Diagnosis Of Oligodendroglioma Research Articles

Primary spinal oligodendroglioma with intracranial extension: a case report

Introduction: Primary spinal cord oligodendrogliomas (PSO) are sporadic tumors that arise from oligodendrocytes in the central nervous system (CNS). They can affect adults and children and make up about 2% of all intramedullary (IM) spinal tumors. Here, the authors present the second case in the literature of a primary spinal oligodendroglioma with intracranial extension. Presentation: A 28-year-old right-handed female presented to our emergency room severely malaised with left-sided hemiparesis, numbness, tingling, and urinary retention with positive Babinski and negative Hoffmann. MRI showed a widespread heterogeneous mass extending from the medulla to C7 with syringomyelia inferior to the mass. The mass was removed surgically, and her neurological condition improved rapidly. The gross, pathological exams, and immunohistochemistry confirmed the diagnosis of oligodendroglioma. Discussion: Up until 2017, there have been 60 documented cases of PSO in the literature and we have found two more cases in our search between 2017 and 2023. Also, there has been only one case recorded with an intracranial extension, making our case the 63rd PSO case and the second one with cranial extension. Conclusion: The golden standard for imaging is MRI. Surgical excision is the main treatment in the literature. Single-stage laminectomy showed promising results and surgical resection was the critical intervention to which the patient responded. This matches what was stated in the literature that surgery is the primary mode of treatment in PSO patients.

Update on quality assurance in neuropathology: Summary of the round robin trials on TERT promoter mutation, H3-3A mutation, 1p/19q codeletion, and KIAA1549::BRAF fusion testing in Germany in 2020 and 2021.

We previously reported on the first neuropathological round robin trials operated together with Quality in Pathology (QuIP) GmbH in 2018 and 2019 in Germany, i.e., the trials on IDH mutational testing and MGMT promoter methylation analysis [1]. For 2020 and 2021, the spectrum of round robin trials has been expanded to cover the most commonly used assays in neuropathological institutions. In addition to IDH mutation and MGMT promoter methylation testing, there is a long tradition for 1p/19q codeletion testing relevant in the context of the diagnosis of oligodendroglioma. With the 5th edition of the World Health Organization (WHO) classification of the central nervous system tumors, additional molecular markers came into focus: TERT promoter mutation is often assessed as a molecular diagnostic criterion for IDH-wildtype glioblastoma. Moreover, several molecular diagnostic markers have been introduced for pediatric brain tumors. Here, trials on KIAA1549::BRAF fusions (common in pilocytic astrocytomas) and H3-3A mutations (in diffuse midline gliomas, H3-K27-altered and diffuse hemispheric gliomas, H3-G34-mutant) were most desired by the neuropathological community. In this update, we report on these novel round robin trials. In summary, success rates in all four trials ranged from 75 to 96%, arguing for an overall high quality level in the field of molecular neuropathological diagnostics.

Non-invasive diagnosis of brain gliomas by histological type using neuroradiomics in standardized regions of interest: towards digital biopsy

To introduce a standardized method for identification of regions of interest when analyzing MR images using radiomics; to test the hypothesis that this approach is effective for distinguishing different histological types of gliomas. We analyzed preoperative MR data in 83 adults with various gliomas (WHO classification, 2016), i.e. oligodendroglioma, anaplastic oligodendroglioma, anaplastic astrocytoma, and glioblastoma. Radiomic features were computed for T1, T1-enhanced, T2 and T2-FLAIR modalities in four standardized volumetric regions of interest by 356 voxels (46.93 mm3): 1) contrast enhancement; 2) edema-infiltration; 3) area adjacent to edema-infiltration; 4) reference area in contralateral hemisphere. Subsequently, mathematical models were trained to classify MR-images of glioma depending on histological type and quantitative features. Mean accuracy of differential diagnosis of 4 histological types of gliomas in experiments with machine learning was 81.6%, mean accuracy of identification of tumor types - from 94.1% to 99.5%. The best results were obtained using support vector machines and random forest model. In a pilot study, the proposed standardization of regions of interest demonstrated high effectiveness for MR-based differential diagnosis of oligodendroglioma, anaplastic oligodendroglioma, anaplastic astrocytoma and glioblastoma. There are grounds for applying and improving this methodology in further studies.

A prognostic estimation model based on mRNA-sequence data for patients with oligodendroglioma.

