Prepared by Douglas Mathis, MD , Joyce Moore Stovall, MD , and Karen SantaCruz, MD , from the Eisenhower VA Medical Center, Leavenworth, KS.

CASE SUMMARY

A 41-year-old active-duty Army officer presented with a new onset of grand mal seizure at an outpatient military clinic. Prior to this episode, he had experienced intermittent headaches for approximately 5 to 7 days with no other significant neurological symptoms. The patient's medical history is unremarkable for major illnesses or surgical procedures. His neurological examination disclosed pronator drift of his left arm and global 1+ reflexes. Computed tomography (CT) (Figures 1 and 2) and magnetic resonance imaging (MRI) (Figure 3) examinations were ordered.

IMAGING FINDINGS

Pre- and postcontrast CT scans of the brain (Figures 1 and 2) of the brain at the time of the initial presentation revealed a dominant ring-enhancing mass at the gray-white matter junction and several small enhancing lesions in the right parieto-occipital area. There was associated vasogenic edema, effacement of the right lateral ventricle, and approximately 5 to 7 mm of midline shift to the patient's left (Figure 1). CT slices through the parieto-occipital area revealed multiple small enhancing lesions at the grey-white matter junction with vasogenic edema (Figures 2).

The postcontrast MRI scans were consistent with the CT scans. MRI demonstrated a large ring-enhancing lesion with a hypointense center of fluid consistency and multiple smaller enhancing lesions in the right parieto-occipital lobe (Figure 3). There was effacement of the right lateral ventricle.

The radiological differential diagnosis included brain metastases, cerebral abscesses, lymphomas in AIDS patients, and toxoplasmosis.

Based on the diagnostic imaging, the patient was started on antibiotic therapy for the proposed diagnosis of multiple cerebral abscesses. The patient was continued on Dilantin and Decadron for seizures.

DIAGNOSIS

Multiple glioblastomas

PATHOLOGIC FINDINGS

Stereotactic-guided needle biopsy of the dominant cystic lesion yielded tea-colored fluid under high pressure. The fluid was sent for gram stain, cultures, sensitivity, and acid-fast bacilli. The fluid contained debris and necrotic tissue but no pus. A frozen section of the stereotactic needle biopsy revealed acute inflammation with many polymorphonuclear lymphocytes, which were thought to be consistent with cerebral abscess, although no frank pus was found. The tests for cryptococcal and toxoplasmosis antigens were negative. The blood cultures were negative for the HIV/AIDS virus.

Microscopic examination (Figure 4) of hematoxylin and eosin stained sections of tumor showed prominent pleomorphism, cellular atypia, and glomeruloid vascular proliferation characteristic of high-grade gliomas. Focal necrosis with pseudopalisading of tumor cells further defined this neoplasm as a glioblastoma multiforme. Glial fibrillary acidic protein (GFAP) immunostaining and an MIB-1 immunostain confirmed the glial nature and aggressive character of the tumor cells. The final pathology returned as glioblastoma multiforme for the multiple lesions. No distinct histological link of multifoci within this tumor could be discerned.

The patient was discharged and received follow-up appointments with the Radiation Oncology and Medical Oncology departments. Radiation Oncology recommended tumor debulking to improve the effectiveness of radiation therapy. The patient underwent a subsequent right temporoparieto-occipital craniotomy with resection of the middle fossa and parieto-occipital glioblastomas. The patient tolerated the surgical procedure well without signs of postoperative neurological deficits. Upon discharge, the patient was ambulating without assistance.

DISCUSSION

Glioblastoma multiforme is the most common primary supratentorial glial neoplasm. It primarily occurs in 40- to 55-year-old men. New onset of generalized seizures is a presenting symptom in approximately 20% of patients. ¹ Other symptoms include headache, nausea and vomiting, personality changes, and psychomotor dysfunction. Glioblastoma multiforme is a glial neoplasm with high cellularity, vascular endothelial proliferation, and nuclear and cytoplasmic pleomorphism. It can present a multiplicity of histological appearances. Glioblastoma usually involves the white matter of the cerebrum: 35% of cases involve the frontal lobe, 33% the parietal lobe, 22% the temporal lobe, and 10% the occipital lobe. ² Frequently, glioblastoma multiforme crosses the corpus callosum extending bilaterally as a single entity in a butterfly pattern. Multiple sclerosis and lymphomas also possess this capability.

Kernohan classification is the most commonly used method of classifiying astrocytomas on a scale from 1 to 4. Glioblastoma multiforme is a grade four, and is histologically the most aggressive. ¹ The World Health Organization and the Radiation Treatment Oncology Group utilize three categories for classification: low-grade astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme. ¹

CT and MRI studies are valuable and are the most frequently used diagnostic imaging modalities for detection of glioblastoma. The CT and MRI appearance of glioblastoma are vasogenic edema, mass effect, cystic and solid components, hemorrhage, and tumor enhancement secondary to compromise of the blood-brain barrier. The latter of these is extremely important in patient management. Its ill-defined margins correlate with the aggressive infiltrative properties of the lesion. The prognosis of glioblastoma multiforme is grave. The mean survival time is usually 6 months from the time of diagnosis.

