Germ cell tumors with neuroglial differentiation do not show molecular features akin to their central nervous system counterpart: experience from extra-gynecological sites.

Teratomas with secondary somatic malignancy showing neuroglial differentiation (central nervous system (CNS)-type tumors) arising from a glial or neuroepithelial component is a very uncommon event and primarily described in the ovary. We aimed to describe the morphological spectrum and molecular features of CNS type of neuroepithelial tumors arising from the germ cell tumors (GCT) in the extra-gynecological sites. All cases of teratoma and mixed GCT arising from the non-gynecological sites over 7 years were screened for CNS type of neuroepithelial tumors. Detailed histological and immunohistochemical analysis was performed. IDH1 and 2 sequencings were performed in the glial tumors. Fluorescent in situ hybridization (FISH) was performed for EWSR1 rearrangement, 19/19q co-deletion, CDKN2A homozygous deletion, EGFR amplification, and C19MC amplification, wherever required. Out of 302 GCTs examined, the neuroglial tumor was detected in 15 cases. It included nine cases of glial tumors (including one pilocytic astrocytoma (grade I), two diffuse astrocytomas (grade II), one oligodendroglioma (grade II), one gemistocytic astrocytoma (grade II), three anaplastic astrocytomas (grade III), and one case of glioblastoma (grade IV)) and six cases of the embryonal tumor with multilayered rosettes (ETMR). None of the gliomas showed IDH mutation by immunohistochemistry or sequencing. The ETMR cases did not show Lin28 expression or C19MC amplification. To conclude, the spectrum of neuroglial tumors arising from teratoma in the extragonadal sites is vast and most commonly includes glial neoplasms and embryonal tumors. Our findings indicate that the genotype and pathogenesis of tumors with neuroglial differentiation in teratoma are distinct from their CNS counterpart.