Clinical and genomic profiles of malignant peripheral nerve sheath tumors in the craniospinal axis.

purposeCraniospinal axis (CSA)-derived malignant peripheral nerve sheath tumors (MPNSTs) are exceedingly rare neoplasms. There is a lack of real-world cohort-based studies comprehensively reviewing the characteristics of such site-specific tumors.

methodsClinical and pathological data were retrospectively collected. Next-generation whole exon sequencing (WES) was performed to map the genomic landscapes, comparing the mutational patterns between MPNSTs arising in the CSA versus extra CSA. Data for extra-CSA MPNSTs were sourced from public databases.

resultsA total of 90 CSA MPNST patients, with a median age of 41.5 years, were included. Most cases (74.4%) developed sporadically, and more than half of the lesions were located intracranially, with the most frequent involvement in CN VIII (11.1%). Histologically, the median Ki-67 was 30%, and 48.9% of tumors were high-grade. The median progression-free survival (PFS) and overall survival (OS) were 17 and 19.5 months, respectively. Subgroup analysis demonstrated significant differences in the clinical, pathological, and prognostic features between the different etiological conditions and tumor sites. Multivariate analysis showed that communicating growth manner, multiple lesions and high-grade classification were independently associated with reduced PFS, while histological grade was independent prognostic factors for OS. WES analysis showed that TTN (61%) was the most recurrently mutated gene. After adjustment for confounders, the SCN1A variant was identified to have an independent association with relapses. Compared with extra-CSA MPNSTs, the CSA MPNSTs showed distinct mutational landscapes.

conclusionOur findings provide evidence-based insights into the specialized management of the CSA MPNST and genetically suggest the possibility of independent entity.