Gliomatosis cerebri (GC) is a diffuse glial tumor that infiltrates the brain extensively. The optimal therapeutic strategy for this tumor has not yet been established. Radiotherapy, temozolomide and other chemotherapeutic modalities have been used to treat GC.1,2 Despite aggressive and often multimodal therapeutic intervention, survival rates for adult and pediatric patients with GC are extremely poor.3 Here we report two cases of GC in which we initially explored a new therapeutic strategy for this disease.
A 55-year-old man complained of intermittent dizziness for 6 months, accompanied by a single epileptic seizure. He was admitted to our hospital in July 2005. His blood pressure was 180/110 mmHg and his karnofsky score (KPS) was 100; data from other general physical and neurological examinations were within normal limits. The patient had hypertension and coronary heart disease for 10 years and was treated with bluish dogbane, captopril and nifedipine taken orally. Brain examination involving T2-weighted magnetic resonance imaging (MRI) showed extensive areas of heterogeneous hyperintensity affecting the bilateral frontal lobe, right parietal lobe and corpus callosum. On T1-weighted images after administration of contrast agent, the lesion was found to be slightly enhanced without a clear boundary with normal brain tissue (Figure 1). Stereotaxic autopsy was carried out and the pathology revealed glial cell hyperplasia and sporadic hemorrhage. Subsequently, the patient received three-dimensional conformal radiotherapy in 30 fractions to a total radiation dose of 54 Gy. Two months later, a MRI rescan revealed that the lesion had rapidly diminished in size. The patient remained stable, but had an occasional feeling of fullness in the head, amnesia and fatigue. Two years later, repeat MRI revealed that the lesion had obviously shrunk and was confined to the right frontal lobe; the center part of the tumor were enhanced obviously after the administration of contrast agent. Consequently, we performed right frontal craniotomy and removed the tumor and the affected frontal pole in May 2007. During the operation we found that the tumor was yellowish in color, soft and had a relatively poor blood supply. Necrosis was found in the center of the lesion, and no clear boundary to the lesion was observed. The pathology revealed obvious hyperplasia around the radiation induced necrosis and some cellular plasminogen degeneration was observed, with cytoblasts showing slightly allotypic neoplastic vascular changes. The molecular pathology results were as follows: P-glycoprotein (P-170), ±; O6-methylguanine DNA-transferase (MGMT), +—++; phosphatase and tensin homolog deleted from chromosome ten (PTEN), +++; epidermal growth factor receptor (EGFR), ±—+; Ki-67 proliferation index (Ki-67), ±; topoisomerase II (TOPO II), ±; and glutathione S-transferase-II (GST-II), +. No complications occurred after surgery and the KPS remained at 100. After the operation the patient lived for an additional 22 months and died in March 2009.
A 39-year old man complained of paroxysmal nasal and pharyngeal discomfort, and headache. He was admitted to our hospital in August 2007. No abnormality was found on general physical and neurologic examination. A brain computed tomography (CT) scan revealed a lesion in the left frontal temporal lobe and basal area, with intracerebral calcification and no obvious edema and enhancement. A lesion affecting the contralateral frontal lobe throughout the corpus callosum was detected in the brain using MRI. The lesions were slightly enhanced on T1-weighted images after the administration of contrast agent, and there was no clear boundary between the lesion and normal brain tissue (Figure 2). Stereotaxic autopsy was undertaken, and the pathology revealed oligodendroastrocytoma, glial cell hyperplasia and local axonal swelling. Subsequently, the patient received three-dimensional conformal therapy in 30 fractions to a total radiation dose of 54 Gy and temozolomide treatment. He remained stable and felt no indisposition after these treatments. Two years later, repeat MRI indicated that the lesion had shrunk and was confined to the left frontal lobe, with no obvious enhancement after the administration of contrast agent. We performed coronary craniotomy and adopted a left frontal approach to remove the tumor and the affected left frontal pole in April 2009. During the operation we found that the tumor was grey in color, a little tenacious and without a membrane. The blood supply was relatively poor and there was no clear boundary to the lesion. Pathology revealed that it was an astrocytoma. The molecular pathology findings were as follows: P-170, +; MGMT, ++; PTEN, +++; EGFR, +; Ki-67, - TOPO II, -; and GST-II, ±. No complications occurred after surgery, and the KPS has remained at 100. The patient has survived for an additional 12 months after treatment and is still alive at the time of writing.
Management of GC is difficult. Because of the diffuse spreading of the neoplasm, surgery is not suitable and large field radiotherapy carries the risk of severe toxicity. Despite aggressive and often multimodal therapeutic intervention, survival rates for adult and childhood patients with GC are extremely poor.2,3 Elshaikh et al2 reported that in general, the outcome for patients with GC who received brain radiotherapy is relatively superior to that achieved by patients who received no treatment. Perkins et al4 reported a partial radiographic response rate to radiotherapy of 33%, but this improvement was maintained in only 50% of patients at 10 months; the median time to disease progression and the median survival time were significantly prolonged in patients with GC aged <40 years who received radiotherapy.
In our study, both patients had symptoms of increased intracranial pressure, so we chose to treat them with radiotherapy. This modality can decrease the intracranial pressure faster than chemotherapy after biopsy. However, the lesions shrank in size beyond our expectation. In the current series, both patients showed a high sensitivity to radiotherapy and underwent surgery to remove the shrunken lesion at 1–2 years after radiotherapy. The relatively good prognosis of these two patients indicates that there may be a subtype of GC, which is highly sensitive to radiation. Further investigation should be carried out to discover the underlying molecular factors that determine the sensitivity of cells in this tumor to radiation. With regard to this subtype of GC, surgery following radiotherapy may be an alternative approach in treating this disease.
1. Sanson M, Cartalat-Carel S, Taillibert S, Napolitano M, Djafari L, Cougnard J, et al. Initial chemotherapy in gliomatosis cerebri. Neurology 2004; 63: 270-275.
2. Elshaikh MA, Stevens GH, Peereboom DM, Cohen BH, Prayson RA, Lee SY, et al. Gliomatosis cerebri: treatment results with radiotherapy alone. Cancer 2002; 95: 2027-2031.
3. Armstrong GT, Phillips PC, Rorke-Adams LB, Judkins AR, Localio AR, Fisher MJ. Gliomatosis cerebri: 20 years of experience at the Children's Hospital of Philadelphia. Cancer 2006; 107: 1597-1606.
4. Perkins GH, Schomer DF, Fuller GN, Allen PK, Maor MH. Gliomatosis cerebri: improved outcome with radiotherapy. Int J Radiat Oncol Biol Phys 2003; 56: 1137-1146.