Coinheritance of BRCA2 and CYLD Germline Pathogenic Variants Associated with Targetable Metastatic Malignant Cylindroma

This study presents a unique case of a 29-year-old man with metastatic malignant cylindroma, highlighting the coinheritance of germline pathogenic variants in both BRCA2 and CYLD genes. The patient, who had a history of scalp cylindromas since age 8, inherited CYLD variants from his mother and BRCA2 variants from his father. His sister also had both variants and was diagnosed with breast cancer and CCS. The proband's malignant cylindroma showed high-grade features and metastasized to the neck, lungs, and brain. Genetic testing confirmed the presence of both BRCA2 and CYLD variants, suggesting the potential use of poly-ADP ribose polymerase inhibitors, typically used for BRCA deficiency, as a novel treatment approach. This case underscores the significance of recognizing the coinheritance of tumor suppressor genes for developing targeted therapies and improving patient outcomes.