We investigated the effectiveness of stereotactic gamma knife Radiosurgery (GKR) for radioresistant brain metastases with the impact upon histology.
Between April 2004 and May 2011, a total of 23 patients underwent GKR for 67 metastatic brain tumors from 12 renal cell cancers, 5 sarcomas and 6 melanomas. The mean age was 56 years (range, 18 to 79 years). Most of the patients were classified as the Radiation Therapy Oncology Group recursive partitioning analysis class II (91.3%). The synchronous metastasis was found in 6 patients (26.1%) and metachronous metastasis in 17 patients (73.9%). We analyzed the local control rate, intracranial progression-free survival (PFS) and overall survival (OS).
The mean tumor volume for GKR was 2.24 cc and the mean prescription dose was 19.4 Gy (range, 10 to 24) to the tumor margin. Out of metachronous metastases, the median duration to intracranial metastasis was 3.3 years in renal cell cancer (RCC), 2.4 years in melanoma and 1.1 years in sarcoma (p=0.012). The total local control rate was 89.6% during the mean 12.4 months follow-up. The six-month and one-year local control rate was 90.2% and 83% respectively. Depending on the pathology, the control rate of RCC was 95.7%, sarcoma 91.3% and melanoma 80.5% during the follow-up. The common cause of local failure was the tumor bleeding in melanoma. The median PFS and OS were 5.2 and 8.4 months in RCC patients, 6.5 and 9.8 months in sarcoma, and 3.8 and 5.1 months in melanoma.
The GKR can be one of the effective management options for the intracranial metastatic tumors from the radioresistant tumors. The melanoma showed a poor local control rate compared to other pathologies because of the hemorrhage.
Intracranial; Metastasis; Radioresistant; Renal cell cancer; Sarcoma; Melanoma
The abducens nerve paresis generally can aid in the presumptive diagnosis of abducens schwannoma along with the typical radiological features of schwannomas. The authors present a case of a 76-year-old male patient with a abducens schwannoma without abducens nerve paresis. Peroperatively, abducens nerve located in the cerebellopontine cistern had normal in contour and diameter, despite the mass originated from this nerve. We hypothesize that anatomic location of abducens nerve may affect the vector of tumor growth to prevent destruction of its origin, the abducens nerve.
Abducens nerve; Anatomical location; Atypical symptom; Cistern; Schwannoma
Intracranial meningiomas are primarily benign tumors with a good prognosis. Although WHO grade II meningiomas are rare (2-10%), WHO grade II meningiomas have higher recurrence and mortality rates than benign. We evaluated the patient recurrence rate and investigated the prognostic factors of WHO grade II meningiomas.
Between 1993 and 2005, 55 patients were diagnosed with WHO grade II meningiomas in our hospital. WHO grade II meningiomas (n=55) were compared with other WHO grades meningiomas (I, n=373; and III, n=20). The patients had a median age of 48.4 years (range, 14-17 years), a male-to-female ratio of 26 : 29, and a mean follow-up time of 45 months (range, 3-175 months).
In WHO grade II meningiomas, only the extent of resection was a significant prognostic factor. Post-operative radiotherapy had no significant influence on tumor recurrence (p=0.053). The relative risk of recurrence was significantly higher in WHO grade II meningiomas with incomplete resection (10/27, RR=37%) than in WHO grade II meningiomas with complete resection (4/28, RR=14%) regardless of post-operative radiotherapy. In the incomplete resection group, Simpson grade III or IV had a significantly high risk of recurrence regardless of post-operative RT (n=3, RR=100%) However, if the degree of resection was Simpson grade II, the recurrence rate was similar to the complete resection group even though post-operative RT was not performed.
Complete resection was the most powerful independent predictive factor of the recurrence rate in WHO grade II meningiomas. Post-operative adjuvant RT was not a significant factor in this study.
