Clinical Spectrum, Radiological Aggressiveness, and Diagnostic Pitfalls of Intraparenchymal Malignant Peripheral Nerve Sheath Tumor: An Institutional Case Series and Integrated Analysis of 33 Cases

Abstract Background and Purpose Intraparenchymal malignant peripheral nerve sheath tumor (MPNST), also referred to as malignant schwannoma, is an exceptionally rare and highly aggressive malignant tumor. Its nonspecific clinical presentation and heterogeneous radiological appearance frequently lead to preoperative misdiagnosis. Current evidence is largely derived from isolated case reports and small case series. This study aimed to define the clinical spectrum, radiological aggressiveness, pathological features, and diagnostic pitfalls of intraparenchymal MPNST through an institutional case series and an integrated analysis of published cases. Materials and Methods We retrospectively reviewed three pathologically confirmed i ntraparenchymal MPNST cases treated at our institution and systematically reviewed previously published intraparenchymal MPNST cases. Individual patient-level data were extracted, including demographic characteristics, clinical presentation, tumor location, preoperative diagnosis, radiological features, histopathological and immunohistochemical findings, treatment strategy, recurrence, dissemination, and survival outcome. Imaging features and outcome variables were defined using standardized criteria, and descriptive statistics were applied. Results A total of 33 patients were included, comprising three institutional cases and 30 published cases. Adolescents and young to middle-aged adults predominated, and males were slightly more common than females. Tumors most frequently involved the supratentorial lobes, particularly the frontal and temporal lobes, with some cases showing multilobar infiltrative growth. Radiologically, these tumors were usually solid or mixed solid-cystic heterogeneous masses with heterogeneous enhancement, necrosis or cystic change, peritumoral edema, ill-defined margins, diffusion restriction, bone destruction, or neurovascular involvement. Histologically, the tumors showed malignant spindle-cell morphology with variable immunophenotypic heterogeneity. S100 and/or SOX10 expression supported nerve sheath differentiation, Ki-67 indices were often elevated, and H3K27me3 loss was observed in a subset of cases. Gross total resection was achieved in 42.4% of cases, recurrence occurred in 48.5%, and the overall prognosis was dismal. Conclusion Intraparenchymal MPNST is a rare malignant tumor with nonspecific symptoms, heterogeneous imaging features, complex pathological profiles, and high recurrence risk. Lobar intraparenchymal involvement may represent an underrecognized phenotype and can mimic glioma, metastasis, or inflammatory lesions. Recognition should rely on a pattern-based assessment integrating clinical background, radiological aggressiveness, pathological immunophenotype, and treatment risk. Maximal safe resection combined with adjuvant therapy and long-term surveillance remains central to management.