A clinicopathologic and molecular biologic study of patients presenting with few adnexal tumors (two to four) from the morphological spectrum of Brooke-Spiegler syndrome

Am J Dermatopathol. 2013 Feb;35(1):19-24. doi: 10.1097/DAD.0b013e318255dd37.


We report 11 individuals, each presenting with few (2-4) adnexal neoplasms histologically confirmed as belonging to the spectrum of lesions typical for Brooke-Spiegler syndrome (BSS) and/or multiple familial trichoepitheliomas. These include spiradenoma, cylindroma, spiradenocylindroma, and trichoblastoma variants. Our objective was to clarify whether this is merely a sporadic, albeit unusual, occurrence of multiple neoplasms in these patients or whether they are related to BSS and its phenotypic variant, multiple familial trichoepithelioma. Six patients presented with 2 neoplasms, 4 had 3 lesions and the last had 4 lesions. In none was there any family history of similar lesions. The 28 neoplasms consisted of 7 spiradenomas, 6 cylindromas, 5 spiradenocylindromas, and 11 trichoblastomas (6 trichoepitheliomas and 5 with mixed patterns). In 1 patient only with 2 spiradenomas, both tumors harbored identical CYLD sequence alterations (c.1112C>A/S371X) in the CYLD gene and both showed loss of heterozygosity on chromosome 16q. The remaining cases yielded neither germ line nor somatic alterations in CYLD. It is concluded that the presentation with few (2-4) cylindromas, spiradenomas, spiradenocylindromas, and trichoepitheliomas is a sporadic occurrence, and that these patients do not have any relationship to BSS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biopsy
  • Chromosomes, Human, Pair 16
  • DNA Mutational Analysis
  • Deubiquitinating Enzyme CYLD
  • Female
  • Genetic Predisposition to Disease
  • Heredity
  • Humans
  • Loss of Heterozygosity
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasms, Adnexal and Skin Appendage / genetics*
  • Neoplasms, Adnexal and Skin Appendage / pathology*
  • Neoplasms, Multiple Primary / genetics*
  • Neoplasms, Multiple Primary / pathology*
  • Neoplastic Syndromes, Hereditary / genetics*
  • Neoplastic Syndromes, Hereditary / pathology*
  • Phenotype
  • Predictive Value of Tests
  • Retrospective Studies
  • Skin / pathology*
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology*
  • Tumor Suppressor Proteins / genetics*


  • Tumor Suppressor Proteins
  • CYLD protein, human
  • Deubiquitinating Enzyme CYLD

Supplementary concepts

  • Familial cylindromatosis