Supratentorial non-RELA, ZFTA-fused ependymomas: a comprehensive phenotype genotype correlation highlighting the number of zinc fingers in ZFTA-NCOA1/2 fusions.

The cIMPACT-NOW Update 7 has replaced the WHO nosology of "ependymoma, RELA fusion positive" by "Supratentorial-ependymoma, C11orf95-fusion positive". This modification reinforces the idea that supratentorial-ependymomas exhibiting fusion that implicates the C11orf95 (now called ZFTA) gene with or without the RELA gene, represent the same histomolecular entity. A hot off the press molecular study has identified distinct clusters of the DNA methylation class of ZFTA fusion-positive tumors. Interestingly, clusters 2 and 4 comprised tumors of different morphologies, with various ZFTA fusions without involvement of RELA. In this paper, we present a detailed series of thirteen cases of non-RELA ZFTA-fused supratentorial tumors with extensive clinical, radiological, histopathological, immunohistochemical, genetic and epigenetic (DNA methylation profiling) characterization. Contrary to the age of onset and MRI aspects similar to RELA fusion-positive EPN, we noted significant histopathological heterogeneity (pleomorphic xanthoastrocytoma-like, astroblastoma-like, ependymoma-like, and even sarcoma-like patterns) in this cohort. Immunophenotypically, these NFκB immunonegative tumors expressed GFAP variably, but EMA constantly and L1CAM frequently. Different gene partners were fused with ZFTA: NCOA1/2, MAML2 and for the first time MN1. These tumors had epigenetic homologies within the DNA methylation class of ependymomas-RELA and were classified as satellite clusters 2 and 4. Cluster 2 (n = 9) corresponded to tumors with classic ependymal histological features (n = 4) but also had astroblastic features (n = 5). Various types of ZFTA fusions were associated with cluster 2, but as in the original report, ZFTA:MAML2 fusion was frequent. Cluster 4 was enriched with sarcoma-like tumors. Moreover, we reported a novel anatomy of three ZFTA:NCOA1/2 fusions with only 1 ZFTA zinc finger domain in the putative fusion protein, whereas all previously reported non-RELA ZFTA fusions have 4 ZFTA zinc fingers. All three cases presented a sarcoma-like morphology. This genotype/phenotype association requires further studies for confirmation. Our series is the first to extensively characterize this new subset of supratentorial ZFTA-fused ependymomas and highlights the usefulness of ZFTA FISH analysis to confirm the existence of a rearrangement without RELA abnormality.

Space-Occupying Tumor Bed Cysts as a Complication of Modern Treatment for High-Grade Glioma.

BACKGROUND: The management of high-grade glioma (HGG) has been affected by recent landmark trials and is now more proactive. More aggressive treatment leads to hospitalization due to side effects, however. Space-occupying tumor bed cysts have been described, but not systematically assessed. We sought to analyze this complication in a contemporary HGG cohort. METHODS: We performed a retrospective review of patients with HGG treated between 2007 and 2013, identified patients with space-occupying tumor bed cysts, and reviewed their hospital notes for relevant variables. Statistical analyses were performed, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS: Tumor bed cysts were found in 12 of 282 patients (4%). The main symptoms were increased intracranial pressure (n = 11), new focal deficits (n = 6), and pseudomeningocele (n = 3), presenting at a median of 19 days since the last resection. Cysts were treated with cystoperitoneal (n = 7) and ventriculoperitoneal (n = 5) shunts, resulting in clinical benefit in 75% of those treated. Intraoperative opening of ventricles is a risk factor, with an OR of 39.339. We propose a classification system comprising 3 cyst types: isolated cyst, cyst with local cerebrospinal fluid (CSF) disturbance, and cyst with global CSF disturbance. CONCLUSIONS: In modern neuro-oncology, the rate of tumor bed cysts complicating HGG management appears stable compared with historical data. Shunt implantation is feasible and effective. We propose a classification system as a common data element for comparison across future studies.

