HAEM5:Chronic lymphocytic leukaemia/small lymphocytic lymphoma - Revision history

Bailey.Glen at 17:12, 3 July 2025

2025-07-03T17:12:19Z

← Older revision		Revision as of 12:12, 3 July 2025
Line 30:		Line 30:
	\|}		\|}

	~~==WHO Essential and Desirable Genetic Diagnostic Criteria==~~
	<span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO book <u>autocompleted</u>; remove any <u>non</u>-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')</span>
	~~{\| class="wikitable"~~
	\|+
	\|WHO Essential Criteria (Genetics)*
	\|
	\|-
	\|WHO Desirable Criteria (Genetics)*
	\|
	\|-
	~~\|Other Classification~~
	\|
	\|}
	<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].
	==Related Terminology==		==Related Terminology==

Bailey.Glen at 21:31, 25 May 2025

2025-05-25T21:31:46Z

← Older revision		Revision as of 16:31, 25 May 2025
Line 157:		Line 157:
	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-
	!Chr #!!~~'''~~Gain, Loss, Amp, LOH~~'''~~!!~~'''~~Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]~~'''~~!!~~'''~~Relevant Gene(s)~~'''~~		!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
	!~~'''~~Diagnostic, Prognostic, and Therapeutic Significance - D, P, T~~'''~~		!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
	!~~'''~~Established Clinical Significance Per Guidelines - Yes or No (Source)~~'''~~		!Established Clinical Significance Per Guidelines - Yes or No (Source)
	!~~'''~~Clinical Relevance Details/Other Notes~~'''~~		!Clinical Relevance Details/Other Notes
	\|-		\|-
	\|<span class="blue-text">EXAMPLE:</span>		\|<span class="blue-text">EXAMPLE:</span>
Line 254:		Line 254:
	!Chromosomal Pattern		!Chromosomal Pattern
	!Molecular Pathogenesis		!Molecular Pathogenesis
	!~~'''~~Prevalence -~~'''~~		!Prevalence -
	~~'''~~Common >20%, Recurrent 5-20% or Rare <5% (Disease)~~'''~~		Common >20%, Recurrent 5-20% or Rare <5% (Disease)
	!~~'''~~Diagnostic, Prognostic, and Therapeutic Significance - D, P, T~~'''~~		!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
	!~~'''~~Established Clinical Significance Per Guidelines - Yes or No (Source)~~'''~~		!Established Clinical Significance Per Guidelines - Yes or No (Source)
	!~~'''~~Clinical Relevance Details/Other Notes~~'''~~		!Clinical Relevance Details/Other Notes
	\|-		\|-
	\|<span class="blue-text">EXAMPLE:</span>		\|<span class="blue-text">EXAMPLE:</span>
Line 335:		Line 335:
	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-
	!Gene!!~~'''~~Genetic Alteration~~'''~~!!~~'''~~Tumor Suppressor Gene, Oncogene, Other~~'''~~!!~~'''~~Prevalence -~~'''~~		!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
	~~'''~~Common >20%, Recurrent 5-20% or Rare <5% (Disease)~~'''~~		Common >20%, Recurrent 5-20% or Rare <5% (Disease)
	!~~'''~~Diagnostic, Prognostic, and Therapeutic Significance - D, P, T ~~'''~~		!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
	!~~'''~~Established Clinical Significance Per Guidelines - Yes or No (Source)~~'''~~		!Established Clinical Significance Per Guidelines - Yes or No (Source)
	!~~'''~~Clinical Relevance Details/Other Notes~~'''~~		!Clinical Relevance Details/Other Notes
	\|-		\|-
	\|<span class="blue-text">EXAMPLE:</span>''EGFR''		\|<span class="blue-text">EXAMPLE:</span>''EGFR''
Line 382:		Line 382:
	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-
	!Gene; Genetic Alteration!!~~'''~~Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)~~'''~~!!~~'''~~Prevalence (COSMIC / TCGA / Other)~~'''~~!!~~'''~~Concomitant Mutations~~'''~~!!~~'''~~Mutually Exclusive Mutations~~'''~~		!Gene; Genetic Alteration!!Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)!!Prevalence (COSMIC / TCGA / Other)!!Concomitant Mutations!!Mutually Exclusive Mutations
	!~~'''~~Diagnostic Significance (Yes, No or Unknown)~~'''~~		!Diagnostic Significance (Yes, No or Unknown)
	!Prognostic Significance (Yes, No or Unknown)		!Prognostic Significance (Yes, No or Unknown)
	!Therapeutic Significance (Yes, No or Unknown)		!Therapeutic Significance (Yes, No or Unknown)

