Mastocytosis in the Skin: Approach to Diagnosis, Evaluation, and Management in Adult and Pediatric Patients

Abstract

Mastocytosis is characterized by the clonal infiltration and proliferation of neoplastic mast cells into target organs. Clinical features of mastocytosis are based in large part on dysregulated mast cell mediator release. Affected individuals may present with isolated skin involvement or multisystemic disease with a spectrum of symptoms including anaphylaxis, pathologic fractures, and chronic gastrointestinal, neurocognitive, musculoskeletal, and constitutional symptoms. The term "mastocytosis in the skin" refers to individuals with cutaneous infiltration and encompasses both localized and systemic forms of disease. Cutaneous involvement is further categorized into cutaneous mastocytoma, diffuse cutaneous mastocytosis, and maculopapular cutaneous mastocytosis based on morphology. In ~95% of patients with systemic mastocytosis, the disease is driven by the KIT D816V somatic variant. The aim of this clinical review is to highlight the diagnostic considerations, management complexities, and evolving treatment landscape that must be considered when evaluating a patient presenting with mastocytosis in their skin. Clinical manifestations, histopathology, and laboratory parameters are essential to diagnosis and determining the disease burden in those with known or suspected systemic mastocytosis. Once appropriately staged, both skin-directed therapy as well as novel systemic treatment options, including selective tyrosine kinase inhibitors, can be considered with the potential to improve patient outcomes.

Fig. 1

Polymorphic maculopapular cutaneous mastocytosis and monomorphic maculopapular cutaneous mastocytosis in children of varied skin phototypes

Fig. 2

Monomorphic maculopapular cutaneous mastocytosis in adults of different skin types

Fig. 3

Histopathologic images showing mast cell infiltration in the skin from a maculopapular cutaneous mastocytosis presentation. (a) A brisk infiltrate of mast cells in the superficial and deep reticular dermis is present with a perivascular and interstitial distribution (hematoxylin and eosin, 20×). (b, c) The mast cells reveal an abnormal morphology characterized by a combination of epithelioid and spindle cell features (hematoxylin and eosin, 100× [b] and 200× [c]). (d) The mast cells are diffusely positive for cluster of differentiation 117 (20×)

Fig. 4

Evaluation of adult and pediatric patients with mastocytosis in the skin. ABD abdominal, DCM diffuse cutaneous mastocytosis, HαT hereditary alpha-tryptasemia, MC mast cell, MPCM maculopapular cutaneous mastocytosis, PB peripheral blood, SBT serum basal tryptase, yo years old