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Fifty-one primary intracranial germ cell tumors (GCT), including germinoma, teratoma, endodermal sinus tumor, choriocarcinoma and mixed GCT, were studied. The incidence of GCT in the surgically removed intracranial neoplasms was 11.1% for pediatric patients and 0.6% for adult patients. The age/sex of the patients and the location of the tumors were analyzed. Morphologic findings of these tumors were identical to that of their gonadal counterparts. Immunohistochemical studies showed that alpha-fetoprotein ([alpha]-AFP), human chorionic gonadotropin (HCG), and placental alkaline phosphatase (PLAP) were helpful, whereas carcinoembryonic antigen (CEA) and cytokeratin (CKER) were of little help in determining the diagnosis. Serum tumor markers, [alpha]-AFP and HCG, were helpful in recognizing GCT producing them. However, they could not be used for specific diagnosis because different tumors could have similar serum levels. Histopathologic study was handicapped by the small size of most specimens (which usually could not include all of the components if the tumor was a mixed GCT), but it was the only means for specific diagnosis.

Supplemental Digital Content is available in the text.The O6-methylguanine-DNA-methyltranferase (MGMT) status is a powerful predictor of response to temozolomide for newly diagnosed glioblastoma (GBM) patients, and it is commonly assessed by immunohistochemistry (IHC), methylation-specific polymerase chain reaction (MSP), quantitative real-time MSP (qMSP), and/or pyrosequencing (PSQ). This study was to compare their predictive power of prognosis in 121 newly diagnosed GBM patients using multivariate Cox regression with bootstrapping. MGMTstatus tested by IHC, MSP, qMSP, or PSQ all showed significant correlation with the progression-free survival and overall survival of GBM patients. The predictive power of IHC for progression-free survival and overall survival was lower than those of the methylation assays, but their differences were not significant. Performing additional methylation assay, especially PSQ, could better predict the prognosis of patients with IHC− tumors. MGMTstatus tested by IHC, MSP, qMSP, or PSQ all showed prognostic significance. An additional MGMTmethylation assay, of which PSQ appeared to be the best, could improve the predictive power for GBM patients with MGMT IHC− tumors.

Subependymal giant cell astrocytoma is a benign brain tumor mostly associated with tuberous sclerosis complex. However, it may be misinterpreted as other high-grade brain tumors due to the presence of large tumor cells with conspicuous pleomorphism and occasional atypical features, such as tumor necrosis and endothelial proliferation. In this study, we first investigated thyroid transcription factor-1 (TTF-1) expression in a large series of subependymal giant cell astrocytomas and other histologic and locational mimics to validate the diagnostic utility of this marker. We then examined TTF-1 expression in non-neoplastic brain tissue to determine the cell origin of subependymal giant cell astrocytoma. Twenty-four subependymal giant cell astrocytoma specimens were subjected to tissue microarray construction. For comparison, a selection of tumors, including histologic mimics (21 gemistocytic astrocytomas and 24 gangliogliomas), tumors predominantly occurring at the ventricular system (50 ependymomas, 19 neurocytomas, and 7 subependymomas), and 134 astrocytomas (3 pleomorphic xanthoastrocytomas, 45 diffuse astrocytomas, 46 anaplastic astrocytomas, and 40 glioblastomas) were used. Immunohistochemical stain for TTF-1 was positive in all 24 subependymal giant cell astrocytomas, whereas negative in all astrocytomas, gangliogliomas, ependymomas, and subependymomas. Neurocytomas were positive for TTF-1 in 4/19 (21%) of cases using clone 8G7G3/1 and in 9/19 (47%) of cases using clone SPT24. In the three fetal brains that we examined, TTF-1 expression was seen in the medial ganglionic eminence, a transient fetal structure between the caudate nucleus and the thalami. There was no BRAFV600Emutation identified by direct sequencing in the 20 subependymal giant cell astrocytomas that we studied. In conclusion, TTF-1 is a useful marker in distinguishing subependymal giant cell astrocytoma from its mimics. Expression of TTF-1 in the fetal medial ganglionic eminence indicates that subependymal giant cell astrocytoma may originate from the progenitor cells in this region.

