pattern are tingible-body macrophages (macrophages containing apoptotic tumor cells)
- The tumour cells are the sky
- Histological characteristics of tumor cells include:[7]
- Medium-sized (~1.5-2x the size of a RBC) with uniform size ("monotonous") -- key feature (i.e. tumor nuclei size similar to that of histiocytes or endothelial cells)
- Round nucleus
- Small nucleoli
- Relatively abundant cytoplasm (basophilic)
- Brisk mitotic rate and apoptotic activity
- Cellular outline usually appears squared off
Video
{{#ev:youtube|CwsQ-wIbbK8}}
References
- ↑ Burkitt lymphoma. Radiopedia. http://radiopaedia.org/articles/burkitt-lymphoma Accessed on October,5 2015
- ↑ Burkitt's Lymphoma. Wikibooks. https://en.wikibooks.org/wiki/Radiation_Oncology/NHL/Burkitt_lymphoma#Pathology Accessed on October,5 2015
- ↑ "NIH study shows Burkitt lymphoma is molecularly distinct from other lymphomas". National Cancer Institute.
- ↑ Staudt L, et al. Burkitt Lymphoma Pathogenesis and Therapeutic Targets from Structural and Functional Genomics. Nature. August 12, 2012 doi:10.1038/nature11378
- ↑ 5.0 5.1 Musilova, K; Mraz, M (2014). "MicroRNAs in B cell lymphomas: How a complex biology gets more complex". Leukemia. doi:10.1038/leu.2014.351. PMID 25541152.
- ↑ Steven H Swerdlow (2008). WHO classification of tumours of haematopoietic and lymphoid tissues. World Health Organization classification of tumours. Lyon, France : International Agency for Research on Cancer. ISBN 978-92-832-2431-0.
- ↑ Bellan C, Lazzi S, De Falco G, Nyongo A, Giordano A, Leoncini L (2003). "Burkitt's lymphoma: new insights into molecular pathogenesis". J. Clin. Pathol. 56 (3): 188–92. PMC 1769902. PMID 12610094. Unknown parameter
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