Mast cell tumor pathophysiology

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.

• 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.^[1][2]
• 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.^[3]
• In systemic mastocytosis, abnormal proliferation and microscopic infiltration of mast cells involves skin, bone marrow, gastrointestinal tract, liver, and spleen.^[4][5]

• Mutations in kinases (especially in the tyrosine kinase Kit) and in enzymes and receptors (histamine H4 receptor, PDGFRα, JAK2, RASGRP4, Src-kinases, c-Cbl-encoded E3 ligase) which are essentially involved in the regulation of proliferation and differentiation of mast cell, and are required to establish a clonal mast cell population.^[6]
• 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.^[7][8]
• Mutations of the C-kit receptor, leading to uncontrolled stimulation of the receptor, is a cause for the disease.^[9]
• 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.^[10]
• The following genes are involved in the pathogenesis of mast cell tumor:^[11][12][13]

• KIT^[14]
  • Exon 17 KIT mutations
• RAS
• JAK2
• TET2^[15]
• DNMT3A
• ASXL1
• CBL
• SRSF2
• RUNX1

• Cells in the superficial/mid dermis that are:

• 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.

Template:WH Template:WS