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Review
. 2016 Jun;10(2):125-30.
doi: 10.1007/s12105-016-0705-x. Epub 2016 Mar 14.

Brooke-Spiegler Syndrome and Phenotypic Variants: An Update

Dmitry V Kazakov  1   2
Affiliations
Review

Brooke-Spiegler Syndrome and Phenotypic Variants: An Update

Dmitry V Kazakov. Head Neck Pathol. 2016 Jun.

Abstract

Brooke-Spiegler syndrome (BSS) is an inherited autosomal dominant disease characterized by the development of multiple adnexal cutaneous neoplasms most commonly spiradenoma, cylindroma, spiradenocylindroma, and trichoepithelioma. Multiple familial trichoepithelioma (MFT) is a phenotypic variant of the disease characterized by the development of numerous trichoepitheliomas (cribriform trichoblastoma) only. Malignant tumors arise in association with preexisting benign cutaneous neoplasms in about 5-10% of the patients . Apart from the skin, major and minor salivary glands have been rarely involved in BSS patients. Extremely rare is the occurrence of breast tumors (cylindroma). The gene implicated in the pathogenesis of the disease is the CYLD gene, a tumor suppressor gene located on chromosome 16q12-q13. Germline CYLD mutations are detected in about 80-85% of patients with the classical BSS phenotype and in about 40-50% of the individuals with the MFT phenotype using a PCR based approach with analysis of exonic sequences and exon-intron junctions of the CYLD gene. There appears to be no genotype-phenotype correlations with respect to the severity of the disease, the possibility of malignant transformation, and development of extracutaneous lesions.

Keywords: Brooke-Spiegler syndrome; CYLD gene; Cylindroma; Spiradenoma; Trichoepithelioma.

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Figures

Fig. 1
Fig. 1
Multiple lesions on the scalp in the patient with Brooke-Spiegler syndrome. Histologically, the lesions were spiradenomas, cylindromas, and spiradenocylindromas
Fig. 2
Fig. 2
Large ulcerated tumor in a patient with Brooke-Spiegler syndrome. Histology is depicted in Fig. 8. The patient died of multiple metastases
Fig. 3
Fig. 3
Multipe familial trichoepitheliomas: small bilateral papules preferentially involving the nasolabial folds. (Courtesy of Dr. Bernhard Zelger, Innsbruck, Austria)
Fig. 4
Fig. 4
Spiradenoma. Bland basaloid cells admixed with lymphocytes and droplets of basal membrane material. Focal ductal differentiation can be recognized
Fig. 5
Fig. 5
Cylindroma. The neoplastic nodules are arranged in a jigsaw puzzle and are composed of monomorphic basaloid cells surrounded by eosinophilic basement membrane material. The cells at the periphery show palisading and are darker than the cells located in the central parts of the nodules
Fig. 6
Fig. 6
Spiradenocylindroma. The lesion manifest in areas of typical cylindroma (lower part) as well as of spiradenoma (upper part)
Fig. 7
Fig. 7
Trichoepithelioma (cribriform trichoblastoma). The neoplasm has two components, namely the follicular germinative epithelium and the specific follicular stroma. The epithelial component is composed of bland basaloid cells arranged in a cribriform pattern, whereas the stroma resembles follicular papillae and the perifollicular sheath
Fig. 8
Fig. 8
High-grade malignant tumor composed of large basophilic cells evolving from a pre-existing spiradenoma, remnants of which can be recognized at the left. The malignant part can be likened to high-grade salivary gland basal cell adenocarcinoma
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