Bailey.Glen at 20:08, 25 May 2025

2025-05-25T20:08:05Z

← Older revision		Revision as of 15:08, 25 May 2025
Line 45:		Line 45:
	<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].		<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].
	==Related Terminology==		==Related Terminology==
	~~<span style="color:#0070C0">(''Instructions: The table will have the related terminology from the WHO <u>autocompleted</u>.)''</span>~~
	{\| class="wikitable"		{\| class="wikitable"
	\|+		\|+
	\|Acceptable		\|Acceptable
	\|		\|B-cell chronic lymphocytic leukaemia / small lymphocytic lymphoma
	\|-		\|-
	\|Not Recommended		\|Not Recommended
	\|		\|N/A
	\|}		\|}

Bailey.Glen at 17:34, 24 March 2025

2025-03-24T17:34:41Z

← Older revision		Revision as of 12:34, 24 March 2025
Line 1:		Line 1:
	{{DISPLAYTITLE:Chronic lymphocytic leukaemia/small lymphocytic lymphoma}}		{{DISPLAYTITLE:Chronic lymphocytic leukaemia/small lymphocytic lymphoma}}

	[[HAEM5:Table_of_Contents\|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]		[[HAEM5:Table_of_Contents\|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]

Line 9:		Line 8:

	Honey Reddi, PhD, Belay Diagnostics		Honey Reddi, PhD, Belay Diagnostics

	~~__TOC__~~

	==WHO Classification of Disease==		==WHO Classification of Disease==

Jennelleh at 13:24, 7 March 2025

2025-03-07T13:24:21Z

Jennelleh at 13:23, 7 March 2025

2025-03-07T13:23:29Z

Show changes

Bailey.Glen: /* Gene Mutations (SNV/INDEL) */

2025-02-13T22:05:45Z

Gene Mutations (SNV/INDEL)

@@ Line 403: / Line 403: @@
 ==Gene Mutations (SNV/INDEL)==
 *IGHV genes are mutated in 50-70% of cases and unmutated in 30-50%.
@@ Line 467: / Line 511: @@
 |}
 Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
 ==Epigenomic Alterations==
 Whole genome methylation studies have identified three epigenetic subgroups of CLL<ref name=":10">{{Cite journal|last=Queirós|first=A. C.|last2=Villamor|first2=N.|last3=Clot|first3=G.|last4=Martinez-Trillos|first4=A.|last5=Kulis|first5=M.|last6=Navarro|first6=A.|last7=Penas|first7=E. M. M.|last8=Jayne|first8=S.|last9=Majid|first9=A.|date=2015-03|title=A B-cell epigenetic signature defines three biologic subgroups of chronic lymphocytic leukemia with clinical impact|url=https://pubmed.ncbi.nlm.nih.gov/25151957|journal=Leukemia|volume=29|issue=3|pages=598–605|doi=10.1038/leu.2014.252|issn=1476-5551|pmid=25151957}}</ref>. These subgroups are related to different stages of B-cell maturation and include naïve B-cell like, intermediate, and memory B-cell like CLL. Naïve B-cell like epigenetic subgroup mainly has unmutated IGHV, whereas the memory B-like subgroup mainly have mutated IGHV genes. The intermediate epigenetic subgroup was also found to have mainly mutated IGHV, however, is associated with a worse prognosis than the memory B-like subgroup. The epigenetic classification was found to be an independent prognostic factor for time to first treatment<ref name=":10" /><ref>{{Cite journal|last=Oakes|first=Christopher C.|last2=Seifert|first2=Marc|last3=Assenov|first3=Yassen|last4=Gu|first4=Lei|last5=Przekopowitz|first5=Martina|last6=Ruppert|first6=Amy S.|last7=Wang|first7=Qi|last8=Imbusch|first8=Charles D.|last9=Serva|first9=Andrius|date=2016-03|title=DNA methylation dynamics during B cell maturation underlie a continuum of disease phenotypes in chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/26780610|journal=Nature Genetics|volume=48|issue=3|pages=253–264|doi=10.1038/ng.3488|issn=1546-1718|pmc=4963005|pmid=26780610}}</ref>.

Bailey.Glen: /* Characteristic Chromosomal or Other Global Mutational Patterns */