Meningioma; Recurrence rate; Post-operative radiotherapy; WHO grade II
Choroid plexus papillomas (CPPs) are generally regarded as benign tumors with typical radiologic and pathologic findings. However, they sometimes have unusual findings. We have analyzed radiologic findings and pathologic growth patterns on CPPs.
The study group included 5 male and 5 female patients (age range, 3 months to 58 years : median, 29 years). The study group included 3 pediatric and 7 adult patients. All patients underwent surgery; 9 patients had a gross total resection and 1 patient had a subtotal resection. We analyzed the radiologic findings (location, size, mottle-like appearance, enhancement, calcifications, and hydrocephalus) and pathologic growth patterns (typical papillary, papillary and solid, and papillary and tubular).
The median follow-up duration was 21.3 months (range, 4-47.8 months). There were no recurrences after initial treatment. All patients had benign CPPs. Pediatric CPPs were 3.2 cm masses (range, 2.7-4 cm) with homogeneous enhancement and a mottle-like appearance, which pathologically showed the papillary growth pattern. Hydrocephalus was present in all pediatric patients. Postoperatively, subdural hygroma had occurred in two patients. In adults, CPPs were located in the fourth ventricle in 6 patients and suprasellar area in 1 patient. The size varied from 0.5-4.2 cm. Hydrocephalus and calcifications occurred in 3 and 4 patients, respectively. Three patients showed the heterogeneous enhancement without a mottle-like appearance and pathologically showed combined papillary and solid growth in 2 patients and papillary and tubular growth in one. Postoperatively, two patients with large masses had injuries of the brainstem and underwent shunt procedures for aggravation of hydrocephalus.
CPPs may show unusual radiologic findings, which preoperatively give the difficulty to be differentiated from other tumors. CPPs with unusual radiologic findings showed the combined pathologic growth patterns.
Choroid plexus papilloma; Complications; Pathology; Radiology
It is rare for low-grade gliomas to disseminate to the leptomeninges. However, low-grade gliomas with dissemination to the leptomeninges have been occasionally reported in children, and have generally been associated with local recurrence. A 16-year-old boy sought evaluation for diplopia and gait disturbance. A brain magnetic resonance imaging (MRI) revealed pontine mass, which was proved to be fibrillary astrocytoma on biopsy, later. Radiation therapy (5400 cGy) was given and the patient's symptoms were improved. He was followed-up radiologically for brain lesion. Seven months after diagnosis he complained of back pain and gait disturbance. A brain MRI showed a newly-developed lesion at the left cerebellopontine angle without an interval change in the primary lesion. A spinal MRI demonstrated leptomeningeal dissemination of the entire spine. Radiation therapy (3750 cGy) to the spine, and adjuvant chemotherapy with a carboplatin plus vincristine regimen were administered. However, he had a progressive course with tumoral hemorrhage and expired 13 months after diagnosis. We report an unusual case of a low-grade brainstem glioma with spinal dissemination, but without local recurrence, and a progressive course associated with hemorrhage.
Children; Leptomeningeal dissemination; Low-grade glioma; Recurrence
We evaluated a modified trans-middle temporal gyrus (MTG) approach with good postoperative visual preservation for patients with trigonal tumors.
Three patients with a trigonal tumor were treated via the modified trans-MTG approach guided by a neuro-navigator. Modified trans-MTG approach involve the incision at the MTG within 5 mm to the superior temporal sulcus. This approach makes a proper trajectory to the trigone but also reduces the retraction injury of MTG as little as possible to prevent postoperative visual field defect. Preoperative and postoperative visual field examination using perimetry was performed to evaluate the visual field.
Three patients underwent surgery for lymphoma in the right trigone, meningioma in the left trigone, and focal enhancing nodule in the right paratrigonal area, respectively. In case of lymphoma, preoperative examination showed a left homonymous hemianopsia : one week later after surgery, a visual field examination was performed and revealed improvement of the visual field defect. In case of the meningioma, the preoperative examination showed no visual field defect : one month later, the visual field had no defect. In case of the enhancing nodule, preoperative visual field testing revealed a partial left homonymous hemianopsia. Visual examination within one month after surgery showed no visual field defect. All three patients treated with the modified trans-MTG approach showed no visual deterioration after surgery.