Impact of epidemiological characteristics of supratentorial gliomas in adults brought about by the 2016 world health organization classification of tumors of the central nervous system.

The latest World Health Organization (WHO) classification of tumors of the central nervous system (CNS) integrates both histological and molecular features in the definition of diagnostic entities. This new approach enrolls novel entities of gliomas. In this study, we aimed to reveal the epidemiological characteristics, including age at diagnosis, gender ratio, tumor distribution and survival, of these new entities. We retrospectively reclassified 1210 glioma samples according to the 2016 CNS WHO diagnostic criteria. In our cohort, glioblastoma multiforme (GBM) with wildtype isocitrate dehydrogenase (IDH) was the most common malignant tumor in the brain. Almost all gliomas were more prevalent in males, especially in the cluster of WHO grade III gliomas and IDH-wildtype GBM. Age at diagnosis was directly proportional to tumor grade. With respect to the distribution by histology, we found that gliomas concurrent with IDH-mutant and 1p/19q-codeleted or with single IDH-mutant were mainly distributed in frontal lobe, while those with IDH-wildtype were dominant in temporal lobe. Lesions located in insular lobe were more likely to be IDH-mutant astrocytoma. In summary, our results elucidated the epidemiological characteristics as well as the regional constituents of these new gliomas entities, which could bring insights into tumorigenesis and personalized treatment of Chinese glioma population.

Cerebral relapsing meningioma: a surgical series with lack of reliability of standard parameters establishing prognosis.

BACKGROUND/AIM: Meningioma is the most frequent meningeal neoplasm, usually without relapse or metastasis. Patient follow-up is challenging, not standardized and is decided in multidisciplinary case discussion. Our aim was to determine the clinical and histological factors influencing the time to relapse. PATIENTS AND METHODS: We conducted a single-Center retrospective study on 38 patients with surgically-excised relapsing meningiomas and collected clinical and pathological data. RESULTS: Our results show that none of the histological factors included in the WHO classification, nor those not included are related to a shorter time to relapse. CONCLUSION: In our study, none of the histological, immunohistochemical and clinical parameters evaluated seem to be able to predict the time to relapse in meningioma.

Subgrouping of gliomas on the basis of genetic profiles.

Management of gliomas depends on histological diagnosis; there are, however, limitations to the systems presently used. Tumors in the same entity can have different clinical courses, especially when they are diagnosed as WHO grade II-III. Previous studies revealed that genetic subgrouping of gliomas provides useful information that could help establishment of treatment procedures on the basis of the genetic background of the tumors. Recently, the authors analyzed the chromosomal copy number aberrations (CNAs) of adult supratentorial gliomas by comparative genomic hybridization using microdissected tissue sections. The tumors were classified into subgroups according to chromosomal CNAs. WHO grade II-III gliomas contained a variety of genetic subgroups that correlated well with the clinical course. Of these, long progression-free survival was observed for tumors with +7q and those with -1p/19q, low-grade tumors of 2 major lineages, and, in our preliminary data, both were closely correlated with mutation of IDH1. Furthermore, in contrast with +7q tumors, the great majority of +7 or +7/-10q groups had wildtype IDH1. Genetic studies suggest that cytogenetic characterization may provide an additional classification system for gliomas, and new criteria could help to establish rational and objective means for analysis of treatment procedures.

Neuronal immunoexpression and a distinct subtype of adult primary supratentorial glioblastoma with a better prognosis.

