Early Appearance of High Grade Glioma on Magnetic Resonance Imaging

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1 Neurol Med Chir (Tokyo) 49, 8 12, 2009 Early Appearance of High Grade Glioma on Magnetic Resonance Imaging Noriyuki NISHI, Shozo KAWAI*, TaijiYONEZAWA, Kenta FUJIMOTO*, andkatsuyamasui* Department of Neurosurgery, Nara Prefectural Mimuro Hospital, Nara; *Department of Neurosurgery, Osaka General Medical Center, Osaka Abstract The early appearance of high grade glioma on magnetic resonance (MR) imaging was retrospectively reviewed in the clinical records and MR images of 52 patients with intracerebral glioma treated in Osaka General Medical Center between 1997 and Three patients had no abnormal findings, and four patients had only hyperintense areas on T 2 -weighted imaging at initial MR examination. Five of the seven patients presented with generalized seizures. Six of the seven patients developed tumor progression within only 5 months. All patients underwent surgical tumor resection and the histological diagnoses were all high grade gliomas, glioblastomas in five, gliosarcoma in one, and anaplastic astrocytoma in one. Surveillance MR imaging should be performed at short intervals in adult patients presenting with seizures but with no or minimal abnormalities on initial MR imaging to identify progression of high grade glioma at the earliest opportunity. Key words: high grade glioma, early appearance, magnetic resonance imaging, seizure Introduction Early diagnosis of high grade glioma is important to achieve the optimum outcome for the patient. Any delay in correct diagnosis is considered to lead to poor outcome. Computed tomography (CT) has failed to detect glioma at initial and later examinations. 4,9,18,20) The introduction of magnetic resonance (MR) imaging has greatly improved the detection of intracranial lesions, 4,8,9,13,22) and apparently solved the difficulty with the diagnosis of glioma. However, neurosurgeons, neurologists, and neuroradiologists still encounter patients with high grade gliomas who present with no or minimal abnormalities on initial MR imaging. 7,9,10,12,15) This study retrospectively reviewed the clinical records and MR imaging findings in patients with intracerebral glioma to characterize the early MR imaging appearance of high grade glioma. Clinical Material and Methods Received February 13, 2007; Accepted October 15, 2008 A total of 52 consecutive patients with intracerebral gliomas were treated in Osaka General Medical Center between January 1997 and December MR imaging was performed using a 1.5-T Signa Advantage (GE Medical Systems, Milwaukee, Wis., U.S.A.) until January 2003 and a 1.5T Intra Master (Philips Medical Systems, Eindhoven, the Netherlands) from February Patients who underwent only CT were excluded. Seven patients, four men and three women aged from 50 to 70 years (mean 62.7 years), showed no or minimal abnormalities on initial MR imaging, whereas the others demonstrated the typical findings of high grade gliomas, such as heterogeneous enhancement and mass effect. The clinical records and the neuroimaging findings of the seven patients were retrospectively reviewed to investigate the initial symptoms, initial MR imaging features, time to recognition of progression, location of the tumors, and histological diagnosis. All patients underwent at least T 1 - weighted, T 2 -weighted, and fluid-attenuated inversion recovery imaging. Four of the seven patients also underwent MR imaging with gadolinium. The patients presenting with seizure underwent electroencephalography (EEG). Whole brain radiation or extensive local irradiation (50 60 Gy) was administered to six patients. Case 6 developed brain edema at the beginning, so radiotherapy was abandoned. Three patients received chemotherapy using ni- 8

2 Early Appearance of High Grade Glioma on MR Imaging 9 Table 1 Clinical, histological, and magnetic resonance (MR) imaging features of cases of occult glioma Case No. Age (yrs) Sex Initial symptom Initial MR imaging features Time to recognition of progression (mos) Location Histological type 1 68 M seizure normal 3 lt temporal glioblastoma 2 50 M seizure normal 5 lt frontal glioblastoma 3 70 F dizziness T 2 hyperintense area 24 rt frontal anaplastic astrocytoma 4 53 M seizure normal 3 lt temporal glioblastoma 5 65 F dizziness T 2 hyperintense area 4 lt temporal glioblastoma 6 68 M seizure T 2 hyperintense area 3 lt temporal gliosarcoma 7 65 F seizure T 2 hyperintense area 3 lt frontal glioblastoma mustine hydrochloride. All patients died of tumor progression. Results Table 1 summarizes