Abstract Background Primary intracranial DICER1-mutant sarcomas (PIS-DICER1) are extremely rare and highly aggressive malignancies predominantly affecting pediatric patients. The presence of a DICER1 mutation defines a distinct biological subgroup, often associated with DICER1 syndrome – a hereditary tumor predisposition syndrome. Tumors located in the corpus callosum with invasion into the falx cerebri present a significant neurosurgical challenge due to their deep midline location and critical adjacent structures. Currently there is no standardized therapeutic approach for these rare tumors, making each case critical for understanding optimal management. Aim To present a challenging case of successfully treated primary intracranial DICER1-mutant sarcoma and the critical role of multimodal therapy, genetic confirmation and family screening within the framework of DICER1 tumor predisposition syndrome. Methods and Results Clinical presentation at age 6 included headache, dizziness and vomiting. Imaging revealed a large cystic-solid mass in the parietal lobe and corpus callosum. A partial resection of the right parietal tumor component was performed; however, gross total resection was unattainable due to invasion of the falx cerebrum and corpus callosum. Histopathology was consistent with a pleomorphic undifferentiated sarcoma. Given the patient’s age and tumor location, molecular profiling was recommended. Genetic analysis identified a previously unreported heterozygous DICER1variant (chr14:95111334, c.2239CT, p.Gln747Ter). Parental testing was negative, confirming a de novo mutation. Following postoperative treatment with multi-agent chemotherapy (VAIA regimen) and proton beam radiotherapy, a complete radiographic response was achieved. This response has been maintained for 20 months since the end of therapy with no evidence of residual or recurrent disease. Conclusions Our experience suggests that multimodal regimen, including maximal safe cytoreduction, intensive polychemotherapy and radiotherapy can achieve durable remission for PIS-DICER1, even after non-radical surgery. It underscores the critical importance of a multidisciplinary approach in managing such rare and challenging tumors.
Kumirova et al. (Tue,) studied this question.