Burkitt's lymphoma pathophysiology: Difference between revisions
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Translocation of chromosome 8 <i>[[myc]]</i> locus with 3 possible partners (accounting for 90% of translocations):<ref>Burkitt's Lymphoma. Wikibooks. https://en.wikibooks.org/wiki/Radiation_Oncology/NHL/Burkitt_lymphoma#Pathology Accessed on October,5 2015</ref> | Translocation of chromosome 8 <i>[[myc]]</i> locus with 3 possible partners (accounting for 90% of translocations):<ref>Burkitt's Lymphoma. Wikibooks. https://en.wikibooks.org/wiki/Radiation_Oncology/NHL/Burkitt_lymphoma#Pathology Accessed on October,5 2015</ref> | ||
*The Ig heavy chain region on chromosome 14: t(8;14) | *The Ig heavy chain region on chromosome 14: t(8;14) | ||
*The kappa light chain locus on chromosome 2: t(2;8) | *The [[Light chain|kappa light chain]] locus on chromosome 2: t(2;8) | ||
*The lambda light chain locus on chromosome 22: t(8;22) | *The [[Light chain|lambda light chain]] locus on chromosome 22: t(8;22) | ||
*WHO committees suggest the following: | *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 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]] | :*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=== | ===Gene targets=== | ||
*Unique genetic alterations promote cell survival in Burkitt's lymphoma, distinct from other types of lymphoma<ref>{{cite web|title=NIH study shows Burkitt lymphoma is molecularly distinct from other lymphomas|url=http://cancer.gov/newscenter/newsfromnci/2012/BurkittReleaseStaudt|publisher=National Cancer Institute}}</ref> | *Unique genetic alterations promote cell survival in Burkitt's lymphoma, distinct from other types of [[lymphoma]]<ref>{{cite web|title=NIH study shows Burkitt lymphoma is molecularly distinct from other lymphomas|url=http://cancer.gov/newscenter/newsfromnci/2012/BurkittReleaseStaudt|publisher=National Cancer Institute}}</ref> | ||
*These ''TCF3'' and ''[[ID3 (gene)|ID3]]'' gene mutations in Burkitt's correspond to a cell survival pathway that may be found to be amenable to [[targeted therapy]].<ref>Staudt L, et al. Burkitt Lymphoma Pathogenesis and Therapeutic Targets from Structural and Functional Genomics. Nature. August 12, 2012 {{DOI|10.1038/nature11378}}</ref> | *These ''TCF3'' and ''[[ID3 (gene)|ID3]]'' gene mutations in Burkitt's correspond to a cell survival pathway that may be found to be amenable to [[targeted therapy]].<ref>Staudt L, et al. Burkitt Lymphoma Pathogenesis and Therapeutic Targets from Structural and Functional Genomics. Nature. August 12, 2012 {{DOI|10.1038/nature11378}}</ref> | ||
===MicroRNA expression=== | ===MicroRNA expression=== | ||
Revision as of 15:05, 9 January 2019
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Burkitt's lymphoma Microchapters |
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Diagnosis |
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Treatment |
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Case Studies |
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Burkitt's lymphoma pathophysiology On the Web |
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American Roentgen Ray Society Images of Burkitt's lymphoma pathophysiology |
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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) signaling, B cell migration/adhesion, cell-cell interactions in immune niches, and the production and class-switching of immunoglobulins[5]
- MiRNAs influences B cells in the following manner:[5]
- Maturation
- Generation of marginal zone
- Follicular
- Plasma
- Memory B cells
Immunohistochemistry
- The tumor cells in Burkitt lymphoma generally strongly express markers of B cell differentiation and they are the following:[6]
- 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.[7]
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
-
![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[8]](/images/3/3c/Large_facial_Burkitt%27s_Lymphoma.JPG)
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[8]
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![Picture of a mouth of a patient with Burkitt lymphoma showing disruption of teeth and partial obstruction of airway[8]](/images/7/7b/Burkitt%27s_lymphoma02.jpg)
Picture of a mouth of a patient with Burkitt lymphoma showing disruption of teeth and partial obstruction of airway[8]
![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[8]](/index.php/File:Large_facial_Burkitt%27s_Lymphoma.JPG)
![Picture of a mouth of a patient with Burkitt lymphoma showing disruption of teeth and partial obstruction of airway[8]](/index.php/File:Burkitt%27s_lymphoma02.jpg)
Microscopic Pathology
- On microscopic histopathological analysis, characteristic findings of Burkitt's lymphoma include:[9]
- 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
- "Starry-sky pattern":
- The stars in the pattern are tingible-body macrophages (macrophages containing apoptotic tumor cells)
- The tumour cells are the sky
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.
- ↑ Chuang, Shih-Sung; Ye, Hongtao; Du, Ming-Qing; Lu, Chin-Li; Dogan, Ahmet; Hsieh, Pin-Pen; Huang, Wan-Ting; Jung, Yun-Chih (2007). "Histopathology and Immunohistochemistry in Distinguishing Burkitt Lymphoma From Diffuse Large B-Cell Lymphoma With Very High Proliferation Index and With or Without a Starry-Sky Pattern". American Journal of Clinical Pathology. 128 (4): 558–564. doi:10.1309/EQJR3D3V0CCQGP04. ISSN 0002-9173.
- ↑ 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.
- ↑ 8.0 8.1 Burkitt's lymphoma. Wikipedia. https://en.wikipedia.org/wiki/Burkitt%27s_lymphomaAccessed on October 5, 2015
- ↑ 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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