Glioblastoma is the most common primary intracranial neoplasm in adults, accounting for about 15% to 20% of all intracranial tumors [
Early diagnosis of glioblastoma should provide a better prognosis because of the added potential of safe excision; however, delayed diagnosis may result in a poor clinical outcome [
Several studies of nonneoplastic cerebral lesions such as infarction, encephalitis, and demyelinating or degenerative diseases have shown that unenhanced computed tomography (CT) reveals either mass hypoattenuation or no positive signs [
This retrospective study was approved by our hospital ethics committee. In total, 225 patients with a pathologically confirmed final diagnosis of glioblastoma underwent imaging examinations from July 2003 to January 2018. Among these 225 patients, 8 with a diagnosis of glioblastoma and no enhancement on postcontrast MR imaging were reviewed in this study. The patients comprised three men and five women ranging in age from 36 to 71 years (mean, 55.3 years). Our team analyzed these patients’ MR images and unenhanced CT scans in the present study.
All eight patients underwent plain MR imaging, contrast-enhanced T1WI, and unenhanced CT. The MR imaging examinations were performed with either a 1.5-T scanner (
Two neuroradiologists who had >9 years of professional experience and were blinded to the clinical data independently reviewed the imaging findings. The reviewers recorded the tumor location, lesion number (solitary or multiple), margin, signal intensity, and density. The signal intensity/density was classified as hypointense/hypodense, isointense/isodense, or hyperintense/hyperdense compared with the adjacent brain parenchyma on the MR images or unenhanced CT images, respectively. On contrast-enhanced MR imaging, the degree of enhancement was recorded as none, moderate, or marked. Other associated findings such as perilesional edema were also recorded. The imaging appearance was independently compared with the pathologic findings.
For five patients in our study, the initial MR imaging examination was performed mainly for evaluation of seizures. General symptoms included mild headache and vertigo in three patients and mild hemiparesis in one. One asymptomatic patient was diagnosed incidentally.
The MR imaging and CT findings for the eight patients in our study are summarized in Table
Imaging findings in eight patients with early-stage glioblastoma.
Patient/age (year)/sex | CT | MR imaging | ||||
---|---|---|---|---|---|---|
Location | Attenuation | T1-weighted image | T2-weighted image | Diffusion-weighted imaging | Enhancement | |
1/36/M | Right temporal lobe | A | HYPO | Inhomogeneous HYP | A | No |
2/57/F | Right temporal and occipital lobe | A | MIX | Inhomogeneous HYP | B | No |
3/41/F | Right temporal lobe and hippocampus | B | ISO | Inhomogeneous HYP | C | No |
4/65/M | Bilateral temporal lobe and hippocampus | A | ISO | Homogeneous HYP | No examination | No |
5/43/F | Right temporal lobe | A | HYPO | Inhomogeneous HYP | C | No |
6/71/F | Brainstem and cerebellum | A | HYPO | Inhomogeneous HYP | B | No |
7/62/F | Left temporal lobe | A | HYPO | Inhomogeneous HYP | B | No |
8/67/M | Left temporal lobe | A | HYPO | Homogeneous HYP | C | No |
CT Attenuation: A, hypoattenuated lesion with hyperattenuated region; B, hypoattenuated lesion with isoattenuated region. Diffusion-weighted imaging: A, hyperintense lesion; B, isointense lesion with hyperintense region; C, isointense lesion with peritumoral hyperintensity. ISO, isointense; HYP, hyperintense; HYPO, hypointense; MIX, mixed isointensity and hypointensity.
Magnetic resonance and computed tomography images of the brain. (a) Axial T1-weighted, (b) axial T2-weighted, (c) fluid-attenuated inversion recovery (FLAIR), (d) diffusion-weighted, and (e) contrast-enhanced magnetic resonance images display a poorly demarcated lesion in the right temporal and occipital lobe. The lesion shows hypointensity to isointensity on T1-weighted imaging and inhomogeneous hyperintensity on T2-weighted and FLAIR imaging with diffuse perilesional edema. The diffusion-weighted image shows an isointense lesion with a hyperintense region (arrowhead). Postcontrast magnetic resonance imaging shows no enhancement. (f) Axial-view head-window unenhanced computed tomography image of the head shows a hyperattenuated region (arrow).
