Case Report: DICER1-mutant primary intracranial sarcoma with concurrent TP53, PDGFRA, and KEAP1 somatic mutations in a 5.5-year-old boy.
This case report describes a 5.5-year-old boy with aggressive DICER1-mutant primary intracranial sarcoma harboring concurrent TP53, PDGFRA, and KEAP1 mutations plus somatic SMARCB1 allelic loss, with progression and new metastatic lesions after subtotal resection and adjuvant chemoradiotherapy.
Open original publication →What the AI sees
This case report describes a 5.5-year-old boy with aggressive DICER1-mutant primary intracranial sarcoma harboring concurrent TP53, PDGFRA, and KEAP1 mutations plus somatic SMARCB1 allelic loss, with progression and new metastatic lesions after subtotal resection and adjuvant chemoradiotherapy.
Research significance
The record supports molecular profiling as an aid to definitive diagnosis; it is only a hypothesis that the concurrent PDGFRA, KEAP1, TP53, or SMARCB1 alterations could inform targeted treatment selection or resistance research, because no functional testing or genotype-directed therapeutic response is reported.
Source abstract
DICER1-mutant primary intracranial sarcoma (DICER1-mutant PIS) is a rare and aggressive central nervous system (CNS) malignancy primarily affecting pediatric patients. We report the case of a 5.5-year-old boy who presented with non-specific prodromal symptoms, including recurrent dizziness and progressive vomiting. Brain neuroimaging revealed a cystic-solid mass in the frontal lobe, characterized by heterogeneous contrast enhancement, significant perilesional edema, and intratumoral hemorrhage. Histopathological examination of the tumor demonstrated marked cellular pleomorphism, atypical mitoses, and distinctive intracytoplasmic eosinophilic globules. Next-generation sequencing confirmed the presence of the canonical hotspot DICER1 p.E1705K alteration, along with concurrent pathogenic mutations in TP53, PDGFRA, and KEAP1. Additionally, somatic SMARCB1 allelic loss due to loss of heterozygosity was identified. Due to its insidious clinical presentation and overlapping morphological characteristics, DICER1-mutant PIS is often challenging to diagnose accurately, and no standardized therapeutic guidelines currently exist. The patient underwent subtotal surgical resection followed by adjuvant chemoradiotherapy. However, intracranial disease progression and the development of new metastatic lesions were observed during long-term follow-up. This case underscores the critical importance of prompt and definitive molecular diagnosis, individualized multidisciplinary treatment approaches, and extended regular surveillance for this high-grade malignancy. It provides valuable real-world evidence that can inform the clinical management of similar rare DICER1-mutant PIS cases.