Phenotypic and Genotypic Characteristics of Mastocytosis According to the Age of Onset

Abstract

Adult's mastocytosis is usually associated with persistent systemic involvement and c-kit 816 mutation, while pediatrics disease is mostly limited to the skin and often resolves spontaneously. We prospectively included 142 adult patients with histologically proven mastocytosis. We compared phenotypic and genotypic features of adults patients whose disease started during childhood (Group 1, n = 28) with those of patients whose disease started at adult's age (Group 2, n = 114). Genotypic analysis was performed on skin biopsy by sequencing of c-kit exons 17 and 8 to 13. According to WHO classification, the percentage of systemic disease was similar (75 vs. 73%) in 2 groups. C-kit 816 mutation was found in 42% and 77% of patients in groups 1 and 2, respectively (p<0.001). 816 c-kit mutation was associated with systemic mastocytosis in group 2 (87% of patients with systemic mastocytosis vs. 45% with cutaneous mastocytosis, p = 0.0001). Other c-kit activating mutations were found in 23% of patients with mastocytosis' onset before the age of 5, 0% between 6 and 15 years and 2% at adults' age (p<0.001). In conclusion, pathogenesis of mastocytosis significantly differs according to the age of disease's onset. Our data may have major therapeutic relevance when considering c-kit-targeted therapy.

Adult-onset mastocytosis in the skin is highly suggestive of systemic mastocytosis

“…It was found clearly preferable over skin in the present study in which KIT D816V was detected in all the bone marrow specimens investigated (58/58) but in only 74% (20/27) of lesional skin biopsies. The latter finding is consistent with the 77% (86/112) prevalence of KIT D816V in skin biopsies found by Lanternier et al 9 However, underlying systemic disease was found in only 73% of their patients.…”

“…22 We failed to detect KIT D816V in microdissected skin mast cells in about 25% of cases despite the fact that it was detectable in bone marrow mast cells. Consistent with the decreased detection rate of KIT mutations in the skin is the observation that only a small subset of skin mast cells expressed CD25 as another indicator of the neoplastic nature of these cells, 9,10,23 while it was found to be strongly expressed by the majority of bone marrow mast cells (in the present study) and mucosal mast cells in patients with intestinal involvement of systemic mastocytosis. 24 These findings may be caused by, for example, expression of different sets of adhesion molecules between normal and neoplastic mast cells, or by expression of different homing receptors for (neoplastic) mast cells in the skin and extracutaneous tissues.…”

“…In previous studies investigating patients with mastocytosis in the skin, the frequency of systemic disease ranged from 41 to 73%. [9][10][11][12] Bone marrow is the tissue of choice for KIT mutational analysis. It was found clearly preferable over skin in the present study in which KIT D816V was detected in all the bone marrow specimens investigated (58/58) but in only 74% (20/27) of lesional skin biopsies.…”

Adult-onset cutaneous mastocytosis in monozygotic twins

“…It has been suggested that the divergent clinical behavior between pediatric and adult mastocytosis may be related to the presence or absence of genomic mutations, in particular involving the c-kit protooncogene. 5 A significantly higher percentage of c-kit mutations (77%) was demonstrated in adult-onset mastocytosis compared with pediatric cases (42%). 5 Therefore the absence of a mutation in our patients could possibly indicate a favorable prognosis comparable to that of childhood UP.…”

“…5 A significantly higher percentage of c-kit mutations (77%) was demonstrated in adult-onset mastocytosis compared with pediatric cases (42%). 5 Therefore the absence of a mutation in our patients could possibly indicate a favorable prognosis comparable to that of childhood UP. Seventy-nine-year-old man with Langerhans cell histiocytosis treated with cladribine…”