L P Priesterbach-Ackley1, H B Boldt2,3, J K Petersen2,3, N Bervoets1, D Scheie4, B P Ulhøi5, M Gardberg6, T Brännström7, S H Torp8, E Aronica9, B Küsters10, W F A den Dunnen11, F Y F L de Vos12, P Wesseling13,14, W W J de Leng1, B W Kristensen2,3. 1. Department of Pathology, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands. 2. Department of Pathology, Odense University Hospital, Odense, Denmark. 3. Research Unit of Pathology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark. 4. Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 5. Department of Pathology, Aarhus University Hospital, Aarhus, Denmark. 6. Department of Pathology, Turku University Hospital and Institute of Biomedicine, University of Turku, Turku, Finland. 7. Department of Pathology, Norrlands University Hospital, Umeå, Sweden. 8. Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. 9. Department of Neuropathology, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands. 10. Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands. 11. Department of Pathology, University Hospital, Groningen, The Netherlands. 12. Department of Medical Oncology, University Medical Center Utrecht, The Netherlands. 13. Princess Máxima Centre for Paediatric Oncology, Utrecht, The Netherlands. 14. Department of Pathology, Amsterdam University Medical Centres/VU Medical Centre, Amsterdam, The Netherlands.
Abstract
AIMS: Methylation profiling (MP) is increasingly incorporated in the diagnostic process of central nervous system (CNS) tumours at our centres in The Netherlands and Scandinavia. We aimed to identify the benefits and challenges of MP as a support tool for CNS tumour diagnostics. METHODS: 502 CNS tumour samples were analysed using (850k) MP. Profiles were matched with the DKFZ/Heidelberg CNS Tumour Classifier. For each case, the final pathological diagnosis was compared to the diagnosis before MP. RESULTS: In 54.4% (273/502) of all analysed cases, the suggested methylation class (calibrated score ≥0.9) corresponded with the initial pathological diagnosis. The diagnosis of 24.5% of these cases (67/273) was more refined after incorporation of the MP result. In 9.8% of cases (49/502), the MP result led to a new diagnosis, resulting in an altered WHO grade in 71.4% of these cases (35/49). In 1% of cases (5/502), the suggested class based on MP was initially disregarded/interpreted as misleading, but in retrospect the MP result predicted the right diagnosis for 3 of these cases. In 6 cases, the suggested class was interpreted as 'discrepant but non-contributory'. The remaining 33.7% of cases (169/502) had a calibrated score <0.9, including 7.8% (39/502) for which no class indication was given at all (calibrated score <0.3). CONCLUSIONS: MP is a powerful tool to confirm and fine-tune the pathological diagnosis of CNS tumours, and to avoid misdiagnoses. However, it is crucial to interpret the results in the context of clinical, radiological, histopathological and other molecular information. This article is protected by copyright. All rights reserved.
AIMS: Methylation profiling (MP) is increasingly incorporated in the diagnostic process of central nervous system (CNS) tumours at our centres in The Netherlands and Scandinavia. We aimed to identify the benefits and challenges of MP as a support tool for CNS tumour diagnostics. METHODS: 502 CNS tumour samples were analysed using (850k) MP. Profiles were matched with the DKFZ/Heidelberg CNS Tumour Classifier. For each case, the final pathological diagnosis was compared to the diagnosis before MP. RESULTS: In 54.4% (273/502) of all analysed cases, the suggested methylation class (calibrated score ≥0.9) corresponded with the initial pathological diagnosis. The diagnosis of 24.5% of these cases (67/273) was more refined after incorporation of the MP result. In 9.8% of cases (49/502), the MP result led to a new diagnosis, resulting in an altered WHO grade in 71.4% of these cases (35/49). In 1% of cases (5/502), the suggested class based on MP was initially disregarded/interpreted as misleading, but in retrospect the MP result predicted the right diagnosis for 3 of these cases. In 6 cases, the suggested class was interpreted as 'discrepant but non-contributory'. The remaining 33.7% of cases (169/502) had a calibrated score <0.9, including 7.8% (39/502) for which no class indication was given at all (calibrated score <0.3). CONCLUSIONS:MP is a powerful tool to confirm and fine-tune the pathological diagnosis of CNS tumours, and to avoid misdiagnoses. However, it is crucial to interpret the results in the context of clinical, radiological, histopathological and other molecular information. This article is protected by copyright. All rights reserved.
Entities:
Keywords:
central nervous system tumours; diagnostics; methylation profiling
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