Chronic lymphocytic leukaemia/small lymphocytic lymphoma

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Haematolymphoid Tumours (5th ed.)

editHAEM5 Conversion Notes
This page was converted to the new template on 2023-12-04. The original page can be found at HAEM4:Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

Primary Author(s)*

Jamie Nagy, PhD, University of Iowa

Honey Reddi, PhD

Cancer Category / Type

Mature B-cell neoplasms

Cancer Sub-Classification / Subtype

Put your text here

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

Put your text here and fill in the table (Instruction: Can include references in the table)

Signs and Symptoms EXAMPLE Asymptomatic (incidental finding on complete blood counts)

EXAMPLE B-symptoms (weight loss, fever, night sweats)

EXAMPLE Fatigue

EXAMPLE Lymphadenopathy (uncommon)

Laboratory Findings EXAMPLE Cytopenias

EXAMPLE Lymphocytosis (low level)


editv4:Clinical Features
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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 Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE t(9;22)(q34;q11.2) EXAMPLE 3'ABL1 / 5'BCR EXAMPLE der(22) EXAMPLE 20% (COSMIC)

EXAMPLE 30% (add reference)

Yes No Yes EXAMPLE

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).

Individual Region Genomic Gain / Loss / LOH

Put your text here and fill in the table (Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.)

Chr # Gain / Loss / Amp / LOH Minimal Region Genomic Coordinates [Genome Build] Minimal Region Cytoband Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE

7

EXAMPLE Loss EXAMPLE

chr7:1- 159,335,973 [hg38]

EXAMPLE

chr7

Yes Yes No EXAMPLE

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 reference).

EXAMPLE

8

EXAMPLE Gain EXAMPLE

chr8:1-145,138,636 [hg38]

EXAMPLE

chr8

No No No EXAMPLE

Common recurrent secondary finding for t(8;21) (add reference).

editv4:Genomic Gain/Loss/LOH
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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.

Characteristic Chromosomal Patterns

Put your text here (EXAMPLE PATTERNS: 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)

Chromosomal Pattern Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE

Co-deletion of 1p and 18q

Yes No No EXAMPLE:

See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

Gene Mutations (SNV / INDEL)

Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references 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.)

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) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE: TP53; Variable LOF mutations

EXAMPLE:

EGFR; Exon 20 mutations

EXAMPLE: BRAF; Activating mutations

EXAMPLE: TSG EXAMPLE: 20% (COSMIC)

EXAMPLE: 30% (add Reference)

EXAMPLE: IDH1 R123H EXAMPLE: EGFR amplification EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).


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.


editv4:Gene Mutations (SNV/INDEL)
The content below was from the old template. Please incorporate above.

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

Epigenomic Alterations

Put your text here

Genes and Main Pathways Involved

Put your text here and fill in the table (Instructions: Can include references in the table.)

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
EXAMPLE: BRAF and MAP2K1; Activating mutations EXAMPLE: MAPK signaling EXAMPLE: Increased cell growth and proliferation
EXAMPLE: CDKN2A; Inactivating mutations EXAMPLE: Cell cycle regulation EXAMPLE: Unregulated cell division
EXAMPLE:  KMT2C and ARID1A; Inactivating mutations EXAMPLE:  Histone modification, chromatin remodeling EXAMPLE:  Abnormal gene expression program

Genetic Diagnostic Testing Methods

Put your text here

Familial Forms

Put your text here (Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.)

Additional Information

Put your text here

Links

HAEM5:Monoclonal B-cell lymphocytosis

References

(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference.)

  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.
  2. 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. 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/.
  4. M, Ratterman; et al. (2014). "Extramedullary chronic lymphocytic leukemia: systematic analysis of cases reported between 1975 and 2012". PMID 24064196.
  5. Lennert K, editor. (1978). Malignant lymphomas other than Hodgkin’s disease. NewYork: Springer Verlag.
  6. 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.
  7. M, Chilosi; et al. (1985). "Immunohistochemical demonstration of follicular dendritic cells in bone marrow involvement of B-cell chronic lymphocytic leukemia". PMID 3891066.
  8. 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)
  9. 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.

*Citation of this Page: “Chronic lymphocytic leukaemia/small lymphocytic lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 12/4/2023, https://ccga.io/index.php/HAEM5:Chronic_lymphocytic_leukaemia/small_lymphocytic_lymphoma.