Burkitt's lymphoma pathophysiology: Difference between revisions

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__NOTOC__
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{{Burkitt's lymphoma}}
{{Burkitt's lymphoma}}
{{CMG}};{{AE}} {{SM}} {{AS}}
{{CMG}};{{AE}} {{SM}} {{AS}}, {{kakbar}}
==Overview==
==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.
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.
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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> 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>
*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>
===MicroRNA expression===
===MicroRNA expression===
*In 2014, it was described that short non-coding RNAs named [[microRNAs]] (miRNAs) have important functions in lymphoma biology  
*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]]<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 influences B cells the following:<ref name="pmid25541152" />
*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]]<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 influences B cells in the following manner:<ref name="pmid25541152" />
**Maturation
**Maturation
**Generation of marginal zone
**Generation of marginal zone
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**Memory B cells
**Memory B cells
===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|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>
The tumor cells in Burkitt lymphoma generally strongly express markers of B cell differentiation and they are the following:<ref name="ChuangYe2007">{{cite journal|last1=Chuang|first1=Shih-Sung|last2=Ye|first2=Hongtao|last3=Du|first3=Ming-Qing|last4=Lu|first4=Chin-Li|last5=Dogan|first5=Ahmet|last6=Hsieh|first6=Pin-Pen|last7=Huang|first7=Wan-Ting|last8=Jung|first8=Yun-Chih|title=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|journal=American Journal of Clinical Pathology|volume=128|issue=4|year=2007|pages=558–564|issn=0002-9173|doi=10.1309/EQJR3D3V0CCQGP04}}</ref>
*([[CD19]]
*[[CD20]]
*[[CD22]])
*[[CD10]]
*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 and there characteristics are the following: <ref name="Ferry2006">{{cite journal|last1=Ferry|first1=J. A.|title=Burkitt's Lymphoma: Clinicopathologic Features and Differential Diagnosis|journal=The Oncologist|volume=11|issue=4|year=2006|pages=375–383|issn=1083-7159|doi=10.1634/theoncologist.11-4-375}}</ref>
*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==
==Gross Pathology==
<gallery heights="175" widths="175">
<gallery heights="175" widths="175">
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==Microscopic Pathology==
==Microscopic Pathology==
* On microscopic histopathological analysis, characteristic findings of Burkitt's lymphoma include:<ref name="pmid12610094">{{cite journal |author=Bellan C, Lazzi S, De Falco G, Nyongo A, Giordano A, Leoncini L |title=Burkitt's lymphoma: new insights into molecular pathogenesis |journal=J. Clin. Pathol. |volume=56 |issue=3 |pages=188–92 |year=2003 |month=March |pmid=12610094 |pmc=1769902 |doi= |url=http://jcp.bmj.com/cgi/pmidlookup?view=long&pmid=12610094}}</ref>
On microscopic histopathological analysis, characteristic findings of Burkitt's lymphoma include:<ref name="pmid12610094">{{cite journal |author=Bellan C, Lazzi S, De Falco G, Nyongo A, Giordano A, Leoncini L |title=Burkitt's lymphoma: new insights into molecular pathogenesis |journal=J. Clin. Pathol. |volume=56 |issue=3 |pages=188–92 |year=2003 |month=March |pmid=12610094 |pmc=1769902 |doi= |url=http://jcp.bmj.com/cgi/pmidlookup?view=long&pmid=12610094}}</ref>
:*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]])
:*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
:*Round nucleus
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[[Image:800px-Burkitt_lymphoma,_touch_prep,_Wright_stain.jpg‎|thumb|none|200px|Burkitt lymphoma, touch prep, wright stain]]


===Video===
===Video===

Latest revision as of 11:23, 19 April 2019

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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], Kamal Akbar, M.D.[4]

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:

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]

  • (CD19
  • CD20
  • CD22)
  • CD10
  • 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.[7]

Malignant B cell characteristics

Malignant B cells have identical DNA recombinations of the V(D)J region of the immunoglobin genes and there characteristics are the following: [8]

  • 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[9]

    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[9]

  • Picture of a mouth of a patient with Burkitt lymphoma showing disruption of teeth and partial obstruction of airway[9]

    Picture of a mouth of a patient with Burkitt lymphoma showing disruption of teeth and partial obstruction of airway[9]

Microscopic Pathology

On microscopic histopathological analysis, characteristic findings of Burkitt's lymphoma include:[10]

  • 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


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References

  1. ↑ Burkitt lymphoma. Radiopedia. http://radiopaedia.org/articles/burkitt-lymphoma Accessed on October,5 2015
  2. ↑ Burkitt's Lymphoma. Wikibooks. https://en.wikibooks.org/wiki/Radiation_Oncology/NHL/Burkitt_lymphoma#Pathology Accessed on October,5 2015
  3. ↑ "NIH study shows Burkitt lymphoma is molecularly distinct from other lymphomas". National Cancer Institute.
  4. ↑ Staudt L, et al. Burkitt Lymphoma Pathogenesis and Therapeutic Targets from Structural and Functional Genomics. Nature. August 12, 2012 doi:10.1038/nature11378
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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. ↑ Ferry, J. A. (2006). "Burkitt's Lymphoma: Clinicopathologic Features and Differential Diagnosis". The Oncologist. 11 (4): 375–383. doi:10.1634/theoncologist.11-4-375. ISSN 1083-7159.
  9. ↑ 9.0 9.1 Burkitt's lymphoma. Wikipedia. https://en.wikipedia.org/wiki/Burkitt%27s_lymphomaAccessed on October 5, 2015
  10. ↑ 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 |month= ignored (help)

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