Comparison of diagnostic performance of radiologist- and AI-based assessments of T2-FLAIR mismatch sign and quantitative assessment using synthetic MRI in the differential diagnosis between astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant and 1p/19q-codeleted.

PURPOSE: This study aimed to compare assessments by radiologists, artificial intelligence (AI), and quantitative measurement using synthetic MRI (SyMRI) for differential diagnosis between astrocytoma, IDH-mutant and oligodendroglioma, and IDH-mutant and 1p/19q-codeleted and to identify the superior method. METHODS: Thirty-three cases (men, 14; women, 19) comprising 19 astrocytomas and 14 oligodendrogliomas were evaluated. Four radiologists independently evaluated the presence of the T2-FLAIR mismatch sign. A 3D convolutional neural network (CNN) model was trained using 50 patients outside the test group (28 astrocytomas and 22 oligodendrogliomas) and transferred to evaluate the T2-FLAIR mismatch lesions in the test group. If the CNN labeled more than 50% of the T2-prolonged lesion area, the result was considered positive. The T1/T2-relaxation times and proton density (PD) derived from SyMRI were measured in both gliomas. Each quantitative parameter (T1, T2, and PD) was compared between gliomas using the Mann-Whitney U-test. Receiver-operating characteristic analysis was used to evaluate the diagnostic performance. RESULTS: The mean sensitivity, specificity, and area under the curve (AUC) of radiologists vs. AI were 76.3% vs. 94.7%; 100% vs. 92.9%; and 0.880 vs. 0.938, respectively. The two types of diffuse gliomas could be differentiated using a cutoff value of 2290/128 ms for a combined 90th percentile of T1 and 10th percentile of T2 relaxation times with 94.4/100% sensitivity/specificity with an AUC of 0.981. CONCLUSION: Compared to the radiologists' assessment using the T2-FLAIR mismatch sign, the AI and the SyMRI assessments increased both sensitivity and objectivity, resulting in improved diagnostic performance in differentiating gliomas.

ImmunoFISH is a reliable technique for the assessment of 1p and 19q status in oligodendrogliomas.

OBJECTIVE: To develop a new ImmunoFISH technique for the study of oligodendrogliomas by combining a standard immunohistochemical stain using MIB-1 antibody with a standard FISH technique using commercial 1p36 and 19q13 chromosomal probes. METHODS: Validation was performed by two observers on a series of 36 pre-selected oligodendrogliomas and compared to the results previously determined by FISH alone. RESULTS: The ImFISH technique is easy to perform and to analyze and is no more time-consuming than the usual FISH technique. Our results show that the inter-observer reliability of ImFISH is high (κ = 0.86 and 0.95 respectively for 1p and 19q). Compared to FISH, the ImFISH exhibits a very high sensitivity (∼100%) and specificity (∼90%) for 1p and/or 19q deleted cases. The sensitivity is high for normal cases (∼85%) and imbalanced cases (∼90%) with a specificity ranging between 50 and 85%. Finally, there were no significant differences between FISH and ImFISH results calculated on 60, 40 or 20 cells. CONCLUSION: Our study demonstrates the reliability of the ImFISH technique in oligodendrogliomas and emphasizes its advantage in poorly cellular tumoral specimen.

Diagnosis of oligodendroglioma: molecular and classical histological assessment in the twenty-first century.

Advances in molecular genetics are currently challenging the traditional morphological categorization of gliomas. Recurrent molecular and cytogenetic aberrations add prognostic and predictive information over and above that provided by standard histomorphological techniques and may influence decisions to re-operate or observe, to deliver radiation or not, or to administer chemotherapy to glioma patients. The importance of routine hematoxylin and eosin (H-E pathological stains cannot be underestimated, especially in resource-poor areas and developing countries where there is likely to be a significant economic opportunity cost for molecular diagnosis services. New research tools for image analyses of histological H-E slides, such as the precise measures of cell area, curvature and nuclear roundness, may provide an increased ability to provide an accurate classification for an inherently subjective process of histological assessment. We discuss the current trends, limitations and impact of molecular classification in this mini review.

MR imaging characteristics of oligodendroglial tumors with assessment of 1p/19q deletion status.

