Brooke-Spiegler Syndrome

Quyn Sherrod, MD; Miguel Gutierrez, MD; Keith Carlson, MD

UCLA/WLA VA Division of Dermatology David Geffen School of Medicine

Los Angeles, California

HistoryHistory

39 year-old, healthy, Caucasian maleMultiple lesions on face and scalp

beginning at 10 years oldNonpainful, nonpruriticPrevious paranasal biopsy consistent

with trichoepitheliomaMother with similar presentation

Physical ExamPhysical Exam

Physical ExamPhysical Exam

Physical ExamPhysical Exam

Physical ExamPhysical Exam

HistopathologyHistopathology

HistopathologyHistopathologyScalp cylindroma-spiradenoma Scalp cylindroma-spiradenoma

HistopathologyHistopathologyScalp cylindromaScalp cylindroma

HistopathologyHistopathologyScalp spiradeomaScalp spiradeoma

HistopathologyHistopathologyFace trichoepitheliomaFace trichoepithelioma

Brooke-Spiegler SyndromeBrooke-Spiegler Syndrome

Brooke-Spiegler SyndromeBrooke-Spiegler Syndrome

Uncommon syndrome with autosomal dominant inheritance pattern

Variable expression and penetranceMore severe phenotype in womenMutiple cutaneous adnexal neoplasmsCylindromas, spiradenomas,

trichepitheliomas on head and neck

Clinical PresentationClinical PresentationBegins during second or third decadeCylindromas, spiradenomas on scalp ‘Turban tumors’ when numerousTrichoepitheliomas more

common on faceProgressive increase in size and

number

GeneticsGenetics

Autosomal dominant mutation affecting epidermal appendages

CYLD gene on chromosome 16q12-q13CYLD functions as a tumor suppresorCYLD inhibits NF-κB transcription factor

in the TNF-α signaling pathway, regulating cell growth

Differential DiagnosisDifferential Diagnosis

Familial cylindromatosis Multiple familial trichoepithelioma Rombo syndrome

– Vermicular atrophoderma - Milia– Basal cell carcinomas - Hypotrichosis– Peripheral vasodilation/cyanosis - Trichoepitheliomas

Bazex syndrome– Follicular atrophoderma - Hypotrichosis– Basal cell carcinomas - Trichoepitheliomas– Hypohidrosis

PrognosisPrognosis

Psychologic impact due to physical disfigurement

Rare malignant transformation of trichoepitheliomas into basal cell carcinomas– -Low metastatic potential

Rare malignant transformation of cylindromas and spiradenomas– -Local infiltration and distant metastases reported

Increased risk for salivary and parotid gland adenomas and adenocarcinomas

TreatmentTreatment

Excision Dermabrasion Electrodessication Cryotherapy Radiotherapy Laser- Argon, erbium:Yag, CO2 Medical therapy with sodium salicylate and

prostaglandin A1 is under investigation– -Inhibit NF-κB activiation

Monitor for clinical signs of malignant transformation

ReferencesReferences Kakagia D, Lambropoulou M, Alexiadis G. Brooke-Spiegler syndrome with

parotid gland enlargement. Eur J Dermatol. 2004 May-Jun;14(3):139-41. Kim C, Kovich OI, Dosik J. Brooke-Spiegler syndrome. Dermatol Online J.

2007 Jan 27;13(1):10. Zhang GL, Huang YJ, Yan KL et al. Diverse phenotype of Brooke-Spiegler

syndrome associated with a nonsense mutation in the CYLD tumor suppressor gene. Exp Dermatol. 2006 Dec;15(12):966-70.

Ly H, Black MM, Robson A. Case of the Brooke-Spiegler syndrome. Australas J Dermatol. 2004 Nov;45(4):220-2.

Szepietowski JC, Wasik F, Szybejko-Machaj G et al. Brooke-Spiegler syndrome. J Eur Acad Dermatol Venereol. 2001 Jul;15(4):346-9.

Ralla D, Harland CC. Brooke-Spiegler syndrome: treatment with laser ablation. Clin Exp Dermatol. 2005 Jul;30(4):355-7.

Lee DA, Grossman ME, Schneiderman P et al. Genetics of skin appendage neoplasms and related syndromes. J Med Genet. 2005 Nov;42(11):811-9.