L1CAM expressing, ZFTA:: NCOA1 fusion-positive supratentorial ependymoma: A case report

Abstract

Ependymomas are uncommon central nervous system tumors arising from the ependymal lining of the ventricular system. Clinically, ependymomas are a heterogeneous group of tumors ranging from benign subependymomas to very aggressive and often fatal childhood ependymomas of the posterior fossa. The previous edition (2016) of the World Health Organization (WHO) classification primarily defined ependymoma subtypes based on their clinicopathological characteristics (with the exception of v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA) RELA-fusion-positive ependymoma), while the WHO 2021 classification instead classifies ependymoma on the basis of their molecular profile and anatomic location. These include supratentorial-zinc finger translocation-associated (ZFTA) fusion-positive, supratentorial-yes-associated protein 1 (YAP 1) fusion-positive, posterior fossa group A and B, spinal, spinal-master regulator of cell cycle entry and proliferative metabolism (MYCN)-amplified, myxopapillary, and subependymoma subtypes. This new approach provides an objective molecular basis for the diagnosis as well as classification of ependymomas. At the same time, it is also helpful to better predict the prognosis of the patients. Notably, first studies on tumor relapse samples indicate that this molecular classification might be more stable in the course of the disease than histology alone. Among these, ZFTA-fusion-positive supratentorial ependymomas (STEs) have the worst outcome and non-RELA ZFTA-fusion ependymomas have even worse outcome; hence, recognition of this fusion is important. L1 cell adhesion molecule (L1CAM) immunoexpression is specific for ZFTA:: RELA fusion and supports the diagnosis of ZFTA-fusion-positive STE where molecular testing is unavailable. We describe a case of L1CAM immunoexpressing and ZFTA:: NCOA fusion-positive STE.