Malignant transformation in craniopharyngioma after radiation therapy: a case report and review of the literature.

OBJECTIVE: Craniopharyngioma is a benign epithelial tumor that is thought to arise from the remnant of the Rathke pouch. Malignant transformation in craniopharyngioma is extremely rare. Herein, we report a case of malignant transformation in craniopharyngioma after radiation therapy. MATERIALS AND METHODS: Histopathological and immunohistochemical analyses were carried out for specimens of the suprasellar tumor (from three resections, with the third surgery performed after radiation therapy). RESULTS: The resected tumors from the first and second surgeries comprised islands of loosely cohesive aggregates of epithelial cells, so-called stellate reticulum. At the periphery of the nests, palisaded columnar epithelium was observed. Wet keratins were scattered, and few mitotic figures were seen. The third surgical specimen was composed of irregular large nests of basaloid cells that had large, round to oval nuclei with prominent nucleoli, and mitotic figures were frequently seen (21/10 high power fields). In the center of the nests, eosinophilic ghost cells, resembling wet keratin, were observed. Accordingly, the diagnosis of malignant transformation in craniopharyngioma was made. Immunohistochemical studies revealed that the p53 protein was over-expressed in the malignant component, whereas its expression was much lower in the benign component. CONCLUSIONS: Similar to the ten previously reported cases of malignant transformation in craniopharyngioma, the present case occurred after radiation therapy. p53 protein overexpression was also observed in the earlier cases of malignant craniopharyngioma as well as in the present case (6/6 cases). We concluded that radiation therapy and p53 mutations could be involved in malignant transformation in craniopharyngioma.

Tentorial enhancement on MR images is a sign of cavernous sinus involvement in patients with sellar tumors.

BACKGROUND AND PURPOSE: This study was undertaken to analyze enhancement patterns of the dura around sellar tumors and to compare the results with tumor invasion or compression of the cavernous sinuses. Postoperative enhancement patterns on MR images were compared with preoperative findings. METHODS: Contrast-enhanced coronal and sagittal MR images were examined prospectively in 96 patients with sellar tumors (65 macroadenomas, 15 microadenomas, 14 Rathke cleft cysts, and two chordomas at the sella). All patients underwent surgical treatment, and pre- and postsurgical features on MR images were compared. RESULTS: Presurgical MR images showed dural enhancement in 36.5% of the patients: asymmetric tentorial enhancement in 24 patients, symmetric tentorial enhancement in seven, and sphenoidal ridge or clivus enhancement in four. Asymmetric tentorial enhancement disappeared after surgical decompression in seven patients. For evaluation of cavernous sinus invasion ipsilateral to the enhancement, sensitivity and specificity of the asymmetric tentorial enhancement sign were 81.3% and 86.3%, respectively. Sensitivity and specificity of the sign were 42.9% and 93.6% for cavernous sinus involvement, including compression and invasion. CONCLUSION: Asymmetric tentorial enhancement is a useful sign in the diagnosis of invasion or severe compression of the cavernous sinus by sellar tumor. The sign may represent venous congestion or collateral flow in the tentorium due to obstructed flow in the medial portion of the cavernous sinus.

Cerebral aneurysms associated with Behçet's disease: a case report.

Cerebral aneurysms in Behçet's disease are very rare. The role of vasculitis in the aetiology of these aneurysms has not been clarified. A 57 year old man with Behçet's disease is described, who had a subarachnoid hemorrhage due to rupture of a peripheral middle cerebral artery aneurysm. He underwent a successful aneurysmal clipping. Three years later he had seizures and was found to have a new aneurysm on the contralateral peripheral middle cerebral artery as well as some radiological features of vasculitis. After 3 months of steroid therapy, the aneurysm disappeared. Although surgical treatment is the first choice for ruptured aneurysms, steroid therapy may be effective for unruptured small aneurysms in patients with Behçet's disease.

Significance of MIB-1 staining indices in meningiomas: comparison of two counting methods.

