Brain Tumor Res Treat.  2024 Jul;12(3):186-191. 10.14791/btrt.2024.0022.

Early High-Grade Transformation of IDH-Mutant Central Nervous System WHO Grade 2 Astrocytoma: A Case Report

Affiliations
  • 1Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
  • 2Department of Pathology, National Cancer Center, Goyang, Korea
  • 3Department of Neurological Surgery, Asan Hospital, University of Ulsan College of Medicine, Seoul, Korea
  • 4Department of Cancer Control, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea

Abstract

High-grade transformation of low-grade gliomas has long been a poor prognostic factor during therapy. In 2016, the World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) adopted isocitrate dehydrogenase (IDH) mutation status in the classification of diffuse astrocytomas. The 2021 classification denoted glioblastomas as IDH-wildtype and graded IDH-mutant astrocytomas as 2, 3, or 4. Gemistocytic morphology, a large proportion of residual tumor, the patient’s age, and recurrence after radiotherapy were previously mentioned as risk factors for high-grade transformation of low-grade gliomas. We report a 34-year-old male patient initially diagnosed with IDH-mutant grade 2 astrocytoma according to the 2021 WHO classification of CNS tumors. As the first surgical resection achieved gross total resection on postoperative MRI, no adjuvant therapy was given and regular follow-up was planned. On 1-year follow-up MRI, two new enhancing nodular lesions appeared at the ipsilateral brain parenchyma abutting the surgical resection cavity. Salvage craniotomy achieved gross total resection, and the pathologic diagnosis was IDH-mutant WHO grade 4 astrocytoma. We describe this tumor in terms of the previous WHO classification to evaluate the risk of high-grade transformation and discuss possible risk factors leading to high-grade transformation of low-grade astrocytoma.

Keyword

Astrocytoma; Case reports; Gemistocytic; Isocitrate dehydrogenase; Malignant; Transformation

Figure

  • Fig. 1 Pre- and postoperative MRI findings of the first operation. A: Initial T1 contrast-enhanced MRI showing an approximately 8-cm diffuse, infiltrative, non-enhancing mass lesion in the left temporal lobe. B: Postoperative T1 contrast-enhanced MRI showing gross total resection with clear margins.

  • Fig. 2 Histopathological examination of the first operation (×200 magnification). Hematoxylin and eosin–stained tissue section showing gemistocytic features, with large eosinophilic cytoplasm with nuclei displaced to the periphery (black arrow). Other neoplastic fibrillary astrocytes show mild nuclear atypia on the background of a loosely structured tumor matrix with microcyst formation (white arrow).

  • Fig. 3 Follow-up MRI 1 year after surgery showing a newly appeared, approximately 2-cm mass in the left insula. T1 non-enhanced (A), T1 contrast-enhanced (B), T2 fluid-attenuated inversion recovery (C), diffusion-weighted (D), susceptibility-weighted (E), and cerebral blood volume (F) images.

  • Fig. 4 Pre- and postoperative MRI findings of the second operation. A: T1 contrast-enhanced MRI showing marked growth of the left insular mass, with a newly appeared daughter mass in the posterior aspect. B: Postoperative T1 contrast-enhanced MRI showing gross total resection of both mass lesions.

  • Fig. 5 Histopathological examination of the second operation (×200 magnification). A: Hematoxylin and eosin–stained tissue section showing microvascular proliferation. B: Same hematoxylin and eosin-stain showing bizarre, monstrous, multinucleated tumor cells with high cellularity (black arrows). The nuclei varied in size, and some cells showed atypical mitoses (white arrow). C: Immunohistochemical staining positive for IDH mutation (using IDH1 R132H monoclonal antibody).

  • Fig. 6 Unexpected postoperative cerebral infarction and follow-up MRI. A: Diffusion-weighted MRI 4 days after surgery revealed multifocal diffusion restriction at the left internal capsule posterior limb, posterior thalamus, and corona radiata, indicative of acute infarction. Diffusion-weighted (B) and T1 contrast-enhanced (C) MRI before standard concurrent chemoradiation therapy showed minimal cerebromalacia at the infarction site without any enhancing lesions.


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