the clinical, histological, and MR imaging features. Five of the seven patients presented with seizures as the initial symptom and had no history of seizures. EEG findings on admission were normal. The other two patients underwent MR imaging for examination of dizziness, but the initial symptoms were considered to be unrelated to the brain tumors. Initial MR imagings found no abnormalities in three patients, and minimal abnormalities in four patients consisting of hyperintense areas on T 2 - weighted imaging, which were misinterpreted as ischemic lesions, in contrast to the typical findings of malignancy such as gadolinium enhancement and mass effect. The overall findings of physical and neurological examinations, EEG, and other neurological imaging were normal in the seven patients, so were interpreted as non-neoplastic and the patients were discharged within a few days. Six of the seven patients developed tumor progression within only 5 months. Four of the tumors were located in the left temporal lobe, two in the left frontal lobe, and one in the right frontal lobe, so mainly occurred in the functionally dominant left cerebral hemispheres. All patients underwent surgical tumor resection. The histological diagnoses were glioblastoma in five patients, gliosarcoma in one, and anaplastic astrocytoma in one. No patient had low grade glioma. Illustrative Cases Fig. 1 Case 1. Axial T 1 -andt 2 -weighted magnetic resonance images on admission showing no abnormalities. Fig. 2 Case 1. Axial T 1 -andt 2 -weighted magnetic resonance images 3 months after onset of seizure revealing a cystic lesion in the left temporal lobe. Case 1: A 68-year-old man, who did not have any history of epilepsy, suffered generalized tonic seizure on February 3, He was admitted to our institute for further examinations 10 days later. Physical examination, blood examination, CT, and EEG found no abnormalities. MR imaging showed no abnormalities in the central nervous system (Fig. 1). No definite focal lesion was identified, so he was

3 10 N. Nishi et al. Fig. 3 Case 4. T 2 -weighted magnetic resonance (MR) image demonstrating a hyperintense area in the left temporal lobe and constriction of the cerebral sulci about 3 months after initial MR imaging. dischargedandfollowedupinourinstitute. He exhibited sensory aphasia and was admitted to our institute on May 5, MR imaging revealed a cystic tumor in the left temporal lobe (Fig. 2). The tumor was removed and the histological diagnosis of glioblastoma was made. He was treated with radiation therapy and died of recurrence of glioblastoma in August Case 4: A 53-year-old man suffered generalized seizure on November 16, 2000 and was transferred to our institute for further examination on the next day. Neurological and physical examinations, EEG, andmrimagingfoundnoabnormalities,sohewas dischargedandfollowedupasoutpatient. T 2 -weighted MR imaging revealed a hyperintense area and constriction of the sulci in the left temporal lobe on February 28, 2001 (Fig. 3), despite the absence of symptoms and normal neurological findings. Positron emission tomography with 2-[ 18 F]fluoro-2-deoxy-D-glucose (FDG-PET) revealed focal increases of uptake in the left temporal lobe. The left temporal lesion was considered to be brain tumor rather than ischemic or degenerative disease. We recommended surgical management including biopsy, but he refused informed consent so we followed him up as an outpatient. He was admitted to our institute with severe headache and sensory aphasia on July 5, MR imaging revealed a heterogeneously enhanced tumor in the temporal lobe (Fig. 4). He underwent subtotal removal of the tumor on July 12, The histological diagnosis was glioblastoma. He was treated with whole brain radiation therapy and discharged. He died of recurrence of glioblastoma on Fig. 4 Case 4. T 1 -weighted magnetic resonance (MR) image with gadolinium 8 months after initial MR imaging showing a heterogeneously enhanced tumor in the temporal lobe. November 13, Discussion In our series, many patients with high grade gliomas had the typical MR imaging findings of high grade gliomas including glioblastoma which appear as prominent heterogeneous intensity on T 2 -weighted images, with marked and irregular enhancement with gadolinium. 21) Only seven patients presented with symptoms before showing such typical MR imaging features. Experience of false-negative detection of glioma by CT indicates that important factors include small tumor size and low cell density, isodense tumor mass, absence of acquired changes in the blood-brain barrier, and poor scan resolution. 