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==Overview== | |||
Chronic lymphocytic leukemia arises from pre-follicular center [[B cell]]s, that are normally involved in the process of human [[immunoglobulin]]s production. Development of chronic lymphocytic leukemia is the result of multiple [[genetic mutation]]s that promote both [[malignant]] leukemic proliferation and [[apoptotic]] resistance of mature B cells. Structural [[genetic mutation]]s involved in the pathogenesis of chronic lymphocytic leukemia include [[chromosome]] 13q deletion, chromosome 17p deletion, and chromosome 11q deletion. On [[microscopic]] [[histopathological]] analysis characteristic findings of chronic lymphocytic leukemia include small lymphoid cells, thin [[cytoplasmic]] border, lack of [[nucleoli]], and presence of smudge cells.<ref name="wiki">Chronic Lymphocytic Leukemia (2015) https://en.wikipedia.org/wiki/B-cell_chronic_lymphocytic_leukemia Accessed on October 12, 2015</ref><ref name="pmid25461996">{{cite journal| author=Nabhan C, Rosen ST| title=Chronic lymphocytic leukemia: a clinical review. | journal=JAMA | year= 2014 | volume= 312 | issue= 21 | pages= 2265-76 | pmid=25461996 | doi=10.1001/jama.2014.14553 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25461996 }} </ref><ref name="pmid25908509">{{cite journal| author=Hallek M| title=Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment. | journal=Am J Hematol | year= 2015 | volume= 90 | issue= 5 | pages= 446-60 | pmid=25908509 | doi=10.1002/ajh.23979 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25908509 }} </ref><ref name="patho">Chronic Lymphocytic Leukemia. Libre Pathology (2015) http://librepathology.org/wiki/index.php/B_cell_small_lymphocytic_lymphoma/chronic_lymphocytic_leukemia Accessed on October, 12 2015</ref> | |||
==Pathogenesis== | ==Pathogenesis== | ||
* Chronic lymphocytic leukemia arises from pre-follicular center B | * Chronic lymphocytic leukemia arises from pre-follicular center [[B cell]]s, that are normally involved in the process of human [[immunoglobulin]]s production. | ||
* Malignant lymphocytic cells infiltrate hematopoietic sites such as the bone marrow where they interfere with the production of | * [[Malignant]] lymphocytic cells infiltrate [[hematopoietic]] sites such as the [[bone marrow]] where they interfere with the production of [[red blood cell]]s. | ||
* Chronic lymphocytic leukemia may also infiltrate the lymph | * Chronic lymphocytic leukemia may also infiltrate the [[lymph node]]s, [[spleen]], and [[liver]].<ref name="wiki">Chronic Lymphocytic Leukemia (2015) https://en.wikipedia.org/wiki/B-cell_chronic_lymphocytic_leukemia Accessed on October 12, 2015</ref> | ||
* Immune deficiency may occur in chronic lymphocytic leukemia as the majority of cases develop hypogammaglobulinemia.<ref name="pmid25461996">{{cite journal| author=Nabhan C, Rosen ST| title=Chronic lymphocytic leukemia: a clinical review. | journal=JAMA | year= 2014 | volume= 312 | issue= 21 | pages= 2265-76 | pmid=25461996 | doi=10.1001/jama.2014.14553 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25461996 }} </ref> | * [[Immune deficiency]] may occur in chronic lymphocytic leukemia as the majority of cases develop [[hypogammaglobulinemia]].<ref name="pmid25461996">{{cite journal| author=Nabhan C, Rosen ST| title=Chronic lymphocytic leukemia: a clinical review. | journal=JAMA | year= 2014 | volume= 312 | issue= 21 | pages= 2265-76 | pmid=25461996 | doi=10.1001/jama.2014.14553 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25461996 }} </ref> | ||
* Warm autoimmune hemolytic anemia may develop due to the production of IgA and IgG autoantibodies among certain cases of chronic lymphocytic anemia. | * [[Warm autoimmune hemolytic anemia]] may develop due to the production of [[IgA]] and [[IgG]] [[autoantibodies]] among certain cases of chronic lymphocytic anemia. | ||