The diagnosis of oligodendroglioma based on the latest World Health Organization Classification of Tumors of the Central Nervous System (WHO CNS 5) criteria requires the codeletion of chromosome arms 1p and 19q and isocitrate dehydrogenase gene (IDH) mutation (mut). Previously identified prognostic indicators may not be completely suitable for patients with oligodendroglioma based on the new diagnostic criteria. To find potential prognostic indicators for oligodendroglioma, we analyzed the expression of mRNAs of oligodendrogliomas in Chinese Glioma Genome Atlas (CGGA). We collected 165 CGGA oligodendroglioma mRNA-sequence datasets and divided them into two cohorts. Patients in the two cohorts were further classified into long-survival and short-survival subgroups. The most predictive mRNAs were filtered out of differentially expressed mRNAs (DE mRNAs) between long-survival and short-survival patients in the training cohort by least absolute shrinkage and selection operator (LASSO), and risk scores of patients were calculated. Univariate and multivariate analyses were performed to screen factors associated with survival and establish the prognostic model. qRT-PCR was used to validate the expression differences of mRNAs. A total of 88 DE mRNAs were identified between the long-survival and the short-survival groups in the training cohort. Seven RNAs were selected to calculate risk scores. Univariate analysis showed that risk level, age, and primary-or-recurrent status (PRS) type were statistically correlated with survival and were used as factors to establish a prognostic model for patients with oligodendroglioma. The model showed an optimal predictive accuracy with a C-index of 0.912 (95% CI, 0.679-0.981) and harbored a good agreement between the predictions and observations in both training and validation cohorts. We established a prognostic model based on mRNA-sequence data for patients with oligodendroglioma. The predictive ability of this model was validated in a validation cohort, which demonstrated optimal accuracy. The 7 mRNAs included in the model would help predict the prognosis of patients and guide personalized treatment.

P07.08.B Surgical management of recurrent lower-grade gliomas: analysis of oncological and functional outcomes and associated factors

Abstract Background Presently, there are no clear evidence-based recommendations for the surgical management of progressive or recurrent lower-grade gliomas (LGGs). In our work, we evaluated the oncological (PFS, OS) and functional (neurological, neuropsychological, quality of life evaluation) outcomes of a series of LGGs treated in a 5-year period. The aim was to identify clinical, imaging, and molecular factors, associated with better outcomes, to be implemented in the treatment decision making process. Material and Methods In our retrospective analysis, 738 recurrent LGGs were included (follow-up 7.9 years; IQR:6-9); 550 were surgically treated, 495 with open resection (with brain mapping techniques), and 55 with tumor biopsy (with frameless stereotactic technique). Results Overall, 521 patients (70.6%) recurred. Of those treated with open resection 63.5% relapsed. Tumor progression was histologically confirmed in 72.5% of cases, no valuable tumor (effect of treatment) in 27.5% of cases (particularly in cases previously treated with RT and CHT), histo-molecular conversion (astrocytoma instead of oligodendroglioma diagnosis) in 7.5% of cases, malignant transformation in 38.7% of cases. Among the clinical (patient functional status, previous PFS, previous EOR, previous CHT and duration of CHT, previous RT), imaging (type of recurrence, i.e. typical versus atypical, speed of growth, contrast enhancement), and molecular (IDH, codeletion, ATRX, MGMT, tumor grade, CDNK status) factors analyzed, longest PFS of recurrent tumors was associated with patient functional status, previous PFS, previous EOR, speed of growth (>6 mm/year), atypical type of recurrence, tumor grade, presence of codeletion, and CDNK status. Best functional outcome associated with surgical resection, EOR, and tumor grade; worst functional outcome with RT and malignant transformation. Longest OS associated with previous EOR, surgical resection, tumor grade, presence of co-deletion. Malignant transformation was associated to previous EOR. Among patients submitted solely to tumor biopsy, changes in MGMT methylation status and in IDH status were observed in 65.3% and 5% of cases, respectively. Modification in IDH status was associated with atypical (distant) type of recurrence. New histo-molecular profile helped in the treatment decision making process. Conclusion Surgical resection of recurrent LGGs is associated with longer PFS and OS. Tumor biopsy should be considered, when surgery considered unfeasible, to tailor adjuvant treatment.

A Rare Case of Oligodendroglioma in Sacrococcygeal Mature Teratoma Diagnosed in Preterm Infant

Sacrococcygeal teratoma is the most common congenital tumor in neonates, and is reported in approximately 1/35,000 to 1/40,000 live births. Oligodendroglioma is a rare central nervous system tumor that is usually found in the cerebral hemisphere of young and middle aged adults. When associated with a teratoma, it is mainly identified in ovarian teratoma in adolescents and adults. We describe a rare case of a preterm infant with oligodendroglioma in a mature sacrococcygeal teratoma. The male neonate was born at a gestational age of 30 weeks with a protruding mass in the sacrococcygeal region. Pelvic magnetic resonance imaging showed a sacrococcygeal teratoma of approximately 11 cm comprising fat components and skeletal structure, that extended from the anterior part of the sacrum to the abdominal cavity. Radical resection was performed at 36 days of age. Macroscopically, the resected intra-abdominal mass had the characteristics of a cystic lesion, and the intrapelvic mass was a predominantly solid mixed cystic-solid lesion. Histologically, this solid lesion in the intrapelvic mass was composed of mature glial tissue, which comprised as a proliferation of monotonous cells with small and round nuclei, surrounded by a perinuclear halo (“fried egg” appearance). Additionally, these cells were immunohistochemically positive for glial fibrillary acidic protein. These findings confirmed the diagnosis of oligodendroglioma in sacrococcygeal mature teratoma. After the treatment, no recurrence was observed during the follow-up period, and no additional intervention was required. However, the patient is undergoing treatment for voiding dysfunction caused by a neurogenic bladder.

