Utility of Immunohistochemistry in the Diagnosis of Porocarcinoma and Other Cutaneous Neoplasms, Anna Sarah Erem, Di Ai, George G Birdsong, Zachary Wolner, Andrew M Bellizzi, Douglas Clark Parker

Summary: Background: Eccrine porocarcinoma (EPC) is a rare, cutaneous adnexal neoplasm with a reported rate of 20-30% metastasis to lymph nodes. EPC may arise de novo or in association with a poroma. Differentiating EPC from other cutaneous epithelial neoplasms, including other malignant adnexal tumors, poorly differentiated squamous cell carcinoma (pdSCC), and metastatic carcinoma, can be challenging. Molecular advances have found YAP1::NUTM1 fusions are more common in EPCs and YAP1::MAML2 in poromas Design: Evaluate the utility of YAP1 C-terminus, YAP1 N-terminus and NUT immunohistochemistry (IHC) on tissue microarray samples of cutaneous neoplasms. A search of our pathology database identified 13 EPCs (9 arising in association with a poroma), 24 poromas, 15 pdSCCs, 7 hidradenocarcinomas, and 9 sebaceous carcinomas (SC). Furthermore, we evaluated the utility of IHC for c-KIT, CEA, EMA, p40 and PRAME in EPCs and other cutaneous neoplasms. Results: Seven of 13 (54%) EPCs had a complete loss of YAP1-C expression, of which 6 (46%) demonstrated strong nuclear NUT positivity, confirming the YAP1::NUTM1 fusion. One case (8%) with loss of YAP1-C had no NUT expression, consistent with YAP1 fusion with a non-NUT partner. One (8%) EPC showed YAP1-C retention with NUT positivity, suggesting a NUT fusion with a different partner. All YAP1 fusion associated EPCs rose in association with a poroma. The majority of poromas (71%) had loss of YAP1 without NUT expression, consistent with YAP1 fusion with a different partner. Four of 24 (17%) poromas had loss of YAP1-C and NUT positivity. One of 13 EPC patients (8%) had local recurrence with lymph node metastasis, while 3 (23%) passed away. None of those patients had YAP1 or NUT fusion. All pdSCCs, hidradenocarcinomas and SCs were NUT negative with strong YAP1-C expression. YAP1 N-terminus was positive in all tumors. C-KIT was positive in 71% EPCs, while only 20% pdSCCs were focally positive. C-KIT was negative in all other tumors. PRAME was only positive in all SCs.