P033 Multiple scalp and neck lesions in an 80-year-old man

Abstract Mosaic CYLD cutaneous syndrome (CCS) is a rare disorder marked by multiple benign adnexal skin tumours (Sun S-C. CYLD: a tumor suppressor deubiquitinase regulating NF-κB activation and diverse biological processes. Cell Death Differ 2009; 17: 25–34). CCS typically manifests in adolescence or early adulthood, with an autosomal dominant pattern of inheritance. Late-onset presentations without a family history are uncommon and may be attributed to somatic mosaic mutations. An 80-year-old man presented with a 5-year history of over 20 painless pink papules and nodules on the scalp and neck, varying in size (2 mm to 3 cm) and colour (skin-coloured to pink). Dermoscopy revealed arborizing telangiectasia with background structureless pink colour. Histopathology from five punch biopsies demonstrated basaloid neoplasms with prominent basement membranes arranged in a ‘jigsaw’ pattern, consistent with a diagnosis of multiple cylindromas. Despite no family history of cutaneous disease, genetic testing detected a pathogenic mosaic variant in the CYLD gene (c.2299A>T; p.Lys767*), confirming a diagnosis of mosaic CCS. Cylindromas are rare, benign, undifferentiated skin tumours, frequently associated with germline CYLD mutations in hereditary conditions such as Brooke–Spiegler syndrome. CYLD, a tumour suppressor gene, regulates the nuclear factor-κB signalling pathway, and its loss-of-function mutations impair negative regulation of cell survival and oncogenesis. Mosaic CCS arises from postzygotic mutations and is rarely reported, particularly in older patients. The observed mosaicism with low minor allele frequency (< 0.01%) likely contributed to the patient’s late-onset signs. Although cylindrocarcinomas are typically benign, malignant transformation can occur in multiple cylindromas, necessitating regular monitoring and surgical management. Scalp-sparing excision techniques are used to manage the risk of recurrence and malignant transformation. Our patient’s children showed no evidence of inherited disease; however, genetic counselling could be carried out to investigate potential germline transmission risks. This case highlights the importance of understanding the genetic basis and clinical variability of CYLD mutation syndromes, which is crucial for accurate diagnosis, risk assessment, management and genetic counselling. It also emphasizes the need for detailed genetic and histopathological evaluations to distinguish mosaic from hereditary forms, especially in cases with atypical late-onset presentations.