Can Apparent Diffusion Coefficient Predict the Grade, Genotype, or Proliferation Index of Oligodendrogliomas.

Background:Genetic subsets of oligodendrogliomas (OD) have distinct chromosomal and biophysical profiles. Pretherapeutic tumor grade and genotype analysis is a challenging aspect of management, with 1p/19q codeletion status and grade of oligodendroglioma among the most important considerations for clinical decision making.Methodology:Seventy-three patients with histopathological diagnosis of oligodendroglioma were selected, and their preoperative 1.5T magnetic resonance imaging (MRI) scans were reviewed through parameters including diffusion weighted image, susceptibility-weighted imaging, and apparent diffusion coefficient (ADC). These images were correlated with patients' histopathological and chromosomal testing. Tumor border irregularity, homogeneity, contrast enhancement, and other MRI characteristics were also studied. For analysis, descriptive statistics were generated, and normality was evaluated for ADC value, age, and Ki-67 tumor proliferation index.Objectives:The study aimed to determine the correlation of ADC with Ki-67, grade, and 1p/19q co-deletion in oligodendroglioma at a tertiary care hospital within a low-middle income country.Results:Ki-67 tumor proliferation index was high in 33 tumors. It was found to be statistically significant (P = 0.048) with respect to ADC, showing that 1p/19q co-deleted tumors have a difference in their Ki-67 index. Ki-67 also showed a significant relationship (P < 0.05) with grade of OD. However, there was no statistically significant relationship between 1p19q chromosomal co-deletion and ADC. Linear regression was carried out as the data set was continuous. Univariate analysis showed no significant result with all P values above 0.10.Conclusion:Mean ADC is a viable tool to predict Ki-67 and assist prognostic clinical decisions. However, mean ADC alone cannot predict 1p/19q codeletion and tumor grades in OD. Further supplementation with other radiological modalities may provide greater yield and positive results.

Intracranial myxoid mesenchymal tumour with EWSR1-ATF1 fusion mimicking high grade glioma

Abstract Aims Molecular profiling is increasingly used in the diagnosis of CNS and non-CNS neoplasms. More than a quarter of all soft tissue tumours are characterized by specific recurrent chromosomal translocations which can be used as molecular signatures. With increasing frequency, EWSR1 rearrangements are found on both mesenchymal tumours and primary glial/neuronal tumours. Here we present a case of intracranial myxoid mesenchymal tumour (IMMT), a rare tumour which is becoming more recognised in recent years, affecting mainly children and young adults, and rarely older adults. It can be found in intraaxial and extraaxial location, with frequent dural connection. The tumour is defined by the genetic hallmark of EWSR1-CREB family gene fusion. Including our case, 16 intracranial tumours with this gene fusion have been reported to date. Our goal is to contribute further to the characterisation of the morphological spectrum, fusion partners and biological behaviour of rare EWSR1-CREB (non-ETS)-rearranged tumours of the CNS. Method Case: The patient is a 27 year old woman with a frontal lobe lesion, radiologically described as a tumour with dural attachment. She underwent surgical debulking, and tumour tissue was histologically examined with conventional immunohistochemistry. Additional genetic testing included targeted mutation screening, FISH, EPIC (Illumina BeadChip) methylation array and next generation sequencing. Histology showed a mitotically active neoplasm with relatively uniform cells, round nuclei and oligodendroglioma-like clear cell change, but no myxoid change. Glomeruloid microvascular proliferation and large areas of tumour necrosis were present. Immunohistochemistry was focally positive for GFAP, and negative or normal for synaptophysin, IDH1 R132H mutation, ATRX and p53. The ki-67 index reached ~20%. Sequencing of IDH1 and IDH2 did not reveal rare IDH mutations, and FISH did not show 1p19q codeletion. Testing for BRAF V600 mutation was negative. Results Although the histology initially suggested a diagnosis of oligodendroglioma, the integrated diagnosis was compatible with glioblastoma, IDH wildtype. Methylation array analysis by EPIC array did not result in classification of currently known entities, neither confirming glioblastoma, nor providing a new diagnosis, when analysed on both brain tumour and sarcoma classifier. This suggested a novel tumour entity not yet represented in the classifier algorithm. Additional testing including next generation sequencing revealed EWSR1 gene rearrangement with fusion partner ATF1 (EWSR1-ATF1 fusion). Based on this, the diagnosis was revised to the emerging new entity of ‘intracranial myxoid mesenchymal tumor’ (IMMT) characterised by EWSR1 fusion with members of the cAMP response element binding protein (CREB) family (ATF1, CREB1 and CREM). Subsequent immunohistochemistry demonstrated positive staining for CD99 and EMA but not desmin. The patient underwent various oncological treatments and is recurrence-free 3 years after initial diagnosis. Conclusion Histologically, IMMT demonstrates a spectrum of features that overlaps with other tumours, but often displays circumscribed growth, uniform cellularity, cytoplasmic clearing and variable myxoid change. The clinical behaviour of these tumours is not fully understood, however provisionally considered intermediate grade. EWSR1-CREB family fusion is not specific but shared with a diverse group of extracranial tumours including soft tissue, salivary gland, odontogenic and myoepithelial tumours. Therefore, clinico-radiologico-pathological correlation is essential to achieve the final diagnosis, and ensure the absence of a primary tumour elsewhere. Familiarisation with IMMT, its characteristic genetic profile and its as yet underreported natural course is crucial, as it can clinically mimic other intracranial tumours such as malignant meningioma or glioma but appears to behave less aggressively than high grade glioma. It is also important to further our understanding of its optimal treatment through review of larger case series and global comparison of patient management.

