Abstract

Hybrid cysts are composed of two or more components of the pilosebaceous unit. The pathogenesis of hybrid cysts remains controversial, and different theories exist, including confluency of multiple pilosebaceous cysts, multilineage differentiation of pluripotent follicular stem cells, and metaplasia. Here, we describe hybrid cysts with infundibular and pilomatrical differentiation from two patients with different genetic syndromes. The first case is a 15-year-old male who presented with a subcutaneous mass on the leg. Histologic evaluation showed a predominantly infundibular cyst with a focal area of pilomatrical differentiation associated with a cluster of shadow cells. The patient was found to have a family history of Gardner syndrome, which is caused by mutations in APC and classically associated with such cysts.  The second case is a 15-year-old male, with history of constitutional mismatch repair deficiency (CMMRD) syndrome and glioblastoma, who presented with several subcutaneous masses. Pathology revealed multiple cysts composed of infundibular and pilomatrical components along a histologic spectrum, with some showing more infundibular and some showing more pilomatrical differentiation. Next generation sequencing performed on the glioblastoma detected a likely germline mutation in TP53, as this mutation was also found in a glioblastoma from a sibling. Interestingly, studies show that p53 normally helps to downregulate beta-catenin, which is over-expressed in pilomatricomas. To our knowledge, this is the first reported case of hybrid cysts associated with both CMMRD and a potential germline mutation in TP53, which together may have acted synergistically to predispose the patient to the formation of these cysts.