Mastocytosis is a rare clonal hematological neoplasm, characterized by cutaneous manifestations in children and categorized as: maculopapular cutaneous mastocytosis (MPCM), diffuse cutaneous mastocytosis (DCM) and mastocytoma. Systemic mastocytosis (SM) typically occurs in adults with c-KIT D816V mutation. Additional genetic mutations (TET2, NRAS, SF3B1, ASXL1, etc.) have been detected using Next-Generation Sequencing (NGS) in the adult population while limited information is available in the pediatric setting. 36 patients (pts) with pediatric mastocytosis diagnosed between 1997 and 2021 were included. Peripheral blood samples were collected to detect c-KIT D816V mutation, using both RT-PCR and ddPCR techniques, and to investigate other molecular mutations using NGS panel for rare and myeloid genes. Median age of lesion onset was 4.7 months (range birth-17.8 years). 58% of the cohort underwent cutaneous biopsy after a median 3.77 months from lesion onset (range 2.49 months-11.6 years). 20 (55%) were classified as MPCM, 10 (28%) as DCM and 6 (17%) as mastocytoma. Median tryptase value at the onset was 5 ng/mL: MPCM (range 1.2-141 ng/mL) vs. DCM (range 2.71-19.4 ng/mL) vs. mastocytoma (range 3.8-7.3 ng/mL). Two MPCM pts developed indolent SM (ISM) after 10 and 20 years from the onset of disease. RT-PCR identified c-KIT D816V mutation in 4 pts (2 MPCM, 1 DCM, 1 ISM). NGS revealed the precedent mutation in 3 pts, c-KIT D816Y and c-KIT Y553C in 2 pts. An additional 10 myeloid gene mutations were detected by NGS: 5 already known (ASXL1 G1397S; JAK2 L393V; c-KIT D816Y; LNK E208Q; TET2 Y867H) and 5 not previously described (ETV6 A215P; c-KIT Y553C; NFE2 I291T; SH2B3 G382D; SH2B3 L438V). A single mutation was found in 7 pts (3 MPCM, 3 DCM, 1 ISM), while two or more mutations in 3 DCM pts. Overall, 9/36 pts (5 DCM, 3 MPCM, 1 mastocytoma) presented spontaneous complete regression of cutaneous lesions after a median time of 25 months (range 17 months-25 years). c-KIT mutations resulted in 35% of the children tested. The RT-PCR technique resulted more sensitive in finding c-KIT D816V, while NGS in detecting other mutations whose prognostic roles require further investigation.

Mastocytosis is characterized by mast cell infiltration in various tissues and organs. More than half of the patients are children. Pediatric mastocytosis has several features that differentiate the disease from adult mastocytosis. Importantly, the disease, which usually starts in the first months of life or at birth, often shows a transient course with spontaneous resolution in adolescence. In most children, mastocytosis is limited to skin. Cutaneous involvement can present as maculopapular cutaneous mastocytosis, mostly with the polymorphic variant, cutaneous mastocytoma, or diffuse cutaneous mastocytosis. When children present with monomorphic maculopapular skin lesions, the variant typically seen in adults, this may indicate rare persistent disease until adulthood, often associated with systemic mastocytosis. Many pediatric patients suffer from symptoms of mast cell activation, ranging from pruritus to flushing and blistering. Children with cutaneous mastocytosis typically exhibit mutations in various regions of the KIT gene, whereas those with systemic disease predominantly carry KIT D816V. Diagnosis is mainly based on noninvasive measures, including skin inspection, elicitation of the Darier's sign, and analyses of the serum tryptase and KIT variant in blood. Treatment options encompass avoidance of triggers of mast cell activation, H1 and H2 antihistamines, cromolyn, and omalizumab. In children with systemic mastocytosis, tyrosine kinase inhibitors tailored to the specific KIT variant may be considered.

Diffuse cutaneous mastocytosis (DCM) is a rare and severe subtype of pediatric mastocytosis, characterized by extensive skin involvement. Comprehensive studies on the clinical and molecular features of DCM remain limited. To describe the clinical, molecular, and treatment-related characteristics and outcomes of a cohort of pediatric patients with a clinical presentation of DCM. This retrospective study analyzed pediatric patients with a clinical presentation of DCM from January 1996 to October 2023 at Necker Children's Hospital in Paris, France. Data on clinical presentation, laboratory results, and KIT sequencing from skin biopsies and bone marrow, if available, were collected and analyzed. These data were compared with previously published findings from a pediatric cohort with maculopapular cutaneous mastocytosis (MPCM). The study included 33 pediatric patients, 18 (54.5%) of whom were male, with a clinical presentation of DCM, including 4 with aggressive systemic mastocytosis (ASM) and 29 with DCM. The mean (SD) age at the onset of the first clinically significant signs was 2.2 (2.2) months. A disease-revealing massive bullous eruption was noted in 9 patients (27.2%). Compared to MPCM, patients with a clinical presentation of DCM had a higher mean baseline serum tryptase level (47.5 μg/L [SD, 38.7; range, 5.0-178.0 μg/L] vs 7.4 μg/L [SD, 6.4; range, 1-45.2]; P < .001), a higher prevalence of anaphylaxis (4 [12.1%] vs 5 [2.4%]; P = .02), and a more frequent association with ASM (4 [12.1%] vs 2 [0.9%]; P = .004). KIT codon 816 variants were identified in 4 patients (19.0%), other KIT variants in 14 patients (66.7%), and wild-type KIT in 3 patients (14.3%). All 4 patients with KIT codon 816 variants had ASM. Seven patients (21.2%) received early systemic treatment (imatinib, midostaurin, or sirolimus depending on the type of KIT variants), starting at a mean (SD) age of 80.8 (135.6) months and continuing for a mean (SD) of 4.0 (2.6) years, with generally good tolerance and efficacy. Of the 15 patients without systemic treatment for more than 6 years, 13 (86.6%) exhibited spontaneous regression. In this cohort study, DCM presentation differs significantly from MPCM, with a higher risk of anaphylaxis and aggressive systemic forms, the latter being consistently associated with the KIT D816V variant. Tyrosine kinase inhibitors and sirolimus were generally effective and well tolerated in this pediatric population, with the choice of treatment depending on the type of KIT variants.

We report an 11-month-old boy with diffuse cutaneous mastocytosis whose severe pruritus and steroid dependence resolved following off-label treatment with omalizumab. A literature review identified five additional pediatric cases in which omalizumab led to complete symptom resolution in an average of 2 months and permitted discontinuation of systemic steroids. Although limited by the small sample size and lack of high-quality data, omalizumab presents as a well-tolerated and potentially effective steroid-sparing agent for pediatric cutaneous mastocytosis.

Xanthelasmoid mastocytosis (XM) is a rare form of diffuse cutaneous mastocytosis whose clinical presentation may resemble multiple juvenile xanthogranulomas. We report the case of a two-year-old child who presented with multiple yellowish papules and nodules, with a firm to elastic consistency, symmetrically distributed over the face, the base of the neck, trunk, and limbs. Dermoscopy and histology confirmed the diagnosis of XM. The patient was successfully treated with H1-antihistamines and high-potency topical corticosteroids. This case highlights the importance of considering XM as a rare variant of diffuse cutaneous mastocytosis that may be confused with multiple juvenile xanthogranulomas.