PURPOSE: Patients with oligodendrogliomas with allelic loss of chromosomal arm 1p and 19q have been shown, especially with anaplastic oligodendrogliomas, to have both a better initial and long-term response to chemotherapy as well as an improved overall survival. Effective treatment of patients with brain tumors requires accurate diagnostic techniques. MR imaging can be used to help differentiate between low- and high-grade tumors. We hypothesize that certain MR imaging characteristics can be used to differentiate between patients with and without 1p and 19q deletion. METHODS: Using the clinical database at the University of Virginia Neuro-Oncology Center, we identified adult patients with grade II and III oligodendroglial tumors who underwent treatment from 2002 to 2007. Age at diagnosis, gender, tumor grade, chromosomal deletion status, duration of follow-up, and MR imaging characteristics were analyzed; the latter was read by a blinded neuroradiologist. RESULTS: One hundred and four patients met the inclusion criteria. Of these patients, 44 manifested 1p/19q co-deletion and 60 patients lacked this deletion. The greatest cross-sectional area (mean) of the tumor measured 23.4 cm(2) for patients with the co-deletion and 31.7 cm(2) for patients with intact alleles (p = 0.008). In addition, inner table thinning was noted directly adjacent to seven tumors with intact 1p and 19q alleles and in no tumors with the 1p/19q co-deletion (p = 0.020). Amongst patients with pure oligodendrogliomas, those with 1p/19q co-deletion had tumors more often confined to a single lobe as compared with those patients without the co-deletion (p = 0.023). Finally, tumors with intact alleles were more often found in the temporal lobe (45.0%) as compared with co-deleted tumors (22.7%) (p = 0.011). CONCLUSION: MR imaging is a valuable imaging modality for differentiating between oligodendrogliomas with or without the 1p/19q deletion. While imaging will never replace definitive tissue diagnosis, imaging characteristics such as tumor size, location, and overlying skull thinning can assist clinicians in assessing patients with oligodendroglial tumors prior to surgical or medical intervention.

Rapid and sensitive assessment of the IDH1 and IDH2 mutation status in cerebral gliomas based on DNA pyrosequencing.

Diffusely infiltrating cerebral gliomas frequently carry point mutations in codon 132 of the isocitrate dehydrogenase 1 (IDH1) gene or in codon 172 of the IDH2 gene, which are both clinically important as diagnostic and prognostic markers. Here, we report on a method that allows for the rapid detection of IDH1 and IDH2 mutations based on pyrosequencing. The method is applicable to routinely processed tissue specimens and provides quantitative mutation data within less than one working day. Due to its high sensitivity, the technique may also be used for the diagnostic assessment of IDH1 or IDH2 mutation in tissue samples with low tumor cell content, such as the infiltration zone of diffuse gliomas. Using pyrosequencing and/or conventional cycle sequencing of IDH1 and IDH2 in 262 gliomas, we confirm frequent mutations in diffuse astrocytic and oligodendroglial gliomas, corroborate a prognostic role for IDH1 mutation in primary glioblastomas and show that pleomorphic xanthoastrocytomas generally lack mutations in these genes.

Assessment of 1p/19q status by fluorescence in situ hybridization assay: A comparative study in oligodendroglial, mixed oligoastrocytic and astrocytic tumors.

BACKGROUND: Due to overlapping histomorphological features, difference in clinical behavior and treatment response, establishing potential molecular markers to facilitate diagnosis of various genetic subtypes of diffuse gliomas is essential. AIM: To analyze 1p/19q status in diffuse gliomas and correlate it with epidermal growth factor receptor (EGFR) and p53 protein expression. MATERIALS AND METHODS: 1p/19q status in 43 cases was evaluated by fluorescence in situ hybridization assay. Glial fibrillary acidic protein (GFAP), EGFR and p53 were assessed by immunohistochemistry. RESULTS: Glial fibrillary acidic protein immunopositivity was observed in oligodendrogliomas within minigemistocytes and gliofibrillary oligodendrocytes as perinuclear homogenous blobs. It also highlighted the intermingled reactive astrocytes. Astrocytomas and the astrocytic component of oligoastrocytomas showed a diffuse fibrillary type of staining. 1p and/or 19q loss was seen in 65% (13/20) of oligodendrogliomas and 66.6% (5/9) of mixed oligoastrocytomas. There was one case each of pediatric oligodendroglioma and mixed oligoastrocytoma, none of which showed 1p/19q loss. None of the astrocytomas including two pediatric cases showed this alteration (P < 0.05). p53 was expressed in 57.1% of astrocytomas (8/14), 33% of mixed oligoastrocytomas (3/9) and 10% of oligodendrogliomas (2/20). Majority of oligodendrogliomas (85%; 17/20) and oligodendroglial areas in mixed oligoastrocytomas (77.7%; 7/9) showed a membranous lace-like immunopositivity with EGFR. In contrast, all astrocytomas (Grade II and III) were EGFR negative. CONCLUSION: Loss of 1p/19q is strongly associated with oligodendroglial phenotype, while astrocytic tumors are more likely to show p53 over-expression. p53 expression and 1p/19q status appear to be mutually exclusive.

