Difference between revisions of "HAEM4:Hairy Cell Leukemia Variant"
Jump to navigation
Jump to search
Bailey.Glen (talk | contribs) (Created page with "==Primary Author(s)*== *Snehal Patel, MD, PhD __TOC__ ==Cancer Category/Type== *Splenic B-cell Lymphoma/Leukemia, Unclassifiable ==Cancer Sub-Classification / Subtype=...") |
Bailey.Glen (talk | contribs) |
||
| (One intermediate revision by the same user not shown) | |||
| Line 1: | Line 1: | ||
| + | {{DISPLAYTITLE:Hairy Cell Leukemia Variant}} | ||
| + | |||
| + | |||
| + | <blockquote class='blockedit'>{{Box-round|title=PREVIOUS EDITION|This page from the 4th edition of Haematolymphoid Tumours is being updated. See 5th edition [[HAEM5:Table_of_Contents|Table of Contents]]. | ||
| + | }}</blockquote> | ||
==Primary Author(s)*== | ==Primary Author(s)*== | ||
| Line 6: | Line 11: | ||
==Cancer Category/Type== | ==Cancer Category/Type== | ||
| − | *[[Splenic B-cell Lymphoma/Leukemia, Unclassifiable]] | + | *[[HAEM4:Splenic B-cell Lymphoma/Leukemia, Unclassifiable]] |
==Cancer Sub-Classification / Subtype== | ==Cancer Sub-Classification / Subtype== | ||
| Line 15: | Line 20: | ||
*HCLv is a rare chronic neoplasm of B-cell origin seen mostly in adults | *HCLv is a rare chronic neoplasm of B-cell origin seen mostly in adults | ||
| − | *Name derives from clinicopathologic similarity to [[Hairy | + | *Name derives from clinicopathologic similarity to [[HAEM5:Hairy cell leukaemia|hairy cell leukemia]] (HCL) but with important differences |
*Marked splenomegaly and marrow infiltration result in left flank discomfort, fatigue, and susceptibility to infections | *Marked splenomegaly and marrow infiltration result in left flank discomfort, fatigue, and susceptibility to infections | ||
*Most respond poorly to monotherapy with a purine analog or interferon alpha (used for HCL) | *Most respond poorly to monotherapy with a purine analog or interferon alpha (used for HCL) | ||
| Line 74: | Line 79: | ||
|Positive||CD11c, CD72, CD103 | |Positive||CD11c, CD72, CD103 | ||
|- | |- | ||
| − | |Negative ([[Hairy | + | |Negative ([[HAEM5:Hairy cell leukaemia|HCL]] markers)||CD25, CD123, annexin A1, TRAP, BRAF V600E |
|- | |- | ||
|Negative | |Negative | ||
| Line 219: | Line 224: | ||
==Links== | ==Links== | ||
| − | *[[Hairy | + | *[[HAEM5:Hairy cell leukaemia]] |
| − | *[[Splenic | + | *[[HAEM5:Splenic diffuse red pulp small B-cell lymphoma]] |
==References== | ==References== | ||
| Line 231: | Line 236: | ||
==Notes== | ==Notes== | ||
<nowiki>*</nowiki>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. | <nowiki>*</nowiki>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. | ||
| + | [[Category:HAEM4]] [[Category:DISEASE]] | ||
Latest revision as of 16:33, 4 December 2023
editPREVIOUS EDITIONThis page from the 4th edition of Haematolymphoid Tumours is being updated. See 5th edition Table of Contents.
