Virchows Archiv

, Volume 473, Issue 2, pp 241–246 | Cite as

A case of multiple familial trichoepitheliomas responding to treatment with the Hedgehog signaling pathway inhibitor vismodegib

  • Vera Baur
  • Thomas Papadopoulos
  • Dmitry V. Kazakov
  • Abbas Agaimy
  • Arndt Hartmann
  • Georg Isbary
  • Ralph M. Wirtz
  • Erwin S. Schultz
Brief Report


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.


CYLD Vismodegib Trichoepithelioma Brooke syndrome Hedgehog pathway 



Brooke–Spiegler syndrome


cylindromatosis gene


familial Cylindromatosis


glioma-associated oncogene


multiple familial trichoepithelioma


multiplex ligation-dependent probe amplification


NFkB essential modulator


patched gene


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.

Authors’ contributions

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.

Informed consent

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

Not applicable


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of DermatologyParacelsus Medical University NurembergNürnbergGermany
  2. 2.Institute of PathologyParacelsus Medical University NurembergNurembergGermany
  3. 3.Department of Pathology, Medical Faculty in PilsenCharles University PraguePilsenCzech Republic
  4. 4.Institute of PathologyFriedrich Alexander University, Erlangen-NurembergErlangenGermany
  5. 5.Roche Pharma-AG, Grenzach-WyhlenGrenzachGermany
  6. 6.STRATIFYER Molecular Pathology GmbH, Cologne and Institute of PathologySt. Elisabeth Hospital, CologneCologneGermany

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