primary intracranial sarcoma, DICER1-mutant

Primary Intracranial Sarcoma, DICER1-Mutant: A Rare and Aggressive Tumor

Primary intracranial sarcomas, DICER1-mutant are rare neoplasms that have been identified through analysis of the whole-genome DNA methylation patterns [1]. These tumors are characterized by a unique genetic profile, which includes mutations in the DICER1 gene.

Key Features:

• Rare and Aggressive: Primary intracranial sarcomas, DICER1-mutant are rare and aggressive pediatric brain tumors [2].
• DICER1 Mutation: The presence of a pathogenic missense mutation in the DICER1 gene is a hallmark of these tumors [3].
• Molecular Testing: Molecular testing can reveal a gain of chromosome 7 and a pathogenic missense mutation in the DICER1 gene [4].

Clinical Course:

Primary CNS sarcoma with DICER1 mutation has an aggressive clinical course, often requiring a combination of surgery, chemotherapy, and radiotherapy for treatment [5].

DICER1 Syndrome:

It's worth noting that primary intracranial sarcomas, DICER1-mutant can occur in the context of DICER1 syndrome, a tumor predisposition syndrome caused by abnormal micro-RNA processing [6].

References:

[1] A Marinelli · 2023 · Cited by 2 [2] H Honma [3] LJ Robinson · 2024 [4] RY Diaz Coronado · 2022 · Cited by 23 [5] SE Kosteniuk · 2023 · Cited by 1

Primary intracranial sarcomas with DICER1 mutations are rare tumors that can present with a range of symptoms depending on their location and size.

Common symptoms:

• Headache [3]
• Dizziness [3]
• Loss of vision [3]
• Vomiting [6]
• Photophobia (sensitivity to light) [6]
• Phonophobia (sensitivity to sound) [6]
• Diplopia (double vision) [6]

Other presenting symptoms:

• Twitching of extremities [8]
• Blindness [8]
• Numbness [8]
• Hearing loss [8]

These symptoms can vary in severity and may be associated with increased intracranial pressure. It's worth noting that the presentation of primary intracranial sarcoma with DICER1 mutation can be highly variable, and not all patients will exhibit these symptoms.

References:

• A rare tumor with a complex clinical course [4]
• Symptoms are most commonly related to the location of PIS [3]
• Other presenting symptoms include twitching of extremities, blindness, numbness, and hearing loss [8]

Diagnostic Tests for Primary Intracranial Sarcoma, DICER1-Mutant

Primary intracranial sarcoma, DICER1-mutant is a rare and aggressive type of brain cancer. Diagnosing this condition requires a combination of clinical evaluation, imaging studies, and molecular testing.

• Imaging Studies: Multimodality imaging features, such as MRI and CT scans, can help identify the tumor's location, size, and characteristics [1].
• Genetic Testing: Targeted next-generation sequencing (NGS) is used to evaluate for somatic mutations within the DICER1 gene [2]. This test can confirm the diagnosis of primary intracranial sarcoma, DICER1-mutant.
• Tissue Sample Sequencing: Tissue sample sequencing of the DICER1 gene can also be used to confirm the diagnosis [3].
• Formalin-Fixed Paraffin-Embedded (FFPE) Tissue or Cytology Slides: This test uses FFPE tissue or cytology slides to assess for somatic mutations involving the DICER1 gene known to be associated with primary intracranial sarcoma, DICER1-mutant [4][7].

These diagnostic tests can help identify the presence of primary intracranial sarcoma, DICER1-mutant and guide further treatment decisions.

References:

[1] RW Eldaya (2024) - Multimodality imaging features of primary intracranial sarcoma, DICER1-mutant

[2] Jul 11, 2023 - Targeted next-generation sequencing for somatic mutations within the DICER1 gene

[3] A Marinelli (2023) - Tissue sample sequencing of the DICER1 gene to confirm diagnosis

[4] This test uses formalin-fixed paraffin-embedded tissue or cytology slides to assess for somatic mutations involving the DICER1 gene known to be associated with primary intracranial sarcoma, DICER1-mutant

[7] This test uses formalin-fixed paraffin-embedded tissue or cytology slides to assess for somatic mutations involving the DICER1 gene known to be associated with primary intracranial sarcoma, DICER1-mutant

Current Treatment Options for Primary Intracranial Sarcoma, DICER1-Mutant

The treatment of primary intracranial sarcoma, specifically those with DICER1 mutations, is a complex and evolving area. While there is no standard treatment protocol, various approaches have been explored in recent studies.

• Chemotherapy: Patients often receive chemotherapy regimens adapted from other brain tumor types (peripheral sarcomas) with low success rates [3]. A dramatic reduction in tumor size was reported via chemotherapy (ifosfamide, carboplatin, and etoposide) and radiotherapy (focal proton therapy) in one case study [5].
• Radiotherapy: Intensity-modulated radiation therapy followed by 6 cycles of ICE (ifosfamide, carboplatin, etoposide) was used to treat a patient with primary intracranial pleomorphic sarcoma with myogenic differentiation and DICER1 mutation [6].
• Surgery: Surgical interventions are often necessary for tumor resection, followed by postoperative radiotherapy and/or systemic chemotherapy to ensure effective treatment [8].

Emerging Therapeutic Strategies

Recent studies have explored the potential of high-throughput drug screening using PDX (patient-derived xenograft) tumor cells. Activation of the retinoic acid receptor (RAR) signaling pathway was found to be effective in treating DICER1-mutant tumors [4, 7].

Future Directions

Further research is needed to establish a standard treatment protocol for primary intracranial sarcoma with DICER1 mutations. The development of targeted therapies and the exploration of novel combination regimens are promising areas of investigation.

References:

[3] Cardona AF (2023) - Currently, there is no standard treatment. [4] Honma H (2024) - Activation of the retinoic acid receptor (RAR) signaling pathway was found to be effective in treating DICER1-mutant tumors. [5] Kosteniuk SE (2023) - A dramatic reduction in tumor size was precipitated via chemotherapy and radiotherapy. [6] Ma Y (2024) - Intensity-modulated radiation therapy followed by 6 cycles of ICE was used to treat a patient with primary intracranial pleomorphic sarcoma with myogenic differentiation and DICER1 mutation. [7] Honma H (2024) - Activation of the retinoic acid receptor (RAR) signaling pathway was found to be effective in treating DICER1-mutant tumors. [8] Clinical, radiologic, histologic, and molecular features of three patients with primary intracranial pleomorphic sarcomas with myogenic differentiation and DICER1 mutation.

The differential diagnosis for primary intracranial sarcoma, DICER1-mutant includes several conditions that need to be ruled out in the diagnostic process.

• Gliosarcoma is one of the main differential diagnoses, which can also present with similar characteristics [1].
• Synovial sarcoma is another condition that should be considered, particularly if the tumor is CD99-negative and CD56-positive [1].
• Primary intracranial tumors with features characteristic of other DICER1-associated tumors should also be on the differential diagnosis list [7].

It's essential to consider these conditions when making a differential diagnosis for primary intracranial sarcoma, DICER1-mutant.

References: [1] A Marinelli · 2023 · Cited by 2 [7] J Kamihara · 2020 · Cited by 53