Advanced <scp>CYLD</scp> Cutaneous Syndrome ( <scp>CCS</scp> ) Treated With the Hedgehog Signaling Pathway Inhibitor Vismodegib Results in a Limited Clinical Response

CYLD Cutaneous syndrome (CCS) is a rare autosomal dominantly inherited disease associated with multiple nodular adnexal skin tumors, most commonly trichoepitheliomas and cylindromas. There is no evidence-based treatment for this disease. This study aimed to present the histological response and to investigate whether molecular and immunohistochemical analyses (exome sequencing) may provide insight into the rapid disease development and lack of response to treatment with Vismodegib. A patient treated with the Hedgehog Pathway Inhibitor Vismodegib. The CYLD (c.1437_1438del, p.Pro480PhefsTer16) frameshift deletion was identified in the family of our patient. In addition, our patient also lost the unaffected allele and was consequently homozygous for the deletion. Treatment with Vimodegib was unfortunately not effective. Furthermore, we observed no possible biomarkers of progression and/or treatment response. Hopefully, further studies will contribute to the genetic understanding of BSS and identify patients at high risk of developing severe disease, thereby supporting the stratification of patients who will benefit from early surgical treatment or treatment with Vismodegib.