A 53-year-old woman with a 16-year history of epilepsy

Abstract

A 53-year-old healthy woman developed symptoms of epilepsy at the age of 37 and had been taking long-term antiepileptic medications to control her seizures. Over the past month, her epilepsy symptoms were poorly controlled, and a computerized tomography scan of the head revealed abnormal signal in the left temporal lobe. Preoperative magnetic resonance imaging (MRI) showed a 3.5 × 1.8 × 1.5 cm mass located in the left temporal lobe. The mass exhibited heterogeneous signal intensity and partial ring enhancement on T1-weighted and T2-weighted images (Figure 1). Microsurgical tumor resection was performed. During the operation, the tumor was located in the cerebral cortex and subcortical region, enveloping blood vessels. Gross total resection of the tumor was achieved. The patient did not receive adjuvant treatment after the operation and had a disease-free survival time of 6 months.

Histological examination revealed diffuse growth of the tumor (Box 1), accompanied by localized microcalcifications. The tumor consisted of oligodendroglia-like cells with oval, hyperchromatic nuclei exhibiting mild pleomorphism, and a clear perinuclear halo. Characteristic nuclear clusters were observed (Figure 2A–C), densely packed together with scant cytoplasm. Mitoses, necrosis, or microvascular proliferation were not present. Immunohistochemically, the tumor exhibited positivity for OLIG2 and synaptophysin (Figure 2D,E), retained ATRX, and tested negative for IDH1 p. R132H and BRAF p. V600E. The Ki-67 labeling index was 3% (Figure 2F).

Next-generation sequencing (NGS) showed the absence of mutations in the hotspots of IDH1/IDH2, BRAF, and TERT genes. Fluorescent in situ hybridization revealed the absence of the 1p/19q codeletion and monosomy of chromosome 14, a finding which prompted whole genome methylation profiling. Applying a DNA methylation-based classification (Bphealth classifier vs12), the tumor was classified as Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (with calibrated scores of 0.90). For more information, please visit the Bphealth classifier website at http://www.bphealth.com/cpzx/287.html.

Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters.

Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC) is a rare molecularly defined entity with distinct histopathological features resembling oligodendroglioma, characterized by the presence of nuclear clusters. Deng et al. [1] first identified this tumor based on a unique methylation profile that distinguished it from previously recognized molecular groups of CNS tumors in 2020. DGONCs predominantly affect pediatric patients, with a median age of 9 years, although individual cases may present at notably older ages (range 2–75 years). There is no gender predilection. DGONCs are typically located in the cerebral hemispheres, often arising from the temporal lobes, and typically do not exhibit tumor dissemination at the time of initial presentation. Radiologically, these tumors typically lack appreciable perilesional edema, appear hyperintense compared to cortex on T2 and FLAIR-weighted imaging, and demonstrate poor enhancement with contrast, if any. Additionally, they often exhibit internal matrix calcification and centrally low ADC values on diffusion-weighted images [2].

Histologically, DGONCs are predominantly composed of small round cells resembling oligodendroglioma-like cells, with characteristic nuclear clusters. Additionally, multinucleated giant cells, and pseudorosettes are observed, accompanied by infiltration of lymphocytes and foamy cells. Mitoses, calcifications, microvascular proliferation, and focal necrosis may also be present. Tumor cells are diffusely OLIG2-positive, and GFAP-negative, while synaptophysin demonstrates a neuropil background. The Ki-67 proliferation index varies from 6% to 30%. DGONC exhibits a unique DNA methylation profile, with approximately 97% of cases showing monosomy of chromosome 14, and a lack of genetic alterations commonly observed in other glioneuronal entities [3]. DNA methylation profiling is so far the only method to clearly identity DGONC. In the absence of DNA methylation profiling, reliance on morphological features may serve as an approximation. Previously, DGONCs have been misdiagnosed as primitive neuroectodermal tumors, atypical extraventricular neurocytoma, oligodendroglioma, glioblastoma, and so on, thus requiring careful differentiation from these tumors.

Most patients with DGONC have a favorable prognosis following surgical resection, with a 5-year progression-free survival rate of 81% and an overall survival rate of 89% [1]. Although isolated cases have reported local recurrence and occasional metastasis, the WHO does not assign a definitive grading for these tumors. Larger studies are required to further investigate these rare tumors.

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Chenning Shao, Lixia Lu, Li Wang, and Can Peng. The first draft of the manuscript was written by Rong Ge. Rong Ge and Chenning Shao gave final approval.

This study was supported by the Medical and Health Research Project of Zhejiang Province (2022KY1185), Ningbo Leading Medical & Health Discipline (2022-F30), and Ningbo Top Medical and Health Research Program (2023010211).

The authors declare no conflicts of interest.

The study was approved by the ethics committee of The Ningbo Clinical Pathology Diagnosis Center, Ningbo, China.

Written informed consent to participate in this study was provided by the patient.