The authors evaluated the predictability of MIB-1 immunohistochemistry for growth and recurrences of meningiomas using two different counting methods: 1) in the area of the highest MIB-1 labeling (HL method) and (2) in randomly selected fields (RS method). The MIB-1 staining indices (SIs) determined by the HL method were approximately twice as high as those by the RS method, and the correlation coefficient between them was high (R = 0.86) in 139 meningiomas when transformed logarithmically. The differences in SIs in histologic grades were significant with either method. Tumor doubling time (Td) was calculated in 22 meningiomas from serial radiologic examinations. The RS method yielded a slightly higher correlation coefficient between log Td and log SI than the HL method. When the authors examined the predictability of recurrence in 112 totally removed meningiomas, the RS method distinguished the recurrent group more definitively. Several benign meningiomas with low SIs by the RS method exhibited focal accumulation of MIB-1-positive cells. Although they were assigned high MIB-1 values by the HL method, these meningiomas did not recur, and therefore obscured the prognostic importance of the MIB-1 value with the HL method. Focal accumulation of MIB-1-positive cells in meningiomas is not likely to correlate with their biologic aggressiveness.

Late dissemination of fourth ventricle ependymoma: a case report.

Dissemination of benign ependymoma is relatively rare, especially when a local tumor is under control. The majority of the failures take place within a few years after surgery. However, we experienced a case in which multiple spinal cord dissemination was found 13 years after resection of the fourth ventricle ependymoma without a local failure. A 38-year-old man had undergone a subtotal resection of the fourth ventricle ependymoma and radiation therapy to the posterior fossa when he was 25 years old. Follow-up MR imaging repeated once every one or two years detected no recurrence until he began to complain of lumbago and numbness of the right foot 13 years after the surgery. MR imaging revealed multiple nodules along the whole spinal cord. Examination of the cerebrospinal fluid detected tumor cells with ependymal cell features. He underwent radiation therapy to the whole spine, and remained stable at 18 months after the therapy. This case alerts us to the necessity for long-term radiological follow-up including the spinal cord even in benign ependymomas, although it is still not certain for how long and how often we should do it.

Noninvasive evaluation of the malignant potential of intracranial meningiomas performed using proton magnetic resonance spectroscopy.

OBJECT: Controversy exists about correlations between histological tumor grade and magnetic resonance (MR) spectroscopy data. The authors studied single-voxel proton MR spectroscopy as a noninvasive way to evaluate grade of malignancy in intracranial meningiomas. METHODS: The authors compared the results of MR spectroscopy with those derived by the MIB-1 staining index (SI) in 29 meningiomas. Proton MR spectroscopy was performed using stimulated echo acquisition and volume-localized solvent-attenuated proton nuclear MR sequences before surgery or other therapy. Twenty-four tumors were histologically benign (13 meningothelial, three fibrous, four transitional, three angiomatous, and one chordoid); four were atypical (Grade II), and one was papillary (Grade III). The mean MIB-1 SI in the benign group was significantly lower than those in the other groups (p = 0.0041). The mean choline-containing compound (Cho)/ creatine and phosphocreatine (Cr) ratios in the benign and nonbenign groups were 2.56+/-1.26 and 7.85+/-3.23, respectively (p = 0.0002). A significant linear correlation was observed between the Cho/Cr ratio and the MIB-1 SI (r0.05 = 0.74, p<0.001). Necrosis was present histologically in four of the five meningiomas classified either as atypical or papillary. Magnetic resonance spectroscopy revealed a methylene signal in these meningiomas that was not detected in benign meningiomas. Of the five meningiomas in which only a lactate signal was observed, two were benign and the MIB-1 SI in these two benign meningiomas was higher than the mean value for the benign group. Alanine, detected in 12 of 30 meningiomas, did not correlate with either tumor grade or Cho/Cr ratio. CONCLUSIONS: Proton MR spectroscopy is a useful diagnostic method for determining the proliferative or malignant potential of meningiomas according to the Cho/Cr ratio. A lactate and/or methylene signal suggests a high-grade tumor.

