DNA methylation-based classification of glioneuronal tumours synergises with histology and radiology to refine accurate molecular stratification

AIMS: Glioneuronal tumours (GNTs) are poorly distinguished by their histology and lack robust diagnostic indicators. Previously, we showed that common GNTs comprise two molecularly distinct groups, correlating poorly with histology. To refine diagnosis, we constructed a methylation-based model for GNT classification, subsequently evaluating standards for molecular stratification by methylation, histology and radiology. METHODS: We comprehensively analysed methylation, radiology and histology for 83 GNT samples: a training cohort of 49, previously classified into molecularly defined groups by genomic profiles, plus a validation cohort of 34. We identified histological and radiological correlates to molecular classification and constructed a methylation-based support vector machine (SVM) model for prediction. Subsequently, we contrasted methylation, radiological and histological classifications in validation GNTs. RESULTS: By methylation clustering, all training and 23/34 validation GNTs segregated into two groups, the remaining 11 clustering alongside control cortex. Histological review identified prominent astrocytic/oligodendrocyte-like components, dysplastic neurons, and a specific glioneuronal element as discriminators between groups. However, these were present in only a subset of tumours. Radiological review identified location, margin definition, enhancement, and T2 FLAIR-rim sign as discriminators. When validation GNTs were classified by SVM, 22/23 classified correctly, comparing favourably against histology and radiology which resolved 17/22 and 15/21 respectively where data were available for comparison. CONCLUSIONS: Diagnostic criteria inadequately reflect glioneuronal tumour biology, leaving a proportion unresolvable. In the largest cohort of molecularly defined glioneuronal tumours, we develop molecular, histological, and radiological approaches for biologically meaningful classification and demonstrate almost all cases are resolvable, emphasising the importance of an integrated diagnostic approach

Congenital lower brachial plexus palsy due to cervical ribs

Congenital brachial plexus palsy (CBPP) usually occurs secondarily to intrapartum trauma, but this is not always the case. Cervical ribs have previously been reported to increase the risk of CBPP in association with birth trauma. We report the cases of two children (one female, one male) with congenital lower brachial plexus palsy in whom the presence of non-ossified cervical ribs was the only identified risk factor. In the female child magnetic resonance imaging (MRI) of the brain, spinal cord, and brachial plexus revealed no abnormality except for the presence of bilateral cervical ribs at the level of the seventh cervical (C7) vertebra. Chest radiography was normal, which suggested that the cervical ribs identified on the MRI were fibrous bands or cartilaginous ribs rather than ossified ribs. In the male child, MRI of the spine and brachial plexus was normal but he was noted to have bilateral cervical ribs at C7. These were not identifiable on chest radiography and, therefore, are likely to reflect fibrous bands or cartilaginous ribs