Primary Author(s)*
- Snehal Patel, MD, PhD
Cancer Category/Type
Cancer Sub-Classification / Subtype
- Hairy Cell Leukemia Variant (HCLv)
Definition / Description of Disease
- HCLv is a rare chronic neoplasm of B-cell origin seen mostly in adults
- Name derives from clinicopathologic similarity to hairy cell leukemia (HCL) but with important differences
- Marked splenomegaly and marrow infiltration result in left flank discomfort, fatigue, and susceptibility to infections
- Most respond poorly to monotherapy with a purine analog or interferon alpha (used for HCL)
- Lack BRAF p.Val600Glu (V600E) mutations but some have mutations in MAP2K1
Synonyms / Terminology
- Prolymphocytic variant of hairy cell leukemia
Epidemiology / Prevalence
- ~0.2% of lymphoid leukemias
- Median age: 70 years
- Males:Females: 2:1
Clinical Features[1][2]
Signs & Symptoms
- Often asymptomatic
- Splenic enlargement and/or discomfort
- B-symptoms (weight loss, fever, night sweats)
- Fatigue
- Bruising
- Lymphadenopathy (uncommon)
Laboratory findings
- Cytopenias
- Lymphocytosis
- No monocytopenia
Sites of Involvement[1][2]
- Spleen (red pulp)
- Bone marrow
- Blood
- Liver
- Lymph node (uncommon)
Morphologic Features[1][2]
- Intermediate-sized lymphoid cells
- Abundant pale blue-grey lacey cytoplasm
- prolymphocytoid or blastoid nuclear features
- Cytoplasmic projections either villous or hair-like
- "Fried egg" appearance of cells (tissue sections)
- Interstitial pattern of marrow involvement
- No/minimal reticulin fibrosis
Immunophenotype[1][2]
| Finding | Marker |
|---|---|
| Positive (B-cell lineage markers) | CD19, CD20 (bright), CD22, CD79b, PAX5, FMC7, sIg (bright, monotypic) |
| Positive | CD11c, CD72, CD103 |
| Negative (HCL markers) | CD25, CD123, annexin A1, TRAP, BRAF V600E |
| Negative | CD5, CD10, CD23, CD38, CD43, BCL1 |
Chromosomal Rearrangements (Gene Fusions)
- No consistent gene fusions
Characteristic Chromosomal Aberrations / Patterns
- Preferential utilization of IGHV4-34 (Immunoglobulin heavy chain variable segment) in 40%[3] and has clinical implications[4]
Genomic Gain/Loss/LOH
| Chromosome Number | Gain/Loss/Amp/LOH | Consequence | Prevalence |
|---|---|---|---|
| 17p13 | Loss | TP53 deletion | 42%[1] |
| 11q22 | Loss | ATM deletion | 22%[1] |
Gene Mutations (SNV/INDEL)
| Gene* | Oncogene/Tumor Suppressor/Other | Presumed Mechanism (LOF/GOF/Other) | Prevalence |
|---|---|---|---|
| MAP2K1 | Oncogene | GOF | 7-50%[1][5][6][7][8] |
| TP53 | Tumor Suppressor | LOF | 29%[7] - 38%[6] |
| KMT2C | Tumor Suppressor | LOF | 25%[6] |
| KDM6A | Tumor Suppressor | LOF | 13%[6] - 50%[8] |
| ARID1A | Tumor Suppressor | LOF | 13%[6] - 25%[8] |
| CREBBP | Tumor Suppressor | LOF | 13%[6] - 25%[8] |
| CCND3 | Oncogene | change of function | 13%[6] |
| U2AF | Oncogene | change of function | 13%[6] |
‡Specific mutations in these genes can be found in cBioPortal and COSMIC.
- There is wide variation in the reported prevalence of MAP2K1 mutations across studies for unclear reasons
Epigenomics (Methylation)
- Epigenetic dysregulation is expected in a subset of HCLv due to mutations in epigenetic regulators:
- KMT2C is a histone methyltransferase
- KDM6A is a histone demethylase
- CREBBP is a histone acetyltransferase
- ARID1A is a SWI/SNF family member
Genes and Main Pathways Involved
| Molecular feature | Pathway | Physiologic outcome |
|---|---|---|
| MAP2K1 activating mutations | MAPK signaling | Unregulated cell growth and proliferation |
| KMT2C, KDM6A, CREBBP, and ARID1A LOF mutations | Histone modification, chromatin remodeling | Abnormal gene expression program |
| TP53 LOF mutations | DNA damage, apoptosis | Cell survival and genomic instability |
Diagnostic Testing Methods
- HCLv is a provisional entity and definitive diagnostic criteria have not been determined
- BRAF p.Val600Glu testing may be useful diagnostically in limited situations to exclude HCL
- BRAF p.Val600Glu may be detected by IHC using a mutant-specific antibody[9][10] or various molecular methods (NGS, real-time PCR, massARRAY, etc.)
