Endolymphatic Sac Tumors With Aberrant Immunophenotypes

Endolymphatic sac tumor (ELST) is a rare, locally destructive, but non-metastasizing neoplasm arising from the intraosseous epithelium of the endolymphatic duct and sac. Morphologically and immunohistochemically, ELST overlaps with metastatic renal cell carcinoma (RCC), and both neoplasms occur with increased frequency in patients with von Hippel–Lindau (VHL) disease. The largest study to date comparing the immunophenotypes of ELST and RCC found that 100% of ELSTs (25/25) were positive for CA9, whereas all tested ELSTs were negative for CD10 (0/16) and RCC (0/15). They concluded that strong expressions of PAX8 and CA9 and negative expressions of CD10 and RCC are helpful in discriminating between metastatic RCC and ELST. We present two ELSTs that defy this postulate and expand the immunophenotypic profile of these tumors. The first ELST occurred in a 66-year-old woman and was positive for PAX8, CA9, and RCC, and negative for CD10. The second ELST occurred in a 61-year-old man and was positive for PAX8 but negative for CA9. No VHL mutation was identified by whole exome sequencing in the latter tumor. Both patients had no history of RCC and no detectable renal mass on imaging at diagnosis and on follow-up. Our findings indicate that recommended immunohistochemical panels for distinguishing ELST from metastatic RCC are not reliable, underscoring the importance of integrating clinical history and radiologic findings to differentiate tumors with overlapping genetics, histology, and immunophenotype for appropriate patient management.