Case Presentation: A 17-year-old male presented to clinic with a pruritic and brown macular rash that was first noticed after ingesting food at a buffet a few months prior to his office visit. The rash began on his upper extremities and spread to his trunk, lower extremities, and head. He has a history of cutaneous mastocytosis diagnosed when he was 2-4 weeks-old with relatively persistent blistering lesions of the face and body until age 10 when the lesions resolved. However, he had a persistent urticarial rash on his chest, back, abdomen, and extremities that spared his face from age 10-17. At presentation, laboratory tests revealed a mild decrease of his white blood cells (WBCs) at 3.6 K/µL (reference range [RR] 4.5 – 11.0 K/µL), an elevated tryptase level of 14.1 ng/mL (RR < 11.5 ng/mL), and a negative KIT mutation. Two shave biopsies of his skin were consistent with perivascular and interstitial mature-appearing round mast cells. There were approximately 500 mast cells per square millimeter (RR 78-113/sq. mm), with the infiltrate predominantly in the papillary dermis. Bone marrow biopsy results showed a normocellular marrow with large, clustered mast cells co-expressing cluster of differentiation (CD)117, CD25, and mast cell tryptase with approximately 5% involvement. Based on his biopsy and bone marrow results, he was diagnosed with systemic mastocytosis. The patient is currently being treated with cetirizine 20 mg once nightly and famotidine 40 mg twice daily.

Discussion: Mastocytosis was first described in the medical literature as a form of urticaria in 1869. The disease has since been delineated and classified as a rare hematopoietic neoplasm with 4.6 new cases per million diagnosed every year in the United States. Mastocytosis has varied clinical presentations from skin-limited disease (cutaneous mastocytosis) that affects mostly pediatric populations, to the more aggressive systemic mastocytosis (SM) with multi-organ involvement that affects mostly adults. Patients with SM are often treated symptomatically at earlier stages with mediator-targeted drugs. Treatment of more aggressive SM may require cytoreductive agents and eventually hematopoietic stem cell transplantation. The diagnosis of SM is based on criteria outlined in the 2016 WHO reclassification document. The major SM criterion is the multifocal infiltration of mast cells (at least 15 mast cells per infiltrate) in bone marrow or in sections of extracutaneous organs. The minor SM criteria include abnormal morphology of mast cells, expression of KIT point mutations at codon 816, expression of CD2 and/or CD25 in mast cells, as well as serum tryptase level above 20 ng/mL. When the major criterion and at least 1 minor criterion or 3 minor criteria are met, the diagnosis of SM is established.

Conclusions: Systemic mastocytosis is a rare hematopoietic neoplasm that involves the abnormal growth of mast cells in one or more organs. The clinical presentation is varied with patients exhibiting different combinations of criteria that the World Health Organization have established for diagnosis of the disease. Treatment depends on the severity of mastocytosis. Indolent forms like those limited to the skin and non-progressive indolent systemic mastocytosis are treated with mediator-targeted drugs while aggressive forms that show progression to leukemic states may require cytoreductive agents and hematopoietic stem cell transplantation.