Brooke-Spiegler syndrome variant: segregation of tumor types with mixed differentiation in two generations

Abstract

Brooke-Spiegler syndrome (BSS) is an autosomal dominantly inherited disease characterized by the development of multiple trichoepitheliomas and cylindromas. Other lesions have been reported to occur in patients with BSS, including parotid basal cell adenomas, milia, organoid nevi, basal cell carcinomas, and spiradenomas. Spiradenomas and cylindromas have so many features in common that they have been regarded as polar extremes belonging to a spectrum of cutaneous adnexal neoplasms. We report on a 61-year-old woman with multiple spiradenomas on the scalp and periauricular areas and her 28-year-old daughter, with multiple facial trichoepitheliomas. Occasional features of pilar and ductal differentiation were found in tissue specimens of tumors from the mother and daughter, respectively. Co-existence of multiple spiradenomas and trichoepitheliomas and segregation of the predominant type of tumor in different members of a family with BSS have been reported occasionally, but never, to our knowledge, in combination. The presence of mixed differentiation in tumor specimens from both patients provides additional evidence in support of the folliculosebaceous apocrine unit (FSAU) hypothesis. Mutations in genes regulating proliferation and differentiation of putative stem cells of the FSAU would give rise to different combinations of adnexal skin tumors as well as to other neoplasms.