Pilocytic astrocytoma vs. ganglioglioma: Progression vs. misdiagnosis, and implications in BRAF testing

Ganglioglioma (GG) is a mixed glio-neuronal tumour, comprised of a neoplastic glial component and dysplastic ganglion cells. GG is a tumour of unclear histogenesis; previous studies examining BRAF mutations and chromosome imprinting has provided evidence that both the neuronal and glial components likely arise from a common precursor. Both p.V600E mutation and KIAA1549-BRAF fusion have been described in pilocytic astrocytoma (PA) and GG, but they differ with regards to the rates of different BRAF alterations, and careful histological examination is an important component of patho-molecular correlations. More recently, cases of PA with gangliocytic differentiation (PA-GD) have been described, and these cases are thus far restricted to those with the KIAA1549-BRAF fusion. Here, we describe three cases of GGs in patients with history of previously diagnosed PAs. The cases differ with respect to the chronologic intervals between the PA and the GG diagnoses. In two of the cases, where the PA-GG diagnostic intervals are less than ten years, pathological review revealed the older specimens to have been misdiagnosed as PAs. In the third case, where the interval spanned multiple decades, the GG was found to be positive for both BRAF p.V600E immunohistochemistry (IHC) and for the KIAA1549-BRAF fusion. Molecular study for the BRAF p.V600E mutation was negative, proving the IHC result to be a false-positive. Our case demonstrates that cases of GG can harbour the KIAA1549-BRAF fusion, even with positive BRAF p.V600E IHC results, and the case highlights a diagnostic challenge that may be encountered.