364P Implementation of a comprehensive streamlined next generation sequencing (NGS) test for glioma including detection of the 1p/19q codeletion

In 2016 the World Health Organization updated the classification of central nervous system tumours to incorporate molecular analysis alongside histopathological evaluation. Under the revised system, diagnosis of oligodendroglioma requires presence of both an IDH mutation and codeletion of chromosomal regions 1p and 19q. In 2019, the All Wales Medical Genomics Service (AWMGS) introduced a bespoke multi-gene NGS panel for a range of tumour types, which included 10 genes/regions implicated in the diagnosis, prognosis and treatment of gliomas.

Le diagnostic histo-moléculaire des tumeurs gliales et glioneuronales

While rare compared to extra-cranial neoplasms, glial and glioneuronal tumors are responsible of high morbidity and mortality. In 2016, the World Health Organization introduced histo-molecular ("integrated") diagnostics for central nervous system tumors based on morphology, immunohistochemistry and the presence of key genetic alterations. This combined phenotypic-genotypic classification allows for a more objective diagnostic of brain tumors. The implementation of such a classification in daily practice requires immunohistochemical surrogates to detect common genetic alterations and sometimes expensive and not widely available molecular biology techniques. The first step in brain tumor diagnostics is to inquire about the clinical picture and the imaging findings. When dealing with a glial tumor, the pathologist needs to assess its nature, infiltrative or circumscribed. If the tumor is infiltrative, IDH1/2 genes (prognostic marker) and chromosomes 1p/19q (diagnosis of oligodendroglioma) need to be assessed. If the tumor appears circumscribed, the pathologist should look for a neuronal component associated with the glial component (glioneuronal tumor). A limited immunohistochemistry panel will help distinguish between diffuse glioma (IDH1-R132H, ATRX, p53) and circumscribed glial/glioneuronal tumor (CD34, neuronal markers, BRAF-V600E), and some antibodies may reliably detect genetic alterations (IDH1-R132H, BRAF-V600E and H3-K27M mutations). Chromosomal imbalances (1p/19q codeletion in oligodendroglioma; chromosome 7 gain/chromosome 10 loss and EGFR amplification in glioblastoma) and gene rearrangements (BRAF fusion, FGFR1 fusion) will be identified by molecular biology techniques. The up-coming edition of the WHO classification of the central nervous system tumors will rely more heavily on molecular alterations to accurately diagnose and treat brain tumors.

1p/19q co-deleted fibrillary astrocytomas: Not everything that is co-deleted is an oligodendroglioma

