BrookeSpiegler Syndrome Quyn Sherrod MD Miguel Gutierrez MD

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

History v 39 year-old, healthy, Caucasian male v Multiple lesions on face and scalp beginning at 10 years old v Nonpainful, nonpruritic v Previous paranasal biopsy consistent with trichoepithelioma v Mother with similar presentation

Physical Exam

Histopathology

Histopathology Scalp cylindroma-spiradenoma

Histopathology Scalp cylindroma

Histopathology Scalp spiradeoma

Histopathology Face trichoepithelioma

Brooke-Spiegler Syndrome

Brooke-Spiegler Syndrome v Uncommon syndrome with autosomal dominant inheritance pattern v Variable expression and penetrance v More severe phenotype in women v Mutiple cutaneous adnexal neoplasms v Cylindromas, spiradenomas, trichepitheliomas on head and neck

Clinical Presentation v Begins during second or third decade v Cylindromas, spiradenomas on scalp v ‘Turban tumors’ when numerous v Trichoepitheliomas more common on face v Progressive increase in size and number

Genetics v Autosomal dominant mutation affecting epidermal appendages v CYLD gene on chromosome 16 q 12 -q 13 v CYLD functions as a tumor suppresor v CYLD inhibits NF-κB transcription factor in the TNF-α signaling pathway, regulating cell growth

Differential Diagnosis Familial cylindromatosis v Multiple familial trichoepithelioma v Rombo syndrome v – – – v Vermicular atrophoderma - Milia Basal cell carcinomas - Hypotrichosis Peripheral vasodilation/cyanosis - Trichoepitheliomas Bazex syndrome – – – Follicular atrophoderma Basal cell carcinomas Hypohidrosis - Hypotrichosis - Trichoepitheliomas

Prognosis v Psychologic impact due to physical disfigurement v Rare malignant transformation of trichoepitheliomas into basal cell carcinomas – -Low metastatic potential v Rare malignant transformation of cylindromas and spiradenomas – -Local infiltration and distant metastases reported v Increased risk for salivary and parotid gland adenomas and adenocarcinomas

Treatment v v v v Excision Dermabrasion Electrodessication Cryotherapy Radiotherapy Laser- Argon, erbium: Yag, CO 2 Medical therapy with sodium salicylate and prostaglandin A 1 is under investigation – -Inhibit NF-κB activiation v Monitor for clinical signs of malignant transformation

References v v v v 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.