2025-02-13T22:05:08Z

Characteristic Chromosomal or Other Global Mutational Patterns

@@ Line 320: / Line 320: @@
 ==Characteristic Chromosomal or Other Global Mutational Patterns==
 Common cytogenetic abnormalities include deletions of 13q, 11q, 6q, and 17p, and trisomy 12. Complex karyotypes (three or more chromosomal abnormalities) are detected in approximately 16% of patients<ref name=":3" /><ref name=":6">{{Cite journal|last=Haferlach|first=C.|last2=Dicker|first2=F.|last3=Schnittger|first3=S.|last4=Kern|first4=W.|last5=Haferlach|first5=T.|date=2007-12|title=Comprehensive genetic characterization of CLL: a study on 506 cases analysed with chromosome banding analysis, interphase FISH, IgV(H) status and immunophenotyping|url=https://pubmed.ncbi.nlm.nih.gov/17805327|journal=Leukemia|volume=21|issue=12|pages=2442–2451|doi=10.1038/sj.leu.2404935|issn=1476-5551|pmid=17805327}}</ref>.
@@ Line 367: / Line 401: @@
 |Patients with a complex karyotype have a shortened overall survival and are associated with 11q and/or 17p deletions<ref name=":6" /><ref>{{Cite journal|last=Jaglowski|first=Samantha M.|last2=Ruppert|first2=Amy S.|last3=Heerema|first3=Nyla A.|last4=Bingman|first4=Anissa|last5=Flynn|first5=Joseph M.|last6=Grever|first6=Michael R.|last7=Jones|first7=Jeffrey A.|last8=Elder|first8=Patrick|last9=Devine|first9=Steven M.|date=2012-10|title=Complex karyotype predicts for inferior outcomes following reduced-intensity conditioning allogeneic transplant for chronic lymphocytic leukaemia|url=https://pubmed.ncbi.nlm.nih.gov/22831395|journal=British Journal of Haematology|volume=159|issue=1|pages=82–87|doi=10.1111/j.1365-2141.2012.09239.x|issn=1365-2141|pmc=3719859|pmid=22831395}}</ref>.
 |}
 ==Gene Mutations (SNV/INDEL)==

Bailey.Glen: /* Individual Region Genomic Gain/Loss/LOH */

2025-02-13T22:04:25Z

Individual Region Genomic Gain/Loss/LOH

@@ Line 225: / Line 225: @@
 ==Individual Region Genomic Gain/Loss/LOH==
 *Approximately 80% of CLL patients have a cytogenetic abnormality detectable by fluorescence ''in situ'' hybridization (FISH)
@@ Line 266: / Line 318: @@
 |Deletion of ''TP53''. Patients with 17p deletion show resistance to genotoxic chemotherapies. ''TP53'' deletion is associated with a poor prognosis<ref name=":5" />.
 |}
 ==Characteristic Chromosomal or Other Global Mutational Patterns==

