Clinicopathologic features and prognosis of epithelioid glioblastoma

Abstract

Objective: To improve the understanding of epithelioid glioblastoma (E-GBM) and provide accurate basis for clinical diagnosis, treatment, and prognosis through the analysis of clinicopathologic characteristics, immunohistochemical expression, molecular characteristics, and prognosis of E-GBM.

Methods: The clinicopathologic characteristics of 33 cases of E-GBM in our hospital from January 2015 to September 2019 were analyzed retrospectively. Kaplan Meier method was used for survival analysis. Multivariate Cox regression analysis was used to screen the independent risk factors affecting the survival time of patients.

Results: Among 33 patients with E-GBM, 16 were male and 17 were female. The age ranged from 9 to 67 years old, with the median age of 36 years old and the average age of 38 years old. The tumor size (calculated by the largest diameter): 1-6 cm, average size: 3.5 cm. The ratio of smoking and non-smoking is 17:16. All the tumors were located in the cerebral hemisphere, and 26 cases (78.79%) of brain MR showed that the tumors invaded the cortex (white matter).

Clinical symptoms: asymptomatic physical examination was found in 6 cases (18.18%), 5 cases (15.15%) had epilepsy history, 2 cases (6.06%) had malignant vomiting, 3 cases (9.09%) had hypertension history, and 17 cases (51.52%) had headache and dizziness. All patients received surgery (total or partial resection). Postoperative radiotherapy was given in 7 cases (21.00%), chemotherapy (TMZ temozolomide) in 3 cases (1.00%), and combined chemoradiotherapy in 16 cases (48.40%). Immunohistochemical staining: the positive rates of CK, GFAP, IDH-1, IDH-2, HMB45, Desmin, BRAF, P53, ATRX, INI-1, S-100, Ki-67 were 20/33, 30/33, 1/33, 1/33, 0/33, 0/33, 33/33, 5/33, 30/33, 33/33, 6/33, Ki-67 of all cases were higher than 40%, among which 11 cases were higher than 60%. The detection of related genes showed that 33 cases (100%) had BRAF V600E mutation. TERT mutation was found in 18 cases (54.5%); IDH1 mutation was found in 1 case (3%); MGMT promoter methylation was found in 15 cases (45.4%); EGFR amplification and 1p/19q co-deletion were not found in any cases.

Conclusion: E-GBM is a highly invasive and rare malignant nervous system tumor, with poor prognosis and lack of clinical specificity. Immunohistochemically, the higher expression of CK, GFAP and Ki67 proliferation index is more conducive to the diagnosis and differential diagnosis of E-GBM. Smoking, brain MR showing tumor invasion of cortex, TERT mutation, radiotherapy, and chemotherapy are independent risk factors affecting the prognosis (survival time) of patients.

Keywords: Cox analysis; Epithelioid; clinical pathology; glioblastoma; prognosis.

Figure 1

Brain MR indicating tumor invading cortex.

Figure 2

A. Tumor necrosis and epithelioid cells (magnification, ×200). B. High magnification of rhabdoid cells (magnification, ×400). C. GFAP focal weakly positive (magnification, ×200). D. CK focal weakly positive (magnification, ×200). E. No deletion of INI-1 (magnification, ×200). F. Higher Ki67 proliferation index (magnification, ×200).

Figure 3

A. BRAF V600E mutation. B. TERT (C228T) mutation. C. TERT (C250T) mutation. D. IDH1 mutation.

Figure 4

Methylation of tumor cells.

Figure 5

A-E. Survival curve of E-GBM patients with different pathologic findings.