We evaluated the predictive value of O6-methylguanine-DNA methyltransferase (MGMT) protein expression and MGMT promoter methylation status in glioblastomas (GBM) treated with temozolomide (TMZ) in a Taiwan medical center. Protein expression by immunohistochemical analysis (IHC) and MGMT promoter methylation detected by methylation-specific polymerase chain reaction (MSP) were performed in a series of 107 newly diagnosed GBMs. We used endothelial cells as an internal reference for IHC staining because the staining intensities of the MGMT-expressing cells in different specimens varied considerably; a positive result was defined as the staining intensity of the majority of tumor cells similar to that of the adjacent endothelial cells. Immunostainings for microglialendothelial markers were included as part of the MGMT IHC evaluation, and in cases that were difficult to interpret, double-labeling helped to clarify the nature of reactive cells. The MGMT protein expression was reversely associated with MGMT promoter methylation status in 83.7 of cases (MSPIHC−and MSP−IHC; Pearson r=−0.644, P<0.001). Twenty-two of 24 (91.7) IHCtumors did not respond to TMZ treatment. Combining MSP and IHC results, all the 15 MSP−IHCGBMs were TMZ resistant. The MGMT status detected by either IHC or MSP was significantly correlated with the TMZ treatment response (both P<0.001) and survival of GBM patients (both P<0.05).

Atypical teratoidrhabdoid tumor (ATRT) is a highly malignant central nervous system tumor often misdiagnosed as some other type of pediatric embryonal tumor, such as medulloblastoma (MB). Distinguishing ATRT from primitive neuroectodermal tumorMB is of clinical significance, as the reported survival rate of patients with ATRT is much lower than that of patients with average-risk primitive neuroectodermal tumorMB. The diagnosis of ATRT currently relies primarily on the morphologic assessment and immunostaining of a few known markers, such as the lack of INI1 protein expression. Immunohistochemical staining of INI1 is considered very sensitive and is highly specific for the detection of INI1genetic defects. Genetic studies have shown that deletion or mutation of the INI1gene, which is located on 22q11.2, occurs in ATRT lesions. During our gene expression microarray analysis, we unexpectedly found a subgroup of ATRT patients still expressing INI1 mRNA, even though INI1 proteins were negative by immunohistochemistry in those cases. Direct DNA sequencing showed no INI1sequence alternation in 3 of 4 ATRTs. Point mutation was found in only 1 allele of the fourth case, which would result in a frameshift mutation and generate a new INI1 protein with an extra 100-aa tail. Global array comparative genomic hybridization analysis confirmed no aberration around the INI1gene at 22q11.2. It also extended our knowledge on the chromosomal aberration situations in our series. This study reveals that a novel yet unidentified posttranscriptional regulatory mechanism(s) for INI1 protein synthesis exists in ATRT tumor cells.

A new molecular classification scheme has recently been adopted that groups all enteroviruses into four species, designated human enterovirus A (HEV-A) through D. In this study, we tried to demonstrate the correlation between this molecular classification scheme and clinical manifestations in patients.

Central neurocytoma is defined as an intraventricular benign brain tumor. Extra-ventricular location of central neurocytoma is rare: only nine cases of spinal neurocytoma had been reported in the English literature. We hereby present a case of atypical neurocytoma involving unusual long segments (8-segment) of cervico-thoracic spinal cord in a 29-year-old woman with emphasis on pre- and post-surgical neuroimaging, pathological correlation, and review the pertinent literature.

Osteopontin, a cancer metastasis-associated gene, is specifically up-regulated in central nervous system (CNS) atypical teratoid/rhabdoid tumor (AT/RT), but its biological behavior in the progression of CNS AT/RT has never been studied. We obtained plasma, cerebrospinal fluid (CSF), and brain tissue specimens from lobectomy or hemispherectomy samples from 39 patients (medulloblastoma, 16; AT/RT, 8; epilepsy, 6; hydrocephalus, 9). By enzyme-linked immunosorbent assay, the median osteopontin levels in plasma and CSF in AT/RT (852.0 and 1,175.0 ng/mL, respectively) were significantly higher than in medulloblastoma (492.5 and 524.5 ng/mL, respectively) and hydrocephalus and epilepsy (208.0 and 168.0 ng/mL, respectively) (P < .05). The results of real-time reverse transcriptase-polymerase chain reaction and immunohistochemical analysis demonstrated that osteopontin expression in AT/RT (n = 5) was significantly higher than in medulloblastoma (n = 8) samples. The differences in osteopontin expression in plasma, CSF, and tumor samples in AT/RT and medulloblastoma correlated with survival differences. In 5 patients with AT/RT, plasma osteopontin levels decreased after treatment but increased with relapse. Osteopontin might be a potential marker to aid in identifying AT/RT recurrence.