OBJECT: In this study, the authors address whether neurofilament protein (NFP) expression can be used as an independent prognostic factor in primary glioblastoma multiformes (GBMs). METHODS: Three hundred and two consecutive adult patients with newly diagnosed supratentorial primary GBMs were analyzed (January 2000-August 2008). Detailed data regarding clinical, imaging, and pathological findings, oncological treatments, and outcomes were recorded. Neurofilament protein immunoexpression served to identify NFP-positive tumor cells (normal entrapped neurons and mature ganglion-like cells excluded). RESULTS: Neurofilament-positive cells were identified in 177 GBMs (58.6%). Patients with NFP-positive GBMs were younger (p < 0.0001), and their GBMs presented with more temporal lobe tumor localization (p = 0.029) and more cortical involvement (p = 0.0003). Neurofilament-negative GBMs presented with more ventricular contact (p < 0.0001) and more tumor midline crossing (p = 0.03). Median overall survival and progression-free survival (PFS) were 13.0 and 7.6 months, respectively, for NFP-positive GBMs, and 7.0 and 5.1 months, respectively, for NFP-negative GBMs. Multivariate analysis revealed NFP immunoexpression, tumor midline crossing, complete resection, and radiotherapy combined with chemotherapy as independent factors associated with overall survival. Neurofilament protein-positive immunoexpression was associated with longer overall survival (hazard ratio [HR] 0.54, 95% CI 0.40-0.74; p < 0.0001) and longer PFS (HR 0.71, 95% CI 0.53-0.96; p = 0.02). CONCLUSIONS: Neurofilament protein-positive immunoexpression represents a strong, therapeutically independent prognostic factor for primary supratentorial GBM clinical outcome among adult patients. Neurofilament protein-GBM's unique pathological features are not only associated with distinct clinical and anatomical behavior, but are also predictive of overall patient survival and PFS. Neurofilament protein immunoexpression may help identify a distinct subgroup of primary GBMs with a favorable prognosis, which should be considered in the design of future targeted therapies.

Quantitative morphological magnetic resonance imaging follow-up of low-grade glioma: a plea for systematic measurement of growth rates.

Supratentorial hemispheric diffuse low-grade gliomas (LGGs), i.e., World Health Organization grade II gliomas, are a heterogeneous group of tumors. During their natural course, LGGs tend to progress to a higher grade of malignancy, leading to neurological disability and ultimately to death. In this review, we will show, that during their low-grade period, these tumors exhibit systematically a spontaneous and continuous radiological growth, whatever their histological subtypes. The radiological tumor growth is easily quantified by measuring the evolution of the equivalent tumor diameter (calculated from the tumor volume), obtaining the velocity of diametric expansion (VDE). The spontaneous VDE of LGGs varies markedly with an average VDE of about 4 mm/year. It depends on intrinsic factors (1p19q codeletion status, P53 overexpression status) and can be modified by extrinsic factors (pregnancy). The spontaneous VDE carries a strong prognostic significance regarding progression-free and overall survivals. As a consequence, VDE should be integrated along with the other "static" parameters (multimodal imaging, histological and molecular analyses) in the initial investigations. In addition, the assessment of VDE obtained before, during, and after a particular oncological treatment helps in analyzing their effects on LGGs on an individual basis, helping to guide the decision making.

Supratentorial WHO grade II glioma invasion: a morphologic study using sequential conventional MRI.

The natural morphological growth and invasion of World Health Organization (WHO) grade II glioma has not been well documented in previous literature. This study retrospectively analysed the morphological invasive characteristics of adult. Data from 20 patients (15 men, 5 women; mean age, 38 years; age range, 22-64 years), who had supratentorial WHO grade II gliomas and consecutively underwent serial preoperative conventional MR examinations were retrospectively analysed, for change in location, and evidence of haemorrhage, enhancement, necrosis, peri-tumoural oedema and mass effect. Seven tumours, initially located in the grey matter (3, insula; 4, frontal cortices), expanded without definite invasion along fibres. Thirteen tumours, originated from the junction of grey and white matter, invaded in different orientations (4, contralateral invasion; 1, ipsilateral remote dissemination; 8, ipsilateral invasion via the surrounding fibres). The increased proportion of haemorrhage, enhancement, necrosis, peri-tumoural oedema and mass effect in the first and last pre-operative examinations were 14% (1/7), 29% (2/7), 43% (3/7), 43% (3/7) and 29% (2/7), respectively, for the 7 tumours initially located in grey matter, and 15% (2/13), 38% (5/13), 31% (4/13), 15% (2/13) and 38% (5/13) respectively for the 13 tumours initially located at the junction of grey and white matter. The growth of supratentorial WHO grade II glioma is a complicated process. The growth directionality may be determined by initial tumour location.

