Abstract
Papular epidermal naevus with ‘skyline’ basal cell layer (PENS) is a rare type of keratinocytic epidermal naevus (KEN),1 mostly reported as an isolated condition or associated with neurological disorders defining the PENS syndrome.2 The most notable histopathological feature – the ‘skyline’ – is characterized by a well-defined basal cell layer in a ‘palisade’ configuration.1 No germline and/or post-zygotic pathogenic gene variant has yet been reported in PENS. We herein describe five patients with PENS displaying a somatic epidermal growth factor receptor (EGFR) exon 20 in-frame insertion (EGFR ex20ins) pathogenic variant (PV).Five patients diagnosed with PENS were seen in the Department of Dermatology of Montpellier University Hospital, France, between 2018 and 2023. Genomic DNA was extracted from lesional skin biopsies. Next-generation sequencing (NGS) analyses used a custom amplicon-based panel designed to detect genomic alterations in exons of at least 20 clinically relevant cancer genes. When possible, Sanger experiments then confirmed the detected alterations. Whole-exome sequencing (WES) was conducted on genomic DNA extracted from peripheral white blood cells (WBC).