Compendium of Cancer Genome Aberrations

HAEM5:Chronic lymphocytic leukaemia/small lymphocytic lymphoma: Difference between revisions

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{{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 (5th ed.)]]


==Primary Author(s)*==
==Primary Author(s)*==
Line 9: Line 8:


Honey Reddi, PhD, Belay Diagnostics
Honey Reddi, PhD, Belay Diagnostics
==WHO Classification of Disease==


__TOC__
{| class="wikitable"
!Structure
!Disease
|-
|Book
|Haematolymphoid Tumours (5th ed.)
|-
|Category
|B-cell lymphoid proliferations and lymphomas
|-
|Family
|Mature B-cell neoplasms
|-
|Type
|Pre-neoplastic and neoplastic small lymphocytic proliferations
|-
|Subtype(s)
|Chronic lymphocytic leukaemia/small lymphocytic lymphoma
|}


==Cancer Category/Type==
==Related Terminology==


Mature B-cell neoplasms
==Cancer Sub-Classification / Subtype==
Chronic lymphocytic leukemia/small lymphocytic lymphoma
==Definition / Description of Disease==
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>.     
==Synonyms / Terminology==
Chronic lymphocytic leukemia, B-cell type; chronic lymphoid leukemia; chronic lymphatic leukemia
==Epidemiology / Prevalence==
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>.
==Clinical Features==
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" />.
{| class="wikitable"
{| class="wikitable"
|'''Signs and Symptoms'''
|+
|Asymptomatic (incidental finding on complete blood counts)
|Acceptable
 
|B-cell chronic lymphocytic leukaemia / small lymphocytic lymphoma
Weight loss, fever, night sweats
 
Fatigue
 
Lymphadenopathy, splenomegaly (less common)
|-
|-
|'''Laboratory Findings'''
|Not Recommended
|absolute lymphocytosis
|N/A
anemia
 
thrombocytopenia
 
paraprotein, usually IgM type (~10% of patients)
hypogammaglobulinemia (~30% of patients at diagnosis)
|}
|}


==Sites of Involvement==
==Gene Rearrangements==
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>.
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
 
==Morphologic Features==
 
'''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" />.
 
'''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.  
 
==Immunophenotype==
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.
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Finding!!Marker
!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|-
|Positive (universal)||CD5, CD43 and strongly positive
|<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)
|<span class="blue-text">EXAMPLE:</span> Common (CML)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
|<span class="blue-text">EXAMPLE:</span>
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). BCR::ABL1 is generally favorable in CML (add reference).
|-
|<span class="blue-text">EXAMPLE:</span> ''CIC''
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
|<span class="blue-text">EXAMPLE:</span> D
|
|<span class="blue-text">EXAMPLE:</span>


for CD23 and CD200
''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
|-
|-
|Negative (universal)||CD10 is negative
|<span class="blue-text">EXAMPLE:</span> ''ALK''
FMC7 is usually negative or
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''


only weakly expressed.
|-
|Subset||CD5― or CD23―, FMC7+,


strong surface immunoglobulin, or
Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
|<span class="blue-text">EXAMPLE:</span> T
|
|<span class="blue-text">EXAMPLE:</span>


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>
Both balanced and unbalanced forms are observed by FISH (add references).
|-
|<span class="blue-text">EXAMPLE:</span> ''ABL1''
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|
|-
|
|
|
|
|
|
|
|
|}
|}
==Chromosomal Rearrangements (Gene Fusions)==


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>.
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 125: Line 138:
|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>.
|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==
==Individual Region Genomic Gain/Loss/LOH==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
{| class="wikitable sortable"
|-
!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
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|<span class="blue-text">EXAMPLE:</span>
7
|<span class="blue-text">EXAMPLE:</span> Loss
|<span class="blue-text">EXAMPLE:</span>
chr7
|<span class="blue-text">EXAMPLE:</span>
Unknown
|<span class="blue-text">EXAMPLE:</span> D, P
|<span class="blue-text">EXAMPLE:</span> No
|<span class="blue-text">EXAMPLE:</span>
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add references).
|-
|<span class="blue-text">EXAMPLE:</span>
8
|<span class="blue-text">EXAMPLE:</span> Gain
|<span class="blue-text">EXAMPLE:</span>
chr8
|<span class="blue-text">EXAMPLE:</span>
Unknown
|<span class="blue-text">EXAMPLE:</span> D, P
|
|<span class="blue-text">EXAMPLE:</span>
Common recurrent secondary finding for t(8;21) (add references).
|-
|<span class="blue-text">EXAMPLE:</span>
17
|<span class="blue-text">EXAMPLE:</span> Amp
|<span class="blue-text">EXAMPLE:</span>
17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
|<span class="blue-text">EXAMPLE:</span>
''ERBB2''
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|<span class="blue-text">EXAMPLE:</span>
Amplification of ''ERBB2'' is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.
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*Approximately 80% of CLL patients have a cytogenetic abnormality detectable by fluorescence ''in situ'' hybridization (FISH)
*Approximately 80% of CLL patients have a cytogenetic abnormality detectable by fluorescence ''in situ'' hybridization (FISH)
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|Deletion of ''TP53''. Patients with 17p deletion show resistance to genotoxic chemotherapies. ''TP53'' deletion is associated with a poor prognosis<ref name=":5" />.
|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 Patterns==
 
==Characteristic Chromosomal or Other Global Mutational Patterns==
Put your text here and fill in the table <span style="color:#0070C0">(I''nstructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
{| class="wikitable sortable"
|-
!Chromosomal Pattern
!Molecular Pathogenesis
!Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|<span class="blue-text">EXAMPLE:</span>
Co-deletion of 1p and 18q
|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
|<span class="blue-text">EXAMPLE:</span> D, P
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|<span class="blue-text">EXAMPLE:</span>
Microsatellite instability - hypermutated
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|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
|<span class="blue-text">EXAMPLE:</span> P, T
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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>.
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>.
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|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>.
|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>.
|}
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==Gene Mutations (SNV/INDEL)==
==Gene Mutations (SNV/INDEL)==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
{| class="wikitable sortable"
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!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
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|<span class="blue-text">EXAMPLE:</span>''EGFR''
<br />
|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
|<span class="blue-text">EXAMPLE:</span> Oncogene
|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
|<span class="blue-text">EXAMPLE:</span> T
|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
|<span class="blue-text">EXAMPLE:</span> Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
|-
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
<br />
|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
|<span class="blue-text">EXAMPLE:</span> P
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|<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
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|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
|<span class="blue-text">EXAMPLE:</span> Activating mutations
|<span class="blue-text">EXAMPLE:</span> Oncogene
|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
|<span class="blue-text">EXAMPLE:</span> T
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|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.


*IGHV genes are mutated in 50-70% of cases and unmutated in 30-50%.
*IGHV genes are mutated in 50-70% of cases and unmutated in 30-50%.
Line 222: Line 368:
{| class="wikitable sortable"
{| class="wikitable sortable"
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!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)
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|}
|}
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.
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==
==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>.
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>.
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==Additional Information==
==Additional Information==


Not Applicable
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>.
 
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>.
 
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" />.
*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)
 
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>.
 
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.
*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.
 
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.
 
Positive (universal) - CD5, CD43 and strongly positive for CD23 and CD200
 
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>


==Links==
==Links==
Retrieved from "https://test.ccga.io/index.php/HAEM5:Chronic_lymphocytic_leukaemia/small_lymphocytic_lymphoma"