Bailey.Glen: /* Gene Rearrangements */

2025-02-13T22:03:56Z

Gene Rearrangements

@@ Line 127: / Line 127: @@
 ==Gene Rearrangements==
 Approximately 32-42% of CLL patients are found to have a translocation noted on conventional G-banding cytogenetics<ref name=":3">{{Cite journal|last=Baliakas|first=Panagiotis|last2=Iskas|first2=Michalis|last3=Gardiner|first3=Anne|last4=Davis|first4=Zadie|last5=Plevova|first5=Karla|last6=Nguyen-Khac|first6=Florence|last7=Malcikova|first7=Jitka|last8=Anagnostopoulos|first8=Achilles|last9=Glide|first9=Sharron|date=2014-03|title=Chromosomal translocations and karyotype complexity in chronic lymphocytic leukemia: a systematic reappraisal of classic cytogenetic data|url=https://pubmed.ncbi.nlm.nih.gov/24166834|journal=American Journal of Hematology|volume=89|issue=3|pages=249–255|doi=10.1002/ajh.23618|issn=1096-8652|pmid=24166834}}</ref><ref>{{Cite journal|last=Van Den Neste|first=E.|last2=Robin|first2=V.|last3=Francart|first3=J.|last4=Hagemeijer|first4=A.|last5=Stul|first5=M.|last6=Vandenberghe|first6=P.|last7=Delannoy|first7=A.|last8=Sonet|first8=A.|last9=Deneys|first9=V.|date=2007-08|title=Chromosomal translocations independently predict treatment failure, treatment-free survival and overall survival in B-cell chronic lymphocytic leukemia patients treated with cladribine|url=https://pubmed.ncbi.nlm.nih.gov/17541398|journal=Leukemia|volume=21|issue=8|pages=1715–1722|doi=10.1038/sj.leu.2404764|issn=0887-6924|pmid=17541398}}</ref><ref>{{Cite journal|last=Mayr|first=Christine|last2=Speicher|first2=Michael R.|last3=Kofler|first3=David M.|last4=Buhmann|first4=Raymund|last5=Strehl|first5=John|last6=Busch|first6=Raymonde|last7=Hallek|first7=Michael|last8=Wendtner|first8=Clemens-Martin|date=2006-01-15|title=Chromosomal translocations are associated with poor prognosis in chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/16179374|journal=Blood|volume=107|issue=2|pages=742–751|doi=10.1182/blood-2005-05-2093|issn=0006-4971|pmid=16179374}}</ref>. Balanced translocations involving ''IGH'' are uncommon (4-9% of patients)<ref>{{Cite journal|last=Cavazzini|first=Francesco|last2=Hernandez|first2=Jose Angel|last3=Gozzetti|first3=Alessandro|last4=Russo Rossi|first4=Antonella|last5=De Angeli|first5=Cristiano|last6=Tiseo|first6=Ruana|last7=Bardi|first7=Antonella|last8=Tammiso|first8=Elisa|last9=Crupi|first9=Rosaria|date=2008-08|title=Chromosome 14q32 translocations involving the immunoglobulin heavy chain locus in chronic lymphocytic leukaemia identify a disease subset with poor prognosis|url=https://pubmed.ncbi.nlm.nih.gov/18547320|journal=British Journal of Haematology|volume=142|issue=4|pages=529–537|doi=10.1111/j.1365-2141.2008.07227.x|issn=1365-2141|pmid=18547320}}</ref>.
@@ Line 164: / Line 223: @@
 |Prolymphocytes are detected in most of these cases. MYC translocations are associated with an inferior prognosis<ref>{{Cite journal|last=Put|first=Natalie|last2=Van Roosbroeck|first2=Katrien|last3=Konings|first3=Peter|last4=Meeus|first4=Peter|last5=Brusselmans|first5=Caroline|last6=Rack|first6=Katrina|last7=Gervais|first7=Carine|last8=Nguyen-Khac|first8=Florence|last9=Chapiro|first9=Elise|date=2012-06|title=Chronic lymphocytic leukemia and prolymphocytic leukemia with MYC translocations: a subgroup with an aggressive disease course|url=https://pubmed.ncbi.nlm.nih.gov/22205151|journal=Annals of Hematology|volume=91|issue=6|pages=863–873|doi=10.1007/s00277-011-1393-y|issn=1432-0584|pmid=22205151}}</ref><ref>{{Cite journal|last=Huh|first=Yang O.|last2=Lin|first2=Katherine I.-Chun|last3=Vega|first3=Francisco|last4=Schlette|first4=Ellen|last5=Yin|first5=C. Cameron|last6=Keating|first6=Michael J.|last7=Luthra|first7=R.|last8=Medeiros|first8=L. Jeffrey|last9=Abruzzo|first9=Lynne V.|date=2008-07|title=MYC translocation in chronic lymphocytic leukaemia is associated with increased prolymphocytes and a poor prognosis|url=https://pubmed.ncbi.nlm.nih.gov/18477041|journal=British Journal of Haematology|volume=142|issue=1|pages=36–44|doi=10.1111/j.1365-2141.2008.07152.x|issn=1365-2141|pmid=18477041}}</ref>.
 |}
 ==Individual Region Genomic Gain/Loss/LOH==

← Older revision		Revision as of 08:24, 7 March 2025
Line 477:		Line 477:
	This disease is <u>defined/characterized</u> as detailed below:		This disease is <u>defined/characterized</u> as detailed below:

	* This is a distinct entity in the [https://tumourclassification.iarc.who.int/welcome/ 5th edition World Health Organization (WHO) classification system]. It was also a distinct entity in the 2016 WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues revised 4th edition<ref name=":1">Campo E, et al., (2017). Chronic lymphocytic leukemia/small lymphocytic lymphoma, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. Revised 4th Edition. IARC Press: Lyon, France, p216-221.</ref>. Chronic Lymphocytic Leukemia (CLL) is a chronic lymphoproliferative disorder characterized by monoclonal B cell proliferation. CLL is defined by the presence of >5x10<sup>9</sup>/L monoclonal B-cells in the peripheral blood. Cells are small, mature appearing lymphocytes with light chain restriction by flow cytometry. The term small lymphocytic lymphoma (SLL) is used for cases with <5x10<sup>9</sup>/L circulating monoclonal B-cells and documented nodal, splenic, or other extramedullary involvement<ref name=":2">{{Cite journal\|last=Hallek\|first=Michael\|last2=Cheson\|first2=Bruce D.\|last3=Catovsky\|first3=Daniel\|last4=Caligaris-Cappio\|first4=Federico\|last5=Dighiero\|first5=Guillaume\|last6=Döhner\|first6=Hartmut\|last7=Hillmen\|first7=Peter\|last8=Keating\|first8=Michael J.\|last9=Montserrat\|first9=Emili\|date=2008-06-15\|title=Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines\|url=https://pubmed.ncbi.nlm.nih.gov/18216293\|journal=Blood\|volume=111\|issue=12\|pages=5446–5456\|doi=10.1182/blood-2007-06-093906\|issn=1528-0020\|pmc=2972576\|pmid=18216293}}</ref>.		*This is a distinct entity in the [https://tumourclassification.iarc.who.int/welcome/ 5th edition World Health Organization (WHO) classification system]. It was also a distinct entity in the 2016 WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues revised 4th edition<ref name=":1">Campo E, et al., (2017). Chronic lymphocytic leukemia/small lymphocytic lymphoma, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. Revised 4th Edition. IARC Press: Lyon, France, p216-221.</ref>. Chronic Lymphocytic Leukemia (CLL) is a chronic lymphoproliferative disorder characterized by monoclonal B cell proliferation. CLL is defined by the presence of >5x10<sup>9</sup>/L monoclonal B-cells in the peripheral blood. Cells are small, mature appearing lymphocytes with light chain restriction by flow cytometry. The term small lymphocytic lymphoma (SLL) is used for cases with <5x10<sup>9</sup>/L circulating monoclonal B-cells and documented nodal, splenic, or other extramedullary involvement<ref name=":2">{{Cite journal\|last=Hallek\|first=Michael\|last2=Cheson\|first2=Bruce D.\|last3=Catovsky\|first3=Daniel\|last4=Caligaris-Cappio\|first4=Federico\|last5=Dighiero\|first5=Guillaume\|last6=Döhner\|first6=Hartmut\|last7=Hillmen\|first7=Peter\|last8=Keating\|first8=Michael J.\|last9=Montserrat\|first9=Emili\|date=2008-06-15\|title=Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines\|url=https://pubmed.ncbi.nlm.nih.gov/18216293\|journal=Blood\|volume=111\|issue=12\|pages=5446–5456\|doi=10.1182/blood-2007-06-093906\|issn=1528-0020\|pmc=2972576\|pmid=18216293}}</ref>.

