Brooke-Spiegler Syndrome and Phenotypic Variants: An Update

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.

Potential Difficulties in Cytological Approach of Basal Cell Adenoma of Salivary Glands: The Experience of a Single Institution

“…Therefore, clinical examination of the skin or oral mucosa is also useful to exclude these skin or oral mucosa neoplasms involving salivary glands [2]. Moreover, attention should be paid to patients with Brooke-Spiegler syndrome, an inherited autosomal dominant disease characterized by the development of multiple adnexal cutaneous tumors with basaloid appearance [16]. These patients may also be affected by basaloid salivary gland tumors, in particular belonging to the membranous variant of BCA [14].…”

Ancillary testing in salivary gland cytology: A practical guide

“…The less common and more clinically aggressive membranous variant of basal cell adenoma (and potentially its malignant counterpart) is characterized by cylindromatosis (CYLD) gene mutation and may be associated with Brooke-Spiegler syndrome. 34,35 Based on limited data, basal cell adenocarcinoma appears to have a distinct and complex genetic profile, with activating mutations in PIK3CA and absent CTNNB1 mutations. 33,36 The majority of basaloid aspirates that are negative for PLAG1, HMGA2, and MYB should be classified as SUMP according to TMS.…”

“…However, in our limited experience, β‐catenin has not proven diagnostically useful in cell blocks, most likely due in part to the characteristic heterogeneous staining pattern that is most prominent in the myoepithelial component of basal cell adenomas. The less common and more clinically aggressive membranous variant of basal cell adenoma (and potentially its malignant counterpart) is characterized by cylindromatosis ( CYLD ) gene mutation and may be associated with Brooke‐Spiegler syndrome . Based on limited data, basal cell adenocarcinoma appears to have a distinct and complex genetic profile, with activating mutations in PIK3CA and absent CTNNB1 mutations .…”

Data Set for the Reporting of Carcinomas of the Major Salivary Glands: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting

“…6 Rarely, multifocality in basal cell adenocarcinoma may raise the possibility of a CYLDassociated syndrome (such as Brooke-Spiegler syndrome). 7 Tumor Dimensions.-Tumor size, specifically the single largest dimension, is a key staging element for the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC), and it is prognostically critical. 8,9 Tumor measurement should be performed macroscopically on the fresh specimen because formalin fixation may cause tumor shrinkage.…”