The modified trans-MTG approach provides a safe and useful technique for trigonal tumors without postoperative visual field deterioration and affords adequate exposure of the trigonal tumor with a short trajectory.
Trigonal tumor; Visual field; Preservation
We have introduced a method of characterization of invading glioma cells by using molecular analysis of marginal invading tumor cells and molecular profiles of glioma tumor margin.
Each of tumor core and marginal tissues was obtained in 22 glioma patients. Tumor core cells and marginal cells from each glial tumor were collected by laser capture microdissection or intraoperative microdissection under the operating microscope. Expression of MMP-2, MMP-9, CD44 and RHAMM mRNA by invading glioma cells compared with tumor core was confirmed by realtime-PCR of twenty-four glioma specimens. Clinical data also were reviewed for invasion and recurrence pattern of the gliomas radiologically and invasive rim pattern microscopically.
Overall results of the molecular analysis showed that relative overexpression of MMP-2, MMP-9 and RHAMM were noted at the invasive edge of human glioma specimens comparing to the tumor core but CD44 was highly expressed in the tumor core comparing to the margin. High marginal expression of MMP-2 and MMP-9 were noted in poorly ill-defined margin on the pathological finding. High marginal expression of CD44 and MMP-2 were demonstrated in the midline cross group on the radiological review, and that of RHAMM and MMP-2 were showed in the aggressive recurrence group. High expression of MMP-2 seems to be involved in the various invasion-related phenomenons.
Up-regulation of MMP-2, MMP-9, CD44 and RHAMM was noted in invasive edge of gliomas according to the various clinical situations.
CD44; Glioma; Laser capture nicrodissection; MMP-2; MMP-9; RHAMM
We report a case of cerebral actinomycosis in a 69-year-old immunocompetent woman. The patient showed a progressive worsened mental status for one week. MRI examination showed an increased size of multiple enhancing nodular lesions associated with mild perilesional edema. We performed an open biopsy for the right frontal enhancing lesion. The intraoperative finding showed a yellowish friable lesion that was not demarcated with normal tissue. Pathologically, an actinomycotic lesion with sulfur granules and inflammatory cells was diagnosed. We report an unusual case of diffuse involvement of cerebral actinomycosis. The presence of the uncapsulated friable lesion that consisted mainly of foamy macrophages and lymphocytes could explain the unusual radiological features.
Actinomycosis; Cerebral abscess; MR imaging
The endocrine dysfunction after the operation for suprasellar arachnoid cysts is not rare. The careful operation to prevent structures can prevent this complication, but it is not enough and effective to prevent it. Authors present technical surgical considerations to prevent this complication with a review of our suprasellar arachnoid cyst patients who had postoperative endocrine dysfunction.
From January 2002 to December 2009, eight patients who had suprasellar arachnoid cysts with visual impairment underwent surgery. The mean age was 57.1 years (range, 33-77). Preoperatively, their endocrine function was clinically normal, and laboratory hormonal levels were within normal ranges. Cyst fenestration was performed by craniotomy (n=6) or by a neuro-endoscopic procedure (n=2), and, simultaneously, along with a cyst wall biopsy.
The surgery was uneventful in all eight patients, and there were no neurological morbidities. However, in four patients, endocrine dysfunction occurred postoperatively. We compared these four patients (group A) to the other 4 patients without endocrine dysfunction (group B) with intraoperative findings and with the histopathological findings of the cyst wall biopsy. The group A patients had more abundant vasculature on the cystic wall than the group B patients according to both the intraoperative findings and the histopathological findings.
