Page 12 - Molecular features of low-grade developmental brain tumours

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constitutive activation of the mechanistic target of rapamycin complex (mTOR) pathway 3,23-26. Although, some genetic alterations are enriched in certain tumour entities they are almost never exclusive to one entity alone. For example, the BRAFV600E mutation is a common genetic driver in GGs (18-56%) and can together with tyrosine kinase activating FGFR1 gene mutations be helpful in distinguishing GGs from DNTs 13,15,16,27,28. However, BRAF mutations also occur in other tumour entities including DNTs, making it difficult to distinguish between GGs and DNTs based only on the presence of these mutations alone 14,17,29. Therefore, an integrated diagnosis combining both histological and molecular features
based on genetic and genomic hallmarks is needed 3,30,31.
Figure 1. Histopathology of a FGFR1 mutated DNT and a BRAFV600E mutated GG. a. HE staining of DNT showing a typical glioneuronal element, with floating neurons (arrows) surrounded by a prominent population of oligodendroglia-like cells (OLC) (insert: higher magnification showing floating neurons). b. NeuN staining showing the neuronal component of DNT. c. HE staining of GG showing the mixture of neuronal cells (dysmorphic neurons), lacking uniform orientation (arrows and insert) and glial cells. d. NeuN staining indicating the neuronal component (nuclear staining, arrows) of GG (insert: higher magnification showing MAP2 positivity indicating the neuronal component in dysmorphic neuron). e. GFAP staining indicating the astroglial tumour component in GG (arrowheads indicates micro-calcifications). f. CD34 staining showing positive cell aggregates infiltrated into adjacent neocortex in GG (insert: higher magnification showing cells with intense CD34 immunoreactivity). Scale bar in a: a: 160 μm; b, c: 80 μm; d, e: 40 μm;
f: 3 mm.
Low-grade epilepsy-associated tumours
Although it is not unusual for brain tumours to clinically manifest with seizures, low-grade epilepsy-associated tumours (LEATs) are generally slowly growing tumours that most often arise in younger age groups with a mean age of seizure onset at 16.5 years 6,32. LEATs were first introduced by Luyken et al. as tumours that were commonly encountered in patients that underwent surgery, who had been investigated and treated for drug-resistant seizure episodes for 2 years or longer 33. The most commonly found tumours that are characterized as LEATs are DNTs and GGs. Additionally, several other low-grade tumours
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