Reactional squamous hyperplasia of the foreskin

Abstract

axillae or groyne area. A skin biopsy obtained from a skin lesion on the waist showed parakeratosis, acanthosis, acantholysis and subcorneal lacunae with acantholytic cells and dyskeratotic keratinocytes (Fig. 1d). As the Blaschkoid distribution of skin lesions indicates keratinocyte-specific somatic mosaicism, we compared the genomic DNA purified from the lesional skin against that from peripheral blood after obtaining written informed consent according to the guidelines of the Institutional Review Boards. Exome sequencing revealed a missense c.479C>T (p.P160L) mutation in ATP2A2 in a mosaic manner (C allele, 110 reads; T allele, 16 reads) and Sanger sequencing confirmed that the mutation was specific to the lesional skin (Fig. 1e). Thus, we diagnosed the patient with segmental Darier disease caused by the somatic mutation of c.479C>T in ATP2A2. Addition of 10 mg/day of oral etretinate brought considerable amelioration (Fig. 1f). Skin lesions are basically limited to seborrhoeic and intertriginous areas in both congenital and type 1 segmental forms of Darier disease. In contrast, our case of type 1 segmental Darier disease was characterized by skin lesions widely spreading from his left waist to thigh in a Blaschkoid distribution. This characteristic phenotype is presumably associated with the p.P160L mutation of ATP2A2. Four patients with the congenital form of Darier disease with p.P160L mutation have been reported, two of whom were documented with detailed skin phenotypes. 4-7 The two patients showed severe skin phenotypes including extensive, hyperkeratotic and macerated plaques distributed widely on the trunk and extremities. 4,6 It is speculated that the p.P160L mutation brings a large amount of rotation in the A domain between E(1)P and E (2)P of SERCA2, causes a proteolytic cut of the link between the A domain and M3, resulting in complete inhibition of SERCA2 activity, and therefore induces the severe disease phenotype. 4,8-10 Thus, the characteristic Blaschkoid distribution of skin lesions observed in our case is considered to be due to type 1 mosaicism of severe Darier disease caused by the p.P160L mutation of ATP2A2 but not due to type 2 mosaicism, which further expands the genotype-phenotype correlations in segmental Darier disease.