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A Case of Primary Intracranial Sarcoma, DICER1-Mutant, in a Child with a Germline DICER1 Mutation
Suzanne Elizabeth Kosteniuk1, George Michaiel2, Christopher Dunham3,4
1Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada.
Abstract:
DICER1 syndrome is a tumor predisposition syndrome caused by abnormal micro-RNA processing which leads to a variety of benign and malignant neoplasms in many organ systems, including the central nervous system. This paper reports the case of a primary intracranial sarcoma, DICER1-mutant, in a patient with a germline DICER1 variant thought most likely to be de novo. The patient is a ten-year-old boy who presented acutely with altered level of consciousness, emesis, and left-sided weakness. Imaging revealed a large right frontal hemorrhagic lesion, which was urgently debulked. Histology demonstrated a high-grade sarcomatous lesion. Molecular studies revealed compound heterozygous DICER1 variants (a frame shift insertion and a missense mutation), and a KRAS missense mutation. The final pathologic diagnosis was rendered to be "primary intracranial sarcoma, DICER1-mutant". Germline genetic testing revealed that the patient possessed a germline DICER1 variant (parental testing was negative). A dramatic reduction in tumor size was precipitated via chemotherapy (ifosfamide, carboplatin, and etoposide) and radiotherapy (focal proton beam therapy). There was no evidence of residual disease at the primary site at the end of the therapy.
Insights
DICER1 syndrome can cause brain tumors. This case details a rare primary intracranial sarcoma in a child with a DICER1 mutation, successfully treated with chemotherapy and radiotherapy.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- DICER1 syndrome is a rare genetic disorder associated with increased cancer risk.
- Abnormal micro-RNA processing due to DICER1 mutations can lead to various neoplasms.
- The central nervous system is a potential site for tumors in DICER1 syndrome.
Observation:
- A 10-year-old boy presented with neurological symptoms indicative of a brain lesion.
- Imaging revealed a large, hemorrhagic right frontal lobe mass.
- Histopathological examination confirmed a high-grade sarcoma.
Findings:
- The tumor harbored compound heterozygous DICER1 variants and a KRAS mutation.
- Germline genetic testing identified a de novo DICER1 variant in the patient.
- Treatment with chemotherapy (ifosfamide, carboplatin, etoposide) and proton beam radiotherapy resulted in complete tumor remission.
Implications:
- This case highlights primary intracranial sarcoma as a rare manifestation of DICER1 syndrome.
- The findings underscore the importance of genetic testing in diagnosing rare pediatric cancers.
- Successful treatment demonstrates the potential efficacy of multimodal therapy in DICER1-mutant sarcomas.
