Basal cell carcinomas arising within multiple trichoepitheliomas

Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.
Journal of Cutaneous Pathology (Impact Factor: 1.58). 07/2008; 35 Suppl 1(s1):59-64. DOI: 10.1111/j.1600-0560.2008.01002.x
Source: PubMed


Although trichoepitheliomas (TEs) are commonly regarded as benign tumors of follicular origin, the natural history of multiple familial trichoepitheliomas (MFT) and their risk for malignancy has been unclear. We describe a 57-year-old male with numerous skin-colored firm papules and plaques present on the central face since 6 years of age. Recently, some lesions had enlarged and ulcerated. Other family members were similarly affected. Biopsies from multiple lesions showed TEs both alone and associated with basal cell carcinoma (BCC) in the same section, suggesting the secondary development of BCCs within TEs. Many prior reports of BCCs arising within TEs in patients with presumed MFT were likely misdiagnosed cases of nevoid BCC. This report is a compelling example of MFT in which BCCs evolved secondarily. Awareness of the potential for the evolution of carcinoma in patients with MFT is important in the management of these patients.

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    • "Conclusions may be presumptuous given that BCC is a common cancer (Lee et al., 2005). However, Pincus et al. reported a patient in which multiple BCCs originated exclusively within the field of his multiple trichoepitheliomas with histopathologic sections showing TE and BCC in direct continuity, supporting transformation of trichoepitheliomas to BCC (Pincus et al., 2008). "
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    ABSTRACT: Germline mutations in the cylindromatosis (CYLD) gene have been described in families with cylindromas, trichoepitheliomas, and/or spiradenomas. Brooke-Spiegler syndrome (BSS) is the autosomal dominant predisposition to skin appendageal neoplasms including cylindromas, trichoepitheliomas, and/or spiradenomas. We review the clinical features, molecular genetics, and the animal models of BSS. To date, a total of 51 germline CYLD mutations have been reported, occurring in exons 9-20, in 73 families with diverse ethnic and racial backgrounds. Of 51 mutations, 86% are expected to lead to truncated proteins. The seven missense mutations reported to date occur only within the ubiquitin (Ub)-specific protease (USP) domain of the CYLD protein and most are associated exclusively with multiple familial trichoepithelioma (MFT). CYLD functions as a tumor suppressor gene. CYLD encodes a deubiquitinating (DUB) enzyme that negatively regulates the nuclear factor (NF)-kappaB and c-Jun N-terminal kinase (JNK) pathways. CYLD DUB activity is highly specific for lysine 63 (K63)-linked Ub chains but has been shown to act on K48-linked Ub chains as well. In 2008, the CYLD USP domain was crystallized, revealing that the truncated Fingers subdomain confers CYLD's unique specificity for K63-linked Ub chains. Recent work using animal models revealed new roles for CYLD in immunity, lipid metabolism, spermatogenesis, osteoclastogenesis, antimicrobial defense, and inflammation.
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    ABSTRACT: We report a patient with multiple trichoepitheliomas whose biopsy material also demonstrated a range of other neoplasms with follicular differentiation, including small nodular trichoblastoma, small nodular basal cell carcinoma (BCC), and areas resembling infundibulocystic BCC/basaloid follicular hamartoma. These were all intimately associated with otherwise typical trichoepitheliomas that dominated the microscopic appearances. Peripheral blood and tumor tissues of the patient and his 2 daughters, who apparently had a milder phenotype, were studied for alterations in the CYLD and PTCH genes, but mutations or loss of heterozygosity was not found in either gene. The occurrence of multiple follicular neoplasms within a single lesion adds evidence that, although in most cases BCC and trichoblastoma are distinct lesions, the 2 neoplasms do encompass a morphological spectrum of follicular differentiation, which is probably more overtly expressed in syndromic patients.
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