Mast cell tumor pathophysiology

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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.
• 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.
• 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.
• The following genes are involved in the pathogenesis of mast cell tumor:

• KIT
• RAS
• JAK2
• TET2
• DNMT3A
• ASXL1
• CBI

Microscopic Pathology

• 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.