Histological and molecular characterization of endolymphatic sac tumor reveals key differences from its primary differential diagnosis, choroid plexus papilloma.

Endolymphatic sac tumors (ELSTs) are rare, slow-growing neoplasms of the inner ear. Microscopically, they exhibit papillary-cystic and glandular histomorphology, closely resembling their primary differential diagnosis, choroid plexus papilloma (CPP). Through in-depth histological, immunohistochemical, and molecular analysis, we identified distinct characteristics of ELST that facilitate its identification and aid in differentiating it from CPP. Immunohistochemical staining that best discriminated between ELST and CPP included EMA, S-100 protein, EpCAM, cytokeratin, transthyretin, CD34, PTEN, PAX8, and YAP. In contrast to CPP, pan-cancer DNA panel next-generation sequencing frequently revealed pathogenic <i>VHL</i> gene alterations in ELST. In conclusion, comprehensive immunohistochemistry enhances the identification of this rare tumor type and helps prevent misdiagnosis. Furthermore, the detection of <i>VHL</i> gene alterations additionally supports the diagnosis of ELST.