Systemic mastocytosis

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Haematolymphoid Tumours (WHO Classification, 5th ed.)

editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification
This 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

WHO Classification of Disease

Structure Disease
Book Haematolymphoid Tumours (5th ed.)
Category Myeloid proliferations and neoplasms
Family Mastocytosis
Type N/A
Subtype(s) Systemic mastocytosis

Definition / Description of Disease

The 2017 World Health Organization (WHO) classification of hematopoietic and lymphoid tumors defines five subtypes of Systemic mastocytosis[1]

  1. Indolent systemic mastocytosis (including the bone marrow mastocytosis subtype)
  2. Smouldering systemic mastocytosis
  3. Systemic mastocytosis with an associated haematological neoplasm
  4. Aggressive systemic mastocytosis
  5. 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

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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
The 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

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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. Do not delete table.)

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)

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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

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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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  1. 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.
  2. P, Valent; et al. (2001). "Diagnostic criteria and classification of mastocytosis: a consensus proposal". PMID 11377686.
  3. 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).
  4. Kh, Lim; et al. (2009). "Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors". PMID 19363219.
  5. 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.
  6. 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 09/6/2024, https://ccga.io/index.php/HAEM5:Systemic_mastocytosis.