One tumour was composed of cells with either an oligodendroglial or an astrocytic phenotype. Perivascular collections of
lymphocytes, eosinophilic granular bodies and Rosenthal fibres were also noted in this case, but the tumour contained neither piloid cells nor ganglion cells. A PLX-4720 supplier delicate branching vasculature of fine capillaries characterized many areas in all tumours, and hyalinized vessels were present in one case. High-grade features including mitotic activity, microvascular proliferation and necrosis were not identified. In all cases, many tumour cells demonstrated immunoreactivities for glial fibrillary acidic protein (GFAP) and S-100, but there was no immunoreactivity for synaptophysin. Neurofilament protein (NFP)-immunopositive axon twigs were variably present between tumour cells, but were generally sparse, indicative of the non-infiltrative nature of BIBW2992 nmr these tumours. Ki-67 immunolabelling was very low in all four cases. There was no immunoreactivity for the IDH1:p.R132H mutant gene product or for MYB. FISH detected no copy number alterations at the BRAF,
MYB or CDKN2A loci. One tumour harboured a BRAF:p.V600E mutation. While microscopic dystrophic calcification is commonly seen in diverse pathologies of the CNS, including LGGs, dense widespread macroscopic calcification is rare [7]. Reports of this phenomenon document its presence in association with several types of glioma: intraventricular pilocytic astrocytoma [1, 4],
diffuse astrocytomas of cerebellum [6], medial temporal lobe [3] and brain stem [5], and grade II ependymomas [2, 8]. Tumours in our series of massively calcified LGGs have architectural and cytological features that are not readily aligned with those of pilocytic astrocytomas, diffuse LGGs or uncommon astrocytomas, such as the pleomorphic xanthoastrocytoma. They tend to be circumscribed, without the infiltrative behaviour of diffuse LGGs, yet have a cytology that is not typical of a pilocytic astrocytoma. This idiosyncratic morphology also characterized three massively calcified astrocytomas from the International Society of Pediatric Oncology (SIOP) LGG1 tumour series [9], which was reviewed by one Tenofovir clinical trial of our authorship (D.W.E.). While other reported cases appear to be more readily interpreted as pilocytic [1, 4] or diffuse astrocytomas [3, 5, 6] or ependymomas [2, 8], we sought to address the difficulties with classification in our series utilizing molecular analysis. One tumour harboured a BRAF:p.V600E mutation, which is found in up to 23% of diffuse astrocytomas and 9% of pilocytic astrocytomas [10, 11], although it is more frequent in pleomorphic xanthoastrocytomas (65–75%) and gangliogliomas (15–25%) [10, 11]. Otherwise, no tumour demonstrated an IDH1:p.