- 多中心 20 例 DNA 甲基化聚类支持 HPAP/GPAP：局限型 IDH 野生型胶质瘤，GFAP/OLIG2/CD34，常伴 MAPK 相关突变。
- 诊断中位年龄 37 岁；估计 10 年生存率 85%；CDKN2A 纯合缺失提示更侵袭。
- 作者建议命名 GPAP，暂定 2–3 级谱系；约 1/4 有胚系易感变异——Wiley OA 全文对本站出口 Cloudflare，本稿为摘要。
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摘要
中枢神经系统肿瘤的 DNA 甲基化谱分析促使识别出 HPAP（具多形性与假乳头特征的高级别胶质瘤）这一近期提出的实体：形态学多变，反复出现 MAP 激酶通路激活事件，生存期长于胶质母细胞瘤。我们旨在独立验证并进一步刻画该实体。我们收集多中心、形态学符合 HPAP 的胶质瘤队列，对其 DNA 甲基化谱进行 t-SNE 降维，并回顾临床、影像、组织学与分子资料。共鉴定出 20 例与既往报道的 HPAP 病例聚类在一起的肿瘤。诊断时中位年龄为 37 岁。影像上表现为膨胀性病变，强化不均，常伴囊肿。组织学上边界清楚，乳头状与多形性特征程度不一。7 例可见明显侵袭性组织学表现。免疫染色显示表达 GFAP、OLIG2 和 CD34。所有病例均为 IDH1/2 野生型，且 pMGMT 未甲基化。反复突变的基因包括 TP53、ATRX、RB1 和 BRAF。5 例患者存在与遗传性肿瘤易感综合征相关基因的胚系致病性变异（MLH1、BRCA2、CHEK2、NF2、RB1）。所有患者均接受手术切除，但后续处理不一。估计 10 年生存率为 85%。CDKN2A 纯合性缺失似乎可识别侵袭性更强的肿瘤。总之，我们的资料提示存在一类边界清楚、即使可出现高级别组织学表现仍具长期生存的新型胶质瘤实体；我们建议命名为「具多形性与假乳头特征的胶质瘤」（Gliomas with pleomorphic and pseudopapillary features），谱系涵盖暂定 2 级与 3 级。正确识别有助于指导治疗选择。
- Multicenter cohort (n=20) validates HPAP/GPAP as circumscribed IDH-wildtype gliomas with GFAP/OLIG2/CD34 and recurrent MAPK-related mutations.
- Median age 37 years; estimated 10-year survival 85%; CDKN2A homozygous deletion may mark more aggressive cases.
- Authors propose the GPAP name with provisional grade 2–3; ~1/4 had germline predisposition variants. Wiley OA full text blocked by Cloudflare from this egress — abstract only.
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Abstract
DNA methylation profiling of CNS tumors led to the identification of HPAP (high-grade glioma with pleomorphic and pseudopapillary features), a recently proposed entity with variable morphology, recurrent MAP-kinase pathway activating events, and longer survival compared to glioblastoma. We aimed to independently validate and further characterize this entity. We retrieved a multicentric cohort of gliomas compatible with HPAP and performed t-SNE dimensionality reduction on their DNA methylation profile. Clinical, radiological, histological, and molecular data were reviewed. Twenty tumors clustering with previously reported HPAP cases were identified. Median age at diagnosis was 37 years. Radiologically, the tumors appeared as expansive lesions with heterogeneous enhancement and frequent cysts. Histologically, they were well-circumscribed, with papillary and pleomorphic features variably present. Marked histological signs of aggressivity were present in seven. Immunostainings showed expression of GFAP, OLIG2, and CD34. All cases were IDH1/2 wildtype and pMGMT unmethylated. Recurrently mutated genes included TP53, ATRX, RB1, and BRAF. Five patients had germline pathogenic variants in genes associated with hereditary tumor predisposition syndromes (MLH1, BRCA2, CHEK2, NF2, RB1). All patients underwent surgical resection, but subsequent management was heterogeneous. Ten-year estimated survival was 85%. CDKN2A homozygous deletion seemed to identify more aggressive tumors. In conclusion, our data suggest the existence of a novel entity of circumscribed gliomas with long-term survival despite possible high-grade histological presentation, for which we propose the nomenclature "Gliomas with pleomorphic and pseudopapillary features" with a spectrum encompassing provisory grade 2 and 3. A proper identification could guide treatment choices.