	The <u>epidemiology/prevalence</u> of this disease is detailed below:		The <u>epidemiology/prevalence</u> of this disease is detailed below:

	* CLL is the most common leukemia in the Western world with an annual incidence of approximately 5/100,000, comprising 25% to 30% of all leukemias in the United States. The incidence increases with age with a median age at diagnosis of 70 years. CLL can also present in younger individuals with approximately 10% of cases diagnosed in individuals less than 55 years of age<ref>{{Cite journal\|last=Parikh\|first=Sameer A.\|last2=Rabe\|first2=Kari G.\|last3=Kay\|first3=Neil E.\|last4=Call\|first4=Timothy G.\|last5=Ding\|first5=Wei\|last6=Schwager\|first6=Susan M.\|last7=Bowen\|first7=Deborah A.\|last8=Conte\|first8=Michael\|last9=Jelinek\|first9=Diane F.\|date=2014-01\|title=Chronic lymphocytic leukemia in young (≤ 55 years) patients: a comprehensive analysis of prognostic factors and outcomes\|url=https://pubmed.ncbi.nlm.nih.gov/23911703\|journal=Haematologica\|volume=99\|issue=1\|pages=140–147\|doi=10.3324/haematol.2013.086066\|issn=1592-8721\|pmc=4007929\|pmid=23911703}}</ref>. CLL occurrence is more prevalent in anglo americans and much lower in asian populations<ref name=":0">Taneja A, Master SR. (2017) Cancer, Leukemia, Lymphocytic, Chronic (CLL) SourceStatPearls [I. Treasure Island (FL): StatPearls Publishing. <nowiki>https://www.ncbi.nlm.nih.gov/books/NBK470433/</nowiki>.</ref>.		*CLL is the most common leukemia in the Western world with an annual incidence of approximately 5/100,000, comprising 25% to 30% of all leukemias in the United States. The incidence increases with age with a median age at diagnosis of 70 years. CLL can also present in younger individuals with approximately 10% of cases diagnosed in individuals less than 55 years of age<ref>{{Cite journal\|last=Parikh\|first=Sameer A.\|last2=Rabe\|first2=Kari G.\|last3=Kay\|first3=Neil E.\|last4=Call\|first4=Timothy G.\|last5=Ding\|first5=Wei\|last6=Schwager\|first6=Susan M.\|last7=Bowen\|first7=Deborah A.\|last8=Conte\|first8=Michael\|last9=Jelinek\|first9=Diane F.\|date=2014-01\|title=Chronic lymphocytic leukemia in young (≤ 55 years) patients: a comprehensive analysis of prognostic factors and outcomes\|url=https://pubmed.ncbi.nlm.nih.gov/23911703\|journal=Haematologica\|volume=99\|issue=1\|pages=140–147\|doi=10.3324/haematol.2013.086066\|issn=1592-8721\|pmc=4007929\|pmid=23911703}}</ref>. CLL occurrence is more prevalent in anglo americans and much lower in asian populations<ref name=":0">Taneja A, Master SR. (2017) Cancer, Leukemia, Lymphocytic, Chronic (CLL) SourceStatPearls [I. Treasure Island (FL): StatPearls Publishing. <nowiki>https://www.ncbi.nlm.nih.gov/books/NBK470433/</nowiki>.</ref>.