Abstract Purpose : To evaluate the effectiveness of complete resection and postoperative radiotherapy in spinal cord ependymomas. Methods and materials : We conducted a retrospective study over 20 patients (13 males and 7 females) with histologically confirmed spinal cord ependymomas between July 1985 and April 2001. Among them, 13 patients had ependymomas, 6 had myxopapillary ependymomas, and 1 had anaplastic ependymoma. All patients received radical surgery for tumor removal with 13 patients achieving complete resection and 7 incomplete resection due to technical difficulty. Among those with incomplete resection, 6 patients received postoperative radiotherapy to tumor bed and only one patient with anaplastic ependymoma received surgery alone. The total tumor dose ranged from 50 to 60 Gy. Results : Among the 20 patients, 19 patients were alive and showed local control. The median survival time of all patients was 109 months, with 104 months in the complete resection alone group and 135 months in the incomplete resection with postoperative radiotherapy group. One patient with anaplastic ependymoma and no postoperative radiotherapy developed leptomeningeal seeding 9 months after surgery. Salvage therapy of radiotherapy and chemotherapy maintained normal neurological functions. The patient expired 34 months from the initial diagnosis due to progression of leptomeningeal seeding. Conclusion : Complete resection alone in spinal cord ependymoma can achieve excellent local control and survival. Patients should receive complete resection if technically possible. Postoperative radiotherapy is not recommended for complete resection. For incomplete resection, postoperative local radiotherapy is recommended and it can also achieve excellent local control and survival. Local radiotherapy with 50-60 Gy is effective and safe. Salvage radiotherapy improves quality of life for local recurrence or leptomeningeal seeding patients.

Case report We report the prenatal observation of fetal ocular skew deviation in a case of a glioblastoma found prenatally at 33 weeks' gestation by MRI. The fetal MRI, obtained by half-Fourier single-shot turbo spin echo (HASTE) pulse sequences, showed a tumor (80 mm in maximum diameter) in the right deep cerebral hemisphere with extension to the mid-cranial fossa and tentorial hiatus in addition to severe hydrocephalus. On coronal MR images a vertical dysconjugated gaze was recognized. One week after the MRI, frequent delayed deceleration prompted an emergency cesarean section. The baby was born with left hemiparesis and central neurogenic hyperventilation, which evolved into decerebrate rigidity and apneustic breathing within 2 h. Post-mortem examination revealed a glioblastoma in the right deep hemisphere, a tumor with brain stem involvement, and transtentorial herniation. Conclusions We suggest, therefore, that recognition of ocular skew deviation on fetal MR images would indicate brain stem involvement and poor postnatal prognosis. Early recognition of the catastrophic sign would lead to proper management.

Approximately 10% of patients with glioblastoma survive more than 2 years after diagnosis. Distinguishing these patients from those who died within 2 years of diagnosis is clinically significant. We studied the MIB-1 labeling index (LI) and DNA topoisomerase II alpha LI of glioblastomas from 34 patients who lived for more than 2 years after diagnosis and of glioblastomas from 34 age- and sex-matched control patients who died within 2 years of diagnosis. The means of MIB-1 and topoisomerase II alpha LIs of the group with a better outcome were lower. With 35 as the cutoff point for the MIB-1 LI and 26 as the cutoff point for the topoisomerase II alpha LI, both MIB-1 and topoisomerase II alpha LIs were related significantly to survival. Our study showed that both MIB-1 and topoisomerase II alpha could help predict long-term survival of patients with glioblastomas. Multivariate analyses revealed that MIB-1 was a better prognostic marker than topoisomerase II alpha.

