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 (WHO Classification, 5th ed.)]] | ||
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Honey Reddi, PhD, Belay Diagnostics | Honey Reddi, PhD, Belay Diagnostics | ||
==WHO Classification of Disease== | ==WHO Classification of Disease== | ||
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|} | |} | ||
== | ==Related Terminology== | ||
{| class="wikitable" | {| class="wikitable" | ||
|+ | |+ | ||
|Acceptable | |Acceptable | ||
| | |B-cell chronic lymphocytic leukaemia / small lymphocytic lymphoma | ||
|- | |- | ||
|Not Recommended | |Not Recommended | ||
| | |N/A | ||
|} | |} | ||
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{| class="wikitable sortable" | {| class="wikitable sortable" | ||
|- | |- | ||
!Chr #!! | !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> | |<span class="blue-text">EXAMPLE:</span> | ||
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!Chromosomal Pattern | !Chromosomal Pattern | ||
!Molecular Pathogenesis | !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> | |<span class="blue-text">EXAMPLE:</span> | ||
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{| class="wikitable sortable" | {| class="wikitable sortable" | ||
|- | |- | ||
!Gene!! | !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 | ||
|- | |- | ||
|<span class="blue-text">EXAMPLE:</span>''EGFR'' | |<span class="blue-text">EXAMPLE:</span>''EGFR'' | ||
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{| class="wikitable sortable" | {| class="wikitable sortable" | ||
|- | |- | ||
!Gene; Genetic Alteration!! | !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) | ||
!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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==Additional Information== | ==Additional Information== | ||
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== | ||