* Richter's transformation may occur among 1-5% of chronic lymphocytic leukemia cases.<ref name="wiki">Chronic Lymphocytic Leukemia (2015) https://en.wikipedia.org/wiki/B-cell_chronic_lymphocytic_leukemia Accessed on October 12, 2015</ref> | * [[Richter's transformation]] may occur among 1-5% of chronic lymphocytic leukemia cases.<ref name="wiki">Chronic Lymphocytic Leukemia (2015) https://en.wikipedia.org/wiki/B-cell_chronic_lymphocytic_leukemia Accessed on October 12, 2015</ref> | ||
* Richter's transformation represents the conversion of chronic lymphocytic leukemia into a more aggressive, rapidly growing large B cell lymphoma. | * Richter's transformation represents the conversion of chronic lymphocytic leukemia into a more aggressive, rapidly growing [[large B cell lymphoma]]. | ||
==Genetics== | ==Genetics== | ||
* Development of chronic lymphocytic leukemia is the result of multiple genetic | * Development of chronic lymphocytic leukemia is the result of multiple [[genetic mutation]]s that promote both [[malignant]] leukemic proliferation and [[apoptotic]] resistance of mature [[B cell]]s.<ref name="pmid25908509">{{cite journal| author=Hallek M| title=Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment. | journal=Am J Hematol | year= 2015 | volume= 90 | issue= 5 | pages= 446-60 | pmid=25908509 | doi=10.1002/ajh.23979 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25908509 }} </ref> | ||
* Structural | * Structural [[genetic mutations]] involved in the pathogenesis of chronic lymphocytic leukemia include:<ref name="wiki">Chronic Lymphocytic Leukemia (2015) https://en.wikipedia.org/wiki/B-cell_chronic_lymphocytic_leukemia Accessed on October 12, 2015</ref><ref name="pmid25908509">{{cite journal| author=Hallek M| title=Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment. | journal=Am J Hematol | year= 2015 | volume= 90 | issue= 5 | pages= 446-60 | pmid=25908509 | doi=10.1002/ajh.23979 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25908509 }} </ref> | ||
:* Chromosome | :* [[Chromosome 13]] long arm deletion (most common genetic mutation) | ||
:* Chromosome | :* [[Chromosome 17]] short arm deletion | ||
:* Chromosome | :* [[Chromosome 11]] long arm deletion | ||
:* Trisomy 12 | :* Trisomy 12 | ||
* Somatic gene mutations involved in the pathogenesis of chronic lymphocytic leukemia include:<ref name="pmid25908509">{{cite journal| author=Hallek M| title=Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment. | journal=Am J Hematol | year= 2015 | volume= 90 | issue= 5 | pages= 446-60 | pmid=25908509 | doi=10.1002/ajh.23979 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25908509 }} </ref> | * Somatic gene mutations involved in the pathogenesis of chronic lymphocytic leukemia include:<ref name="pmid25908509">{{cite journal| author=Hallek M| title=Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment. | journal=Am J Hematol | year= 2015 | volume= 90 | issue= 5 | pages= 446-60 | pmid=25908509 | doi=10.1002/ajh.23979 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25908509 }} </ref> | ||
:* NOTCH1 gene located on chromosome 9 | :* NOTCH1 gene located on [[chromosome 9]] | ||
:* MYD88 gene located on chromosome 3 | :* MYD88 gene located on [[chromosome 3]] | ||
:* TP53 gene located on chromosome 7 | :* TP53 gene located on [[chromosome 7]] | ||
:* ATM gene located on chromosome 11 | :* ATM gene located on [[chromosome 11]] | ||
:* SF3B1 gene located on chromosome 2 | :* SF3B1 gene located on [[chromosome 2]] | ||
:* FBXW7 gene located on chromosome 4 | :* FBXW7 gene located on [[chromosome 4]] | ||
:* CHD2 gene located on chromosome 15 | :* CHD2 gene located on [[chromosome 15]] | ||
* Production of | * Production of [[cytokine]]s, [[angiogenic]] factors, and [[chemokine]]s by the surrounding [[macrophage]]s and [[T cell]]s provide important stimuli for the [[malignant]] [[B cell]]s proliferation in chronic lymphocytic leukemia. | ||
==Microscopic Pathology== | ==Microscopic Pathology== | ||
