Abstract

We present a mesenchymal tumor with features mimicking a EWSR1::SMAD3 positive fibroblastic tumor but with a novel JAZF1::ZBTB4 fusion. A 50-year-old male noted a palpable lesion on the posterior right ear that was clinically thought to be a pilar cyst. Histopathologic examination revealed a bland, monotonous spindle cell proliferation composed of well-formed, highly cellular fascicles with abrupt transitions to collagenous areas imparting a palisaded appearance. The strong immunohistochemical nuclear staining for ERG and absence of CD31, CD34, caldesmon, desmin or S100 expression suggested an EWSR1::SMAD3 positive fibroblastic tumor. These tumors favor acral areas and can be locally aggressive. Further testing with next-generation sequencing detected novel fusion partners JAZF1::ZBTB41. JAZF1 is a zinc finger transcription factor that has a been associated with endometrial stromal sarcomas, and ZBTB41 is involved with transcriptional regulation of RNA polymerase II and has been described as a fusion partner of RET in a subset of lung adenocarcinomas. ZBTB41 has also been implicated as a potential gene involved in cervical cancer. This new fusion suggests that these fibroblastic tumors may have a broader clinical presentation with other defining rearrangements that require further elucidation.