When performing a surgical cyst wall fenestration, surgeons should try to minimize the destruction of the cystic wall vasculature and not to make the fenestration at a site that contains many vascular striae.
Cyst fenestration; Endocrine dysfunction; Suprasellar arachnoid cyst
Neuroblastoma is a common tumor of children. We report a patient with extensive calvarial metastases of a neuroblastoma as an initial presentation. A 2-year-old girl presented with a history of gradually increasing head size and fever. A brain CT showed a multilobulated, large, extra-axial tumor involving both frontotemporoparietal areas with a sunray-spiculated hyperostosis of the skull and marked contrast enhancement. A brain MRI demonstrated extensive calvarial lesions with simultaneous involvement of the orbits. A biopsy was performed and a ganglioneuroblastoma was diagnosed. On systemic evaluation, an enlarged abdominal mass was detected. After neo-adjuvant chemotherapy, most of the tumors disappeared except for a tumor in the left parietal area; there was a corresponding decrease in the circumference of the head. We performed surgery for the remnant mass. Intensive chemotherapy was administered and a bone marrow transplantation was performed. Adequate neo-adjuvant chemotherapy followed by surgery to the neuroblatoma with extensive metastases to the skull and orbit may be helpful.
Calvarium; Chemotherapy; Neuroblastoma; Metastasis
Pilomyxoid astrocytoma (PMA) is a newly recognized variant of a pilocytic astrocytoma. This report describes a case of a pilomyxoid astrocytoma that occurred in the opticohypothalamus. The patient was a 18-year-old girl who complained decreased visual acuity and visual field over a period of two years. Magnetic resonance imaging (MRI) showed an irregular lobulated tumor with heterogeneous enhancement at the suprasellar region involving the hypothalamus. The mass was partially removed via the subfrontal approach. Its pathology was confirmed to be PMA. Adjuvant chemotherapy with cisplatin and vincristine was started following tumor resection. After four cycles, the mass showed a partial response to the chemotherapy. Although long-term outcome is yet to be determined, the administration of combined cisplatin and vincristine treatment seems to be an effective regimen for a pilomyxoid astrocytoma.
Adjuvant chemotherapy; Opticohypothalamus; Pilomyxoid astrocytoma
We report our surgical experience in the treatment of 16 consecutive patients with benign craniovertebral junction (CVJ) tumor, observed from 2003 to 2008 at our department.
We had treated 6 foramen magnum meningiomas, 6 cervicomedullary hemangioblastomas, 1 accessory nerve schwannoma, 1 hypoglossal nerve schwannoma, 1 C2 root schwannoma, and 1 cavernous hemangioma. Clinical results were evaluated by Karnofsky Performance Scale (KPS) and all patients underwent preoperative neuroradiological evaluation with computed tomography (CT) and magnetic resonance image (MRI). Angiography was performed in 15 patients and preoperative embolization was done in 2 patients.
Five far-lateral, 1 supracondylar and 10 midline suboccipital approaches were performed. Gross total removal was achieved in 15 cases (94%) and subtotal removal in 1 patient (6%). None of the patients required occipitocervical fusion. Radiological follow-up showed no recurrence in cases totally removed. Postoperative decrease of KPS scores was recorded in only 1 patient. The treatment of cervicomedullary solid hemangioblastoma presented particular issues : by preoperative embolization, we removed tumor totally without an excessive bleeding or brainstem injury. In one of foramen magnum meningioma, we carried out subtotal removal due to hard tumor consistency and encasement of neurovascular structures.
: The choice of surgical approaches and the extent of bone resection should be defined according to the location and size of individual tumors. Moreover, we emphasize that preoperative neuroradiological evaluations on presumptive tumor type could be helpful to the surgeon in tailoring the technique and providing the required exposure for different lesions, without unnecessary surgical steps.
Benign tumor; Complication; Craniovertebral junction; Neuroradiology; Surgical resection
We determined whether the expression of GRIM-19 is correlated with pathologic types and malignant grades in gliomas, and determined the function of GRIM-19 in human gliomas.
