Dermatology: Practical and Conceptual


Image Letter | Dermatol Pract Concept. 2023;13(2):e2023082 1

Brooke-Spiegler Syndrome: Age-Related 
Progression in a Family Group

Andrea Michelerio1,2, Eloisa Arbustini3, Camilla Vassallo2

1 Department of Clinical-Surgical, Diagnostic and Pediatric Science, University of Pavia, Pavia, Italy

2 Dermatology Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

3 Centre for Inherited Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

Citation: Michelerio A, Arbustini E, Vassallo C. Brooke-Spiegler Syndrome: Age-Related Progression in a Family Group.  
Dermatol Pract Concept. 2023;13(2):e2023082. DOI: https://doi.org/10.5826/dpc.1302a82

Accepted: July 15, 2022; Published: April 2023

Copyright: ©2023 Michelerio et al. This is an open-access article distributed under the terms of the Creative Commons  
Attribution-NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted 
noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited.

Funding: None.

Competing Interests: None.

Authorship: All authors have contributed significantly to this publication.

Corresponding Author: Andrea Michelerio, M.D., Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 
and Dermatology Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. E-mail: andrea.michelerio01@universitadipavia.it

Case Presentation

A 56-year-old woman complained about numerous 

skin-colored papules localized on the face, mostly on the 

periorbital area, the nasolabial folds and the forehead 

( Figure 1, A and B). The first lesions had appeared during 

early adulthood and had slowly grown in number and size 

during the following years. Some had been removed and the 

histopathological examinations had revealed trichoepithelio-

mas, cylindromas and an eccrine spiradenomas.

The 81-year-old mother of the proband presented 

numerous nontender, skin-colored nodules and papules, 

varying in size, especially on her forehead, nasolabial 

folds, preauricular and occipital areas (Figure 1, C and 

D). The 24-years-old daughter of the proband presented 

few barely detectable papules on the nasolabial folds 

(Figure 1, E and F). A heterozygous pathogenetic variant 

(c.2552dup p.His851Glnfs*39) in exon 19 of the CYLD 

gene was found in the three women, confirming the diag-

nosis of Brooke-Spiegler syndrome (BSS).

Teaching Point

BSS is a rare autosomal dominant inherited syndrome due to 

germline mutations in the cylindromatosis (CYLD) gene, a 

tumor suppressor gene located on chromosome 16q12–q13. 

The disease is characterized by multiple adnexal cutaneous 

neoplasms such as cylindromas, trichoepitheliomas, and spi-

radenomas [1,2]. These appear as multiple papules or nod-

ules on the head and neck but can also arise on the trunk, 

genitals and armpits. The neoplasms typically develop at pu-

berty and progressively accumulate through adulthood [1]. 

They are usually benign but may undergo malignant trans-

formation in about 5%–10% of the patients [1]. Rarely sali-

vary gland tumors can be found [1]. The treatment is limited 

to repeated surgical excisions.



2 Image Letter | Dermatol Pract Concept. 2023;13(2):e2023082

Figure 1. Brooke-Spiegler syndrome. (A,B) The 56-year-old proband with multiple confluent 

skin-colored papules located on the face, especially in the periorbital area, in the nasolabial folds 

and forehead. (C,D) The 81-year-old mother of the proband with multiple discrete and confluent 

skin-colored papules and nodules. (E,F) The 24-years-old daughter of the proband, few barely 

detectable papules on the nasolabial folds (arrow).



Image Letter | Dermatol Pract Concept. 2023;13(2):e2023082 3

References

1. Kazakov DV. Brooke-Spiegler Syndrome and Phenotypic Vari-

ants: An Update. Head Neck Pathol. 2016;10(2):125-130. 

DOI: 10.1007/s12105-016-0705-x. PMID: 26971504. PMCID: 

PMC4838966.

2. Andersson MK, Kölby L, Nilsson JA, Stenman G. Clinical, 

 genetic and experimental studies of the Brooke-Spiegler (CYLD) 

skin tumor syndrome. J Plast Surg Hand Surg. 2019;53(2):71-75. 

DOI: 10.1080/2000656X.2018.1547736. PMID: 30676842.