View source for HAEM4Backup: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

__TOC__

==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<ref>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.</ref> 

#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<ref>{{Cite journal|last=P|first=Valent|last2=Hp|first2=Horny|last3=L|first3=Escribano|last4=Bj|first4=Longley|last5=Cy|first5=Li|last6=Lb|first6=Schwartz|last7=G|first7=Marone|last8=R|first8=Nuñez|last9=C|first9=Akin|date=2001|title=Diagnostic criteria and classification of mastocytosis: a consensus proposal|url=https://pubmed.ncbi.nlm.nih.gov/11377686/|language=en|pmid=11377686}}</ref> . 

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<ref>{{Cite journal|last=Ibrahim|first=Feryal A.|last2=Abdulla|first2=Mohammad A.J.|last3=Soliman|first3=Dina|last4=Sabbagh|first4=Ahmad Al|last5=Nawaz|first5=Zafar|last6=Akiki|first6=Susanna Jane|last7=Shwaylia|first7=Hawraa|last8=Yassin|first8=Mohamed A.|date=2020|title=A Rare Case of Systemic Mastocytosis with Associated Hematologic Neoplasm (SM-AHN) Involving Chronic Myeloid Leukemia: A Case Report and Literature Review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252834/|journal=The American Journal of Case Reports|volume=21|pages=e923354–1–e923354-9|doi=10.12659/AJCR.923354|issn=1941-5923|pmc=7252834|pmid=32398637}}</ref>  

==Clinical Features==
The clinical symptoms, disease course and prognosis is determined by both to systemic mastocytosis and to the associated haematological disorder<ref>{{Cite journal|last=Kh|first=Lim|last2=A|first2=Tefferi|last3=Tl|first3=Lasho|last4=C|first4=Finke|last5=M|first5=Patnaik|last6=Jh|first6=Butterfield|last7=Rf|first7=McClure|last8=Cy|first8=Li|last9=A|first9=Pardanani|date=2009|title=Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors|url=https://pubmed.ncbi.nlm.nih.gov/19363219/|language=en|pmid=19363219}}</ref> <ref>{{Cite journal|last=Horny|first=H-P|last2=Sotlar|first2=K|last3=Sperr|first3=W R|last4=Valent|first4=P|date=2004|title=Systemic mastocytosis with associated clonal haematological non-mast cell lineage diseases: a histopathological challenge|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770310/|journal=Journal of Clinical Pathology|volume=57|issue=6|pages=604–608|doi=10.1136/jcp.2003.014860|issn=0021-9746|pmc=1770310|pmid=15166264}}</ref><sup>,</sup><ref>{{Cite journal|last=Valent|first=P.|last2=Sotlar|first2=K.|last3=Sperr|first3=W. R.|last4=Escribano|first4=L.|last5=Yavuz|first5=S.|last6=Reiter|first6=A.|last7=George|first7=T. I.|last8=Kluin-Nelemans|first8=H. C.|last9=Hermine|first9=O.|date=2014|title=Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4155468/|journal=Annals of Oncology|volume=25|issue=9|pages=1691–1700|doi=10.1093/annonc/mdu047|issn=0923-7534|pmc=4155468|pmid=24675021}}</ref> 

==Sites of Involvement==

Similar to systemic mastocytosis and associated neoplasms. 

==Morphologic Features==

Similar to systemic mastocytosis and associated neoplasms. 

==Immunophenotype==

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{| class="wikitable sortable"
|-
!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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{| class="wikitable sortable"
|-
!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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{| class="wikitable sortable"
|-
!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).

{| class="wikitable sortable"
|-
!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===
{| class="wikitable sortable"
|-
!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==

Unknown

==Other Information==

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==Links==

Put your links here (use "Link" icon at top of page)

==References==
<references />

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==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.