Bailey.Glen at 21:22, 4 December 2023

2023-12-04T21:22:10Z

← Older revision		Revision as of 16:22, 4 December 2023
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	==Cancer Category/Type==		==Cancer Category/Type==

	[[Mastocytosis]]		[[HAEM4:Mastocytosis]]

	==Cancer Sub-Classification / Subtype==		==Cancer Sub-Classification / Subtype==

Bailey.Glen at 18:41, 3 November 2023

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 ==Primary Author(s)*==
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Bailey.Glen: Created page with "==Primary Author(s)*== Jordan Lowery, MD and Thuy Phung, MD, PhD Department of Pathology, University of South Alabama, Mobile, AL TOC ==Cancer Category/Type== Mas..."

2023-11-03T18:00:16Z

Created page with "==Primary Author(s)*== Jordan Lowery, MD and Thuy Phung, MD, PhD Department of Pathology, University of South Alabama, Mobile, AL __TOC__ ==Cancer Category/Type== Mas..."

New page

==Primary Author(s)*==

Jordan Lowery, MD and Thuy Phung, MD, PhD

Department of Pathology, University of South Alabama, Mobile, AL

__TOC__

==Cancer Category/Type==

[[Mastocytosis]]

==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.<ref name=":0">{{Cite journal|last=J|first=Monnier|last2=S|first2=Georgin-Lavialle|last3=D|first3=Canioni|last4=L|first4=Lhermitte|last5=M|first5=Soussan|last6=M|first6=Arock|last7=J|first7=Bruneau|last8=P|first8=Dubreuil|last9=C|first9=Bodemer|date=2016|title=Mast cell sarcoma: new cases and literature review|url=https://pubmed.ncbi.nlm.nih.gov/27602777/|language=en|doi=10.18632/oncotarget.11812|pmc=PMC5323235|pmid=27602777}}</ref><ref name=":1">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.</ref>

==Synonyms / Terminology==

Malignant Mast Cell Tumor

Malignant Mastocytoma

==Epidemiology / Prevalence==

Mast cell sarcoma is a rare entity with no clear gender predilection.<ref name=":1" /><ref name=":0" /> Cases have been reported in a wide range of ages from infancy to 77 years of age.<ref name=":2">{{Cite journal|last=Rj|first=Ryan|last2=C|first2=Akin|last3=M|first3=Castells|last4=M|first4=Wills|last5=Mk|first5=Selig|last6=Gp|first6=Nielsen|last7=Ja|first7=Ferry|last8=Jl|first8=Hornick|date=2013|title=Mast cell sarcoma: a rare and potentially under-recognized diagnostic entity with specific therapeutic implications|url=https://pubmed.ncbi.nlm.nih.gov/23196796/|language=en|pmid=23196796}}</ref><ref>{{Cite journal|last=Ma|first=Bautista-Quach|last2=Cl|first2=Booth|last3=A|first3=Kheradpour|last4=Cw|first4=Zuppan|last5=Eh|first5=Rowsell|last6=L|first6=Weiss|last7=J|first7=Wang|date=2013|title=Mast cell sarcoma in an infant: a case report and review of the literature|url=https://pubmed.ncbi.nlm.nih.gov/23211696/|language=en|pmid=23211696}}</ref> Most cases seem to arise de novo, but two cases have developed in patients with a history of cutaneous mastocytosis.<ref name=":0" />

==Clinical Features==

The presentation is variable. The disease is initially localized, followed by distant spread and a terminal phase resembling mast cell leukemia.<ref name=":1" /> Progression usually occurs quickly and prognosis is poor. Mast cell sarcoma often results in death within a few months.<ref name=":0" /> Treatment includes imatinib, a tyrosine kinase inhibitor that blocks [[PDGFRA|PDGF-R]] (platelet-derived growth factor receptor) and the tyrosine kinase proteins encoded by ''[[ABL1|abl]]'' (the Abelson proto-oncogene) and ''KIT'', or other tyrosine kinase inhibitors.<ref name=":2" /> Surgical debulking, radiation and chemotherapy are the usual first-line therapies.<ref>{{Cite journal|last=P|first=Valent|last2=C|first2=Akin|last3=Dd|first3=Metcalfe|date=2017|title=Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts|url=https://pubmed.ncbi.nlm.nih.gov/28031180/|language=en|doi=10.1182/blood-2016-09-731893|pmc=PMC5356454|pmid=28031180}}</ref><ref>{{Cite journal|last=Cr|first=Weiler|last2=J|first2=Butterfield|date=2014|title=Mast cell sarcoma: clinical management|url=https://pubmed.ncbi.nlm.nih.gov/24745684/|language=en|pmid=24745684}}</ref> Hematopoietic stem cell transplantation represents a potential curative treatment, but evidence of its efficacy is lacking.<ref name=":0" />

==Sites of Involvement==

Bone, gastrointestinal tract, lymph nodes, skin, spleen, liver, oropharyngeal tract, meninges, uterus, testicles and eyes.<ref name=":0" />

==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.<ref name=":0" /> 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.<ref name=":1" />