Anomalous p27kip1 expression in a subset of malignant gliomas.

p27Kip (p27) expression was immunohistochemically investigated in 28 astrocytic tumors, and compared with the cell proliferation index (MIB-1 staining index). Normal rat brains and surgical specimens from human nonneoplastic brain lesions were used as controls. In the rat brains, the astrocytes were exclusively p27-positive. The reactive astrocytes in various disease processes sometimes lacked p27 expression. The distribution of p27-positive cells was uniform in low-grade astrocytomas and heterogeneous in high-grade tumors. Double staining of p27 and MIB-1 showed a reciprocal pattern in most cases. The frequency of p27 expression was inversely correlated with MIB-1 staining index and tumor grade. However, several malignant gliomas showed high p27 expression in spite of high MIB-1 staining indices. In such cases, MIB-1-positive cells were occasionally p27-positive. In this paper we discuss the etiology of the anomalous p27 expression in a subset of malignant gliomas.

Atypical Rathke's cleft cyst associated with ossification.

We report a case of symptomatic Rathke's cleft cyst with ossification. CT scans showed curvilinear calcification on the wall of the cyst. MR images revealed a cystic sellar lesion with a nodular solid mass extending to the floor of the third ventricle. This case shows that calcification of the suprasellar cyst does not always suggest craniopharyngioma. Rathke's cysts should be histologically differentiated from craniopharyngiomas because their treatments are different.

Preoperative identification of meningiomas that are highly likely to recur.

OBJECT: Although generally they are well-circumscribed benign tumors, meningiomas recur even after complete removal. The aims of this study are to identify preoperatively groups of patients who have a high risk of meningioma recurrence by reviewing their clinicoradiological features and to plan appropriate treatments. METHODS: One hundred one patients who underwent macroscopically complete removal of meningiomas were observed postoperatively for at least 5 years or until tumor recurrence. Preoperative radiological findings and clinical characteristics were assessed. Fifteen meningiomas recurred during the follow-up period, which extended to a maximum duration of 18 years. On univariate analysis, tumor size and shape, relation to the major sinuses, calcification, bone changes, and characteristics of the tumor-brain interface were significant predictive factors for recurrence. Patient age and gender were not deemed significant. Multivariate analysis revealed that only the shape of the tumor was significant; both "mushrooming" and lobulated meningiomas were more likely to recur than round ones. Recurrences most frequently occurred at the edge of the dural resection after a Simpson Grade I removal, whereas local recurrences were predominant after a Simpson Grade II or III removal. CONCLUSIONS: Meningiomas with mushrooming or lobulated shapes should be treated more aggressively with a wider dural excision. This is not usually necessary for round tumors, although it may be beneficial in younger patients.

Shock syndrome induced by bromocriptine test in a patient with prolactinoma--case report.

A 72-year-old male developed shock syndrome after a single dose of bromocriptine. He had undergone uncomplicated subtotal removal of an invasive prolactinoma in our department. The patient had normal ranges of pituitary hormones apart from hyperprolactinemia (167.7 ng/ml) after surgery. An acute suppression test with bromocriptine (2.5 mg per os) was done in the supine position 6 days following surgery. Three and a half hours after bromocriptine administration, he suddenly complained of anterior chest discomfort in bed. Cyanosis and profuse diaphoresis were noted. His blood pressure was 80/60 mmHg. Electrocardiography revealed sporadic premature contractions and slight depression in the ST segments. He recovered in about 10 hours after a rapid infusion of corticosteroid and lactic Ringer solution, and was discharged without sequelae. This is a very rare complication of bromocriptine, but the cardiovascular function of patients taking bromocriptine for therapeutic and diagnostic purpose should be monitored carefully.

Estimation of volume doubling time and cell loss in an experimental rat glioma model in vivo.

We estimated the volume doubling time (Vd) of the ethyl-nitrosourea-induced rat glioma by serial magnetic resonance imaging, and the results were compared with potential doubling time (Tp) determined immunohistochemically. Vd ranged from 3.3 to 29.2 days (11.3 +/- 7.74) and Tp ranged from 2.3 to 13.3 days (6.81 +/- 3.33). Each tumour showed a wide range of bromodeoxyuridine (BUdR) labelling indices (LI), however, Vd and Tp correlated well with BUdR-LI. Vd was estimated as 17.6 x BUdR-LI-0.63 (R = -0.76, P < 0.001, n = 13) and Tp was estimated as 22.6 x BUdR-LI-1.02 (R = -0.92, P < 0.0001, n = 12). In addition, we compared the apoptotic indices (AI), determined by terminal deoxynucleotidyltransferase (Tdt)-mediated biotinylated dUTP-biotin nick-end labelling (TUNEL) techniques, with BUdR-LI and mitoses indices (MI). The results were: AI = 0.23 + 0.25Ln(BUdR-LI) (R = 0.971, n = 8, P < 0.0001) and AI = 1.05 + 0.29Ln(MI) (R = 0.937, n = 8, P < 0.001). Cell loss factors (CLF) also correlated well with BUdR-LI and MI. However, CLF calculated from Tp and Vd were lower than the values previously presumed, probably because of shorter Vd than true doubling time for tumour cell population. These results suggest that even malignant tumours retain a mechanism of adjusting their growth at least partly.

