Mast cell sarcoma
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:Mast Cell Sarcoma.
(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples). Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support)
Primary Author(s)*
Jordan Lowery, MD and Thuy Phung, MD, PhD
Department of Pathology, University of South Alabama, Mobile, AL
Cancer Category / Type
Cancer Sub-Classification / Subtype
Mast Cell Sarcoma
Definition / Description of Disease
Localized, solid tumor composed of highly atypical mast cells with a destructive growth pattern and metastatic potential.[1][2]
Synonyms / Terminology
Malignant Mast Cell Tumor
Malignant Mastocytoma
Epidemiology / Prevalence
Mast cell sarcoma is a rare entity with no clear gender predilection.[2][1] Cases have been reported in a wide range of ages from infancy to 77 years of age.[3][4] Most cases seem to arise de novo, but two cases have developed in patients with a history of cutaneous mastocytosis.[1]
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 FeaturesThe content below was from the old template. Please incorporate above.The presentation is variable. The disease is initially localized, followed by distant spread and a terminal phase resembling mast cell leukemia.[2] Progression usually occurs quickly and prognosis is poor. Mast cell sarcoma often results in death within a few months.[1] Treatment includes imatinib, a tyrosine kinase inhibitor that blocks PDGF-R (platelet-derived growth factor receptor) and the tyrosine kinase proteins encoded by abl (the Abelson proto-oncogene) and KIT, or other tyrosine kinase inhibitors.[3] Surgical debulking, radiation and chemotherapy are the usual first-line therapies.[5][6] Hematopoietic stem cell transplantation represents a potential curative treatment, but evidence of its efficacy is lacking.[1]
Sites of Involvement
Bone, gastrointestinal tract, lymph nodes, skin, spleen, liver, oropharyngeal tract, meninges, uterus, testicles and eyes.[1]
Morphologic Features
Mast cell sarcoma exhibits a solid growth pattern. Microscopically, this tumor is poorly differentiated and heterogeneous. Mast cell sarcoma cells are usually medium to very large, with pleomorphic or epithelioid cellular features and oval or bilobed nuclei. Multinucleated giant cells may be identified.[1] Histologic features may even vary between sites within the same patient. The typical features of systemic mastocytosis, including multifocal dense infiltrates of greater than 14 mast cells, are rarely seen in mast cell sarcoma.[2]
Immunophenotype
| Finding | Marker |
|---|---|
| Positive | Tryptase, stem cell factor receptor KIT (CD117), common leukocyte antigen (CD45), macrosialin (CD68R), amiopeptidase N (CD13), C5a receptor (CD88), GM-CSF receptor alpha chain (CD116)[7] |
| Negative | CD1a, CD2, CD3, CD5, CD14, CD15, CD19, CD20, CD34, CD114[7] |
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)
The KIT Asp816Val mutation confers resistance to imatinib.[8] Other reported mutations in the KIT gene, including Asn822Lys and Leu779Phe, may also confer resistance to tyrosine kinase inhibitors, as suggested by patient outcomes and proximity to the tyrosine kinase domain.[9][10]
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)
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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.
Gene Mutation Oncogene/Tumor Suppressor/Other Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) Prevalence (COSMIC/TCGA/Other) KIT exon 17 c.2447A>T, p.Asp816Val Proto-oncogene GOF 3 cases[1] KIT exon 17 c.2395C>T, p.Leu779Phe Proto-oncogene GOF 1 case[10] KIT exon 8 c.1255del p.Asp419Tfs*4
Proto-oncogene GOF 1 case[11] KIT exon 17 c.2466T>A p.Asn822Lys
Proto-oncogene GOF 1 case[9] KIT exon 11 c.1679T>G p.Val560Gly
Proto-oncogene GOF 1 case[12]
Epigenomic Alterations
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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 |
editv4:Genes and Main Pathways InvolvedThe content below was from the old template. Please incorporate above.The KIT proto-oncogene encodes the KIT (CD117) tyrosine kinase protein receptor. KIT is found on hematopoietic progenitor cells, mast cells, germ cells, melanocytes, and interstitial cells of Cajal. Most hematopoietic stem cells loose KIT expression during maturation. However, mature mast cells continue to express KIT. Stem Cell Factor protein is the ligand which binds to KIT protein, leading to dimerization and activation of signaling cascades involved in a wide variety of cellular roles, including regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function. In addition to mast cell disorders, mutations in this gene are found in gastrointestinal stromal tumors and acute myeloid leukemia.[13][14]
Genetic Diagnostic Testing Methods
Although non-sequencing methods have been used, sequencing of the entire KIT gene by Sanger sequencing, pyrosequencing or next generation sequencing (NGS) is recommended to identify unknown KIT mutations.[1]
Familial Forms
Most reported cases are sporadic.[1] However, one reported case of mast cell sarcoma arose in a background of familial indolent mastocytosis with urticaria pigmentosa. No KIT mutations were identified in this case.[12]
Additional Information
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Links
References
(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference.)
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 J, Monnier; et al. (2016). "Mast cell sarcoma: new cases and literature review". doi:10.18632/oncotarget.11812. PMC 5323235. PMID 27602777.CS1 maint: PMC format (link)
- ↑ 2.0 2.1 2.2 2.3 Arber DA, et al., (2017). Mast cell sarcoma, 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. 62-69.
- ↑ 3.0 3.1 Rj, Ryan; et al. (2013). "Mast cell sarcoma: a rare and potentially under-recognized diagnostic entity with specific therapeutic implications". PMID 23196796.
- ↑ Ma, Bautista-Quach; et al. (2013). "Mast cell sarcoma in an infant: a case report and review of the literature". PMID 23211696.
- ↑ P, Valent; et al. (2017). "Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts". doi:10.1182/blood-2016-09-731893. PMC 5356454. PMID 28031180.CS1 maint: PMC format (link)
- ↑ Cr, Weiler; et al. (2014). "Mast cell sarcoma: clinical management". PMID 24745684.
- ↑ 7.0 7.1 A, Chott; et al. (2003). "Morphologic and immunophenotypic properties of neoplastic cells in a case of mast cell sarcoma". PMID 12826896.
- ↑ C, Akin; et al. (2003). "Effects of tyrosine kinase inhibitor STI571 on human mast cells bearing wild-type or mutated c-kit". PMID 12901973.
- ↑ 9.0 9.1 A, Bugalia; et al. (2011). "Mast cell sarcoma of the small intestine: a case report". PMID 21778298.
- ↑ 10.0 10.1 Ys, Kim; et al. (2013). "Pediatric mast cell sarcoma of temporal bone with novel L799F (2395 C>T) KIT mutation, mimicking histiocytic neoplasm". PMID 23388130.
- ↑ Rj, Ryan; et al. (2013). "Mast cell sarcoma: a rare and potentially under-recognized diagnostic entity with specific therapeutic implications". PMID 23196796.
- ↑ 12.0 12.1 S, Georgin-Lavialle; et al. (2013). "Mast cell sarcoma: a rare and aggressive entity--report of two cases and review of the literature". PMID 23129735.
- ↑ "KIT - Mast/stem cell growth factor receptor Kit precursor - Homo sapiens (Human) - KIT gene & protein".
- ↑ L, Falchi; et al. (2018). "Kit Mutations: New Insights and Diagnostic Value". PMID 30007460.
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: “Mast cell sarcoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 12/13/2023, https://ccga.io/index.php/HAEM5:Mast_cell_sarcoma.