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Virchows Arch. 2018 Aug;473(2):241-246. doi: 10.1007/s00428-018-2397-y. Epub 2018 Jun 22.

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

Author information

1
Department of Dermatology, Paracelsus Medical University Nuremberg, Prof.-Ernst Nathan Straße 1, 90419, Nürnberg, Germany.
2
Institute of Pathology, Paracelsus Medical University Nuremberg, Prof.-Ernst Nathan Straße 1, 90482, Nuremberg, Germany.
3
Department of Pathology, Medical Faculty in Pilsen, Charles University Prague, Alej Svobody 80, 304 60, Pilsen, Czech Republic.
4
Institute of Pathology, Friedrich Alexander University, Erlangen-Nuremberg, Krankenhausstrasse 8-10, 91054, Erlangen, Germany.
5
Roche Pharma-AG, Grenzach-Wyhlen, Emil-Barell Straße 1, 79639, Grenzach, Germany.
6
STRATIFYER Molecular Pathology GmbH, Cologne and Institute of Pathology, St. Elisabeth Hospital, Cologne, Werthmannstraße 1, 50935, Cologne, Germany.
7
Department of Dermatology, Paracelsus Medical University Nuremberg, Prof.-Ernst Nathan Straße 1, 90419, Nürnberg, Germany. Erwin.Schultz@klinikum-nuernberg.de.

Abstract

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.

KEYWORDS:

Brooke syndrome; CYLD; Hedgehog pathway; Trichoepithelioma; Vismodegib

PMID:
29934657
DOI:
10.1007/s00428-018-2397-y
[Indexed for MEDLINE]

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