Mast Cell Sarcoma
editPREVIOUS EDITIONThis page from the 4th edition of Haematolymphoid Tumours is being updated. See 5th edition Table of Contents.
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
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] |
Gene Mutations (SNV/INDEL)
| 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[8] |
| KIT exon 8 | c.1255del
p.Asp419Tfs*4 |
Proto-oncogene | GOF | 1 case[9] |
| KIT exon 17 | c.2466T>A
p.Asn822Lys |
Proto-oncogene | GOF | 1 case[10] |
| KIT exon 11 | c.1679T>G
p.Val560Gly |
Proto-oncogene | GOF | 1 case[11] |
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.[12][13]
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]
Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)
The KIT Asp816Val mutation confers resistance to imatinib.[14] 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.[10][8]
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.[11]
Links
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.
- ↑ 8.0 8.1 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.
- ↑ 10.0 10.1 A, Bugalia; et al. (2011). "Mast cell sarcoma of the small intestine: a case report". PMID 21778298.
- ↑ 11.0 11.1 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.
- ↑ C, Akin; et al. (2003). "Effects of tyrosine kinase inhibitor STI571 on human mast cells bearing wild-type or mutated c-kit". PMID 12901973.