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Brooke-Spiegler syndrome

  • Author(s): Kim, Carolyn
  • Kovich, Olympia I
  • Dosik, Jonathan
  • et al.
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Brooke-Spiegler syndrome
Carolyn Kim MD, Olympia I Kovich MD, Jonathan Dosik MD
Dermatology Online Journal 13 (1): 10

New York Univeristy Department of Dermatology

Abstract

A 46-year-old woman with Brooke-Spiegler syndrome has multiple cutaneous adnexal neoplasms on her face and scalp. One of the lesions has concurrent features of cylindroma, trichoepithelioma, and spiradenoma in the same specimen. Etiology, clinical features, malignant transformation, and treatment modalities for Brooke-Spiegler syndrome are reviewed.



Clinical synopsis

A 46-year-old woman presented with numerous lesions on her face and scalp. She reported that the lesions started as isolated, small bumps on her face when she was in her early twenties, and slowly grew more numerous until the bumps appeared as cobblestoned skin. Approximately 10 years after the onset of facial lesions, she noticed small nodular growths on her scalp. Over the past decade, she has had multiple excisions of the scalp nodules and experienced continual growth of new lesions. All of the lesions are asymptomatic. Her parents and her teenage children are unaffected.

Along the hairline and on the forehead, temples, nose, medial aspects of the cheeks, nasolabial folds, and upper lip areas were numerous, small, 1-3 mm, flesh-colored, nontender, nonpruritic papules. On the scalp are multiple 5-7 mm, firm, dome-shaped, nontender nodules, with no associated loss of hair.


Figure 1Figure 2

Histopathology reveals circumscribed aggregates of small epithelial cells that are partially rimmed by eosinophilic basement membrane material. Additionally, there is a proliferation of basaloid cells arranged as branching cords with focal follicular differentiation.


Comment

Brooke-Spiegler syndrome is an uncommon disease with a predisposition to develop cutaneous adnexal neoplasms such as cylindromas, trichoepitheliomas, spiradenomas, trichoblastomas, basal-cell carcinomas, follicular cysts, organoid nevi, and malignant transformation of pre-existing tumors in the affected individuals [1]. Brooke-Spiegler syndrome is inherited in autosomal-dominant fashion, although expression and penetrance are variable. Lesions usually begin to appear in the second or third decades and gradually increase in number and size throughout adult life. Women are affected more frequently than are men. Mutations in the CYLD tumor-suppressor gene have been implicated in the phenotype diversity [2].

Cylindromas, trichoepitheliomas, and spiradenomas, which are the most commonly observed tumors, are typically located on the head and neck. Scalp cylindromas can become numerous and may eventually cover the entire scalp, which results in the so-called turban tumors and may result in partial or complete hair loss. Although cylindromas are usually benign neoplasms, malignant transformation to cylindrocarcinomas is rare but well documented. The malignant cylindroma is locally aggressive, often metastasizes, and requires careful followup surveillance [3, 4]. Trichoepitheliomas are usually numerous and located on the face. In addition to neoplasms of the skin appendages, patients with Brooke-Spiegler syndrome also are at risk for developing tumors of the salivary glands, such as basal-cell adenomas and adenocarcinomas of the parotid glands and minor salivary glands [5].

Multiple trichoepitheliomas may be seen also in two other rare syndromes: Rombo syndrome (vermicular atrophoderma, milia, hypotrichosis, basal-cell carcinomas, trichoepitheliomas, and peripheral vasodilatation with cyanosis) and Bazex syndrome (follicular atrophoderma, hypotrichosis, occasional trichoepitheliomas, basal-cell carcinomas, and localized or generalized hypohidrosis) [6].

The histolopathologic spectrum of Brooke-Spiegler syndrome is broad and encompasses benign adnexal neoplasms of apocrine, follicular, and sebaceous differentiation, which can occur independently and conjointly. The most unusual findings are neoplasms with hybrid features, such as spiradenocylindromas, spiradenoma-trichoepitheliomas, cylindroma-trichoepitheliomas, and even the concurrence of all three adnexal tumors in one lesion [1, 7].

Treatment methods for adnexal neoplasms include excision, dermabrasion, electrodesiccation, cryotherapy, and radiotherapy. In addition, successful treatment with lasers such as the argon, CO2, and erbium:Yag plus CO2 have been reported [8]. Medical treatments for cylindromas that are currently being tested include sodium salicylate and prostaglandin A1, which are thought to restore growth control by inhibiting NF-B activity [9].

References

1. Kazakov DV, et al. Brooke-Spiegler syndrome: report of a case with combined lesions containing cylindromatous, spiradenomatous, trichoblastomatous, and sebaceous differentiation. Am J Dermatopathol 2005;27:27

2. Gutierrez PP, et al. Phenotype diversity in familial cylindromatosis: a frameshift mutation in the tumor suppressor gene CYLD underlies different tumors of skin appendages. J Invest Dermatol 2002;119:527

3. Hu G, et al. A novel missense mutation in CYLD in a family with Brooke-Spiegler syndrome. J Invest Dermatol 2003; 121:732

4. De Francesco V, et al. Carcinosarcoma arising in a patient with multiple cylindromas. Am J Dermatopathol 2005;27:21

5. Bowen S, et al. Mutations in the CYLD gene in Brooke-Spiegler syndrome, familial cylindromatosis, and multiple familial trichoepithelioma: lack of genotype-phenotype correlation. J Invest Dermatol 2005;124:919

6. Szepietowski JC, et al. Brooke-Spiegler syndrome. J Eur Acad Dermatol Venereol 2001;15:346

7. Ly H, et al. Case of the Brooke-Spiegler syndrome. Australas J Dermatol 2004;45:220

8. Rallan D, Harland CC. Brooke-Spiegler syndrome treatment with laser ablation. Clin Exp Dermatol 2005;30:355

9. Brummelkamp TR, et al. Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF- B. Nature 2003; 424: 738

© 2007 Dermatology Online Journal