A case of multiple familial trichoepitheliomas responding to treatment with the Hedgehog signaling pathway inhibitor vismodegib
Multiple familial trichoepitheliomas (MFT) is an autosomal dominantly inherited disease characterized by multiple skin appendage tumors. We describe a patient showing a continuous spectrum of follicular differentiated neoplasms including classical trichoepitheliomas but also infiltrative growing and finally metastasizing malignant follicular differentiated tumors. Germline mutation analysis revealed a nonsense mutation in the cylindromatosis (CYLD) gene. Gene expression analysis by real-time PCR of tumor tissue showed overexpression of glioma-associated oncogene Gli1 mRNA. Treatment with the Hedgehog pathway inhibitor vismodegib resulted in a significant regression of the highly differentiated trichoepitheliomas. Gli upregulation is indicative of an active Hedgehog signaling pathway. We hypothesize that its upregulation is indirectly caused by CYLD mutation which promotes tumor development. Vismodegib treatment could thus provide a new treatment option for patients with this debilitating disorder.
KeywordsCYLD Vismodegib Trichoepithelioma Brooke syndrome Hedgehog pathway
multiple familial trichoepithelioma
multiplex ligation-dependent probe amplification
NFkB essential modulator
suppressor of fused
TNF receptor-associated factor
We thank Prof. Dr. André Reis and Dr. rer. nat. Cornelia Kraus from the Institute of Human Genetics in Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Germany, for performing the analysis of PTCH gene and Mrs. Kirsten Bochmann for graphical assistance.
All authors fulfill the ICMJE criteria for authorship.
Compliance with ethical standards
The authors declare to follow the rules of good clinical practice and adhere to COPE (Committee on Publication Ethics) guidelines.
Conflict of interest
RW is employee of STRATIFYER Molecular Pathology GmbH. GI is employee of Roche Pharma AG. All other authors declared not to have any competing interests.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
Research involving human participants and/or animals
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