Although there are criteria for interpretation of the staining results for Her-2/neu in the DAKO HercepTest, the determination of staining intensity and percentage of complete membrane staining is subjective. We studied 46 cases of invasive breast carcinoma to evaluate interobserver reproducibility among 5 pathologists. Complete agreement was achieved in 22 (48%) of46 cases. Generalized kappa values indicated substantial agreement (0.80). Discrepancies between negative (0, 1+) and positive (2+, 3+) results occurred in 2 cases (kappa = 0.96). One was because of a tangential cut of the basal part of the tumor that mimicked complete membranous staining, and the other was a borderline case that revealedfocal (5%-15%) complete membranous staining. Distinguishing weakly (2+) from strongly (3+) positive results showed agreement in only 13 (59%) of 22 positive cases (kappa = 0.38). If more than 50% of tumor cells revealing strong complete membrane staining were regarded as strongly positive, agreement would be improved (kappa = 0.78). While there was a high percentage (70%-80%) of negative cases during routine evaluation, the good interobserver agreement and high negative predictive value made immunohistochemical analysis an effective screening test to exclude negative cases.

Although various histopathologic features have been associated with aggressive behavior or recurrence of meningiomas, there is little agreement about which features are the most important and in what combination. The objective of this study was to formulate diagnostic criteria for atypical meningioma. Eighty-three patients with meningiomas who underwent macroscopic total resection and had been followed until they developed recurrent disease or for at least 10 years were studied. Thirteen histopathologic parameters that related to recurrence of the tumor were evaluated in each patient. All possible combinations of histologic parameters that were related significantly to recurrence were used to formulate scoring models. The model that included the fewest parameters and that could distinguish tumor recurrence best within 10 years was chosen as the final model. The final model included three parameters: loss of architecture, mitoses ≥ 1.5/mm², and necrosis. Of the 52 tumors with a score &lt; 2 (0 or 1 of the 3 parameters), all except 1 tumor did not recur within 10 years, and they were all considered benign meningiomas. Of the 31 tumors with a score ≥ 2 (2 or 3 of the 3 parameters), 94% recurred within 10 years (76% recurred within 5 years), and they were considered atypical meningiomas. The estimated 5-year and 10-year recurrence rates for the benign meningiomas were 0.0% and 1.9%, respectively, for benign meningiomas and 71.0% and 93.5%, respectively, for atypical meningiomas (P &lt; 0.001). The estimated 5-year and 10-year mortality rates also were significantly different (0.0% and 0.0% vs. 22.1% and 26.7%, respectively; P &lt; 0.001). The MIB-1 labeling index (LI) for the entire group studied ranged from 0.4 to 33.5 (mean LI, 8.4). Fifty-two tumors with an LI of &lt; 10 did not recur within 10 years. Of the 31 tumors with an LI ≥ 10, 97% recurred (71% within 5 years). Histopathology and MIB-1 LI were able to predict clinical outcomes of patients with meningioma. The authors propose that atypical meningioma may be diagnosed when two of the following three criteria are present: loss of architecture, mitoses ≥ 1.5/mm², and necrosis. Cancer 2002;94:1538–47. © 2002 American Cancer Society. DOI 10.1002/cncr.10351

Object:We used MR after sonography to help us in prenatal counseling in 58 complicated pregnancies from 1998 to 2000.Methods:All fetal MR examinations were undertaken with a 1.5-T magnet using a body-phased-array coil and an ultrafast imaging technique, half-Fourier single-shot turbo spin-echo (HASTE). Twelve fetuses were found to have major anomalies, and in each of these cases either delivery was induced or the pregnancy was terminated. In 6 of the fetuses, with anomalies of the central nervous system, postmortem examinations were then performed after they failed to survive, and these constitute the patient sample investigated in the current study. The fetal gestational ages in these 6 cases ranged from 24 to 32 weeks. MR imaging demonstrated morphological details of the anomalies. They were: alobar holoprosencephaly in 2, middle interhemispheric fusion in 1, alobar holoprosencephaly with Dandy-Walker malformations in 1, a Dandy-Walker variant in 1 and twin-twin transfusion syndrome with hypoxic-ischemic injury to the brain in 1.Conclusions:Postmortem examinations confirmed the MR diagnoses, and these observations support us in improving our understanding of the pathogenesis of fetal CNS anomalies.