Tumor tissues were isolated and frozen at -80℃ just after surgery. The tissues consisted of normal brain tissue (4), astrocytomas (2), anaplastic astrocytomas (2), oligodendrogliomas (13), anaplastic oligodendrogliomas (11), and glioblastomas (16). To profile tumor-related genes, we applied RNA differential display using a Genefishing™ DEG kit, and validated the tumor-related genes by reverse transcription polymerase chain reaction (RT-PCR). A human glioblastoma cell line (U343MG-A) was used for the GRIM-19 functional studies. The morphologic and cytoskeletal changes were examined via light and confocal microscopy. The migratory and invasive abilities were investigated by the simple scratch technique and Matrigel assay. The antiproliferative activity was determined by thiazolyl blue Tetrazolium bromide (MTT) assay and FACS analysis.
Based on RT-PCR analysis, the expression of GRIM-19 was higher in astrocytic tumors than oligodendroglial tumors. The expression of GRIM-19 was higher in high-grade tumors than low-grade tumors or normal brain tissue; glioblastomas showed the highest expression. After transfection of GRIM-19 into U343MG-A, the morphology of the sense-transfection cells became larger and more spindly. The antisense-transfection cells became smaller and rounder compared with wild type U343MG-A. The MTT assay showed that the sense-transfection cells were more sensitive to the combination of interferon-β and retinoic acid than U343MG-A cells or antisense-transfection cells; the anti-proliferative activity was related to apoptosis.
GRIM-19 may be one of the gene profiles which regulate cell death via apoptosis in human gliomas.
Cell line; GRIM-19; Gene Fishing; Glioblastoma; Human glioma
Abnormalities of the bone are frequently encountered in patients with meningioma, and hyperostosis and endostosis are common bone alterations in these tumors. Extensive bony destruction is very unusual in patients with meningioma. We report six cases of intracranial meningioma associated with an osteolytic lesion of the skull and discuss the underlying mechanisms that may be responsible for bone destruction in patients with meningioma.
Six patients were classified into three groups, severe, moderate and mild, according to the degree of osteolytic bony destruction. The tumor was classified as intracranial or extracranial, depending on its location. We investigated the potential role of matrix metalloproteinase (MMP) in meningioma-associated osteolysis. The levels of MMP expression were determined by gelatin zymography, reverse transcription-quantitative PCR analysis (RT-PCR) and immunohistochemical analysis.
Complete surgical removal of the lesion was performed in each patient. Histological examination revealed benign meningioma in four cases, and two cases of atypical meningioma. Patients did not have a poor prognosis except one case of recurred atypical meningioma. Gelatin zymography and RT-PCR detected high levels of MMP-2 in almost all extracranial masses in comparison with the intracranial masses and MMP-9 in two. There was no difference in the severity of bone destruction. Immunohistochemical analysis revealed MMP-2 expression in the vicinity of the bone destruction, and a few MMP-9-positive stainings were observed.
Osteolysis of the skull in patients with meningiomas might not be indicative of malignant pathological features and poor prognosis. Invasion to the extracranial portion and osteolysis might be associated with MMP-2 expression in meningioma.
Matrix metalloproteinase; Meningioma; Osteolytic
Hyaluronidase (HAse), a degrading enzyme of hyaluronic acid (HA), is highly expressed in patients with malignant glioma. The purpose of this study was to verify whether HAse is related to the invasion of glioma cells. We also investigated if glioma cells with higher mobility in 2-dimensioal (2-D) method have also higher mobility at 3-dimensional (3-D) environment.