The presence of chromosome 1p/19q co-deletion is one of the hallmark required criteria for the diagnosis of oligodendroglioma, using the 2016 World Health Organization (WHO) Classification of Tumours of the Central Nervous System. Descriptions in the literature of astrocytomas, primarily glioblastomas, demonstrating partial losses on one or the other chromosome have been described. The significance of these small deletions is uncertain. Only rarely have cases of fibrillary astrocytoma been described as having co-deletion, which may potentially cause diagnostic confusion with oligodendroglioma. The goal of this study is to examine a large number of fibrillary astrocytomas to document how often 1p/19q co-deletions are present by Fluorescent In Situ Hybridization (FISH) testing (the testing method of choice in many institutions) and to evaluate what other markers may be helpful in avoiding misdiagnosis.This study is a retrospective evaluation of 359 fibrillary astrocytomas (55 grade II, 62 grade III and 242 grade IV) encountered between June 2016 and June 2019, we identified 11 tumors (3.1%) that had 1p/19q co-deletion by FISH testing. The clinical and pathologic features of these cases were reviewed. The 11 cases with co-deletion included 5 females who ranged in age from 37 to 86 years (median 63 years). Tumors arose in the temporal lobe in 5 patients, frontal lobe in 2, parietal lobe in 2, occipital lobe in 1, and cerebellum in 1. Final diagnoses included glioblastoma in 8 patients, anaplastic astrocytoma in 2, and diffuse astrocytoma in 1. Only 1 case (anaplastic astrocytoma) demonstrated evidence of IDH-1 immunoreactivity; none of the other 10 tumors showed evidence of an IDH1/2 mutation by PCR testing. Four tumors demonstrated p53 immunostaining of 30% or more. ATRX mutation as evidenced by loss of staining was observed in only 2 cases. Evidence of EGFR amplification by FISH testing was noted in 5 cases. Of particular note in the one case that demonstrated both 1p/19q co-deletion and an IDH-1 mutation, LOH testing was done and showed only partial losses on both chromosomes. Additionally, this tumor also demonstrated evidence of ATRX and p53 mutations by immunohistochemistry. In conclusion, co-deletions were noted in a minority of astrocytomas (3.1% of cases in the current study). Only 1 of 11 of these cases also demonstrated evidence of an IDH mutation, potentially raising differential diagnostic confusion with oligodendroglioma. Use of LOH 1p/19q testing, if available, or other markers such as ATRX, p53 and EGFR may be helpful in avoiding misclassification of such tumors as oligodendroglioma.

EPID-14. OCCURRENCE OF SYSTEMIC CANCER IN PATIENTS WITH OLIGODENDROGLIOMAS: POPULATION CHARACTERIZATION AND COMPLICATIONS

Abstract Following clinic observations of patients with the diagnosis of oligodendroglioma and a systemic cancer, a chart review was done to understand the possible complications that a systemic cancer might bring to the treatment of the patient. Inclusion criteria was histological diagnosis of diffuse or anaplastic oligodendroglioma and another non-skin systemic cancer. Exclusion criteria was the diagnosis of genetic syndrome that predispose tumorigenesis. A total of 12 patients and 13 cancers were identified. 1p19q co-delection information was available for all patients except for 2. The most common systemic cancers were breast (46%) and gynecological cancers (16%). Different from CBTRUS data, men were underrepresented, being 31% of the patients, but difference did not reach statistical significance (p =0.08). Regarding age, patients were older than expected (53 + 12 years old, p&lt; 0.0001). Systemic cancer was diagnosed after the oligodendroglioma diagnosis in 54% of the cases. Age at the diagnosis of systemic cancer was 54 + 10 years old. All patients are alive, except for two. Thromboembolism was seen in 25% of the patients (p=0.2 when comparing with literature for oligodendroglioma), and occurred always after the oligodendroglioma diagnosis. Thrombocytopenia was not associated to prior chemotherapy. No deviation of glioma treatment was seen. This chart review of patients with Oligodendroglioma and a systemic cancer identifies that this population is older than expected and thromboembolism rates are similar to the literature. The overrepresentation of women in this cohort represents the profile of systemic cancer that accompanied oligodendrogliomas. It is unclear why breast and other gynecological cancers were the most common. Further studies, likely multicentric due to the rarity of this diagnosis, as further research in large repository data should be performed to confirm this finding.

PATH-58. REAPPRAISAL OF HISTOLOGICAL FEATURES AND MOLECULAR ANALYSIS OF LOWER GRADE GLIOMAS AND ASSOCIATION WITH OVERALL SURVIVALS

Abstract INTRODUCTION Based on WHO 2016 classification of grade II and III glioma (lower grade glioma/LrGG), the pathological diagnosis of oligodendroglioma is associated with IDH mutation status and 1p/19q codeletion. It was reported that the classical oligodendroglioma features closely related to the presence of 1p/19q codeletion. In this study, we compared histology of oligodendroglial features with molecular prognostic factors such as ATRX, TERT, IDH1/2 and copy number aberrations and their relations with patients’ prognoses. METHODS In this study, we analyzed 94 cases of primary LrGG resected in 1990 to 2016 in Keio University Hospital, Japan. Using WHO 2007 classification of LrGG, we re-diagnosed the tumors based on their histological features and compared them to their initial diagnoses (made by the pathologists on the time of resections). The presence of classic for oligodendroglioma (CFO) features were closely documented. ATRX mutation was analyzed by immunohistochemistry. IDH1/2 and TERT mutation status were analyzed using Sanger sequence. Copy number aberrations analyzed using comparative genomic hybridization (CGH). In addition, we analyzed IDH-mut/codeleted tumors with cancer genetic panel. RESULTS Re-diagnosis shown there is a shift of trend toward oligodendroglioma diagnoses from astrocytoma and a trend of change from grade II to grade III. IDH-mut/codel tumors shown no correlation between CFO and molecular prognostic factors nor CNAs but there was correlation between overall survival and molecular factors such as CIC (p= 0.046) and FUBP1(p= 0.03). IDH-mut/non-codel tumors shown no correlation between CFO and overall survival but ATRX and gain of 8q were found to be correlated with pathological diagnosis. CONCLUSION There is a lot of change in histological diagnosis of oligodendroglioma from each eras. IDH-mut/codel tumors shown there is correlation between FUBP1 and CIC with overall survivals. IDH-mut/noncodel tumors shown there is correlation between gain of 8q with overall survivals.