	The <u>clinical features</u> of this disease are detailed below:		The <u>clinical features</u> of this disease are detailed below:

	* Most (90%) patients with CLL are asymptomatic and are diagnosed based on routine blood tests<ref name=":1" />. Only 5-10% of patients with CLL present with symptoms of fever, weight loss, night sweats, and/or fatigue<ref name=":0" />.		*Most (90%) patients with CLL are asymptomatic and are diagnosed based on routine blood tests<ref name=":1" />. Only 5-10% of patients with CLL present with symptoms of fever, weight loss, night sweats, and/or fatigue<ref name=":0" />.
	* Signs and symptoms - Asymptomatic (incidental finding on complete blood counts); Weight loss, fever, night sweats; Fatigue; Lymphadenopathy, splenomegaly (less common)		*Signs and symptoms - Asymptomatic (incidental finding on complete blood counts); Weight loss, fever, night sweats; Fatigue; Lymphadenopathy, splenomegaly (less common)
	* Laboratory findings - Absolute lymphocytosis' Anemia; Thrombocytopenia; Paraprotein, usually IgM type (~10% of patients) hypogammaglobulinemia (~30% of patients at diagnosis)		*Laboratory findings - Absolute lymphocytosis' Anemia; Thrombocytopenia; Paraprotein, usually IgM type (~10% of patients) hypogammaglobulinemia (~30% of patients at diagnosis)

	The <u>sites of involvement</u> of this disease are detailed below:		The <u>sites of involvement</u> of this disease are detailed below:

	* CLL/SLL involves the blood, bone marrow, and secondary lymphoid tissues such as the spleen, lymph nodes, and Waldeyer ring. Extranodal involvement (e.g. of the skin, gastrointestinal tract, or CNS) occurs in a small subset of cases<ref>{{Cite journal\|last=M\|first=Ratterman\|last2=K\|first2=Kruczek\|last3=S\|first3=Sulo\|last4=Td\|first4=Shanafelt\|last5=Ne\|first5=Kay\|last6=C\|first6=Nabhan\|date=2014\|title=Extramedullary chronic lymphocytic leukemia: systematic analysis of cases reported between 1975 and 2012\|url=https://pubmed.ncbi.nlm.nih.gov/24064196/\|language=en\|pmid=24064196}}</ref>.		*CLL/SLL involves the blood, bone marrow, and secondary lymphoid tissues such as the spleen, lymph nodes, and Waldeyer ring. Extranodal involvement (e.g. of the skin, gastrointestinal tract, or CNS) occurs in a small subset of cases<ref>{{Cite journal\|last=M\|first=Ratterman\|last2=K\|first2=Kruczek\|last3=S\|first3=Sulo\|last4=Td\|first4=Shanafelt\|last5=Ne\|first5=Kay\|last6=C\|first6=Nabhan\|date=2014\|title=Extramedullary chronic lymphocytic leukemia: systematic analysis of cases reported between 1975 and 2012\|url=https://pubmed.ncbi.nlm.nih.gov/24064196/\|language=en\|pmid=24064196}}</ref>.

	The <u>morphologic features</u> of this disease are detailed below:		The <u>morphologic features</u> of this disease are detailed below:

	* Lymph Nodes: Enlarged lymph nodes show diffuse architectural effacement by a proliferation of small lymphocytes with variably prominent scattered paler proliferation centers (pseudofollicles)<ref>Lennert K, editor. (1978). Malignant lymphomas other than Hodgkin’s disease. NewYork: Springer Verlag.</ref>. The predominant cell in the diffuse areas is a ''typical CLL cell'' (small lymphocyte with scant cytoplasm, and clumped chromatin). Proliferation centers are composed of small lymphocytes, prolymphocytes, and paraimmunoblasts. Mitotic activity is usually very low.		*Lymph Nodes: Enlarged lymph nodes show diffuse architectural effacement by a proliferation of small lymphocytes with variably prominent scattered paler proliferation centers (pseudofollicles)<ref>Lennert K, editor. (1978). Malignant lymphomas other than Hodgkin’s disease. NewYork: Springer Verlag.</ref>. The predominant cell in the diffuse areas is a ''typical CLL cell'' (small lymphocyte with scant cytoplasm, and clumped chromatin). Proliferation centers are composed of small lymphocytes, prolymphocytes, and paraimmunoblasts. Mitotic activity is usually very low.
	* Bone Marrow: Biopsy may show interstitial, nodular, mixed (nodular and interstitial), or diffuse involvement. Diffuse involvement is usually associated with more advanced disease<ref>{{Cite journal\|last=E\|first=Montserrat\|last2=N\|first2=Villamor\|last3=Jc\|first3=Reverter\|last4=Rm\|first4=Brugués\|last5=D\|first5=Tàssies\|last6=F\|first6=Bosch\|last7=Jl\|first7=Aguilar\|last8=Jl\|first8=Vives-Corrons\|last9=M\|first9=Rozman\|date=1996\|title=Bone marrow assessment in B-cell chronic lymphocytic leukaemia: aspirate or biopsy? A comparative study in 258 patients\|url=https://pubmed.ncbi.nlm.nih.gov/8611442/\|language=en\|pmid=8611442}}</ref>. Paratrabecular aggregates are not typical. Proliferation centers can be observed, although they are not as prominent as in lymph nodes, and follicular dendritic cells may be present<ref>{{Cite journal\|last=M\|first=Chilosi\|last2=G\|first2=Pizzolo\|last3=F\|first3=Caligaris-Cappio\|last4=A\|first4=Ambrosetti\|last5=F\|first5=Vinante\|last6=L\|first6=Morittu\|last7=F\|first7=Bonetti\|last8=L\|first8=Fiore-Donati\|last9=G\|first9=Janossy\|date=1985\|title=Immunohistochemical demonstration of follicular dendritic cells in bone marrow involvement of B-cell chronic lymphocytic leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/3891066/\|language=en\|pmid=3891066}}</ref>. Most cases have > 30% CLL cells in the bone marrow aspirate<ref name=":2" />.		*Bone Marrow: Biopsy may show interstitial, nodular, mixed (nodular and interstitial), or diffuse involvement. Diffuse involvement is usually associated with more advanced disease<ref>{{Cite journal\|last=E\|first=Montserrat\|last2=N\|first2=Villamor\|last3=Jc\|first3=Reverter\|last4=Rm\|first4=Brugués\|last5=D\|first5=Tàssies\|last6=F\|first6=Bosch\|last7=Jl\|first7=Aguilar\|last8=Jl\|first8=Vives-Corrons\|last9=M\|first9=Rozman\|date=1996\|title=Bone marrow assessment in B-cell chronic lymphocytic leukaemia: aspirate or biopsy? A comparative study in 258 patients\|url=https://pubmed.ncbi.nlm.nih.gov/8611442/\|language=en\|pmid=8611442}}</ref>. Paratrabecular aggregates are not typical. Proliferation centers can be observed, although they are not as prominent as in lymph nodes, and follicular dendritic cells may be present<ref>{{Cite journal\|last=M\|first=Chilosi\|last2=G\|first2=Pizzolo\|last3=F\|first3=Caligaris-Cappio\|last4=A\|first4=Ambrosetti\|last5=F\|first5=Vinante\|last6=L\|first6=Morittu\|last7=F\|first7=Bonetti\|last8=L\|first8=Fiore-Donati\|last9=G\|first9=Janossy\|date=1985\|title=Immunohistochemical demonstration of follicular dendritic cells in bone marrow involvement of B-cell chronic lymphocytic leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/3891066/\|language=en\|pmid=3891066}}</ref>. Most cases have > 30% CLL cells in the bone marrow aspirate<ref name=":2" />.
	* Peripheral Blood: Smudge or basket cells are typically observed. In most cases, besides typical CLL cells, other lymphoid cells like prolymphocytes are also observed, but they usually constitute < 15% of the lymphoid cells.		*Peripheral Blood: Smudge or basket cells are typically observed. In most cases, besides typical CLL cells, other lymphoid cells like prolymphocytes are also observed, but they usually constitute < 15% of the lymphoid cells.

	The <u>immunophenotype</u> of this disease is detailed below:		The <u>immunophenotype</u> of this disease is detailed below:

