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.