Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
editPREVIOUS EDITIONThis page from the 4th edition of Haematolymphoid Tumours is being updated. See 5th edition Table of Contents.
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Primary Author(s)*
Jamie Nagy, PhD, University of Iowa
Honey Reddi, PhD
Cancer Category/Type
Mature B-cell neoplasms
Cancer Sub-Classification / Subtype
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Definition / Description of Disease
This is a distinct entity in the 2016 World Health Organization (WHO) classification system[1]. Chronic Lymphocytic Leukemia (CLL) is a chronic lymphoproliferative disorder characterized by monoclonal B cell proliferation.
CLL Tables - A list of clinically significant and/or recurrent CNAs and CN-LOH with potential or strong diagnostic, prognostic and treatment implications in CLL. Table derived from Chun et al., 2018 [[2]] with permission from Cancer Genetics. See CLL Tables: Regions of Recurrent Copy Number Change and CN-LOH.
Synonyms / Terminology
Chronic lymphocytic leukaemia, B―cell type; chronic lymphoid leukaemia; chronic lymphatic leukaemia
Epidemiology / Prevalence
It is the most common adult leukemia in Western populations, comprising 25% to 30% of all leukemias in the United States. The median age at diagnosis is 70 years. CLL occurrence is more prevalent in anglo americans and much lower in asian populations[3].
Clinical Features
Most (90%) patients with CLL are asymptomatic and only 5-10% of patients with CLL present with symptoms of fever, weight loss, night sweats, and/or fatigue[3].
Sites of Involvement
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[4].
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)[5]. 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[6]. 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[7]. Most cases have > 30% CLL cells in the bone marrow aspirate[8].
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
Circulating leukemic B cells express CD19, low surface IgM/lgD, CD20, CD22, and CD79b. Additionally the markers below may be strongly expressed or absent.
| Finding | Marker |
|---|---|
| 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+[9] |
Chromosomal Rearrangements (Gene Fusions)
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| Chromosomal Rearrangement | Genes in Fusion (5’ or 3’ Segments) | Pathogenic Derivative | Prevalence |
|---|---|---|---|
| EXAMPLE t(9;22)(q34;q11.2) | EXAMPLE 3'ABL1 / 5'BCR | EXAMPLE der(22) | EXAMPLE 5% |
| EXAMPLE t(8;21)(q22;q22) | EXAMPLE 5'RUNX1 / 3'RUNXT1 | EXAMPLE der(8) | EXAMPLE 5% |
Characteristic Chromosomal Aberrations / Patterns
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Genomic Gain/Loss/LOH
| Chromosome Number | Gain/Loss/Amp/LOH | Region |
|---|---|---|
| EXAMPLE 8 | EXAMPLE Gain | EXAMPLE chr8:0-1000000 |
| EXAMPLE 7 | EXAMPLE Loss | EXAMPLE chr7:0-1000000 |
Put your text here and/or fill in the table
CLL Tables - A list of clinically significant and/or recurrent CNAs and CN-LOH with potential or strong diagnostic, prognostic and treatment implications in CLL. Table derived from Chun et al., 2018 [PMID 30554732] with permission from Cancer Genetics. See CLL Tables: Regions of Recurrent Copy Number Change and CN-LOH.
Gene Mutations (SNV/INDEL)
Prevalence (COSMIC, May 2018) NOTCH1 12% SF3B1 12% ATM 12% TP53 11% NFKBIE 4% XPO1 4% BTK 4% MED12 3% BIRC3 3% MYD88 3% LRP1b 3% POT1 3% BRAF 2% FAT1 2%
| Gene | Mutation | Oncogene/Tumor Suppressor/Other | Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) | Prevalence (COSMIC/TCGA/Other) |
|---|---|---|---|---|
| EXAMPLE TP53 | EXAMPLE R273H | EXAMPLE Tumor Suppressor | EXAMPLE LOF | EXAMPLE 20% |
Other Mutations
| Type | Gene/Region/Other |
|---|---|
| Concomitant Mutations | EXAMPLE IDH1 R123H |
| Secondary Mutations | EXAMPLE Trisomy 7 |
| Mutually Exclusive | EXAMPLE EGFR Amplification |
Epigenomics (Methylation)
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Genes and Main Pathways Involved
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Diagnostic Testing Methods
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Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)
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Familial Forms
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Other Information
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Links
References
- ↑ 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.
- ↑ K, Chun; et al. (2018). "Assessing copy number aberrations and copy-neutral loss-of-heterozygosity across the genome as best practice: An evidence-based review from the Cancer Genomics Consortium (CGC) working group for chronic lymphocytic leukemia". PMID 30554732.
- ↑ 3.0 3.1 Taneja A, Master SR. (2017) Cancer, Leukemia, Lymphocytic, Chronic (CLL) SourceStatPearls [I. Treasure Island (FL): StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK470433/.
- ↑ M, Ratterman; et al. (2014). "Extramedullary chronic lymphocytic leukemia: systematic analysis of cases reported between 1975 and 2012". PMID 24064196.
- ↑ Lennert K, editor. (1978). Malignant lymphomas other than Hodgkin’s disease. NewYork: Springer Verlag.
- ↑ E, Montserrat; et al. (1996). "Bone marrow assessment in B-cell chronic lymphocytic leukaemia: aspirate or biopsy? A comparative study in 258 patients". PMID 8611442.
- ↑ M, Chilosi; et al. (1985). "Immunohistochemical demonstration of follicular dendritic cells in bone marrow involvement of B-cell chronic lymphocytic leukemia". PMID 3891066.
- ↑ M, Hallek; et al. (2008). "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". doi:10.1182/blood-2007-06-093906. PMC 2972576. PMID 18216293.CS1 maint: PMC format (link)
- ↑ A, Criel; et al. (1999). "The concept of typical and atypical chronic lymphocytic leukaemia". PMID 10194119.
Notes
*Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.
*The hierarchical tumour classification structure displayed on this page is reproduced from the WHO Classification of Tumours with permission from the copyright holder, ©International Agency for Research on Cancer.