Abstract 5264: Glioblastoma degraded to low-grade astrocytoma two-years after surgical resection: A rare case report

Abstract

Abstract Background: Glioblastoma (GBM) is the most common and malignant brain tumor. The prognosis of patients with GBM is poor, with a five-year survival rate of 5% and a median overall survival of 12-16 months. In addition, there is a high risk for the recurrence of GBM patient, with the median time of 9.5 months. However, little was reported about the degradation of GBM recurrence. Methods: Immunohistochemistry (IHC) staining and next-generation sequencing (NGS) were conducted to address the histopathological and molecular features of the patient. Results: This patient was firstly diagnosed with GBM in April 2019, followed by surgical resection to completely remove tumor occupancy. IHC staining of the tumor sample showed positive expression of P53, S-100, GFAP, EGFR, MGMT, and a 60% expression of Ki67. Thus, this tumor was clinically classified as WHO grade 4 according to its histopathological features. Then we performed NGS and found that the tumor contained four SNVs (EGFR c.865G>A, EPHA5 c.2152C>T, RB1 c.1615G>T, TP53 c.742C>T), EGFR gene amplification, and without IDH1 or IDH2 mutation. These molecular features of the tumor were classified as WHO grade 4 and were consistent with the histopathological grading. In May 2021, two recurrent tumors were found in this patient and were surgical resected again. However, IHC staining of the tumor sample showed positive expression of P53, S-100, and GFAP, while EGFR and MGMT were undetectable, and expression of Ki67 was only 5%. Thus, these recurrent tumors were diagnosed as low-grade astrocytoma (WHO grade 2) according to their histopathological features. Furthermore, NGS was performed with one of those recurrent tumors and showed that it contained 38 SNVs including those four variants in the primary tumor, EGFR gene amplification, and without IDH1 or IDH2 mutation. According to the fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), IDH-wildtype astrocytoma combined with EGFR gene amplification should be classified as IDH-wildtype GBM (WHO grade 4), which was different from the histopathological grading. From our points of view, though these recurrent tumors are actually high-grade glioma from their ‘molecular identity’, maybe they have not developed to high-grade tumors at the time of diagnosis because of our timely follow-up examination. Conclusion: In summary, we reported a rare GBM patient survived for two-years post surgical resection and recurred with a low-grade astrocytoma in histopathological diagnosis. However, the molecular features revealed that the recurrent tumor should be diagnosed as a high-grade glioma, suggesting the clinical importance of combining the molecular and conventional histopathological diagnosis. Moreover, we provided a clinical evidence of histological degradation of GBM, and showed a rare clinical case of inconsistence of histopathological and molecular diagnosis in recurrent GBM. Citation Format: Zhipeng Su, Xiang Zhang, Bella Guo, Ximeng Zhao, Qun Li, Tonghui Ma. Glioblastoma degraded to low-grade astrocytoma two-years after surgical resection: A rare case report [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5264.