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.

中文翻译：

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为成人间变性毛细胞星形细胞瘤建立的组织分子标准不适用于儿科人群。

上皮星形细胞瘤（PA）是最常见的小儿神经胶质瘤，由单个驱动程序MAPK途径改变引起。根据2016年WHO分类分类为I级肿瘤，预后良好，手术后10年生存率> 95％。然而，极少数病例表现出变性的特征，包括意想不到的高有丝分裂/增殖指数，因此对诊断和治疗提出了挑战。基于小的组织分子系列和病例报道，在诊断或复发时出现的此类肿瘤已被许多名称指定，包括具有变性特征的毛细胞星形细胞瘤（PAAF）。最近主要针对成年病例进行的DNA甲基化分析研究表明，PAAF表现出特定的甲基化特征，因此，与典型的PA [具有piloid特征的甲基化类间变性星形细胞瘤-（MC-AAP）]构成了截然不同的甲基化类别。然而，MC-AAP在儿童中的诊断和预后意义仍有待确定。我们根据严格的标准对最大的PAAF小儿队列进行了综合研究：形态与PA的诊断兼容，伴或不伴坏死，≥4个有丝分裂的2.3 mm2，以及MAPK通路改变。我们对31种肿瘤进行了临床，影像学，形态学和分子分析，包括DNA甲基化分析。我们仅发现了一种属于MC-AAP的肿瘤（3％），其他表现出典型的PA甲基化分布（77％），IDH野生型胶质母细胞瘤（7％）和弥漫性软脑膜神经胶质神经胶质瘤（3％）。 ，3例（10％）与已知的DNA甲基化类别不匹配。在有坏死与无坏死的PAAF之间（p = 0.07），或有4-6个有丝分裂的PAAF与有7个或更多有丝分裂的PAAF之间，未观察到明显的结果差异（p = 0.457）。我们的发现认为，在成年PA中为发育不全建立的诊断性组织分子标准在儿科环境中没有诊断或预后价值。为了准确地定义儿童中这种特殊的实体，有必要进行进一步的广泛而综合的研究。我们的发现认为，在成年PA中为发育不全建立的诊断性组织分子标准在儿科环境中没有诊断或预后价值。为了准确地定义儿童中这种特殊的实体，需要进行进一步的广泛而综合的综合研究。我们的发现认为，在成年PA中为发育不全建立的诊断性组织分子标准在儿科环境中没有诊断或预后价值。为了准确地定义儿童中这种特殊的实体，有必要进行进一步的广泛而综合的研究。