NIMG-32. CHALLENGES OF IMAGING INTERPRETATION TO PREDICT OLIGODENDROGLIOMA GRADE

Abstract BACKGROUND A recent report examining 75 Oligodendrogliomas indicated that specific imaging features may help predict grading and guide target selection for biopsy when resection is not possible. This report attempted to validate these findings in a separate sample and evaluate interrater reliability. METHODS Two Neuro-Oncologists, blinded to radiology report and grading reviewed diagnostic pre-radiation MRI. Imaging features and reviewer interpretations were evaluated included contrast enhancement, necrosis, calcification, and restricted diffusion; examiner concordance is reported. RESULTS Sixty-two patients with diagnosis of Oligodendroglioma (50 WHO grade II, 12 WHO grade III); 54 were molecularly confirmed as IDH-mutant/1p19q co-deleted based on the NOB Natural History Study. Four patients (grade III) were excluded due to lack of imaging studies. Among 58 evaluable patients, their location was frontal (n=32), temporal (n=14), parietal (n=4), occipital (n=1), and multi-lobe (n=11). Extent of resection: gross total 9, subtotal 36, biopsy 17. Partial to extensive contrast enhancement was present in 18/58 patients (6 grade II, 33%; 12 grade III, 67%); Kappa interrater agreement k= 0.37 on grade II and k=0.50 on grade III; extensive enhancement was present in 4/58 (all grade III), k= 0.70. Necrosis noted in 7/58 patients (all grade III), k=0.61. Calcification noted in 7/17 patients reviewed (all grade III), k=1.0; restriction noted in only 2/39 patients reviewed (all grade III), k=1.0. CONCLUSIONS THE presence of extensive enhancement, necrosis, calcification and restricted diffusion were only present in grade III with substantial agreement between readers, but there was lower agreement for partial enhancement. Image reviewers commented on the variability of enhancement intensity in normal structures between scans, likely contributing to this poor concordance. Tumor areas with extensive enhancement and/or necrosis are associated with higher grade and can guide biopsy if resection is not feasible. Discrepancies in imaging interpretation may be ameliorated by implementing a standardized imaging protocol.

430P - Tolerability of PCV in low grade glioma: A real world experience

BackgroundIn the phase III RTOG 9802 trial, median overall survival (OS) increased from 7.8 years with radiotherapy alone to 13.3 years (P = .002) with adjuvant procarbazine, lomustine, and vincristine (PCV) following surgery for low grade glioma. Although the PCV regimen improved survival, there were significant toxicities. We hypothesised more frequent toxicities would be observed in clinical practice. We aimed to identify and quantify toxicities in the real world setting in a National Neuro-Oncology centre. MethodsPatients with low grade glioma who received PCV following radiotherapy from Nov 2014 to Nov 2018 were identified from Institutional databases. Data on toxicities, dose reductions, dose delays and treatment discontinuation were collected from paper and electronic patient records. ResultsA total of 41 patients with low grade glioma were identified. Patients were predominantly male (n=28) and the median age at diagnosis was 41. Of these, 28/41 patients had a diagnosis of oligodendroglioma and 13/41 had astrocytoma. The majority of patients had tumours with favourable molecular features such as IDH mutations (n=38) and 1p19q co deletions (n=23). Only 4 patients completed 6 cycles of chemotherapy without any dose modification or delay. 16 patients completed PCV with dose reductions and dose delays at various levels. The dose intensity was as follows: procarbazine: 69%, lomustine: 71% and vincristine: 68%. Neutropaenia and thrombocytopaenia (table) were the major causes of treatment discontinuation (14/21 patients). Three patients had disease progression during chemotherapy and two patient’s treatment was discontinued due to abnormal LFTs. Three patients opted not to continue chemo due to intolerability in context of grade 3 to 4 fatigue and GI symptoms. At median follow up of 17 months, 9/41 patients have had disease progression.Table: 430PTable: 430POur Study %RTOG 9802%Patient Completed PCV4856Median Number of Cycles Completed33.5ThrombocytopeniaG2 (50-75)719G3 (25-50)1718G4 (<25)20NeutropeniaG2(1-1.5)879G3(0.5-0.1)3135G4(<0.5)78 ConclusionsFrequent toxicities are observed with PCV in clinical practice. Our data suggest it might be preferable to adjust doses from the start of chemotherapy to improve tolerability. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