Malignant glioma cell lines (U87MG, U251MG, U343MG-A, and U373MG) were used, and their HAse expressions were evaluated by HA zymography. The migration ability was evaluated by simple scratch technique. The invasiveness of each cell lines was evaluated by Matrigel invasion assay and HA hydrogel invasion assay. In HA hydrogel invasion assay, colonies larger than 150 µm were regarded as positive ones and counted. Statistical analysis of migration ability and invasion properties of each cell lines was performed using t-test.
In scratch test to examine migration ability of each cell lines, U87MG cells were most motile than others, and U343MG-A least motile. The HAse was expressed in U251MG and U343MG-A cell lines. However, U87MG and U373MG cell lines did not express HAse activity. In Matrigel invasion assay, the cell lines expressing HAse (U251MG and U343MG-A) were more invasive in the presence of HA than HAse deficient cell lines (U87MG and U373MG). In HA hydrogel invasion assay, the HAse-expressing cell lines formed colonies more invasively than HAse-deficient ones.
Malignant Glioma cells expressing HAse were more invasive than HAse-deficient ones in 3-dimensional environment. Therefore, it might be suggested that invasion of malignant gliomas is suppressed by inhibition of HAse expression or HA secretion. Additionally, the ability of 2-D migration and 3-D invasion might not be always coincident to each other in malignant glioma cells.
Hyaluronic acid; Hyaluronidase; Invasion; Migration; Malignant glioma; Hyaluronic acid hydrogel
A 49-year-old woman presented with headache, vomiting and visual disturbance. Neurological examination revealed bitemporal hemianopsia with poor visual acuity. Magnetic resonance imaging showed a bulky intra-suprasellar mass, which was isointense with brain parenchyma on T1-weighted images, and slightly hyperintense on T2-weighted images. After gadolinium administration, the mass was homogeneously enhanced. The mass was partially removed by the endonasal transsphenoidal approach and then the remnant mass was totally removed by the transcranial approach five months later. We found a yellowish mass which was attached to the diaphragm sellae in operation field. Histopathological examination of the tumor revealed the characteristic features of a schwannoma. We report an unusual case of an intra-suprasellar schwannoma resembling a non-functioning pituitary macroadenoma both clinically and radiologically.
Intrasellar; Schwannoma; Diaphragma sellae
Primary cerebellar glioblastoma multiforme (GBM) is a rare tumor in adults that accounts for just 1% of all cases of GBM. Due to their rarity, cerebellar GBMs are not yet completely understood about the pathogenesis and the prognosis. Here, we present a case of GBM in a 69-year-old man. Neurologic examination revealed the presence of cerebellar signs. Magnetic resonance imaging (MRI) showed a 4.5 × 3.6 cm-sized, ill-defined, heterogeneously enhancing mass in the left cerebellum and two patchy hyperintense lesions in the right cerebellum with minimal enhancement. After operation, glioblastoma was histologically confirmed. Postoperative radiotherapy with concomitant and adjuvant temozolomide chemotherapy was subsequently followed. Here, a case of unusual GBM in the cerebellum is reported with review of literature regarding the pathogenesis, the differential diagnosis and prognosis. There was no evidence of recurrence during postoperative one year. This patient showed a good prognosis in spite of the multiple lesions.
Cerebellum; Differential diagnosis; Glioblastoma multiforme; Pathogenesis
A 64-year-old woman was referred to our hospital with a one-month history of progressive headache. Magnetic resonance imaging (MRI) showed a hemorrhagic mass adjacent to the left inferior cerebellar hemisphere associated with a peripheral rim of signal void. Angiography demonstrated an avascular mass and the provisional diagnosis was a large cavernous angioma in the cerebellum. Intraoperative findings revealed a thrombosed giant aneurysm of the left distal posterior inferior cerebellar artery (PICA). We report an unusual case of a completely thrombosed giant aneurysm simulating a large cavernous angioma in the cerebellum. The cerebellar cisternal location of the mass may be a clue for the pre-operative diagnosis of an aneurysm.
Posterior inferior cerebellar artery (PICA); Thrombosed giant aneurysm; Cavernous angioma