Possible role of single-voxel (1)H-MRS in differential diagnosis of suprasellar tumors.

The objective of the present study was investigation of the possible role of proton magnetic resonance spectroscopy ((1)H-MRS) for differential diagnosis of suprasellar tumors. Forty patients (23 men and 17 women; median age, 45 years) with suprasellar, hypothalamic, and third ventricle neoplasms underwent long-echo (TR: 2000 ms, TE: 136 ms, 128-256 acquisitions) single-voxel (1)H-MRS before surgical treatment. The volume of the voxel was either 3.4 cc or 8 cc. Spectroscopic data were analyzed by calculation of the various metabolite ratios as well as by determination of the type of the pathological (1)H-MR spectra. There were 19 pituitary adenomas, 7 gliomas, 5 craniopharyngiomas, 3 chordomas, meningioma, hemangiopericytoma, malignant lymphoma, germinoma, Rathke cleft cyst, and hypothalamic hamartoma (one of each). Six tumors were recurrent after initial surgical resection with or without irradiation. Comparison of the individual metabolite ratios revealed only few subtle differences among neoplasms. In the same time, pattern analysis with determination of the type of the pathological (1)H-MR spectra disclosed certain specific characteristics, which seemingly can be used for tumor typing. Meanwhile, metabolic imaging was less effective for characterization of recurrent neoplasms. In conclusion, in cases of initially diagnosed suprasellar tumors with involvement of the hypothalamus and extension into the third ventricle pattern analysis of the single-voxel (1)H-MRS can provide valuable information, which, in addition to structural MRI, can be effectively used for diagnostic purposes.

Central nervous system atypical teratoid rhabdoid tumor: experience at the National Institute of Pediatrics, Mexico City.

OBJECTIVE: The purpose of this study is to present our experience with ten cases of Central nervous system atypical teratoid rhabdoid tumor (CNS/ATRT). PATIENTS AND METHODS: A series of ten patients with CNS/ATRT, were diagnosed and treated between 1990 and 2005, at the National Institute of Pediatrics, in Mexico City. The gender, age of presentation, clinical features, tumor localization, imaging studies, grade of tumor resection, complications, adjuvant therapy, and survival are presented. RESULTS: The mean age at diagnosis was 37.8 months, seven cases were male, and their average clinical course was 1.3 months. The more common clinical presentation was intracranial hypertension with cranial nerve deficits; location was infratentorial in four patients and supratentorial in six. Hydrocephalus was present as the most common complication (seven cases). In nine patients, the grade of resection was total or subtotal. In one case, it was only possible to perform a biopsy. There were two cases with longer survival (9 and 16 months), and their tumors were resected in total or subtotal manner and received adjuvant therapy (radiotherapy and chemotherapy). CONCLUSIONS: Preliminary results, show that in older children, we can improve their survival with the subtotal or total resection of the tumor and the addition of chemotherapy and radiotherapy.

Malignant predominantly minigemistocytic glioma in two infants: a distinctive glioma variant?

We report unusual distinctive histopathological features in malignant supratentorial tumours of two infants (patient 1: congenital, patient 2: 30 months). Both patients had paraventricularly located well-delineated tumours. Gross total resection could be performed and postoperative chemotherapy was administered. At the last follow-up, 18 (patient 1) and 10 months (patient 2) postoperatively, both patients were in continuous complete remission. Histologically, both tumours were characterized by high cellular density and monomorphic appearance. Tumour cells were small to medium-sized and the majority of cells showed a distinctive minigemistocytic shape. A small fraction of cells lacked a distinct cytoplasm. Mitotic figures were abundant, tumour necrosis and hypertrophic vascular proliferations were absent. Immunohistochemically, the tumour cells expressed glial (GFAP, S100) and focally neuronal (NFP) proteins. Comparative genomic hybridization showed few, dissimilar chromosomal aberrations in the two tumours. Although sharp demarcation and monomorphic architecture of both tumours are reminiscent of a primitive neuroectodermal tumour, cytological and immunohistochemical glial differentiation refer to a glial tumour origin. To our knowledge the histopathological features of the described tumours do not correspond unequivocally to any established glioma variant and could represent a distinctive new glioma subtype.

