Low‐grade glial neoplasms of germ cell origin may represent maturation of embryonic‐type neuroectodermal elements

Abstract

Aims: Glial tumours of germ cell origin are relatively rare in men, occurring predominantly after chemotherapy. Many exhibit low-grade histological features within a spectrum that includes teratomas with mature glial/ganglioglial elements and pure low-grade tumours with glial/ganglioglial phenotype (LGGT) that resemble gliomas/gangliogliomas of the central nervous system. Because foci of glial differentiation are very often seen in association with embryonic-type neuroectodermal tumour (ENT), we hypothesise that LGGTs may represent differentiation of embryonic-type neuroectodermal elements of teratoma and/or ENT. Methods and results: To address this hypothesis, we compared LGGTs, ENT, non-teratomas, and teratomas using microRNA and DNA methylation analyses. Seven LGGTs underwent microRNA-371~373 analysis and genomic methylation profiling. Evidence of a prior or concurrent germ cell tumour component containing embryonic neuroectoderm (including overt ENT) was present in 4 LGGTs. None of the tested LGGTs were positive for miR-371a-3p, with three cases demonstrating low levels of expression within the so-called "grey zone". Unsupervised clustering based on microRNA-371~373 showed two clusters, one comprising non-teratomas and another including teratomas, ENTs, and LGGTs. Clustering according to top-differentially methylated probes did not demonstrate a clear separation according to histology. Genome-wide assessment of mean methylation levels using violin plots demonstrated that LGGT show a methylation profile "intermediate" between ENT and teratoma. Conclusions: These results suggest that LGGTs of germ cell origin result from the maturation of ENT components.