Postoperative sella: evaluation with fast spin echo T2-weighted high-resolution imaging.

OBJECTIVE: The purpose of this study was to investigate the magnetic resonance features of the postoperative sella with fast spin echo (FSE) T2-weighted high-resolution imaging and to evaluate the benefits of the sequence using a follow-up magnetic resonance imaging protocol after transsphenoidal surgery. METHODS: Coronal spin echo (SE) T1-weighted and FSE T2-weighted images were prospectively obtained in 24 patients after surgery for pituitary adenomas. We observed the signals and the contour of normal structures, fluid collection, implanted materials, and mass lesions, including granulation tissue and adenoma. RESULTS: The pituitary gland was delineated in 51 of 59 FSE T2-weighted images, 90.2% of which presented clear boundaries. Whereas the gland was detected in 49 of 58 SE T1-weighted images, only 20.4% showed the boundaries. A mass lesion was identified in each of 12 patients with good resolution on FSE T2-weighted images. SE T1-weighted images detected mass lesions in 7 of 12 patients without distinctive boundaries. Contrast enhancement had little advantage in clarifying the boundaries between normal and abnormal structures. For the detection of mass lesions in the sella, the kappa values for interobserver agreement were 0.8 for FSE T2-weighted images and 0.25 for SE T1-weighted images. CONCLUSION: FSE T2-weighted imaging is a reliable method with which to assess the sella with sufficient resolution after transsphenoidal surgery. The combination of unenhanced SE T1-weighted and FSE T2-weighted images may reduce the use of contrast material after pituitary surgery.

Anaplastic ganglioglioma with dissemination to the spinal cord: a case report.

BACKGROUND: Gangliogliomas are rare tumors that generally arise in the temporal lobe. Although most are benign, malignant gangliogliomas have been reported. The clinical course of anaplastic gangliogliomas has not been well understood. CASE REPORT: An anaplastic ganglioglioma of the right parieto-occipital lobe is reported in a 7-year-old girl who presented with left homonymous hemianopsia and papilledema. Neurologic examination revealed a choked disc and a left homonymous hemianopsia. A computed tomographic scan and magnetic resonance imaging showed a large enhancing mass with calcification. Radiation therapy was administered after subtotal resection of the tumor. Histologic and immunohistochemical studies showed a typical appearance of anaplastic ganglioglioma. Spinal dissemination developed 3 months after the operation. In spite of spinal axis radiation and chemotherapy, she expired 15 months after the diagnosis. CONCLUSION: Although the clinical course of anaplastic gangliogliomas is not always aggressive, our case indicates the importance of strict follow-up assessments of the whole craniospinal axis.

Metastatic adenocarcinoma presenting as a homogeneously high density mass on CT.

We report a case of metastatic adenocarcinoma to the brain that appeared as a homogeneously hyperdense mass on CT. The lesion was initially diagnosed as an intracerebral hematoma. On serial CT scans, the high density lesion progressively enlarged. Pathology showed coagulation necrosis without hemorrhage or calcification. Analysis of the tumor revealed elevation of the protein content relative to the normal brain. We conclude that the high CT attenuation was due to the elevated protein content.

Alteration of bcl-2 and bax expression in embolized meningiomas.

We examined the expression of the p53 and bcl-2 family in embolized meningiomas and investigated the interaction between them. p53 and its downstream effector p21 accumulated mainly in perinecrotic areas, where apoptosis was also observed. bcl-2 was often expressed in the areas distant from necrosis, whereas Bax was immunostained more intensely in the perinecrotic areas. Double staining for both p53 and Bcl-2 showed a reciprocal pattern. This appeared to be due to the down-regulation of Bcl-2 by p53. However, regulation of Bax by p53 was not distinct. The expression of p21 was not apparent 13 days after embolization, and apoptosis was observed until 6 days after embolization. The effect of embolization was most likely temporary, although growth arrest has been reported to persist for a long time in a limited number of embolized cases.

p53 accumulation and apoptosis in embolized meningiomas.

