Desmosomal-Type Acantholysis—A New Histologic Pattern Related to Mutations of Genes for Desmosomal Proteins

Desmosomes are specialized cell-cell junctions that play a crucial role in maintaining the structural integrity of both cornifying and non-cornifying epithelium. Disruption of desmosomal cohesion in autoimmune, infectious, and other diseases is typically associated with acantholysis, often leading to intraepidermal blisters and erosions. In recent decades, genetic mutations have been identified that impair desmosomal integrity to varying degrees, giving rise to a spectrum of genodermatoses. These conditions, which include palmoplantar keratoderma, epidermolysis bullosa, and ichthyoses, can range from mild to severe, with some forms being syndromic and life-threatening. We investigated dermatopathologic changes in patients with mutations in genes encoding desmosomal proteins seen in consultations at our genodermatoses unit. A series of cases, including keratosis palmoplantaris areata et striata (striated palmoplantar keratoderma type 1), Carvajal-Huerta syndrome, severe dermatitis-multiple allergies-metabolic wasting (SAM) syndrome, ectodermal dysplasia-skin fragility syndrome, and inflammatory peeling skin disease, was examined histologically and, when necessary, immunohistochemically. Findings from our cohort were compared with histopathological consultation cases from our dermatopathology laboratory and previously published cases in the literature. Through these observations, we defined a distinct form of acantholysis associated with desmosomal protein mutations, which we term "desmosomal-type acantholysis." We outline the spectrum of this newly characterized pattern and highlight its differences from conventional forms of acantholysis. Furthermore, for the first time, we describe incidental cases where "desmosomal-type acantholysis" appears sporadically in solitary acanthoma and in association with a melanocytic nevus.