Pathobiology : journal of immunopathology, molecular and cellular biology · 2026
Malignant Progression of Subependymal Giant Cell Astrocytoma-Imitating Fibrous Meningioma in a Child Carrying a Germline <italic>CHEK2</italic> Mutation.
СтатьяКлинический случайНазвание и аннотация: Перевод в очереди
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Szmyd Bartosz, Braun Marcin, Pastorczak Agata, Jaskólski Dariusz Jan, Madzio Joanna, Miarka-Walczyk Karolina, Urbańska Zuzanna, Grajkowska Wiesława, Trubicka Joanna, Adamek Dariusz, Barańska Dobromiła, Młynarski Wojciech, Trelińska Joanna
Аннотация
INTRODUCTION: The subependymal giant cell astrocytoma (SEGA) predominantly occurs in patients with tuberous sclerosis. Here, we present an unusual aggressive transformation of SEGA-imitating fibrous meningioma in a child carrying a germline CHEK2 mutation.
METHODS: This case study was conducted at a tertiary pediatric oncology center in accordance with current diagnostic and therapeutic standards. Tumor classification followed WHO CNS5 criteria and was complemented by genome-wide DNA methylation profiling. Comprehensive molecular workup included germline and somatic whole exome sequencing, copy number analysis, and RNA sequencing.
RESULTS: An 8.5-year-old girl presented with an intraventricular tumor initially diagnosed as SEGA based on imaging and partial resection histology. Treatment with an mTOR inhibitor led to 4 years of stability before rapid progression and death due to postoperative brain edema. Re-examination of both specimens revealed transformation into an aggressive anaplastic meningioma, while the initial lesion was reclassified as fibrous meningioma. Whole exome and microarray analyses excluded germline TSC1/TSC2 defects but identified a pathogenic germline CHEK2 variant (c.1466del, p.Asn489ThrfsTer23). Somatic alterations involving NF1 and TP53 were found in the primary tumor.
CONCLUSIONS: Constitutional CHEK2 mutations combined with somatic NF1 defect may have promoted the malignant progression of SEGA-imitating fibrous meningioma and its favorable initial response to mTOR inhibitors.
METHODS: This case study was conducted at a tertiary pediatric oncology center in accordance with current diagnostic and therapeutic standards. Tumor classification followed WHO CNS5 criteria and was complemented by genome-wide DNA methylation profiling. Comprehensive molecular workup included germline and somatic whole exome sequencing, copy number analysis, and RNA sequencing.
RESULTS: An 8.5-year-old girl presented with an intraventricular tumor initially diagnosed as SEGA based on imaging and partial resection histology. Treatment with an mTOR inhibitor led to 4 years of stability before rapid progression and death due to postoperative brain edema. Re-examination of both specimens revealed transformation into an aggressive anaplastic meningioma, while the initial lesion was reclassified as fibrous meningioma. Whole exome and microarray analyses excluded germline TSC1/TSC2 defects but identified a pathogenic germline CHEK2 variant (c.1466del, p.Asn489ThrfsTer23). Somatic alterations involving NF1 and TP53 were found in the primary tumor.
CONCLUSIONS: Constitutional CHEK2 mutations combined with somatic NF1 defect may have promoted the malignant progression of SEGA-imitating fibrous meningioma and its favorable initial response to mTOR inhibitors.