4,9,14,18,20) We suggest that MR imaging may fail to detect gliomas due to similar factors. The early appearance of high grade gliomas on MR imaging may manifest as minimally abnormal small hyperintense areas on T 2 -weighted imaging which might be misinterpreted as ischemic change. 11,15) MR imaging detects malignant changes only several months later. Similarly, initial MR imaging showed no or minimal abnormalities, whereas subsequent MR imaging revealed high grade gliomas within a short time in our seven patients. Five of our seven patients presented with seizure as the initial symptoms. Three authors have reported patients with negative findings on initial CT or MR imaging who all later presented with seizures, 8) eight of nine patients with negative findings on MR imaging presented with seizures, 11) and five of eight patients presented with only seizures, indicating that seizures are the most sensitive clinical indicator

4 Early Appearance of High Grade Glioma on MR Imaging 11 of glioma. 13) Study of epileptogenic areas removed from patients with negative findings on MR imaging identified small tumor-like nodules in the temporal lobe. 5) Some of these nodules showed early histological evidence of neoplastic transformation, suggesting possible involvement as the origins for the further development of glioma. Six of our seven patients had high grade glioma in the left cerebral hemisphere, four of which were in the left temporal lobe. The present study suggests that high grade glioma in the left temporal lobe, even if very small or undetectable, may manifest as seizure or similar symptoms. Accordingly, we suggest that seizure should be considered as an indicator of occult high grade glioma. Adult patients who present with seizure but with no or minimal abnormalities on MR imaging should possibly be scheduled for follow-up MR imaging. MR imaging findings changed from negative to positive within 3 to 5 months, except in Case 3 within 24 months, and indicated high grade gliomas. Many patients have developed CT or MR imaging changes within 6 months, 4,8,9,11,15,18,20) and rapid follow-up CT or MR imaging is recommended. 11,12,20) However, the interval of surveillance CT or MR imaging is unclear. Many patients presented with malignant progression within 5 6 months, so we recommend that surveillance MR imaging be performed a few times in the initial 6 months. Small gliomas are histologically benign, 17) but the patients may develop high grade gliomas later with poor outcome, even if initial CT and/or MR imaging findings were negative. 4,8,9,11,13 15,18,20,22) Similarly, all of our patients developed high grade gliomas. The origin of malignant tumor cells in the brain is unknown, and the initiation of high grade glioma needs further investigation. More sensitive tools and methods than usual imaging may be necessary to identify neoplasm or nonneoplasm in the early stages. Diffusion-weighted MR imaging is suitable for the early diagnosis of malignant glioma. 1,10) No cases were examined by diffusion-weighted MR imaging in our seven patients. The findings of diffusion-weighted MR imaging will be very interesting. Technetium-99m scintigraphy 7) and transcranial sonography 2) may be useful, and FDG-PET has received much attention. 3,6,16,19) FDG-PET revealed that the hyperintense area on T 2 -weighted imaging was neoplasm in Case 4, so we consider FDG-PET is very valuable for the diagnosis of brain neoplasm. In the future, FDG-PET may facilitate the diagnosis of brain neoplasms in patients with normal findings on initial MR imaging. The present study of patients with gliomas not identified by initial MR imaging showed that such gliomas are characterized by initial manifestation as seizure, possibly related to the most common location in the left temporal lobe, short interval of only 5 months before tumor progression, and high likelihood of malignant progression. Surveillance MR imaging should be continued at short intervals in adult patients presenting with seizure and normal or minimally abnormal findings on initial MR imaging to identify and begin treatment of high grade glioma at the earliest opportunity. References 1) Baehring JM, Bi WL, Bannykh S, Piepmeier JM, Fulbright RK: Diffusion MRI in the early diagnosis of malignant glioma. JNeurooncol82: , ) Becker G, Krone A, Schmitt K, Woydt M, Hofmann E, Lindner A, Bogdahn U, Gahn G, Roosen K: Preoperative and postoperative follow-up in highgrade gliomas: comparison of transcranial color-coded real-time sonography and computed tomography findings. 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