Panel review of anaplastic oligodendroglioma from European Organization For Research and Treatment of Cancer Trial 26951: assessment of consensus in diagnosis, influence of 1p/19q loss, and correlations with outcome.

The diagnosis of anaplastic oligodendroglioma (AOD) or anaplastic oligoastrocytoma (AOA) is subject to interobserver variation. The aim of this study was to estimate consensus in typing and grading of these tumors using tumor material collected in a large prospective randomized phase III study and to correlate the consensus diagnosis with the 1p/19q status of the tumors and the clinical outcome. The available pathology material of the first 150 patients, randomized into the European Organization for Research and Treatment of Cancer Trial 26951, was reviewed by an independent panel of 9 neuropathologists. The presence of deletions of 1p and 19q was assessed by fluorescence in situ hybridization with locus-specific probes. The panel reached consensus on the diagnosis of AOD in 52% of the tumors that had been diagnosed as AOD by the local pathologists, whereas only 8% of the local diagnosis of AOA was confirmed with consensus. The concordance on the panel diagnosis of AOD was high (intraclass correlation = 86%). The survival curves for AOD with 1p/19q loss, AOD without these losses, and AOA without 1p/19q loss ran separately in this order. The absence of necrosis and the presence of endothelial abnormalities were correlated with better outcomes. In multivariate analysis, patients' age, 1p/19q loss, and necrosis were identified as independent prognostic factors.

Longitudinal assessment of genetic and epigenetic markers in oligodendrogliomas.

PURPOSE: Because little is known about the evolution of genetic and epigenetic changes that occur during tumor progression in oligodendrogliomas, we evaluated these changes in paired early and progressive oligodendrogliomas. EXPERIMENTAL DESIGN: 1p36, 19q13, 10q22-26, and O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status were assessed in 46 paired early and progressive oligodendrogliomas from 23 patients. RESULTS: In early tumors, 60.8% were of low grade compared with only 17% low-grade tumors at recurrence. Of 17 early tumors described as pure oligodendrogliomas, 76.5% remained in this lineage, regardless of their grade, whereas others changed to astrocytic tumors. Oligoastrocytic tumors had a significantly higher tendency to transform to astrocytic tumors. All pure oligodendrogliomas with 1p/19q codeletions remained phenotypically unchanged, unlike mixed tumors with codeletions, of which 83% changed their cell lineage. Of tumors with early 1p deletion, 80% remained oligodendroglial at progression, whereas 75% of tumors with an intact 1p changed to astrocytic phenotype. 10q loss was uncommon in both early and progressive tumors. The proportional gain in methylation at progression was 31% for tumors with early 1p deletion, unlike tumors with an intact 1p, which had an 87.5% gain of methylation at progression. CONCLUSIONS: Pure oligodendrogliomas with 1p/19q deletion tend to retain their cell phenotype and genetic profile unlike tumors with no deletions or mixed histology. MGMT promoter methylation is more pronounced at tumor progression, particularly in tumors with an intact 1p. These observations suggest that MGMT promoter methylation is a late event in progressive oligodendrogliomas, and therefore, their chemosensitivity is not necessarily related to MGMT methylation status.

Proposal of a scoring scale as a survival predictor in intracranial oligodendrogliomas.

INTRODUCTION: Histological, clinical and radiological features, and molecular genetic analysis are among the factors that have been considered in defining the prognosis of oligodendrogliomas (OD), but they have yielded conflicting results. The purpose of this study was to test out a scoring scale based on clinical, radiological, pathological and molecular features. MATERIAL AND METHOD: To identify factors with prognostic significance, we analyzed 87 treated patients with a histological diagnosis of OD. Of the parameters analyzed, age, onset, clinical status, radiological enhancement, histological necrosis, mitosis and chromosomal anomalies emerged as significant prognosis factors using univariate analysis. Multivariate analysis revealed age and chromosomal anomalies as independent factors of survival. RESULTS: The factors with a significant prognostic value were combined to determine which grouping factors best predict outcome. The proposed score is a pure number resulting from a combination of: 2 major factors: age and chromosomal anomalies (scored 3-0); 5 minor factors: onset, clinical examination, necrosis, mitoses (scored 1-0), and radiological enhancement (scored 2-0). According to our scale, 10 survival curves were produced for overall survival. Recursive partitioning of patients with the nearest score and outcome produced four groups with a significant difference in survival (p=10(-5)). The power of both the scale and the partitioned groups for predicting outcome was more accurate than the WHO and St Anne grading systems, and the molecular sub-classification. CONCLUSIONS: Our scale is a plausible way of classifying patients harboring intracranial OD according to expected survival.