* On microscopic histopathological analysis characteristic findings of chronic lymphocytic leukemia include:<ref name="pmid25461996">{{cite journal| author=Nabhan C, Rosen ST| title=Chronic lymphocytic leukemia: a clinical review. | journal=JAMA | year= 2014 | volume= 312 | issue= 21 | pages= 2265-76 | pmid=25461996 | doi=10.1001/jama.2014.14553 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25461996 }} </ref><ref name="pmid25908509">{{cite journal| author=Hallek M| title=Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment. | journal=Am J Hematol | year= 2015 | volume= 90 | issue= 5 | pages= 446-60 | pmid=25908509 | doi=10.1002/ajh.23979 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25908509 }} </ref> | * On microscopic histopathological analysis characteristic findings of chronic lymphocytic leukemia include:<ref name="pmid25461996">{{cite journal| author=Nabhan C, Rosen ST| title=Chronic lymphocytic leukemia: a clinical review. | journal=JAMA | year= 2014 | volume= 312 | issue= 21 | pages= 2265-76 | pmid=25461996 | doi=10.1001/jama.2014.14553 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25461996 }} </ref><ref name="pmid25908509">{{cite journal| author=Hallek M| title=Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment. | journal=Am J Hematol | year= 2015 | volume= 90 | issue= 5 | pages= 446-60 | pmid=25908509 | doi=10.1002/ajh.23979 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25908509 }} </ref> | ||
:* Small lymphoid | :* Small [[lymphoid]] [[cell]]s | ||
:* | :* Thin [[cytoplasmic]] border | ||
:* Dense nucleus | :* Dense [[nucleus]] | ||
:* Lack of nucleoli | :* Lack of [[nucleoli]] | ||
:* Clumped chromatin aggregates | :* Clumped [[chromatin]] aggregates | ||
:* Smudge cells | :* Smudge cells | ||
:* Gumprecht nuclear shadows | :* Gumprecht nuclear shadows | ||
* On Immunohistochemistry characteristic findings of chronic lymphocytic leukemia include:<ref name="patho">Chronic Lymphocytic Leukemia. Libre Pathology (2015) http://librepathology.org/wiki/index.php/B_cell_small_lymphocytic_lymphoma/chronic_lymphocytic_leukemia Accessed on October, 12 2015</ref> | * On Immunohistochemistry characteristic findings of chronic lymphocytic leukemia include:<ref name="patho">Chronic Lymphocytic Leukemia. Libre Pathology (2015) http://librepathology.org/wiki/index.php/B_cell_small_lymphocytic_lymphoma/chronic_lymphocytic_leukemia Accessed on October, 12 2015</ref> | ||
:* CD5 +ve | :* [[CD5]] +ve | ||
:* | :* [[CD19]] +ve | ||
:* CD20 +ve | :* [[CD20]] +ve | ||
:* CD23 +ve/-ve | :* [[CD23]] +ve/-ve | ||
:* CD43 +ve | :* [[CD43]] +ve | ||
:* Cyclin D1 -ve | :* [[Cyclin D1]] -ve | ||
:* CD38 -ve/+ve | :* [[CD38]] -ve/+ve | ||
* Shown below is a series of microscopic images seen in multiple myeloma: | * Shown below is a series of microscopic images seen in multiple myeloma: | ||
<gallery> | <gallery> | ||
Latest revision as of 18:19, 13 October 2015
Overview
Chronic lymphocytic leukemia arises from pre-follicular center B cells, that are normally involved in the process of human immunoglobulins production. Development of chronic lymphocytic leukemia is the result of multiple genetic mutations that promote both malignant leukemic proliferation and apoptotic resistance of mature B cells. Structural genetic mutations involved in the pathogenesis of chronic lymphocytic leukemia include chromosome 13q deletion, chromosome 17p deletion, and chromosome 11q deletion. On microscopic histopathological analysis characteristic findings of chronic lymphocytic leukemia include small lymphoid cells, thin cytoplasmic border, lack of nucleoli, and presence of smudge cells.[1][2][3][4]
Pathogenesis
- Chronic lymphocytic leukemia arises from pre-follicular center B cells, that are normally involved in the process of human immunoglobulins production.
- Malignant lymphocytic cells infiltrate hematopoietic sites such as the bone marrow where they interfere with the production of red blood cells.
- Chronic lymphocytic leukemia may also infiltrate the lymph nodes, spleen, and liver.[1]
- Immune deficiency may occur in chronic lymphocytic leukemia as the majority of cases develop hypogammaglobulinemia.[2]
- Warm autoimmune hemolytic anemia may develop due to the production of IgA and IgG autoantibodies among certain cases of chronic lymphocytic anemia.
