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Published on: January 14, 2014
Radiographic Enhancing Progression Without Molecular or Histologic Progression in IDH-Mutant Grade 2 Astrocytoma
Carolina Pusec1, Karam Han2, Krithi Gopinath3
1Department of Neurology, University of Wisconsin Madison, Madison, Wisconsin, USA.
Abstract:
Central nervous system (CNS) World Health Organization (WHO) Grade 2 isocitrate dehydrogenase (IDH)-mutant astrocytomas are classified as low-grade gliomas with typically slow growth for many years followed by eventual malignant transformation and death. Here, we present a case of a patient with an IDH-mutant Grade 2 astrocytoma who developed early radiographic tumor progression per Response Assessment in Neuro-Oncology (RANO) 2.0 as evidenced by new enhancement on MRI T1 postcontrast 4 months after initiation of an IDH inhibitor. Subsequent re-resection, one month later (or five months postinitiation of ivosidenib treatment), of the enhancing signal retained the Grade 2 designation without any histological or molecular progression per CNS WHO 2021 criteria. Specifically, the Ki-67 proliferative index remained stable at approximately 2%, and copy number alterations were largely unchanged, including no CDKN2A/B homozygous deletion and relatively low chromosome copy number complexity. On histological examination, there was no elevation in mitotic activity and no features of necrosis or microvascular proliferation to suggest a more aggressive phenotype. The tumor demonstrated increased gemistocytic morphology and rare foci of foamy macrophages, as compared to prior. Following the second resection, the patient received sequential radiation therapy and adjuvant temozolomide chemotherapy treatment and has remained clinically stable on observation with surveillance MRIs for over 18 months. This case highlights the importance of re-resection in IDH-mutant gliomas, identifies the potential limitations of the response assessment criteria to differentiate treatment effect from true tumor progression, and emphasizes the need for ongoing investigation into novel genetic alterations, molecular signatures, and histologic markers to more accurately predict radiographic tumor behavior and guide more personalized, targeted treatment strategies for patients with IDH-mutant gliomas.
Insights
A case of IDH-mutant Grade 2 astrocytoma showed radiographic progression but lacked histological progression after IDH inhibitor treatment. Re-resection and standard therapies led to clinical stability, highlighting challenges in assessing tumor behavior.
Area of Science:
- Neuro-oncology
- Molecular Pathology
- Radiology
Background:
- Central nervous system (CNS) World Health Organization (WHO) Grade 2 isocitrate dehydrogenase (IDH)-mutant astrocytomas are low-grade gliomas with potential for malignant transformation.
- Early radiographic progression can complicate treatment decisions for these tumors.
Purpose of the Study:
- To present a case of IDH-mutant Grade 2 astrocytoma with early radiographic progression despite treatment.
- To discuss the implications of histological and molecular findings in differentiating treatment effects from true tumor progression.
- To emphasize the role of re-resection and subsequent therapies in managing such cases.
Main Methods:
- Case report of a patient with IDH-mutant Grade 2 astrocytoma treated with an IDH inhibitor.
- Radiographic assessment using Response Assessment in Neuro-Oncology (RANO) 2.0 criteria.
- Histological and molecular analysis (Ki-67, copy number alterations) of resected tumor tissue.
- Subsequent treatment with radiation therapy and temozolomide chemotherapy.
Main Results:
- The patient developed new MRI enhancement 4 months after initiating an IDH inhibitor, suggesting radiographic progression.
- Re-resection revealed the tumor retained Grade 2 designation without histological or molecular progression (stable Ki-67, unchanged copy number alterations).
- The patient remained clinically stable for over 18 months after radiation and temozolomide treatment.
Conclusions:
- Re-resection can be crucial in managing IDH-mutant gliomas presenting with radiographic progression.
- Current response assessment criteria may have limitations in distinguishing treatment effects from true tumor progression.
- Further research into novel markers is needed for personalized treatment strategies in IDH-mutant gliomas.