==Immunophenotype==

{| class="wikitable sortable"
|-
!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)<ref name=":3">{{Cite journal|last=A|first=Chott|last2=P|first2=Guenther|last3=A|first3=Huebner|last4=E|first4=Selzer|last5=Rm|first5=Parwaresch|last6=Hp|first6=Horny|last7=P|first7=Valent|date=2003|title=Morphologic and immunophenotypic properties of neoplastic cells in a case of mast cell sarcoma|url=https://pubmed.ncbi.nlm.nih.gov/12826896/|language=en|pmid=12826896}}</ref>
|-
|Negative||CD1a, CD2, CD3, CD5, CD14, CD15, CD19, CD20, CD34, CD114<ref name=":3" />
|}

==Gene Mutations (SNV/INDEL)==

{| class="wikitable sortable"
|-
!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<ref name=":0" />
|-
|''KIT'' exon 17
|c.2395C>T, p.Leu779Phe
|Proto-oncogene
|GOF
|1 case<ref name=":4">{{Cite journal|last=Ys|first=Kim|last2=H|first2=Wu|last3=Ab|first3=Pawlowska|last4=Ma|first4=Bautista-Quach|last5=Q|first5=Huang|last6=K|first6=Gaal|last7=Kl|first7=Chang|date=2013|title=Pediatric mast cell sarcoma of temporal bone with novel L799F (2395 C>T) KIT mutation, mimicking histiocytic neoplasm|url=https://pubmed.ncbi.nlm.nih.gov/23388130/|language=en|pmid=23388130}}</ref>
|-
|''KIT'' exon 8
|c.1255del
p.Asp419Tfs*4
|Proto-oncogene
|GOF
|1 case<ref>{{Cite journal|last=Rj|first=Ryan|last2=C|first2=Akin|last3=M|first3=Castells|last4=M|first4=Wills|last5=Mk|first5=Selig|last6=Gp|first6=Nielsen|last7=Ja|first7=Ferry|last8=Jl|first8=Hornick|date=2013|title=Mast cell sarcoma: a rare and potentially under-recognized diagnostic entity with specific therapeutic implications|url=https://pubmed.ncbi.nlm.nih.gov/23196796/|language=en|pmid=23196796}}</ref>
|-
|''KIT'' exon 17
|c.2466T>A
p.Asn822Lys
|Proto-oncogene
|GOF
|1 case<ref name=":5">{{Cite journal|last=A|first=Bugalia|last2=A|first2=Abraham|last3=P|first3=Balasubramanian|last4=A|first4=Srivastava|last5=S|first5=Nair|date=2011|title=Mast cell sarcoma of the small intestine: a case report|url=https://pubmed.ncbi.nlm.nih.gov/21778298/|language=en|pmid=21778298}}</ref>
|-
|''KIT'' exon 11
|c.1679T>G
p.Val560Gly
|Proto-oncogene
|GOF
|1 case<ref name=":6">{{Cite journal|last=S|first=Georgin-Lavialle|last2=C|first2=Aguilar|last3=R|first3=Guieze|last4=L|first4=Lhermitte|last5=J|first5=Bruneau|last6=S|first6=Fraitag|last7=D|first7=Canioni|last8=Mo|first8=Chandesris|last9=F|first9=Suarez|date=2013|title=Mast cell sarcoma: a rare and aggressive entity--report of two cases and review of the literature|url=https://pubmed.ncbi.nlm.nih.gov/23129735/|language=en|pmid=23129735}}</ref>
|}

==Genes and Main Pathways Involved==

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.<ref>{{Cite journal|title=KIT - Mast/stem cell growth factor receptor Kit precursor - Homo sapiens (Human) - KIT gene & protein|url=https://www.uniprot.org/uniprot/P10721}}</ref><ref>{{Cite journal|last=L|first=Falchi|last2=S|first2=Verstovsek|date=2018|title=Kit Mutations: New Insights and Diagnostic Value|url=https://pubmed.ncbi.nlm.nih.gov/30007460/|language=en|pmid=30007460}}</ref>

==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.<ref name=":0" />

==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==

The ''KIT'' Asp816Val mutation confers resistance to imatinib.<ref>{{Cite journal|last=C|first=Akin|last2=K|first2=Brockow|last3=C|first3=D'Ambrosio|last4=As|first4=Kirshenbaum|last5=Y|first5=Ma|last6=Bj|first6=Longley|last7=Dd|first7=Metcalfe|date=2003|title=Effects of tyrosine kinase inhibitor STI571 on human mast cells bearing wild-type or mutated c-kit|url=https://pubmed.ncbi.nlm.nih.gov/12901973/|language=en|pmid=12901973}}</ref> 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.<ref name=":5" /><ref name=":4" />

==Familial Forms==

Most reported cases are sporadic.<ref name=":0" /> 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.<ref name=":6" />

==Links==

[[KIT]]

==Reference==
<references />

HAEM4:Mast Cell Sarcoma - Revision history

Bailey.Glen at 21:22, 4 December 2023

Bailey.Glen at 18:41, 3 November 2023

Bailey.Glen: Created page with "==Primary Author(s)*== Jordan Lowery, MD and Thuy Phung, MD, PhD Department of Pathology, University of South Alabama, Mobile, AL __TOC__ ==Cancer Category/Type== Mas..."

Bailey.Glen: Created page with "==Primary Author(s)*== Jordan Lowery, MD and Thuy Phung, MD, PhD Department of Pathology, University of South Alabama, Mobile, AL TOC ==Cancer Category/Type== Mas..."