Brooke-Spiegler syndrome

CYLD cutaneous syndrome (current preferred term — encompasses BSS, multiple familial trichoepithelioma and familial cylindromatosis); turban tumour syndrome (older descriptive term)

Brooke-Spiegler syndrome is an autosomal dominant adnexal tumour predisposition syndrome caused by germline loss-of-function mutations of the CYLD tumour-suppressor gene on chromosome 16q12.1. Affected individuals develop multiple, often disfiguring, slow-growing benign adnexal tumours from late adolescence — most commonly cylindromas (especially of the scalp, where confluence produces the classical "turban tumour" appearance), spiradenomas and trichoepitheliomas. Penetrance is high. The 2019 WHO classification grouped Brooke-Spiegler syndrome, multiple familial trichoepithelioma and familial cylindromatosis as a single entity — CYLD cutaneous syndrome — to reflect their shared underlying genetic defect. The principal long-term oncological concern is the small but definite risk of malignant transformation to spiradenocarcinoma, cylindrocarcinoma or membranous basal cell adenocarcinoma, particularly in long-standing scalp cylindromas. Multidisciplinary care (dermatology, plastic surgery, clinical genetics) is essential.

CurrentLast reviewed 26 April 2026

Genetics

Germline loss-of-function mutations of CYLD on chromosome 16q12.1 — a deubiquitinating enzyme regulating NF-κB and Wnt signalling.
Autosomal dominant; high penetrance (~90% by age 40).
"Second hit" loss of the wild-type allele in tumour tissue drives lesion formation.
Variable phenotype — some patients dominated by cylindromas, others by trichoepitheliomas, others by spiradenomas; frequently a mix.

Clinical features

Cylindromas — firm, smooth, pink-red dermal nodules on the scalp, head and neck; confluence produces the classical "turban tumour".
Spiradenomas — usually painful, firm, blue-grey nodules on the trunk and extremities.
Trichoepitheliomas — multiple small skin-coloured papules concentrated around the nasolabial folds, eyelids and forehead; classically becomes confluent in late adulthood.
Onset typically late adolescence to early adulthood; lesions accumulate over decades, often hundreds in older patients.
Cosmetic disfigurement and functional impact (eyelid, ear, scalp) are major patient concerns.
Salivary gland tumours (parotid spiradenoma) reported.

Malignant transformation

Estimated 5–10% lifetime risk of malignant transformation in any single tumour.
Most common transformations:
- Spiradenocarcinoma — see monograph.
- Cylindrocarcinoma — malignant transformation of cylindroma; aggressive.
- Membranous basal cell adenocarcinoma (basal cell adenocarcinoma of salivary gland-type) of the scalp.
Warning signs: abrupt growth, ulceration, pain or bleeding in a previously stable nodule that has been present for many years.
Any clinical change should prompt biopsy.

Diagnosis

Clinical recognition — multiple typical adnexal tumours from young adulthood + family history.
Excisional biopsy of a representative lesion confirms histology.
Genetic counselling and germline CYLD testing.
Cascade testing of first-degree relatives.

Management

Excision of individual symptomatic, disfiguring or atypical lesions.
For extensive scalp involvement: total scalp excision and reconstruction with split-thickness skin graft or tissue expander / free flap (specialist plastic surgery centre).
CO₂ laser ablation, electrosurgery, dermabrasion for facial trichoepitheliomas — multiple sessions, recurrence common.
Topical / intralesional therapies (salicylic acid, imiquimod, sirolimus) — emerging; limited evidence.
Annual full-skin review; biopsy any changing or atypical lesion.
Multidisciplinary team — dermatology, plastic surgery, clinical genetics, often facial-aesthetic plastic surgery.
Genetic counselling for the patient and family.