Mast cell tumor pathophysiology: Difference between revisions
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*The D816V [[point mutation]] within the tyrosine kinase Kit (C-kit) that is detected in 80% of cases is considered a driver mutation causing the permanent receptor activation and consequent proliferation, and thus neoplastic expansion of the mutated mast cell clone.<ref name="AdolfMillonig2012">{{cite journal|last1=Adolf|first1=Stefanie|last2=Millonig|first2=Gunda|last3=Seitz|first3=Helmut Karl|last4=Reiter|first4=Andreas|last5=Schirmacher|first5=Peter|last6=Longerich|first6=Thomas|last7=Mueller|first7=Sebastian|title=Systemic Mastocytosis: A Rare Case of Increased Liver Stiffness|journal=Case Reports in Hepatology|volume=2012|year=2012|pages=1–6|issn=2090-6587|doi=10.1155/2012/728172}}</ref> | *The D816V [[point mutation]] within the tyrosine kinase Kit (C-kit) that is detected in 80% of cases is considered a driver mutation causing the permanent receptor activation and consequent proliferation, and thus neoplastic expansion of the mutated mast cell clone.<ref name="AdolfMillonig2012">{{cite journal|last1=Adolf|first1=Stefanie|last2=Millonig|first2=Gunda|last3=Seitz|first3=Helmut Karl|last4=Reiter|first4=Andreas|last5=Schirmacher|first5=Peter|last6=Longerich|first6=Thomas|last7=Mueller|first7=Sebastian|title=Systemic Mastocytosis: A Rare Case of Increased Liver Stiffness|journal=Case Reports in Hepatology|volume=2012|year=2012|pages=1–6|issn=2090-6587|doi=10.1155/2012/728172}}</ref> | ||
*The following genes are involved in the pathogenesis of mast cell tumor: | *The following genes are involved in the pathogenesis of mast cell tumor: | ||
:*''KIT'' | :*''KIT''<ref name="pmid23807778">{{cite journal |vauthors=Berezowska S, Flaig MJ, Ruëff F, Walz C, Haferlach T, Krokowski M, Kerler R, Petat-Dutter K, Horny HP, Sotlar K |title=Adult-onset mastocytosis in the skin is highly suggestive of systemic mastocytosis |journal=Mod. Pathol. |volume=27 |issue=1 |pages=19–29 |date=January 2014 |pmid=23807778 |doi=10.1038/modpathol.2013.117 |url=}}</ref> | ||
:**Exon 17 ''KIT'' mutations | :**Exon 17 ''KIT'' mutations | ||
:** | :** | ||
Revision as of 18:36, 7 March 2019
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Mast cell tumor Microchapters |
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Mast cell tumor pathophysiology On the Web |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Suveenkrishna Pothuru, M.B,B.S. [2]
Overview
Mast cell tumor arises from the mast cell, which is a type of white blood cell involved in the inflammatory process. The progression to mast cell tumor usually involves the uncontrolled stimulation of the receptor for stem cell factor following mutation of C-kit cell surface receptor. On microscopic histopathological analysis, mast cells in the superficial and mid dermis that are lymphocyte like with dense granular cytoplasm which tend to be more abundant around blood vessels is characteristic finding of mast cell tumor.
Pathophysiology
Mast Cell
- Mast cells are bone marrow derived multi-functional immune cells and are normally found throughout the connective tissue of the body.
- It is a normal component of the immune system and as it releases histamine it is associated with allergic reactions.
- Mast cell granules contain histamine, heparin, platelet-activating factor, leukotrienes, prostaglandins, cytokines and proteases.
- It is thought that the effects of mast cell tumor relate at least in part to mediator release.
- The clinical features of mast cell tumor arise from release of mast cell mediators, inflitration of tissues by mast cells, local build-up of mast cells and associated neoplasms.
- In systemic mastocytosis, abnormal proliferation and microscopic infiltration of mast cells involves skin, bone marrow, gastrointestinal tract, liver, and spleen.
Genetics
- Mutations in kinases (particularly in the tyrosine kinase Kit) and in enzymes and receptors (JAK2, PDGFRα, RASGRP4, Src-kinases, c-Cbl-encoded E3 ligase, histamine H4 receptor) which are crucially involved in the regulation of mast cell activity have been identified as necessary to establish a clonal mast cell population.[1]
- Mast cells express a cell surface receptor, C-kit (CD117), which is the receptor for stem cell factor. In laboratory studies, stem cell factor appears to be important for the proliferation of mast cells.
- Mutations of the C-kit receptor, leading to uncontrolled stimulation of the receptor, is a cause for the disease.
- The D816V point mutation within the tyrosine kinase Kit (C-kit) that is detected in 80% of cases is considered a driver mutation causing the permanent receptor activation and consequent proliferation, and thus neoplastic expansion of the mutated mast cell clone.[2]
- The following genes are involved in the pathogenesis of mast cell tumor:
- KIT[3]
- Exon 17 KIT mutations
- RAS
- JAK2
- TET2
- DNMT3A
- ASXL1
- CBI
- KIT[3]
Microscopic Pathology
- Lymphocyte-like with more cytoplasm that is granular
- Cells may have spindled or stellate morphology
- Tend to be more abundant around vessels
- Eosinophils may present
-
![Micrograph showing a mast cell tumor.[4]](/images/f/fa/Mastocytosis_Histology.jpg)
Micrograph showing a mast cell tumor.[4]
![Micrograph showing a mast cell tumor.[4]](/index.php/File:Mastocytosis_Histology.jpg)
References
- ↑ Molderings, Gerhard J; Brettner, Stefan; Homann, Jürgen; Afrin, Lawrence B (2011). "Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options". Journal of Hematology & Oncology. 4 (1): 10. doi:10.1186/1756-8722-4-10. ISSN 1756-8722.
- ↑ Adolf, Stefanie; Millonig, Gunda; Seitz, Helmut Karl; Reiter, Andreas; Schirmacher, Peter; Longerich, Thomas; Mueller, Sebastian (2012). "Systemic Mastocytosis: A Rare Case of Increased Liver Stiffness". Case Reports in Hepatology. 2012: 1–6. doi:10.1155/2012/728172. ISSN 2090-6587.
- ↑ Berezowska S, Flaig MJ, Ruëff F, Walz C, Haferlach T, Krokowski M, Kerler R, Petat-Dutter K, Horny HP, Sotlar K (January 2014). "Adult-onset mastocytosis in the skin is highly suggestive of systemic mastocytosis". Mod. Pathol. 27 (1): 19–29. doi:10.1038/modpathol.2013.117. PMID 23807778.
- ↑ 4.0 4.1 Mastocytosis. Libre Pathology. http://librepathology.org/wiki/Mastocytosis accessed on March 1st, 2016