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Pleomorphic xanthoastrocytoma is a heterogeneous entity with pTERT mutations prognosticating shorter survival.


ABSTRACT: Pleomorphic xanthoastrocytoma (PXA) in its classic manifestation exhibits distinct morphological features and is assigned to CNS WHO grade 2 or grade 3. Distinction from glioblastoma variants and lower grade glial and glioneuronal tumors is a common diagnostic challenge. We compared a morphologically defined set of PXA (histPXA) with an independent set, defined by DNA methylation analysis (mcPXA). HistPXA encompassed 144 tumors all subjected to DNA methylation array analysis. Sixty-two histPXA matched to the methylation class mcPXA. These were combined with the cases that showed the mcPXA signature but had received a histopathological diagnosis other than PXA. This cohort constituted a set of 220 mcPXA. Molecular and clinical parameters were analyzed in these groups. Morphological parameters were analyzed in a subset of tumors with FFPE tissue available. HistPXA revealed considerable heterogeneity in regard to methylation classes, with methylation classes glioblastoma and ganglioglioma being the most frequent mismatches. Similarly, the mcPXA cohort contained tumors of diverse histological diagnoses, with glioblastoma constituting the most frequent mismatch. Subsequent analyses demonstrated the presence of canonical pTERT mutations to be associated with unfavorable prognosis among mcPXA. Based on these data, we consider the tumor type PXA to be histologically more varied than previously assumed. Histological approach to diagnosis will predominantly identify cases with the established archetypical morphology. DNA methylation analysis includes additional tumors in the tumor class PXA that share similar DNA methylation profile but lack the typical morphology of a PXA. DNA methylation analysis also assist in separating other tumor types with morphologic overlap to PXA. Our data suggest the presence of canonical pTERT mutations as a robust indicator for poor prognosis in methylation class PXA.

SUBMITTER: Ebrahimi A 

PROVIDER: S-EPMC8751269 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Pleomorphic xanthoastrocytoma is a heterogeneous entity with pTERT mutations prognosticating shorter survival.

Ebrahimi Azadeh A   Korshunov Andrey A   Reifenberger Guido G   Capper David D   Felsberg Joerg J   Trisolini Elena E   Pollo Bianca B   Calatozzolo Chiara C   Prinz Marco M   Staszewski Ori O   Schweizer Leonille L   Schittenhelm Jens J   Harter Patrick N PN   Paulus Werner W   Thomas Christian C   Kohlhof-Meinecke Patricia P   Seiz-Rosenhagen Marcel M   Milde Till T   Casalini Belén M BM   Suwala Abigail A   Wefers Annika K AK   Reinhardt Annekathrin A   Sievers Philipp P   Kramm Christof M CM   Etminam Nima N   Unterberg Andreas A   Wick Wolfgang W   Herold-Mende Christel C   Sturm Dominik D   Pfister Stefan M SM   Sill Martin M   Jones David T W DTW   Schrimpf Daniel D   Reuss David E DE   Aldape Ken K   Abdullaev Zied Z   Sahm Felix F   von Deimling Andreas A   Stichel Damian D  

Acta neuropathologica communications 20220110 1


Pleomorphic xanthoastrocytoma (PXA) in its classic manifestation exhibits distinct morphological features and is assigned to CNS WHO grade 2 or grade 3. Distinction from glioblastoma variants and lower grade glial and glioneuronal tumors is a common diagnostic challenge. We compared a morphologically defined set of PXA (histPXA) with an independent set, defined by DNA methylation analysis (mcPXA). HistPXA encompassed 144 tumors all subjected to DNA methylation array analysis. Sixty-two histPXA m  ...[more]

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