Nonenhancing peritumoral hyperintense lesion on diffusion-weighted imaging in glioblastoma: a novel diagnostic and specific prognostic indicator

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OBJECTIVE

Glioblastoma differentials include intracranial tumors, like malignant lymphomas and metastatic brain tumors with indiscernible radiological characteristics. The purpose of this study was to identify a distinct radiological feature for the preoperative differentiation of glioblastoma from its differentials, which include malignant lymphomas and metastatic brain tumors.

METHODS

Preoperative MR images, including diffusion-weighted imaging (DWI) studies (b = 1000 and 4000 sec/mm2), obtained in patients with newly diagnosed malignant tumor, were analyzed retrospectively after receiving approval from the institutional review board. Sixty-four patients with histologically confirmed glioblastoma, 32 patients with malignant lymphoma, and 46 patients with brain metastases were included. The presence of a nonenhancing peritumoral DWI high lesion (NePDHL, i.e., hyperintense lesion in a nonenhancing peritumoral area on DWI) was confirmed in both DWI sequences. Gray matter lesions were excluded. Lesions were termed “definite” if present within 3 cm of the hyperintense tumor border with a signal intensity ratio ≥ 30% when compared with the contralateral normal white matter in both sequences. Discriminant analysis between the histological diagnosis and the presence of Definite-NePDHL was performed, as well as Kaplan-Meier survival analysis incorporating the existence of Definite-NePDHL.

RESULTS

In 25% of glioblastoma patients, Definite-NePDHL was present, while it was conspicuously absent in patients with malignant lymphoma and metastatic brain tumors. The specificity and positive predictive value were 100%. In the glioblastoma subset, a higher preoperative Karnofsky Performance Scale score (p = 0.0028), high recursive partitioning analysis class (p = 0.0006), and total surgical removal (p = 0.0012) were associated with better median overall survival. Patients with Definite-NePDHL had significantly early local (p = 0.0467) and distant/dissemination recurrence (p < 0.0001) and poor prognosis (p = 0.0007).

CONCLUSIONS

The presence of Definite-NePDHL is very specific for glioblastoma and indicates poor prognosis. Definite-NePDHL is a significant indicator of early local and distant/dissemination recurrence in patients with glioblastoma. Studying peritumoral DWI and high–b-value DWI is useful for tumor differentiation.

ABBREVIATIONS ADC = apparent diffusion coefficient; ADCMIN = minimum absolute ADC; BBB = blood-brain barrier; CNWM = contralateral normal white matter; DTI = diffusion tensor imaging; DWI = diffusion-weighted imaging; IDH-1 = isocitrate dehydrogenase 1; KPS = Karnofsky Performance Scale; NePDHL = nonenhancing peritumoral DWI high lesion; ROI = region of interest; RPA = recursive partitioning analysis; SIR = signal intensity ratio; T1WI = T1-weighted imaging; T2*WI = T2*-weighted imaging.

Article Information

Correspondence Fumiyuki Yamasaki, Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. email: fyama@hiroshima-u.ac.jp.

INCLUDE WHEN CITING Published online March 31, 2017; DOI: 10.3171/2016.10.JNS161694.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Upper: Case 1. MR images obtained in a patient with glioblastoma (WHO Grade IV) with cystic and hemorrhagic components. FLAIR (A) and postcontrast MR (B) images showing the nonenhanced peritumoral region (arrow). The same nonenhancing peritumoral region showing high signal intensity on DWI at b = 1000 sec/mm2 (C) and b = 4000 sec/mm2 (D) (arrow). This lesion was defined as a Definite-NePDHL. Lower: Case 2. MR images obtained in a patient with multiple lesions in the left cerebral hemisphere with the differentials being multiple brain metastases or malignant lymphomas. FLAIR (A) and postcontrast (B) images showing a nonenhancing peritumoral region (arrow). The same area (arrow) is seen as a high signal intensity lesion on DWI at b = 1000 s/mm2 (C) and b = 4000 s/mm2 (D). This represents a case positive for Definite-NePDHL. The lesion was also histologically confirmed to be glioblastoma (WHO Grade IV).

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    Case 3. MR images obtained in a case of malignant lymphoma of the brain. FLAIR (A) and postcontrast MR (B) images showing a nonenhanced peritumoral region (arrows). The same area is seen as high signal intensity on DW images at b = 1000 sec/mm2 (C) and b = 4000 sec/mm2 (D) (arrows), but does not fulfill the criteria of SIR > 30% compared with the CNWM. This lesion was defined as Probable-NePDHL.

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    Parallel box plots showing the ADCMIN values at b = 1000 sec/mm2 (A) and b = 4000 sec/mm2 (B) in patients with glioblastoma (GBM), malignant lymphoma (ML), and brain metastases (Mets). Each box shows the 25th to 75th percentile and median value, and the whiskers show the range.

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    Kaplan-Meier survival curves illustrating the cumulative survival rates for patients with glioblastoma. A–C: Comparisons were made between patients with KPS score ≥ 80 and KPS score ≤ 70 (A), Definite-NePDHL (D-NePDHL)–positive and –negative patients (B), and patients who underwent total and nontotal removal (C). D: Overall survival for glioblastoma stratified by RPA classification showing significant differences in overall survival between the RPA classes: Group 1 (Classes 3 and 4) versus Group 2 (Classes 5 and 6).

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    Kaplan-Meier survival curves (log-rank test) showing that tumor progression (A) and distant/dissemination recurrence (B) occurred significantly earlier in patients positive for Definite-NePDHL than patients negative for Definite-NePDHL.

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