Background/Objectives: Primary intracranial sarcoma is a recognized entity within the World Health Organization Classification of Tumours of the Central Nervous System (CNS) and comprises an aggressive subgroup of mesenchymal, non-meningothelial neoplasms. Among these, tumours associated with DICER1 alterations have recently been characterized as a distinct molecular subset. Although globally rare, primary intracranial sarcomas consistent with the DICER1-associated spectrum demonstrate an unusually high incidence in Peru, where they represent the second most common high-grade pediatric CNS malignancy after medulloblastoma. This study aimed to describe their clinicopathological features and outcomes in a large national cohort.
Methods: We retrospectively analyzed 112 pediatric cases diagnosed between 2011 and 2025 at the National Cancer Institute of Peru, integrating histopathology, immunohistochemistry and clinical outcomes.
Results: The median age was 7 years, and most tumours were supratentorial, predominantly affecting the frontal and parietal lobes. Histologically, they exhibited spindle, pleomorphic and undifferentiated round cell patterns, with frequent hyaline globules and aberrant vasculature. Immunohistochemistry showed recurrent ATRX loss, p53 overexpression and high proliferative indices, whereas myogenic markers were variably expressed. Median overall survival was 25 months, with 12-, 36- and 60-month survival rates of 65.7%, 45.9% and 44.0%, respectively. None of the tested markers (ATRX, p53 and Ki-67) demonstrated prognostic significance.
Conclusion: This is the largest pediatric series of DICER1-mutant primary intracranial sarcomas reported from a low- and middle-income country. The findings confirm their poor prognosis and biological heterogeneity, highlighting the urgent need for integrated molecular and epidemiological research to identify risk factors and improve patient outcomes.