- The mutant-specific antibody does not detect other BRAF mutations
- BRAF p.Val600Glu and Non-p.Val600Glu mutations and MAP2K1 mutations can be interrogated with NGS in a single assay[2]
- IGHV4-34 utilization can be detected by NGS and Sanger sequencing of IgH mRNA
Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)
| Alteration | Clinical Significance | Note |
|---|---|---|
| BRAF activating mutations | Diagnostic | Excludes HCL |
| MAP2K1 activating mutations | Prediction | May be targetable with MEK inhibitors[11] |
| IGHV4-34 | Prediction | Reduced response to purine analogs[4] |
| IGHV4-34 | Prognostic | Less favorable prognosis[4] |
- The 2017 WHO notes that whether cases that are classified as classical HCL but lack BRAF mutations and harbor MAP2K1 mutations are more like HCLv remains to be established
Familial Forms
- Not described
Other Information
- N/A
Links
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Angelova, Evgeniya A.; et al. (2018). "Clinicopathologic and molecular features in hairy cell leukemia-variant: single institutional experience". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 31 (11): 1717–1732. doi:10.1038/s41379-018-0093-8. ISSN 1530-0285. PMID 29955146.
- ↑ 2.0 2.1 2.2 2.3 2.4 Maitre, Elsa; et al. (2019). "Hairy cell leukemia: 2020 update on diagnosis, risk stratification, and treatment". American Journal of Hematology. 94 (12): 1413–1422. doi:10.1002/ajh.25653. ISSN 0361-8609.
- ↑ Xi, Liqiang; et al. (2012). "Both variant and IGHV4-34–expressing hairy cell leukemia lack the BRAF V600E mutation". Blood. 119 (14): 3330–3332. doi:10.1182/blood-2011-09-379339. ISSN 0006-4971. PMC 3321859. PMID 22210875.CS1 maint: PMC format (link)
- ↑ 4.0 4.1 4.2 Arons, Evgeny; et al. (2009). "VH4-34+ hairy cell leukemia, a new variant with poor prognosis despite standard therapy". Blood. 114 (21): 4687–4695. doi:10.1182/blood-2009-01-201731. ISSN 0006-4971. PMC 2780305. PMID 19745070.CS1 maint: PMC format (link)
- ↑ Mason, Emily F.; et al. (2017). "Detection of activating MAP2K1 mutations in atypical hairy cell leukemia and hairy cell leukemia variant". Leukemia & Lymphoma. 58 (1): 233–236. doi:10.1080/10428194.2016.1185786. ISSN 1029-2403. PMID 27241017.
- ↑ 6.0 6.1 6.2 6.3 6.4 6.5 6.6 6.7 Durham, Benjamin H.; et al. (2017). "Genomic analysis of hairy cell leukemia identifies novel recurrent genetic alterations". Blood. 130 (14): 1644–1648. doi:10.1182/blood-2017-01-765107. ISSN 1528-0020. PMC 5630011. PMID 28801450.
- ↑ 7.0 7.1 Waterfall, Joshua J.; et al. (2014). "High prevalence of MAP2K1 mutations in variant and IGHV4-34-expressing hairy-cell leukemias". Nature Genetics. 46 (1): 8–10. doi:10.1038/ng.2828. ISSN 1546-1718. PMC 3905739. PMID 24241536.
- ↑ 8.0 8.1 8.2 8.3 Maitre, Elsa; et al. (2018). "New generation sequencing of targeted genes in the classical and the variant form of hairy cell leukemia highlights mutations in epigenetic regulation genes". Oncotarget. 9 (48): 28866–28876. doi:10.18632/oncotarget.25601. ISSN 1949-2553. PMC 6034755. PMID 29989027.
- ↑ Ritterhouse, Lauren L.; et al. (2015). "BRAF V600E mutation-specific antibody: A review". Seminars in Diagnostic Pathology. 32 (5): 400–408. doi:10.1053/j.semdp.2015.02.010.
- ↑ Loo, Eric; et al. (2017). "BRAF V600E Mutation Across Multiple Tumor Types: Correlation Between DNA-based Sequencing and Mutation-specific Immunohistochemistry". Applied Immunohistochemistry & Molecular Morphology: 1. doi:10.1097/PAI.0000000000000516. ISSN 1541-2016.
- ↑ Andritsos, Leslie A.; et al. (2018). "Trametinib for the treatment of IGHV4-34, MAP2K1-mutant variant hairy cell leukemia". Leukemia & Lymphoma. 59 (4): 1008–1011. doi:10.1080/10428194.2017.1365853. ISSN 1042-8194.
EXAMPLE Book
- Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, 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. IARC Press: Lyon, France, p129-171.
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.