An Acral Mixed Tumor With Histopathologic Features of Clear Cell Hidradenoma: The Value of Molecular Assessment in Challenging Cutaneous Adnexal Tumors

ABSTRACT: Cutaneous adnexal tumors are a heterogeneous group of neoplasms with diverse histopathologic features. Clear cell hidradenoma (CCH) and cutaneous mixed tumors are benign adnexal neoplasms that may share overlapping morphologic characteristics, making diagnosis challenging, particularly at uncommon acral sites. We report the case of a 60-year-old man who presented with a long-standing nodule on the hand. Histopathologic evaluation suggested a possible diagnosis of clear cell hidradenoma. There were also myxoid areas and a focal chondroid area as well, which are features seen in cutaneous mixed tumors. To further clarify the diagnosis, next-generation sequencing identified an in-frame TRPS1-PLAG1 gene fusion, confirming a diagnosis of cutaneous mixed tumor with phenotypic features of clear cell hidradenoma. This case highlights the diagnostic complexity of acral adnexal tumors with overlapping morphologic features. Molecular testing, such as next-generation sequencing, can be an essential adjunct in distinguishing between morphologically similar adnexal neoplasms, thereby guiding accurate diagnosis and management.