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AT-A-GLANCE

AT-A-GLANCE MASTOCYTOSIS

  • The hallmark of mastocytosis is a pathologic accumulation of mast cells in tissues.

  • Mastocytosis occurs at any age but children are more commonly affected.

  • Cutaneous findings consist of hyperpigmented macules, papules, or nodules, or a diffuse infiltration of the dermis.

  • Most children only have skin involvement, whereas adults are more likely to have systemic disease.

  • Mastocytosis is usually associated with somatic activating mutations of c-kit with the 816 codon mutation being most common.

  • Many patients have few, if any, symptoms, but some experience varying degrees of flushing, pruritus, hypotension, nausea, dyspepsia, and diarrhea.

  • Most common extracutaneous tissues involved are the bone marrow, liver, spleen, and lymph nodes.

  • Some patients may develop an associated myeloproliferative or myelodysplastic disorder.

  • No effective cure currently exists; treatment is focused on controlling symptoms

MAST CELLS
  • Mast cells are derived from pluripotent stem cells.

  • Stem cell factor is the ligand for KIT and is required for mast cell proliferation and survival.

  • Mast cells release both preformed and newly generated mediators.

EPIDEMIOLOGY

Mastocytosis represents a group of disorders characterized by an abnormal accumulation of mast cells in one or more organs. Although the true incidence of this disease is unknown, most cases arise in children, with approximately 70% of cases occurring by 6 months of age and more than 90% occurring within the first 2 years of life.1-5 Congenital mastocytosis is less common, representing approximately 18% to 31% of childhood cases.2-4 The prevalence of childhood-onset mastocytosis is reported to range from 2.0 to 5.4 cases/1000 population.1,2 The prevalence of adult-onset systemic mastocytosis (SM) in Denmark has been reported to be approximately 1/10,000 population over a 14-year period.6 Mastocytosis has no gender preference, and it has been reported in all races.5 While most mastocytosis patients have no family history, there are reports of more than 70 familial cases, including monozygotic twins, some of which were discordant for this disease.7-9

PATHOGENESIS

Mast cells arise from the bone marrow as agranular, undifferentiated, CD34+, KIT+ (CD117) pluripotent progenitor cells. After migrating into tissues, immature mast cells assume their typical granular morphology.10 KIT, a Type III tyrosine kinase is the product of the protooncogene c-kit located on chromosome 4q12. This enzyme is expressed on mast cells, as well as melanocytes, primitive hematopoietic stem cells, primordial germ cells, and interstitial cells of Cajal and serves as the receptor for its ligand, stem cell factor (SCF). Crosslinking of KIT by SCF is essential for mast cell maturation. The gene for SCF is located on chromosome 12, and encodes a protein that localizes to the cell membrane.10,11 Membrane-bound and a soluble forms of SCF exist, both of which are capable of inducing KIT activation. Soluble KIT is thought to arise from chymase-induced cleavage of the membrane bound form.12 SCF is produced by bone marrow stromal cells, fibroblasts, ...

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