Abstract

Malignant proliferating trichilemmal tumor (MPTT) is a rare, aggressive adnexal neoplasm with trichilemmal differentiation. Its benign counterpart, proliferating trichilemmal cyst/tumor, which arises from the outer root sheath of the hair follicle, is thought to be the precursor lesion. Given the rarity of MPTT, little is known about the molecular alterations and other disease conditions associated with MPTT. Herein, we present a case of multifocal MPTTs in a 31-year-old woman with a history of incontinentia pigmenti (IP), whose tumors were found to harbor TP53 and POLE mutations by next generation sequencing (NGS). The patient presented with multiple, exophytic, partially ulcerated nodules, measuring up to 9 cm, on the scalp, left posterior neck and shoulder. Clinical differential diagnoses included cylindroma and PTT. Biopsy specimen revealed numerous solid and cystic nodules within the dermis and subcutis; the cystic component showed features of trichilemmal cysts/PTTs, with prominent epithelial infoldings into the cyst lumina with abrupt keratinization and peripherally arranged basaloid cells. The solid component mostly exhibited expansile growth pattern, with focal areas of infiltrative tumor cells forming cords/nests in a desmoplastic stroma. The tumor was strongly positive for p53 by immunohistochemistry. The overall histologic features were those of MPTT. In order to identify potentially targetable genetic alterations, additional molecular studies by NGS were performed, which revealed TP53 and POLE mutations. Given the reported clinical benefit to immune checkpoint inhibitor therapy in patients with pathogenic POLE mutations, the patient was subsequently treated with pembrolizumab. Although the clinical significance of the presence of POLE mutation in the setting of MPTT remains to be determined, our case highlights the unusual association between IP and MPTT and the utility of NGS to uncover potentially targetable mutations like POLE in this rare tumor.

Financial Disclosure:
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