Journal of Pathology and Translational Medicine

Case Study

Intracranial malignant peripheral nerve sheath tumor with myxoid morphology evolving across recurrences: a case report: Frantisek Vana, Petra Pokorna, Petr Pospisil, Zdenek Mackerle, Marketa Hermanova, Iva Staniczkova Zambo, Martin Barak, Robin Jugas, Radim Jancalek, Ondrej Slaby, Michal Hendrych; Received August 6, 2026 Accepted September 16, 2026 Published online November 11, 2026; DOI: https://doi.org/10.4132/jptm.2026.09.17 [Epub ahead of print]

Abstract PDF: A malignant peripheral nerve sheath tumor (MPNST) is a rare, aggressive spindle-cell sarcoma that exceptionally occurs intracranially. Herein, we report a case of intracranial spindle-cell neoplasm with abundant myxoid stroma. The immunophenotype of the primary tumor did not align with any known peripheral nerve sheath tumor and the lesion did not correspond to any methylation category defined by the Heidelberg classifier with a sufficiently high classification score, although MPNST was the highest-scoring category. Over the course of repeated recurrences, the tumor acquired increased cellularity, mitotic activity and loss of H3K27me3 expression. Subsequent methylation profiling supported a diagnosis of MPNST. The tumor harbored a gain-of-function variant in NRAS p.Gly13Arg and TP53 p.Arg273Cys from the initial tumor onwards, consistent with previous reports describing activation of Ras/mitogen-activated protein kinase as an early event in MPNST tumorigenesis. These findings illustrate the diagnostic complexity of rare intracranial sarcomas with myxoid morphology and suggest that some may represent early MPNST.

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