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


Cancer Sub-Classification / Subtype


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]

  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

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.


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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
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

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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

Gene Mutations (SNV/INDEL)

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)

Other Mutations

Type Gene/Region/Other
Concomitant Mutations EXAMPLE IDH1 R123H
Secondary Mutations EXAMPLE Trisomy 7
Mutually Exclusive EXAMPLE EGFR Amplification

Epigenomics (Methylation)

Methylation status is not determined for SM-AHN.

Genes and Main Pathways Involved

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Diagnostic Testing Methods

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Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)

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.

Familial Forms


Other Information

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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.


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