Brooke-Spiegler syndrome: Report of two cases not associated with a mutation in the CYLD and PTCH tumor-suppressor genes

Giovanni Ponti, Sabina Nasti, Lorena Losi, Lorenza Pastorino, Annamaria Pollio, Luisa Benassi, Stefania Giudice, Giorgia Bertazzoni, Eugenia Veratti, Paola Azzoni, Bianchi Scarrá, Stefania Seidenari

Research output: Contribution to journalArticlepeer-review


Brooke-Spiegler syndrome represents an autosomal dominant disease characterized by the occurrence of multiple cylindromas, trichoepitheliomas and (sporadically) spiroadenomas. Patients with Brooke-Spiegler syndrome are also at risk of developing tumors of the major and minor salivary glands. Patients with Brooke-Spiegler syndrome have various mutations in the CYLD gene, a tumor-suppressor gene located on chromosome 16q. To date, 68 unique CYLD mutations have been identified. We describe two families with Brooke-Spiegler syndrome, one with familial cylindromatosis and one with multiple familial trichoepithelioma, which showed wide inter-family phenotypic variability. Analysis of germline mutations of the CYLD and PTCH genes was performed using peripheral blood. In addition, formalin-fixed paraffin-embedded tumor samples were analyzed for PTCH somatic mutations and cylindroma cell cultures were obtained directly from patients for further growth and analysis. Clinically, the major features of Brooke-Spiegler syndrome include the presence of heterogeneous skin tumors and wide inter- and intra-familial phenotypic variability. Histopathologically, both cylindromas and trichoepitheliomas were found in affected individuals. Mutations or loss of heterozygosity was not found in CYLD and PTCH genes. In CYLD and PTCH mutation-negative patients, other genes may be affected and further studies are needed to clarify whether these patients may be affected by de novo germline mutations.

Original languageEnglish
Pages (from-to)366-371
Number of pages6
JournalJournal of Cutaneous Pathology
Issue number3
Publication statusPublished - Mar 2012


  • Brooke-Spiegler syndrome
  • CYLD
  • cylindroma
  • familial trichoepithelioma
  • PTCH
  • spiroadenoma
  • trichoepithelioma

ASJC Scopus subject areas

  • Dermatology
  • Pathology and Forensic Medicine
  • Histology


Dive into the research topics of 'Brooke-Spiegler syndrome: Report of two cases not associated with a mutation in the CYLD and PTCH tumor-suppressor genes'. Together they form a unique fingerprint.

Cite this