Genetically distinct and clinically relevant subtypes of glioblastoma defined by array-based comparative genomic hybridization (array-CGH).

To optimize treatment strategies for patients with glioblastoma, a more precise understanding of the molecular basis of this disease clearly is necessary. Therefore, numerous studies have focused on the molecular biology of glioblastoma and its linkage to clinical behavior. Here we investigated 70 glioblastomas using the array-based comparative genomic hybridization (array-CGH) with GenoSensor Array 300 to identify recurrent DNA copy number imbalances associated with patient outcomes. Univariate log-rank analysis of array-CGH data revealed 46 copy number aberrations (CNAs) associated with outcome. Among them, 26 CNAs were associated with shortened survival whereas the remaining 20 CNAs correlated with good prognosis. A hierarchical cluster analysis disclosed two genetically distinct groups of glioblastomas (1 and 2; 56 and 14 tumors, respectively). Univariate log-rank test discerned significant difference in survival between both genetic subsets while the 5-year survival rate consisted of 0 for group 1 and 63% for group 2. Multivariate analysis revealed that unfavorable genetic signature is an independent prognostic factor increasing a risk of patient death (hazard ratio, 4.38; P=0.00001). In conclusion, our current study suggests that glioblastomas can be subdivided into clinically relevant genetic subsets. Therefore, array-CGH screening of glioblastomas could provide clinically useful information and, perhaps, potentially improve the quality of treatment.

Interstitial 125I radiosurgery of supratentorial de novo WHO Grade 2 astrocytoma and oligoastrocytoma in adults: long-term results and prognostic factors.

BACKGROUND: Detailed long-term outcome data are not available for adult patients with World Health Organization (WHO) Grade 2 astrocytoma or oligoastrocytoma. METHODS: A previously published short-term data set of 239 adult patients with circumscribed de novo supratentorial astrocytoma (187 patients) and oligoastrocytoma (52 patients) treated with interstitial iodine-125 ((125)I) radiosurgery as primary treatment (1979-1992) was revisited. Survival, progression-free survival, functionally independent survival, postrecurrence survival, and time to malignant transformation were estimated with the Kaplan-Meier method. Prognostic factors were obtained from the Cox multivariate proportional hazards model. RESULTS: Five-, 10-, and 15-year survival was 56%, 37%, and 26%, respectively (median follow-up, 10.3 yrs). Progression-free survival was 45%, 21%, and 14%, respectively. The corresponding malignant transformation rates were 33%, 54%, and 67%. No leveling off of the Kaplan-Meier curves could be observed for any of the chosen endpoints. Age > 50 years, a tumor volume > 20 mL, and/or a Karnofsky score < or = 80 were associated with decreased survival or progression-free survival. Age > 35 years and/or a tumor volume > 20 mL increased risk of malignant transformation. Prognostic factors determined subsets of patients with 10-year survival ranging from as low as 6% to as high as 55% and progression-free survival ranging 1-31%. CONCLUSIONS: Long-term tumor stabilization is rare. As outcome is mainly determined by treatment-independent factors, minimization of any treatment-related risk must be considered essential.

Evidence for a clinically distinct new subtype of grade II astrocytomas in patients with long-term epilepsy.