- Richter's transformation may occur among 1-5% of chronic lymphocytic leukemia cases.[1]
- Richter's transformation represents the conversion of chronic lymphocytic leukemia into a more aggressive, rapidly growing large B cell lymphoma.
Genetics
- Development of chronic lymphocytic leukemia is the result of multiple genetic mutations that promote both malignant leukemic proliferation and apoptotic resistance of mature B cells.[3]
- Structural genetic mutations involved in the pathogenesis of chronic lymphocytic leukemia include:[1][3]
- Chromosome 13 long arm deletion (most common genetic mutation)
- Chromosome 17 short arm deletion
- Chromosome 11 long arm deletion
- Trisomy 12
- Somatic gene mutations involved in the pathogenesis of chronic lymphocytic leukemia include:[3]
- NOTCH1 gene located on chromosome 9
- MYD88 gene located on chromosome 3
- TP53 gene located on chromosome 7
- ATM gene located on chromosome 11
- SF3B1 gene located on chromosome 2
- FBXW7 gene located on chromosome 4
- CHD2 gene located on chromosome 15
- Production of cytokines, angiogenic factors, and chemokines by the surrounding macrophages and T cells provide important stimuli for the malignant B cells proliferation in chronic lymphocytic leukemia.
Microscopic Pathology
- On microscopic histopathological analysis characteristic findings of chronic lymphocytic leukemia include:[2][3]
- On Immunohistochemistry characteristic findings of chronic lymphocytic leukemia include:[4]
- Shown below is a series of microscopic images seen in multiple myeloma:
-
![Chronic lymphocytic leukemia demonstrated on low magnification[4]](/images/9/9b/Chronic_lymphocytic_leukemia_-_low_mag.jpg)
Chronic lymphocytic leukemia demonstrated on low magnification[4]
-
![Chronic lymphocytic leukemia demonstrated on intermediate magnification[4]](/images/5/55/Chronic_lymphocytic_leukemia_-_intermed_mag.jpg)
Chronic lymphocytic leukemia demonstrated on intermediate magnification[4]
-
![Chronic lymphocytic leukemia demonstrated on high magnification[4]](/images/2/24/Chronic_lymphocytic_leukemia_-_high_mag.jpg)
Chronic lymphocytic leukemia demonstrated on high magnification[4]
-
![Chronic lymphocytic leukemia demonstrated on very high magnification[4]](/images/7/77/Chronic_lymphocytic_leukemia_-_very_high_mag.jpg)
Chronic lymphocytic leukemia demonstrated on very high magnification[4]
![Chronic lymphocytic leukemia demonstrated on low magnification[4]](/index.php/File:Chronic_lymphocytic_leukemia_-_low_mag.jpg)
![Chronic lymphocytic leukemia demonstrated on intermediate magnification[4]](/index.php/File:Chronic_lymphocytic_leukemia_-_intermed_mag.jpg)
![Chronic lymphocytic leukemia demonstrated on high magnification[4]](/index.php/File:Chronic_lymphocytic_leukemia_-_high_mag.jpg)
![Chronic lymphocytic leukemia demonstrated on very high magnification[4]](/index.php/File:Chronic_lymphocytic_leukemia_-_very_high_mag.jpg)
- ↑ 1.0 1.1 1.2 1.3 Chronic Lymphocytic Leukemia (2015) https://en.wikipedia.org/wiki/B-cell_chronic_lymphocytic_leukemia Accessed on October 12, 2015
- ↑ 2.0 2.1 2.2 Nabhan C, Rosen ST (2014). "Chronic lymphocytic leukemia: a clinical review". JAMA. 312 (21): 2265–76. doi:10.1001/jama.2014.14553. PMID 25461996.
- ↑ 3.0 3.1 3.2 3.3 3.4 Hallek M (2015). "Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment". Am J Hematol. 90 (5): 446–60. doi:10.1002/ajh.23979. PMID 25908509.
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 Chronic Lymphocytic Leukemia. Libre Pathology (2015) http://librepathology.org/wiki/index.php/B_cell_small_lymphocytic_lymphoma/chronic_lymphocytic_leukemia Accessed on October, 12 2015