Systemic mastocytosis
Haematolymphoid Tumours (5th ed.)
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editHAEM5 Conversion NotesThis page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Systemic Mastocytosis.
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Primary Author(s)*
Abdullah Osme, MD, University Hospitals Cleveland Medical Center, Case Western Reserve University
Shashi Shetty, Ph.D. FACMG, FCCMG, University Hospitals Cleveland Medical Center, Case Western Reserve University
Cancer Category / Type
Mastocytosis
Cancer Sub-Classification / Subtype
Mastocytosis
Systemic Mastocytosis
Systemic Mastocytosis with an Associated Hematological Neoplasm
Definition / Description of Disease
The 2017 World Health Organization (WHO) classification of hematopoietic and lymphoid tumors defines five subtypes of Systemic mastocytosis[1]
- Indolent systemic mastocytosis (including the bone marrow mastocytosis subtype)
- Smouldering systemic mastocytosis
- Systemic mastocytosis with an associated haematological neoplasm
- Aggressive systemic mastocytosis
- Mast cell leukaemia
The term systemic mastocytosis with an associated haematological neoplasm (SM-AHN) refers to cases with systemic mastocytosis and associated hematological neoplasms combination at the same time. In addition to systemic mastocytosis, usually a myeloid disease of non-mast cell lineage is detected, such as a myelodysplastic syndrome, myeloproliferative neoplasm, myelodysplastic/myeloproliferative neoplasm or acute myeloid leukaemia[2] .
This page will focus specifically only on systemic mastocytosis with an associated hematological neoplasm.
Synonyms / Terminology
Systemic mastocytosis with an associated clonal hematological non-mast cell lineage disease (SH-AHNMD)
Epidemiology / Prevalence
SM-AHN represents 5-40% of cases of systemic mastocytosis[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 FeaturesThe content below was from the old template. Please incorporate above.The clinical symptoms, disease course and prognosis is determined by both to systemic mastocytosis and to the associated haematological disorder[4] [5],[6]
Sites of Involvement
Similar to systemic mastocytosis and associated neoplasms.
Morphologic Features
Similar to systemic mastocytosis and associated neoplasms.
Immunophenotype
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| Finding | Marker |
|---|---|
| Positive (universal) | EXAMPLE CD1 |
| Positive (subset) | EXAMPLE CD2 |
| Negative (universal) | EXAMPLE CD3 |
| Negative (subset) | EXAMPLE CD4 |
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). |
editv4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).Please incorporate this section into the relevant tables found in:
- Chromosomal Rearrangements (Gene Fusions)
- Individual Region Genomic Gain/Loss/LOH
- Characteristic Chromosomal Patterns
- Gene Mutations (SNV/INDEL)
In systemic mastocytosis cases, an associated haematological neoplasm can be diagnosed before, simultaneously, or after. Any defined myeloid or lymphoid malignancy can occur as an associated haematological neoplasm, but most commonly myeloid neoplasms predominate, with chronic myelomonocytic leukaemia and myelodysplastic/myeloproliferative neoplasm, and unclassifiable are seen {1694,1696,1697, 3735,3751,3793}.
The most commonly detected AHN is chronic myelomonocytic leukaemia. Lymphoid neoplasms are rare.
The activating KIT D816V mutation is seen in most cases of SM-AHN, and usually this mutation is detectable in the systemic mastocytosis compartment and in the AHN cells. Additional mutations in other genes (e.g. TET2, SRSF2, ASXL1, CBL, RUNX1 and the RAS family of oncogenes) may also be detected depending based on the type of AHN. And these mutations will impact on the prognosis.
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). |
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.The KIT gene mutation is useful in the diagnosis of systemic mastocytosis (SM) or mixed lineage hematopoietic neoplasms with a mast cell component and to stratify prognosis of core-binding factor (CBF) acute myeloid leukemia (AML).
Gene Mutation Oncogene/Tumor Suppressor/Other Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) Prevalence (COSMIC/TCGA/Other) TI 16V8 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
Methylation status is not determined for SM-AHN.
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
Unknown
Additional Information
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Links
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References
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- ↑ Arber DA, et al., (2017). Mastocytosis, 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, p 66-69.
- ↑ P, Valent; et al. (2001). "Diagnostic criteria and classification of mastocytosis: a consensus proposal". PMID 11377686.
- ↑ Ibrahim, Feryal A.; et al. (2020). "A Rare Case of Systemic Mastocytosis with Associated Hematologic Neoplasm (SM-AHN) Involving Chronic Myeloid Leukemia: A Case Report and Literature Review". The American Journal of Case Reports. 21: e923354–1–e923354-9. doi:10.12659/AJCR.923354. ISSN 1941-5923. PMC 7252834 Check
|pmc=value (help). PMID 32398637 Check|pmid=value (help). - ↑ Kh, Lim; et al. (2009). "Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors". PMID 19363219.
- ↑ Horny, H-P; et al. (2004). "Systemic mastocytosis with associated clonal haematological non-mast cell lineage diseases: a histopathological challenge". Journal of Clinical Pathology. 57 (6): 604–608. doi:10.1136/jcp.2003.014860. ISSN 0021-9746. PMC 1770310. PMID 15166264.
- ↑ Valent, P.; et al. (2014). "Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal". Annals of Oncology. 25 (9): 1691–1700. doi:10.1093/annonc/mdu047. ISSN 0923-7534. PMC 4155468. PMID 24675021.
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. *Citation of this Page: “Systemic mastocytosis”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 12/13/2023, https://ccga.io/index.php/HAEM5:Systemic_mastocytosis.