P04.14 Loss of oligodendroglial features at recurrence in five diffuse low-grade glioma patients treated with repeated surgery

Abstract BACKGROUND Diffuse low-grade gliomas (DLGG) are characterized by a continuous growth and an unavoidable anaplastic transformation. IDH mutation and 1p19q codeletion have been integrated to the 2016 WHO classification to define the oligodendroglioma entity. Whenever feasible, neurosurgical resection is the first treatment option. At recurrence, a second surgical resection is proposed in selected cases. The consistency of molecular patterns (IDH mutation, 1p19q codeletion) at recurrence has been poorly studied in DLGG. MATERIAL AND METHODS We conducted a retrospective study on consecutive DLGG patients treated at our institution with repeated surgery (2006–2017). Clinical and biological data were collected for both the initial and subsequent surgery. Additional immunohistochemistry (including tumor morphology, ATRX and p53) and genetic analyses (TERT promoter mutation, CIC mutation, CGHa) were also performed on tumors with joint loss of IDH mutation and of 1p19q codeletion at recurrence. RESULTS A total of 71 patients were identified. Analyses were carried out on 56 patients (molecular data missing: n=15). Nine patients (16.1%) presented with a loss of their IDH mutation at second surgery. Five of them (8.9%) had an additional loss of their 1p19q codeletion. These five cases (3 men, median age 36.6 years) were all treated with surgery as the first oncological treatment. The first surgery revealed in all cases tumors with morphological oligodendroglial features, IDH mutation and 1p19q codeletion. Further molecular analysis strengthened the diagnosis of oligodendroglioma (TERT promoter and CIC mutations, no ATRX loss, no expression of p53). Four patients were followed-up after the first surgery; one patient received Temozolomide 14 months later due to FLAIR tumor volume growth. Because of the regrowth of the residual FLAIR tumor volume, a second surgery was performed in all patients, after a median time of 38.9 months. The morphological oligodendroglial features were lost, and the genetic analyses revealed in all cases no IDH mutation, no 1p19q codeletion, no ATRX loss and no expression of p53. No evidence of anaplasia was found histologically or by CGHa analysis in these recurrent tumors. CONCLUSION We describe five DLGG patients with a shared histo-molecular evolution characterized by the loss of the initial IDH mutation and of oligodendroglial features at second surgery. While rare, this possible evolution must be acknowledged as it can impact the subsequent therapeutic strategy. This observation is the first of a loss of founder alterations in DLGG genesis (i.e. IDH mutation and 1p19q codeletion); the involved mechanism likely differs from the previously described oligoclonal selection caused by spontaneous tumor genetic drift and/or pressure of chemotherapy, and could be linked with the Darwinian selection of a subpopulation of tumor cells after the first surgery.

The Applicability of Haarlem Integrated Diagnostic System in Diffuse Glial Tumors and Molecular Methods Affecting Prognosis

Background:With the help of genetic studies, it is possible to obtain information about diagnosis and prognosis of glial tumors.Aims:To categorize the cases according to the new World Health Organization Central Nervous System classification by reconsidering the histologic features of oligodendrogliomas, astrocytomas and oligoastrocytomas. We also evaluated whether these genetic features have prognostic significance.Study Design:Diagnostic accuracy study.Methods:Between the years 2011 and 2016, 60 gliomas were examined. Archival material from the Department of Pathology was used for histopathological, immunohistochemical, and molecular analyses. All the cases were classified and graded according to the new 2016 World Health Organization criteria. IDH1 (R132H), alpha thalassemia/mental retardation syndrome, and p53 antibodies were applied immunohistochemically. The 1p/19q status and platelet-derived growth factor receptor-α/CEP4 amplification were evaluated by fluorescence in situ hybridization. After molecular tests, if the diagnosis of oligodendroglioma or astrocytoma is not diagnosed, case should be diagnosed as oligoastrocytoma. Sensitivity, specificity, positive predictive level, negative predictive level, and accuracy rate were evaluated in accordance with the specified threshold levels.Results:Except for 1 case (3.7%), all cases of grade 2 and grade 3 oligoastrocytoma were diagnosed with astrocytoma or oligodendroglioma without any change of grade. Except for 2 case (6.8%), all cases of grade 2 and grade 3 oligodendroglioma were diagnosed oligodendroglioma. All astrocytomas (100%) were given same diagnosis. There is no specific or sensitive test for the diagnosis of oligoastrocytoma. However, 1p/19q codeletion was spesific (100%) and sensitive (100%) for oligodendroglioma. ATRX and p53 mutation showed high spesificity (100% and 95.1% respectively) for diagnosing astrocytoma. Platelet-derived growth factor receptor-α/ CEP4 was not detected in any of the cases. There was association between isocitrate dehydrogenase mutation and 1p/19q loss with longer survival (respectively p=0.147 and p=0.178).Conclusion:In grade 2 and grade 3 glial tumors, pathological diagnosis is not possible only by histological examination. Overall, there was a diagnosis change in 28 cases (46.6%). Especially in cases of oligoastrocytoma, the diagnosis is changed by molecular tests.