Magnetic resonance and computed tomography images of the brain. (a) Axial fluid-attenuated inversion recovery (FLAIR), (b) T1-weighted, (c) T2-weighted, and (d) contrast-enhanced magnetic resonance images show a poorly demarcated lesion involving the bilateral temporal lobe and hippocampus. The lesion shows homogeneous isointensity on T1-weighted imaging and homogeneous hyperintensity on T2-weighted and FLAIR imaging without perilesional edema or mass edema. The diffusion-weighted image shows an isointense lesion with a hyperintense region. Postcontrast magnetic resonance imaging shows no enhancement. (e) Axial-view head-window unenhanced computed tomography images of the head show a hyperattenuated region (arrow). (f) At the 7-week follow-up, the contrast-enhanced T1-weighted image shows a markedly larger ring and heterogeneously enhanced mass.
Magnetic resonance and computed tomography images of the brain and histopathological findings of the lesion. (a) T1-weighted, (b) T2-weighted, (c) diffusion-weighted, and (d) contrast-enhanced magnetic resonance images show a poorly demarcated lesion in the right temporal lobe and hippocampus. The lesion shows homogeneous hypointensity on T1-weighted imaging and homogeneous hyperintensity on T2-weighted imaging relative to the brain without perilesional edema or mass edema. The diffusion-weighted image shows an isointense lesion with ring-like peritumoral hyperintensity. Postcontrast magnetic resonance imaging shows no enhancement. (e) Axial-view head-window unenhanced computed tomography images of the head show a hypoattenuated lesion with an isoattenuated region (arrow) in the right temporal lobe. (f) At the 4-week follow-up, a contrast-enhanced T1-weighted image shows a markedly heterogeneous enhanced mass lesion with adjacent pachymeningeal enhancement. (g) Histopathological examination shows proliferation of atypical cells with irregular cytoplasm and chromatin-condensed heterogeneous nuclei, necrotic changes, and microvascular proliferation (hematoxylin and eosin, ×100). (h) A small number of p53-positive cells are present. (i) Glial fibrillary acidic protein immunostaining is positive. (j) Ki-67 positivity is seen in 30% of all cells.
The final diagnosis of glioblastoma was confirmed by histopathological examination based on the World Health Organization criteria [
Our retrospective study showed that the MR imaging findings of glioblastoma were isointensity to hypointensity on T1WI, hyperintense ill-defined lesions on T2WI, little or no mass edema, and no contrast enhancement. The CT finding of a hyperattenuated or isoattenuated region combined with the DWI finding of the same region containing an inhomogeneous hyperintense lesion or isointense lesion with a hyperintense region may be specific for a diagnosis of early-stage glioblastoma. This study also suggests that MR imaging has excellent follow-up performance. During follow-up, we observed the development of typical diagnostic characteristics such as a heterogeneously enhanced bulky mass with central necrosis [
Patients with a wide range of ages can develop glioblastoma [
According to previous reports [
The diagnosis of early-stage glioblastoma based on its appearance on routine MR imaging can be challenging. However, early diagnosis and treatment involving gross total excision are likely to prolong the progression-free and overall survival periods [
Advanced MR imaging approaches might help to differentiate glioblastoma from nonneoplastic cerebral lesions, but they may not offer a complete answer to the diagnostic question of how to differentiate these two conditions. Increased accumulation of
Early-stage glioblastoma may be difficult to differentiate from a nonneoplastic lesion. Close follow-up of these patients is very important. Within several months, these masses progress to typical MR imaging features such as a heterogeneous-enhanced bulky mass with central necrosis, which is more easily diagnosed. Based on previous studies, the average time from the initial scan to final diagnosis of glioblastoma is 4.5 months (range, 1.25–10 months) [
In conclusion, the appearance of early-stage glioblastoma on MR imaging is characterized by a small, ill-defined, isointense to hypointense lesion on T1WI and hyperintense lesion on T2WI, with little or no mass edema and no contrast enhancement. Within several months, this appearance can progress to a bulky mass with enhancement that is typical of glioblastoma. As mentioned above, it is not easy to differentiate early-stage glioblastoma from nonneoplastic lesions using routine MR imaging. However, the combination of a hyperattenuated or isoattenuated region on CT with a region that appears hyperintense in the lesion or part of the lesion on DWI is highly specific for the diagnosis. DWI plus unenhanced CT is more accurate than routine MR imaging alone for diagnosis of early-stage glioblastoma. This is very important because of the extremely poor prognosis, particularly for
The data used to support the findings of this study are available from the corresponding author upon request.
Ethical approval was obtained from the local institutional review board (Ethical Committee of Affiliated Hospital of Qingdao University).
Hexiang Wang and Zhenyou Liu contributed equally, and both of them are co-first authors.
The authors declare that they have no conflicts of interest.
The authors acknowledge financial support by the Affiliated Hospital of Qingdao University within the funding program Open Access Publishing. This study received financial support from the Natural Science Foundation of Shandong Province (ZR2019MH067) and the Taishan Scholars Program (no. tsqn20161070).