Optimal histologic criteria for the classification of and grading of ependymomas, including their anaplastic forms, remain elusive. This is especially true because of the poor correlation of these criteria with clinical outcome. The aim of this study was to identify the histopathologic parameters that could distinguish different prognostic groups of patients with ependymomas. Eighty-one patients with ependymal tumors, including those originally diagnosed ependymomas, anaplastic ependymomas and myxopapillary ependymomas, were enrolled in this study. Thirteen histologic parameters, including hypercellularity, nuclear pleomorphism, mitoses, endothelial proliferation, necrosis, clear cell, thrombi, dystrophic calcification, psammoma bodies, bone, cartilage, Rosenthal fibers and MIB-1 labeling index (LI), were evaluated in each patient and correlated with clinical outcome. We assigned one score for each histopathologic parameter evaluated and used a stepwise selection method with entry model based on the significance of the log-rank statistic to formulate a scoring model. Four parameters were chosen in this process, including mitoses ≥ 4/10 hpf (1.7/mm2), hypercellularity, endothelial proliferation and necrosis. The sum of these four parameters (scores) was the histopathologic score of the tumor. The progression-free survival (PFS) and overall survival (OS) of patients with histopathologic scores 0 and 1 were significantly better than those with histopathologic scores 2, 3 and 4 (p < 0.001 and p = 0.005, respectively). Because of the latter finding, we proposed that anaplastic ependymoma could be diagnosed by the presence of any two of the aforementioned four parameters. Multivariate analyses including clinical and histopathologic variables showed that histopathologic score ≥ 2 and subtotal resection were the factors related to increased risk of recurrence, while histopathologic score ≥ 2 was the only factor related to overall survival. Based on the above findings, we concluded that histopathology is an important prognostic indicator for patients with ependymomas.

Objective.The goal of this study was to assess whether the MIB-1 labeling index (LI) and conventional parameters could distinguish between a good and a poor prognosis in patients with squamous cell cervical carcinoma of the same FIGO stage.

Expression of the cell adhesion molecules including E‐cadherin and its cytosolic binding proteins, α‐ and β‐catenins, has been widely studied in a variety of tumours, but not, to date, in thymic epithelial tumours. To observe the expression pattern of these adhesion molecules, immunohistochemical stains for E‐cadherin (E‐CD) and α‐ and β‐catenins were performed on 89 cases of thymoma which were classified as cortical (57 cases), mixed (18 cases), and medullary (14 cases), based on the classification of Marino and Müller‐Hermelink. The majority of cortical thymomas showed diffuse and homogenous membrane immunoreactivity for these molecules (88 per cent for E‐CD; 86 per cent for α‐catenin; 91 per cent for β‐catenin) and the remaining cases showed heterogeneous immunoreactivity, whereas almost all mixed and medullary thymomas revealed decreased expression or were negative. In each histological subtype of thymoma, the expression did not correlate with invasion or with the presence of myasthenia gravis. These results indicate that the expression of E‐CD and α‐ and β‐catenins is more closely associated with the histological subtypes of thymoma than with their biological behaviour. © 1998 John Wiley & Sons, Ltd.

Choroid plexus tumors are rare and account for only 2.3% (8/352) of primary childhood intracranial neoplasms in our series. Most of our patients were under 2 years of age. The tumors had a predilection for the lateral ventricle. Calcification was found in half of these tumors, and ossification was seen in 1 case. Histological features of malignancy including invasion, loss of differentiation, and severe nuclear pleomorphism pointed to a poor prognosis. Such features were found in 2 cases. Neither a large number of mitoses nor necrosis was a constant feature in cases of malignancy. Transthyretin, a marker for choroid plexus tumors, was positive in all cases. However, negative S-100 or positive carcinoembryonic antigen was not necessarily associated with a more aggressive histological pattern. All the papillomas could be totally resected without recurrence, and all the patients with carcinoma died within a few months.

