Brooke-Spiegler syndrome: report of a case with a novel mutation in the CYLD gene and different types of somatic mutations in benign and malignant tumors.

The authors report a case of Brooke-Spiegler syndrome (BSS) with a novel germline CYLD mutation and various somatic mutations identified in the lesional tissues. The patient was a 46-year-old man with multiple lesions on the face. The available histopathological material included 24 trichoepitheliomas, 2 large nodular basal cell carcinomas (BCCs), 2 spiradenomas, 1 spiradenocylindroma and 1 trichoblastoma composed of large and small nodules with prominent clear cell differentiation. Whereas one of the two BCCs manifested a conventional morphology, the second neoplasm additionally showed foci with high grade cytological features characterized by marked pleomorphism and numerous mitotic figures. There were also numerous signet ring cells and cells containing intracytoplasmic eosinophilic inclusions. The germline mutation was a substitution mutation c.1684 + 1G> A. Somatic mutations were investigated in eight tissue blocks from which high quality genomic DNA had been successfully extracted. Somatic mutations included loss of heterozygosity (LOH) in four lesions and a single sequence mutation, namely a single base deletion c. 2322delA causing a frameshift mutation E774DfsX2. LOH occurred in both BCCs, one trichoepithelioma and one spiradenoma. In the remaining three lesions, the somatic event remained undetected.