	* CLL cells express CD19, CD20, CD5, CD23, CD43, CD200, and LEF1<ref>{{Cite journal\|last=Dorfman\|first=David M.\|last2=Shahsafaei\|first2=Aliakbar\|date=2010-11\|title=CD200 (OX-2 membrane glycoprotein) expression in b cell-derived neoplasms\|url=https://pubmed.ncbi.nlm.nih.gov/20959655\|journal=American Journal of Clinical Pathology\|volume=134\|issue=5\|pages=726–733\|doi=10.1309/AJCP38XRRUGSQOVC\|issn=1943-7722\|pmid=20959655}}</ref><ref>{{Cite journal\|last=Matutes\|first=E.\|last2=Owusu-Ankomah\|first2=K.\|last3=Morilla\|first3=R.\|last4=Garcia Marco\|first4=J.\|last5=Houlihan\|first5=A.\|last6=Que\|first6=T. H.\|last7=Catovsky\|first7=D.\|date=1994-10\|title=The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL\|url=https://pubmed.ncbi.nlm.nih.gov/7523797\|journal=Leukemia\|volume=8\|issue=10\|pages=1640–1645\|issn=0887-6924\|pmid=7523797}}</ref>. The levels of surface CD20, surface immunoglobulin and CD79b is low compared to normal B-cells<ref>{{Cite journal\|last=Moreau\|first=E. J.\|last2=Matutes\|first2=E.\|last3=A'Hern\|first3=R. P.\|last4=Morilla\|first4=A. M.\|last5=Morilla\|first5=R. M.\|last6=Owusu-Ankomah\|first6=K. A.\|last7=Seon\|first7=B. K.\|last8=Catovsky\|first8=D.\|date=1997-10\|title=Improvement of the chronic lymphocytic leukemia scoring system with the monoclonal antibody SN8 (CD79b)\|url=https://pubmed.ncbi.nlm.nih.gov/9322589\|journal=American Journal of Clinical Pathology\|volume=108\|issue=4\|pages=378–382\|doi=10.1093/ajcp/108.4.378\|issn=0002-9173\|pmid=9322589}}</ref>. Cells have kappa or lambda restricted Ig light chain expression.		*CLL cells express CD19, CD20, CD5, CD23, CD43, CD200, and LEF1<ref>{{Cite journal\|last=Dorfman\|first=David M.\|last2=Shahsafaei\|first2=Aliakbar\|date=2010-11\|title=CD200 (OX-2 membrane glycoprotein) expression in b cell-derived neoplasms\|url=https://pubmed.ncbi.nlm.nih.gov/20959655\|journal=American Journal of Clinical Pathology\|volume=134\|issue=5\|pages=726–733\|doi=10.1309/AJCP38XRRUGSQOVC\|issn=1943-7722\|pmid=20959655}}</ref><ref>{{Cite journal\|last=Matutes\|first=E.\|last2=Owusu-Ankomah\|first2=K.\|last3=Morilla\|first3=R.\|last4=Garcia Marco\|first4=J.\|last5=Houlihan\|first5=A.\|last6=Que\|first6=T. H.\|last7=Catovsky\|first7=D.\|date=1994-10\|title=The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL\|url=https://pubmed.ncbi.nlm.nih.gov/7523797\|journal=Leukemia\|volume=8\|issue=10\|pages=1640–1645\|issn=0887-6924\|pmid=7523797}}</ref>. The levels of surface CD20, surface immunoglobulin and CD79b is low compared to normal B-cells<ref>{{Cite journal\|last=Moreau\|first=E. J.\|last2=Matutes\|first2=E.\|last3=A'Hern\|first3=R. P.\|last4=Morilla\|first4=A. M.\|last5=Morilla\|first5=R. M.\|last6=Owusu-Ankomah\|first6=K. A.\|last7=Seon\|first7=B. K.\|last8=Catovsky\|first8=D.\|date=1997-10\|title=Improvement of the chronic lymphocytic leukemia scoring system with the monoclonal antibody SN8 (CD79b)\|url=https://pubmed.ncbi.nlm.nih.gov/9322589\|journal=American Journal of Clinical Pathology\|volume=108\|issue=4\|pages=378–382\|doi=10.1093/ajcp/108.4.378\|issn=0002-9173\|pmid=9322589}}</ref>. Cells have kappa or lambda restricted Ig light chain expression.

	Positive (universal) - CD5, CD43 and strongly positive for CD23 and CD200		Positive (universal) - CD5, CD43 and strongly positive for CD23 and CD200
Line 507:		Line 507:
	Negative (universal) - CD10 is negative, FMC7 is usually negative or only weakly expressed.		Negative (universal) - CD10 is negative, FMC7 is usually negative or only weakly expressed.

	Subset - ~~CD5―~~ or ~~CD23―~~, FMC7+, strong surface immunoglobulin, or CD79b+<ref>{{Cite journal\|last=A\|first=Criel\|last2=L\|first2=Michaux\|last3=C\|first3=De Wolf-Peeters\|date=1999\|title=The concept of typical and atypical chronic lymphocytic leukaemia\|url=https://pubmed.ncbi.nlm.nih.gov/10194119/\|language=en\|pmid=10194119}}</ref>		Subset - CD5- or CD23-, FMC7+, strong surface immunoglobulin, or CD79b+<ref>{{Cite journal\|last=A\|first=Criel\|last2=L\|first2=Michaux\|last3=C\|first3=De Wolf-Peeters\|date=1999\|title=The concept of typical and atypical chronic lymphocytic leukaemia\|url=https://pubmed.ncbi.nlm.nih.gov/10194119/\|language=en\|pmid=10194119}}</ref>

	==Links==		==Links==