The objectives of this research were (I) to determine whether the use of partially absorbable vascular grafts would improve their nonthrombogenic performance and whether they are more prone to aneurysmal dilation and subsequent failure in vivo. and (2) to find out the relationships, if any. between these in vivo and the previously reported in vitro data with an emphasis on how the in vitro changes in fabric structure and properties related to these in vivo data. Bicomponent vascular fabrics were made from Dacron and polyglycolic acid (PGA) yarns with a range of composition ratios of the PGA to Dacron. Both woven and single Jersey knit fabrics were made, and implanted in dogs for 4 months. The following findings and relationships were obtained. (1) The bicomponent vascular fabrics resulted in a full-wall healing in the thoracic aorta of dogs. All bicomponent vascular grafts in survived dogs exhibited 100% patency, no thrombus or aneurysmal formation, no hematoma or seroma around the grafts, and no fibrin coagula in the inner capsules. The gross morphology of the regenerated tissues was very similar visually to the adjacent original arterial tissue. Histologically, the luminal surface was lined with a layer of endothelial cells with myofibroblasts, fibroblasts. and collagens underneath. (2) The extent of the full-wall healing depended on the type of fabric structure. the concentration of absorbable yarns, the location of absorbable yarns (for the woven group only), and initial water permeability. It is believed that the concentration effect was related to the level of macrophage activation from the degradation products of the absorbable yarns, while the location effect was attributed to the various types of fabric structure change on the degradation of the absorbable yarns. (3) In general, the knitted group (K), was better than the woven group (W). K3 showed the best in vivo performance in the knitted group. (4) In the woven group, W3 was the best. The incorporation of absorbable yarns in the weft direction of the bicomponent fabrics (W3) resulted in a velourlike, loose and porous fabric surface for facilitating tissue ingrowth. The placement of absorbable yarns in the warp direction (W1), however, did not show this unique surface morphology. Calcification was, however, occasionally observed in the woven samples with low initial water permeability. These observed in vivo performances correlated well with our previously reported in vitro study.

A cerebral primitive neuroectodermal tumor with astrocytic differentiation and extracranial metastases in a 28-day-old infant is reported. The infant presented with a progressively enlarged head, cutaneous lesions in the neck, and enlarged cervical lymph nodes. A computed tomography brain scan demonstrated a giant thalamic tumor with subarachnoid dissemination and hydrocephalus. Biopsy material from the cervical lesions showed a picture of glioma with anaplastic astrocytes. The patient received a ventriculoperitoneal shunt operation and palliative chemotherapy, but died at 3 months of age. Autopsy was performed. Histological studies, which included immunohistochemical stains of the thalamic tumor, showed small, round, primitive, neoplastic cells with focal astrocytic differentiation.

Intracranial germinoma associated with neurofibromatosis 1 (NF-1) has never been documented previously. We report a case of familial NF-1 with a germinoma involving the right basal ganglion and thalamus. A 12-year-old boy presented with multiple café-au-lait spots and a family history of neurofibromatosis in his mother, one of two siblings, and his maternal grandfather. His intracranial lesion was subtotally resected. Histologically, it was a pure germinoma. Serum a-feto protein and ß-human chorionic gonadotropin levels were within the normal range. Postoperative myelographic examination and cerebrospinal fluid cytology study showed no evidence of subarachnoid seeding. The patient received postoperative combination chemotherapy resulting in complete response and clearance of the residual tumor. Although this finding of an intracranial germinoma in a patient with familial NF-1 may be coincident, it is suggestive of a potential genetic predisposition. Longitudinal evaluation for the possibility of neoplasm, especially germ cell tumor, in basal ganglion lesions in NF-1 patients is necessary.

A patient underwent simple enucleation for a suspected angiomyolipoma in the right kidney and histopathology revealed a mixture of renal cell carcinoma with angiomyolipoma. To our knowledge only 1 other case of a combination of a renomedullary tumor has been reported previously.

Approximately 10% of patients with glioblastoma survive more than 2 years after diagnosis. Distinguishing these patients from those who died within 2 years of diagnosis is clinically significant. We studied the MIB-1 labeling index (LI) and DNA topoisomerase IIα LI of glioblastomas from 34 patients who lived for more than 2 years after diagnosis and of glioblastomas from 34 age- and sex-matched control patients who died within 2 years of diagnosis. The means of MIB-1 and topoisomerase IIα LIs of the group with a better outcome were lower. With 35 as the cutoff point for the MIB-1 LI and 26 as the cutoff point for the topoisomerase IIα LI, both MIB-1 and topoisomerase IIα LIs were related significantly to survival. Our study showed that both MIB-1 and topoisomerase IIα could help predict long-term survival of patients with glioblastomas. Multivariate analyses revealed that MIB-1 was a better prognostic marker than topoisomerase IIα.