Role of POU4F3 in the Diagnosis of Cutaneous Follicular Tumors

ABSTRACT Background Detection of keratin 20+ intratumoral Merkel cells can help differentiate benign cutaneous follicular tumors from malignant histopathologic mimics, though interpretive challenges highlight the need for additional diagnostic markers. POU4F3, a sensitive and specific nuclear marker for neoplastic Merkel cells, has yet to be thoroughly investigated as a marker for non‐neoplastic Merkel cells within follicular neoplasms. Methods We compared the performance of POU4F3 and keratin 20 in the detection of intratumoral Merkel cells. POU4F3 and keratin 20 immunostains were performed on 78 cases representing benign follicular tumors (trichoblastoma/trichoepithelioma, desmoplastic trichoepithelioma, trichofolliculoma, and basaloid follicular hamartoma), tumors with unclear pathogenesis (fibroepithelioma of Pinkus and cutaneous lymphadenoma), and malignant mimics (microcystic adnexal carcinoma and basal cell carcinoma). Results POU4F3+ intratumoral Merkel cells were detected in all cases of trichofolliculoma, basaloid follicular hamartoma, and fibroepithelioma of Pinkus, and in most cases of trichoblastoma/trichoepithelioma (94%), desmoplastic trichoepithelioma (91%), and cutaneous lymphadenoma (60%). POU4F3+ intratumoral Merkel cells were observed in 22% of microcystic adnexal carcinomas and absent in all basal cell carcinomas. Concordance between POU4F3 and keratin 20 expression was observed in 95% of cases. Conclusions These findings support POU4F3's diagnostic value in distinguishing benign follicular tumors from malignant histopathologic mimics.