Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Pathology, Staten Island University Hospital, New York, NY, USA.
Mod Pathol. 2020 Jul;33(7):1298-1306. doi: 10.1038/s41379-020-0491-6. Epub 2020 Feb 11.
We describe a morphologically distinct pattern of tumor infarction and associated sarcoma-like changes, mimicking focal anaplasia, in otherwise WHO grade I meningiomas. The described cases (n = 9) all demonstrated a discrete spindle-cell (pseudosarcomatous) component with brisk mitotic activity (12-14 mitoses/10 HPF), elevated Ki-67 (mean 75.5 ± 25.0%, quantified), absence of PR, SSTR2A, or EMA expression, and potential SMA expression (50%). Despite these high-grade features, all nine patients remained free of progression or recurrence post resection (follow-up mean: 49.8 months). In contrast, among a comparison (control) cohort of consecutive WHO grade II and III meningiomas (n = 16), as expected, progression rate was high (68.8%, P = 0.002, Fisher's exact, average time to progression = 25 months, follow-up mean: 39.8 months). While necrosis was a frequent feature among atypical/anaplastic meningiomas (12/16, 75%), and elevated mitoses and proliferative index were present consistent with histologic grade, a well-defined zonal pattern with pseudosarcomatous component was not present among these tumors. DNA methylation-based analysis readily distinguished meningiomas by copy number profiles and DNA-based methylation meningioma random forest classification analysis (meningioma v2.4 classifier developed at University of Heidelberg); all pseudosarcomatous cases analyzed (4/9) matched with high level calibrated classifier score to "MC benign-1", with isolated loss of chromosome 22q identified as the sole copy number alteration. In contrast, multiple chromosomal losses were detected among the comparison cohort and classifier results demonstrated good concordance with histologic grade. Our findings suggest that pseudosarcomatous alterations represent reactive changes to central meningioma infarction, rather than focal anaplasia, and further support the use of DNA methylation-based analysis as a useful adjunct for predicting meningioma behavior. These indolent tumors should be distinguished from their atypical and anaplastic counterparts.
我们描述了一种形态上明显不同的肿瘤梗死模式和相关的肉瘤样改变，类似于局灶性间变，在其他 WHO 分级 I 脑膜瘤中。所描述的病例（n=9）均表现出离散的梭形细胞（假肉瘤样）成分，有活跃的有丝分裂活动（12-14 个有丝分裂/10 HPF），Ki-67 升高（平均 75.5±25.0%，定量），缺乏 PR、SSTR2A 或 EMA 表达，以及潜在的 SMA 表达（50%）。尽管具有这些高级别特征，但所有 9 例患者在切除后均无进展或复发（随访平均：49.8 个月）。相比之下，在连续的 WHO 分级 II 和 III 脑膜瘤的对照组（n=16）中，正如预期的那样，进展率很高（68.8%，P=0.002，Fisher 精确检验，平均进展时间为 25 个月，随访平均：39.8 个月）。虽然坏死是非典型/间变脑膜瘤的常见特征（12/16，75%），并且存在与组织学分级一致的高有丝分裂和增殖指数，但在这些肿瘤中没有出现明确的具有假肉瘤成分的区域模式。基于 DNA 甲基化的分析通过拷贝数谱和基于 DNA 的甲基化脑膜瘤随机森林分类分析（在海德堡大学开发的脑膜瘤 v2.4 分类器）很容易区分脑膜瘤；分析的所有假肉瘤病例（4/9）与高水平校准分类器评分“MC 良性-1”匹配，唯一的拷贝数改变是 22q 染色体缺失。相比之下，在对照组中检测到多个染色体缺失，并且分类器结果与组织学分级具有良好的一致性。我们的发现表明，假肉瘤样改变代表中央脑膜瘤梗死的反应性改变，而不是局灶性间变，进一步支持使用基于 DNA 甲基化的分析作为预测脑膜瘤行为的有用辅助手段。这些惰性肿瘤应与非典型和间变的脑膜瘤相区别。
