Brooke-Spiegler Syndrome, Multiple Familial Trichoepithelioma, and Familial Cylindromatosis
Brooke-Spiegler Syndrome (BSS), familial cylindromatosis, and multiple familial trichoepithelioma (MFT) are all autosomal dominant syndromes with overlapping clinical characteristics with allelic variance. Features of BSS include multiple skin appendage tumors such as cylindromas (tumors arising in the hair follicle stem cells), trichoepitheliomas (tumors arising in the hair follicle), and spiradenomas (benign tumors arising in the sweat gland). MFT is characterized by nonmalignant skin tumors, primarily trichoepitheliomas, and familial cylindromatosis manifests predominantly as cutaneous cylindromas. Onset of tumors for these syndromes is typically in late childhood or early adolescence, suggesting a hormonal influence. There is some evidence of greater severity in females than in males. UV radiation appears to be a major initiating factor for cylindromas. Typical tumor sites for cylindromas in familial cylindromatosis are the scalp (81% of carriers), the trunk (69% of carriers), and the pubic area (42% of carriers). Other tumors that can be associated with these syndromes include parotid gland tumors, basal cell adenomas, and basal cell carcinomas. Refer to Table 2, Basal Cell Carcinoma (BCC) Syndromes, for more information about BSS.
Incidence and Mortality
Estimated new cases and deaths from small intestine cancer in the United States in 2013:
New cases: 8,810.
Adenocarcinoma, lymphoma, sarcoma, and carcinoid tumors account for the majority of small intestine malignancies, which, as a whole, account for only 1% to 2% of all gastrointestinal malignancies.[2,3,4,5] As in other gastrointestinal malignancies, the predominant modality of treatment is surgery when resection is possible, and cure...
Because mutations in CYLD on16q12-q13 have been identified in individuals with each of these disorders, these syndromes are thought to represent different phenotypic manifestations of the same disease. Penetrance for mutations in CYLD is reported to be 60% to 100%.[3,5] In one study, 85% of the BSS families, 100% of familial cylindromatosis families, and only 44% of MFT families were found to have mutations in CYLD. A second locus for MFT maps to 9p21, but the gene for this locus remains unknown.
Given the potential for progressive enlargement, the preferred approach for cylindromas is ablation while the tumors are small and easily managed. Electrosurgery or Mohs micrographic surgery may be utilized for therapy, although excision of large lesions may require skin grafting for closure. Trichoepitheliomas and spiradenomas typically remain smaller in size; thus, after the diagnosis is confirmed by skin biopsy, unless there is impingement on critical structures, further intervention is not required. If therapy is deemed necessary and appropriate, either electrosurgery or ablative laser therapy is a valid option. Radiotherapy is not recommended for treatment of any of these tumors because a potential for increased tumor induction.