Abstract

The detection of non-neoplastic intratumoral Merkel cells can aid in differentiating benign cutaneous follicular tumors from malignant neoplasms with overlapping histologic features. Keratin 20 is widely used as a marker for intratumoral Merkel cells, yet interpretive challenges highlight the need for additional diagnostic markers. POU4F3 has recently been identified as a sensitive and specific nuclear marker for neoplastic Merkel cells, but its expression in non-neoplastic Merkel cells and its relevance in follicular neoplasms have yet to be thoroughly investigated. We aimed to evaluate the expression of POU4F3+ intratumoral Merkel cells in benign and malignant follicular tumors and compare the staining pattern of POU4F3 with that of keratin 20. Immunohistochemical studies targeting POU4F3 and keratin 20 were performed on 78 cases representing eight tumor types: trichoblastoma/trichoepithelioma, desmoplastic trichoepithelioma, Fibroepithelioma of Pinkus, trichofolliculoma, basaloid follicular hamartoma, cutaneous lymphadenoma, microcystic adnexal carcinoma, and basal cell carcinoma. 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+ staining was 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. These findings support POU4F3’s diagnostic value in distinguishing benign follicular tumors from malignant histologic mimics.