Preoperative embolization of meningiomas is performed to decrease blood loss at surgery. While it is also expected to reduce tumor recurrence by producing necrosis at the site of dural attachment, very little has been described about what happens to the non-necrotic tumor cells. We investigated how the proliferative activities of meningiomas were modified after embolization. In nine meningiomas which were embolized preoperatively, proliferative potentials and expression of cell cycle inhibitors were assessed immunohistochemically using MIB-1, anti-53 (DO-1 and DO-7), and anti-p21 (WAF1/CIP1) monoclonal antibodies. To determine whether a cell underwent apoptotic death besides necrosis, we applied the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling method. Results were compared with control meningiomas without embolization. MIB-1 positive cells often gathered in perinecrotic areas, although the mean MIB-1 staining index of the embolized meningiomas was not significantly different from the control. p53 and its downstream effector p21 accumulated mainly in the perinecrotic areas in eight of the nine embolized meningiomas. Apoptosis was also observed in the concomitant areas. Double staining for both MIB-1 and p21 frequently showed positive cells for both antibodies. The accumulation of MIB-1 positive cells in the embolized meningiomas may not be a sign of fast growth or malignancy, but it may implicate arrest of cell cycle by the p21. This study indicates that embolized meningiomas exhibit not only necrosis but also apoptosis and cell cycle arrest. The latter effects appear to be at least partly p53 dependent.

Serial magnetic resonance imaging findings of Rasmussen's encephalitis--case report.

A 12-year-old boy presented with Rasmussen's encephalitis. Serial magnetic resonance (MR) imaging one year after the onset of seizure showed no abnormality. T2-weighted imaging detected a high intensity lesion in the left frontal cortex when the frequency of seizures increased 11 months later. MR imaging showed the lesion rapidly spread into the white matter, then gradually regressed after biopsy and immunoglobulin therapy, and mild focal atrophy of the left frontal lobe in spite of recurrence of seizures 3 months after the therapy. Histological examination of the biopsy sample showed the characteristic findings of Rasmussen's encephalitis. Five months after the biopsy, another new high intensity lesion was detected next to the previous one, although his seizures were well controlled at that time. Although the extent of the high intensity lesion did not correlate with the frequency of seizures, such sequential changes in MR imaging appearance seemed to reflect the course of this disease.

Clinical significance of Ki-67 staining index in acoustic neurinoma.

The correlation between various clinical parameters and MIB-1 (Ki-67) staining indices was evaluated in 58 acoustic neurinomas. The index ranged from 0.37% to 6.61% (mean 1.70%), and did not correlate with age, sex, or initial tumor volume. Sixteen of the 18 tumors removed subtotally or partially showed regrowth, and two showed a volume reduction. The 16 patients with regrowth were divided into two groups according to Ki-67 staining index, < 2.00% and > or = 2.00%. These groups had a significant difference in tumor doubling time (TDT). In addition, there was a significant logarithmic correlation between Ki-67 staining index and TDT. Ki-67 staining index can be used as an index of regrowth rate in partially or subtotally removed acoustic neurinomas. Intraoperative assessment of Ki-67 staining index may be useful for better management planning as well as the estimation of prognosis.

Solitary plasmacytoma of the skull vault--case report.

A 55-year-old female presented with a rare solitary plasmacytoma restricted to the skull vault without systemic myelomatosis. She had a 9-month history of a slowly growing soft mass in the right temporal region. Neuroradiological examination revealed a skull defect and an extradural tumor. The whole layer of the skull was destroyed by the tumor, but the dura was not involved. The tumor was totally removed, and postoperative radiotherapy was given. Follow-up examination after 2 years showed she was free from local recurrence or evidence of systemic involvement. Complete surgical resection with adjuvant radiation therapy is the treatment of choice. Although the prognosis is good, regular lifelong examinations for myelomatosis are required.