Diagnóstico molecular de pérdida de heterocigosidad para 1p/19q en tumores oligodendrogliales por PCR multiplex en el Instituto Nacional de Enfermedades Neoplásicas, Lima- Perú.

La pérdida de heterocigosidad 1p/19q tiene valor pronóstico clínico y está fuertemente asociada con características histológicas clásicas de oligodendroglioma. Objetivos: El presente artículo, propone un método molecular para determinar la pérdida de heterocigosidad (LOH por sus siglas en inglés) para 1p/19q y permitir la clasificación de tumores oligodendrogliales. Material y Métodos: Se utilizaron muestras en fresco del Banco de Tejidos Tumorales del Instituto Nacional de Enfermedades Neioplásicas (INEN) y biopsias de tejido embebido en parafina de tumores oligodendrogliales, con diagnóstico patológico de oligodendroglioma y oligoastrocitoma. Los métodos propuestos son PCR Multiplex y amplificación de fragmentos por electroforesis capilar de los productos de PCR, y fueron aplicados a un total de 39 casos que presentaban grado histológico II y III. Resultados: Los resultados obtenidos permiten una adecuada clasificación molecular de los tumores oligodendrogliales.

Oligodendroglioma with Sarcomatous Transformation: Case Report and Literature Review

AbstractOligodendrogliomas are infiltrative tumors of the central nervous system considered to be morphologically stable and to offer a better prognosis. Here, we describe the case of a 36-year-old man with an initial diagnosis of oligodendroglioma, World Health Organization (WHO) grade II, who presented transformation to a sarcomatous form, while maintaining the oligodendroglial component as well as the genetic characteristics of the initial tumor without having undergone any complementary treatments previously. Despite the favorable genetic characteristics, the tumor presented poor response to complementary treatments, and rapid progression, including spinal metastasis.

Assessment of the impact of glioma diagnostic reclassification following the new 2016 WHO classification on a series of cases.

The aim of this project is to assess diagnostic reclassification based on molecular data over morphology in a series of glial tumours since the introduction of the 2016 WHO classification of brain tumours. Retrospective review of glial tumours (oligodendrogliomas and astrocytomas) treated in our centre between January 2012 and June 2016 in which a review of diagnosis was performed when molecular studies were added. Statistical analysis included evaluation of variables of epidemiology, morphology and molecular data (mainly IDH mutation and 1p19q codeletion), diagnostic changes after new classification was considered, and clinical impact in cases of diagnostic reclassification. From a total of 147 glial tumours reviewed in our centre, molecular diagnosis was obtained in 74 cases (50.3%). Initial diagnosis changed in 23 cases (31%), and 20 (87%) of them had a prior histological diagnosis of oligodendroglioma (69.6% grade ii and 17.4% grade iii). Only 3 of these 23 cases diagnosis changed from astrocytoma to oligodendroglioma. Among reclassified tumours, there was a common molecular pattern, as findings showed mutant IDH in 16 cases (69.6%) and no codeletion in 20 cases (87%). According to the cell of origin, of the whole group of 27 oligodendrogliomas in our series (reclassified and non-reclassifed), 20 cases (74%) became astrocytomas, despite typical oligodendroglial morphology, due to absence of 1p19q codeletion. There was a trend for diagnosis reclassification in younger patients (<40 years), P=.065, mainly in those with a prior diagnosis of oligodendroglioma, with no statistical differences based on gender or clinical data. Besides, reclassification was more common among tumours with mutant IDH (69.6%), P=.003, than those with wild type IDH. In terms of survival, despite receiving different treatments, no significant changes were detected between reclassified and non-reclassified tumours after a mean follow-up of 16 months, partly related to lower grade of these lesions. Within the spectrum of the glial tumours treated in our institution, this new classification including molecular genetics over morphological data has provided marked diagnostic changes. These changes appear mainly in tumours previously diagnosed as oligodendrogliomas and in younger patients, with molecular patterns of mutant IDH and 1p19q codeletion. Although diagnosis reclassification may affect clinic, prognosis or therapeutic management of these tumours, deeper and prospective studies on these specific aspects are needed.