OBJECTIVE: The authors tested the hypothesis that among Grade II astrocytomas with a particularly long seizure history, a subgroup is hidden with a different prognosis and possibly histological characteristics. To do so, clinical and histological characteristics of two groups of World Health Organization Grade II astrocytoma patients were analyzed: the long-term epilepsy-associated tumor (LEAT) astrocytoma group, with a mean duration of 12.5 years of seizures (n = 19), and the ordinary astrocytomas (n = 87), with a mean length of seizure history of 1.5 years (Non-LEAT). METHODS: All astrocytomas operated on between 1988 and 1999 were collected and followed up for 2 to 13 years (median, 7.0 yr). The 19 LEAT astrocytomas belonged to a group of 207 long-term epilepsy-associated tumors from the epilepsy surgery program. The 87 Non-LEAT cases were 60 so-called ordinary or diffuse World Health Organization Grade II astrocytomas and 27 oligoastrocytomas without long-term epilepsy operated on during the same time period. All tumor cases have been reviewed and partly reclassified as a result of the use of modern immunohistochemical techniques. Statistical analyses for possible discriminating factors included chi(2) test, Fisher's exact test, Kaplan-Meier curves, and multifactorial analysis. RESULTS: Histological subtyping revealed a possible new isomorphic astrocytoma subtype in seven patients. By use of Kaplan-Meier curves, this isomorphic subtype had 50% fewer recurrences at 7.5 years and an estimated long-term survival of 80%. LEAT astrocytomas differed from ordinary Non-LEAT astrocytomas in overall length of history, younger age at first seizure, and higher percentage of 10-year survivors (80%). Temporal location did not influence outcome, and the presence of epilepsy per se was also not a prognostic factor. CONCLUSION: Differences between astrocytomas with a very long seizure history and those with a very short seizure history do exist. Significant factors for prognosis were age at surgery and presence of postoperative tumor residue but not the presence of epilepsy per se. A new subtype of astrocytomas, provisionally called isomorphic LEA astrocytoma, has putatively been identified with significantly better survival and lower recurrence rate. The negative prognostic factor of a gemistocytic differentiation pattern in diffuse astrocytomas was confirmed.

Supratentorial glioblastoma in adults: identification of subsets and their clinical correlation.

The concept of different genetic pathways leading to glioblastoma multiforme (GBM) has gained considerable acceptance, and two major groups are now described, primary or de novo GBM and secondary GBM. The present study was undertaken to elucidate whether additional pathways exist and to determine whether there is any correlation between these different variants and clinical parameters, such as age, duration of symptoms, and outcome. For this purpose, immunophenotyping was performed to study the simultaneous expression of p53 protein and epidermal growth factor receptor (EGFR) in 58 cases of adult supratentorial GBM. By this method, four variants of GBM could be distinguished: 34% were p53 positive only, 38% were EGFR positive only, 14% were double negative (p53 negative/EGFR negative), and 14% were double positive (p53 positive/EGFR positive). Interestingly, all nine cases of secondary GBM in which there was clinical and histological evidence of progression from a preexisting low-grade lesion were p53 positive. Differences were observed with regard to the age distribution of the four variants, in that the p53 negative/EGFR negative tumors occurred most frequently in the younger age group (21-40 years). In the elderly group (61-80 years), two-thirds of the tumors were p53 negative/EGFR positive primary GBMs, and no case of the double positive or double negative variant was encountered. The differences in duration of symptoms and symptom-free survival according to age group and genetic subset were not statistically significant. There were no differences in outcome within each age category for any GBM variant, although the longest mean symptom-free survival was noted among patients aged 41-60 years with the p53 positive/EGFR negative variant. This study therefore indicates that at least four subsets of GBM exist, but despite different genotypes, the biologic behavior remains similar. Other genetic alterations therefore need to be investigated to identify prognostic makers.

[Supratentorial tumors in childhood]. / Supratentorielle Tumoren im Kindesalter.

In Germany about 400 children are diagnosed of having a brain tumour each year. About half of them are located in the supratentorial region. Despite the fact, that brain tumours are the most common solid tumour in childhood, they are very heterogeneous, regarding clinical symptoms, pathology, treatment and prognosis. Imaging studies play an important role for diagnosis and follow-up.

Supratentorial grade II astrocytoma: biological features and clinical course.

