YAP1::MAML2, YAP1::NUTM1, and RNF13::PAK2 rearrangements in trichoblastomas and adnexal tumors with panfollicular differentiation: expanding the spectrum of YAP1/PAK-fused skin adnexal tumors.

In 2019, YAP1::MAML2 and YAP1::NUTM1 rearrangements were demonstrated in the majority of poromas and in porocarcinomas. Recently, our group demonstrated recurrent fusions of PAK (p21 (RAC1) activated kinase) 1/2/3 genes in a subset of poromas and porocarcinomas frequently harboring hair follicle and sebaceous differentiation. To expand the spectrum of YAP1/PAK-fused tumors, we report six adnexal neoplasms with follicular differentiation with in frame YAP1::MAML2, YAP1::NUTM1, or RNF13::PAK2 fusion transcripts. Four cases of trichoblastoma and two neoplasms with panfollicular differentiation were included. Median age was 66 (range 39-76). Two patients were female. Tumors were located on the head (n = 4), chest (n = 1), or leg (n = 1). Microscopically, tumors were located in the dermis (n = 4) and/or subcutaneous tissue (n = 5), and showed macro (n = 6), micronodular (n = 5), and cystic (n = 4) structures. A delicate fibrillar stroma was present in 5 cases. Infundibulocystic structures, cell balls, and sebocytes were observed in 5, 1, and 3 cases, respectively. Immunohistochemistry revealed BerEP4 expression and Merkel cell hyperplasia in 5 and 2 cases, respectively. YAP1 (C-terminal) loss was observed in 5 cases. Accordingly YAP1::MAML2 (n = 2), YAP1::NUTM1 (n = 1), or RNF13::PAK2 (n = 1) inframe fusion transcripts were detected in the four trichoblastomas. YAP1::MAML2 fusions were also detected in the two tumors with panfollicular differentiation. In conclusion, we report six cases of follicular tumors with YAP1::MAML2, YAP1::NUTM1, or RNF13::PAK2 fusions and therefore suggest that in addition to poroid tumors, YAP1 and PAK2 fusions might be the oncogenic driver in a subset of adnexal tumors with prominent follicular differentiation.