CPC12 Coinheritance of <i>BRCA2</i> and <i>CYLD</i> germline pathogenic variants associated with targetable metastatic malignant cylindroma

Abstract CYLD cutaneous syndrome (CCS) presents during puberty with the development of hair follicle tumours, including cylindromas, spiradenomas or trichoepitheliomas, and is associated pathogenic variants in tumour suppressor gene CYLD. Germline BRCA2 are an increased risk breast, ovarian, pancreatic prostate cancer. Coinheritance both genes has not been previously reported, here, we present a 29-year-old man metastatic malignant cylindroma, where knowledge germline targetable therapeutic implications. The proband presented cylindromas on his scalp from age 8 years, inherited mother who had CCS. proband’s father paternal grandmother early-onset breast 33-year-old sister diagnosed cancer CCS; genetic testing revealed Aged 28 growing, ulcerated cylindroma scalp. Histology biphasic neoplasm, showing high-grade features arising within pre-existing benign cylindroma. epithelioid component showed brisk mitotic activity (25 mitoses per mm2) large infiltrative nests central comedo-type necrosis. Immunohistochemistry positivity for epithelial membrane antigen, CK7, p63 patches CK5/6, whereas carcinoembryonic S100 human melanoma black-45 were negative. Several weeks after excision lump left side patient’s neck; biopsy histology consistent Radiological imaging deposits right axilla, lungs brain. Genetic CYLD, as seen sister. patient received radiotherapy neck, partial resolution symptoms gamma-knife ablation brain metastases. DNA extracted was analysed using high-resolution single-nucleotide polymorphism array, which demonstrated loss heterozygosity loci. somatic this support use unlicensed therapeutics that target BRCA deficiency, such poly-ADP ribose polymerase inhibitors, have used to treat This case emphasizes importance recognizing coinheritance rare conditions, can provide novel management options improve outcomes.