The spectrum of morphological findings in pediatric central nervous system MN1-fusion-positive neuroepithelial tumors

Childs Nerv Syst. 2023 Feb;39(2):379-386. doi: 10.1007/s00381-022-05741-y. Epub 2022 Dec 19.

Abstract

Purpose: Central nervous system high-grade neuroepithelial tumor with MN1 alteration (CNS-HGNET-MN1) is a rare entity defined by its DNA methylation pattern and pathologically considered to be high-grade with mixed patterns, stromal hyalinization, and with astrocytic differentiation. Our aim was to present six pediatric cases to contribute to the characterization of this group of tumors.

Material and methods: Six female patients aged 4 to 12 years with CNS tumors with MN1 alteration identified using genome-wide methylation arrays and/or RT-PCR were included. Clinicopathological, morphological, immunohistochemical, and molecular findings were analyzed.

Results: Tumor location was the parietal lobe in four and the intramedullary spinal cord in two. Two were morphologically diagnosed as ependymomas, one as gliofibroma, one as a HGNET-MN1 altered and the other two were difficult to classify. All were well-defined tumors, with a cystic component in three. Only two tumors had extensive stromal hyalinization, three had pseudopapillary formations, and four had other patterns. Multinucleated, clear, and rhabdoid cells were present. Necrosis and histiocyte clusters were also observed. Proliferative index was >10 in four. GFAP, EMA, CK, and SYN were variable, while Olig2 staining was mostly positive. Four of six patients with supratentorial tumors and complete resections were alive and tumor free after 2 to 10 years of follow-up. The two cases with medullary involvement and incomplete resections were alive and undergoing treatment 2 years after surgery.

Conclusion: Neuroepithelial-MN1 tumors are challenging and suspicion requires molecular confirmation. Our pediatric data contribute to the knowledge for accurate diagnosis. Although further studies with a larger number of cases should be conducted in order to draw more robust conclusions regarding clinico-pathological features, here we present valuable pediatric data to increase the knowledge that may lead to the accurate management of this group of tumors.

Keywords: Astroblastoma; CNS HGNET-MN1; Ependymoma; MN1; Pediatric brain tumors.

MeSH terms

  • Brain Neoplasms* / pathology
  • Central Nervous System Neoplasms* / pathology
  • Child
  • Female
  • Humans
  • Neoplasms, Neuroepithelial* / genetics
  • Spinal Cord / pathology
  • Supratentorial Neoplasms*
  • Trans-Activators
  • Tumor Suppressor Proteins / genetics

Substances

  • MN1 protein, human
  • Trans-Activators
  • Tumor Suppressor Proteins