Because of its unpredictable clinical course, treatment strategies for low-grade (grade II) astrocytoma vary from "wait and see" to gross tumour resection followed by immediate radiotherapy. Clinical studies on grade II astrocytoma show that 5-year-survival ranges from 27% to 85% of patients with very few consistent prognostic variables besides the patient's age and the presence of neurological deficit. There is no universally recognised choice of therapy for patients with astrocytoma grade II, partly because of the shortcomings of histological classification systems. Routine microscopy tends to underestimate malignancy grading of astrocytomas and in most cases cannot distinguish between indolent and progressive subtypes. Recent studies suggest that proliferation and genetic markers can be used to identify subgroups of astrocytoma grade II with a rapid progressive clinical course. Therefore these markers should be included in ongoing and future clinical studies of patients with astrocytoma grade II.

[Significance of stereotactic biopsy for the management of WHO grade II supratentorial glioma]. / Der Stellenwert der stereotaktischen Hirnbiopsie für das Management von Patienten mit supratentoriellen Gliomen WHO-Grad-II.

OBJECTIVE: The aim of this prospective study was to compare the diagnostic value of magnetic resonance imaging (MRI) and stereotactic biopsy in patients harboring WHO grade II gliomas. METHODS: Stereotactic biopsy was performed in 62 adult patients with low-signal, nonenhancing, space-occupying lesions on T1 MR imaging between 1998 and 2001. The results of histological analysis were compared to the preoperative imaging diagnoses. Any adverse perioperative sequel was considered as morbidity. Applied treatment strategies are described. RESULTS: Transient perioperative morbidity for the stereotactic approach was 4.8% (three patients), and there was no mortality or permanent morbidity. In four patients, neoplastic lesions could be excluded (gliosis: three patients, encephalitis: one), and WHO grade III gliomas were seen in five patients (14.8.% false positive rate of neurodiagnostic imaging). The diagnostic reliability of stereotactic biopsy was 96.8%. The following treatment strategies were initiated: microsurgery (17 patients), interstitial radiosurgery (12 patients), combination of microsurgery and interstitial radiosurgery (21 patients), external beam irradiation (six patients),and chemotherapy (two patients). Four patients were initially not treated. CONCLUSIONS: Diagnostic neuroimaging is not sufficient for the planning of rational treatment strategies in patients harboring WHO grade II gliomas. Frame-based stereotactic biopsy is a prerequisite for individualized treatment strategies.

A comparative survival evaluation and assessment of interclassification concordance in adult supratentorial astrocytic tumors.

Classification and grading of astrocytic tumors has been the subject of several controversies and no universally accepted classification system is yet available. Nevertheless, acceptance of a common system is important for assessing prognosis as well as easy comparative evaluation and interpretation of the results of multi-center therapeutic trials. We report the results of a single center study on comparative survival evaluation along with assessment of inter-classification concordance in 102 cases of supratentorial astrocytic tumors in adults ((3) (3)16 years of age). Hematoxylin and eosin (H&E) stained slides of these 102 cases were reviewed independently by two pathologists and each case classified or graded according to four different classification systems viz. Kernohan, Daumas-Duport (SAM-A), TESTAST-268 and WHO. The histological grading was then correlated with the survival curves as estimated by the Kaplan-Meier method. The most important observation was that similar survival curves were obtained for any one grade of tumor by all the four classification systems. Fifty three of the 102 cases (51.9%) showed absolute grading concordance using all 4 classifications with maximum concordant cases belonging to grades 2 and 4. Intra-classification grade-wise survival analysis revealed a statistically significant difference between grade 2 and grades 3 or 4, but no difference between grades 3 and 4 in any of the classification systems. It is apparent from the results of this study that if specified criteria related to any of the classification systems is rigorously adhered to, it will produce comparable results. Hence, preferential adoption of any one classification system in practice will be guided by the relative ease of histologic feature value evaluation with maximum possible objectivity and reproducibility. We recommend the Daumas-Duport (SAM-A) system since it appears to be the simplest, most objectivized for practical application and highly reproducible with relative ease.