In this case, the contrast-enhanced CT scan and MRI feature multiple well-defined, ring-enhancing lesions with cystic and solid components in the right parieto-occipital cortex that were thought to be cerebral abscesses. Multiple ring-enhancing glioblastomas can emulate brain metastases, cerebral abscesses, lymphomas in AIDS patients, and toxoplasmosis. Accurate histopathologic assessment of multiple brain masses mandates appropriate selections of areas to perform stereotactic guided biopsies.

Multiple glioblastomas are uncommon and represent only 2.5% to 5% of all glioblastomas, usually involving one or more lobes of one or both cerebral hemispheres. According to Lafitte et al, ³ multiple gliomas can appear early (synchronous), at the time of the initial diagnosis, or they can appear at a later time (metachronous) subsequent to the initial diagnosis. Multiple glioblastomas are classified as multicentric, if they arise independently in different sites; or multifocal, if they spread from a primary focus to other sites in the brain. ³ It has been hypothesized that multifocal gliomas undergo genetic cloning, and yield many satellite lesions from a single tumor. ⁴ This distinction necessitates histopathologic assessment of genetic material for determination of clonality.

Multifocal gliomas can infiltrate the overlying meninges of the cerebral cortex and subependymal route of the lateral ventricles, which effects tumor seeding of the cerebrospinal fluid pathways in the meningeal and subarachnoid spaces. The CT scan and MRI of patients with multifocal glioblastomas will reveal enhancement of the meninges or ventricles close to the lesion if there is dissemination. ⁵ Postcontrast enhancement of the meninges or the ventricles on this patient's CT scan and MRI was not observed. Ultimately, making the distinction between multifocal and multicentric glioblastomas offers little practical clinical value. ⁴

Perhaps the metabolic and functional attributes of proton MR spectroscopy would have assisted in making the diagnosis of brain tumors. Clinical proton MR spectroscopy can detect the four types of metabolites in the brain that have a long echo time (135 to 270 msec): choline compounds, creatine/phosphocreatine, N-acetylaspartate (NAA), and lactate. Clinical proton MR spectroscopy distinguishes the metabolites in the brain that peak at a short echo time (20 msec): lipids, myo-inositol, glycine, glutamine/glutamate and macromolecules. ⁶ The phenotypes of the distinct metabolites will reflect different MR peaks. The quantitative analysis of normal and pathological brain tissue is reflected by amplitudes on an empirical algorithm. MR spectra of brain tumors are interpreted on the basis of the relative amplitudes for choline, creatine, NAA, lactate, and lipids. In a normal brain MR spectroscopy, the highest amplitude is the NAA peak; choline and creatine ratio are about equal and markedly decreased when compared with NAA; and the lipid and lactate concentrations are not elevated. ^6,7 In low-grade gliomas, the choline metabolite in the proton spectrum is slightly increased above the NAA metabolite, and lactate is elevated. ^6,7 In high-grade gliomas (anaplastic astrocytoma and glioblastoma multiforme) choline is markedly increased, NAA is markedly decreased, and lactic acid and lipids are frequently high. ^6,7 Areas of decreased NAA, choline, and creatine metabolites with increased lactic acid and lipids are usually where the necrotic portions of high-grade tumors are found. ^6,7 Selection of stereotactic guided needle biopsy samples should be avoided in such areas, because of the high probability of yielding inflammatory or necrotic cells.

A new Single-Voxel Proton Brain Exam (PROBE/SV; GE Medical Systems, Milwaukee, WI) is an automated and operationally simplified MR spectroscopic technique that provides automatic online data processing and display. ⁶ The selection of the voxel location area of interest to focus on can be acquired to determine if there is a low-grade or high-grade neoplasm, inflammatory process, and/or tumor necrosis. The voxel selection location should be obtained from an area that is at least 1 cm ³ in size and demonstrates elevated choline. ⁷ The PROBE/VS MR spectroscopic technique can help to improve the physician's confidence on selections of areas to perform the stereotactic-guided biopsy for histopathological assessment. The exam can decrease 1) the number of biopsies, 2) the chance of voxel contamination from unwanted tissue, 3) patient morbidity, and 4) the number of diagnostic tests needed. It can be helpful in differentiating between radiation necrosis and tumor recurrence following radiation and chemotherapy.

SUMMARY

Multiple glioblastomas on CT and conventional MRI can emulate brain metastases, cerebral abscesses, lymphomas in AIDS patients, and toxoplasmosis. PROBE/SV data, an automated MR spectroscopic technique, in conjuction with CT and conventional MRI, can play a beneficial role in aiding physicians in obtaining a more accurate diagnosis. This automated MR spectroscopic technique can be helpful in formulating the patient's therapeutic plan.

ACKNOWLEDGMENTS

The authors thank Mrs. J. Gosselin, medical librarian of DDE VAMC, for her help in retrieving articles; Mrs. S. Collins, medical clerk, for retrieving patient information; Mr. K. Jahn, radiologic technician for computer assistance; and Mr. A. Swieca for the photography.