The histomolecular criteria established for adult anaplastic pilocytic astrocytoma are not applicable to the pediatric population - Archive ouverte HAL
Article Dans Une Revue Acta Neuropathologica Année : 2019

The histomolecular criteria established for adult anaplastic pilocytic astrocytoma are not applicable to the pediatric population

Frederic Fina
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Christelle Dufour
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Fabrice Chretien
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Pascale Varlet

Résumé

Pilocytic astrocytoma (PA) is the most common pediatric glioma, arising from a single driver MAPK pathway alteration. Classified as a grade I tumor according to the 2016 WHO classification, prognosis is excellent with a 10-year survival rate > 95% after surgery. However, rare cases present with anaplastic features, including an unexpected high mitotic/proliferative index, thus posing a diagnostic and therapeutic challenge. Based on small histomolecular series and case reports, such tumors arising at the time of diagnosis or recurrence have been designated by many names including pilocytic astrocytoma with anaplastic features (PAAF). Recent DNA methylation-profiling studies performed mainly on adult cases have revealed that PAAF exhibit a specific methylation signature, thus constituting a distinct methylation class from typical PA [methylation class anaplastic astrocytoma with piloid features-(MC-AAP)]. However, the diagnostic and prognostic significance of MC-AAP remains to be determined in children. We performed an integrative work on the largest pediatric cohort of PAAF, defined according to strict criteria: morphology compatible with the diagnosis of PA, with or without necrosis, ≥ 4 mitoses for 2.3 mm2, and MAPK pathway alteration. We subjected 31 tumors to clinical, imaging, morphological and molecular analyses, including DNA methylation profiling. We identified only one tumor belonging to the MC-AAP (3%), the others exhibiting a methylation profile typical for PA (77%), IDH-wild-type glioblastoma (7%), and diffuse leptomeningeal glioneuronal tumor (3%), while three cases (10%) did not match to a known DNA methylation class. No significant outcome differences were observed between PAAF with necrosis versus no necrosis (p = 0.07), or with 4-6 mitoses versus 7 or more mitoses (p = 0.857). Our findings argue that the diagnostic histomolecular criteria established for anaplasia in adult PA are not of diagnostic or prognostic value in a pediatric setting. Further extensive and comprehensive integrative studies are necessary to accurately define this exceptional entity in children.
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Dates et versions

hal-02441067 , version 2 (11-10-2023)
hal-02441067 , version 1 (21-03-2024)

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Albane Gareton, Arnault Tauziède-Espariat, Volodia Dangouloff-Ros, Alexandre Roux, Raphaël Saffroy, et al.. The histomolecular criteria established for adult anaplastic pilocytic astrocytoma are not applicable to the pediatric population. Acta Neuropathologica, 2019, 139 (2), pp.287-303. ⟨10.1007/s00401-019-02088-8⟩. ⟨hal-02441067v2⟩
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