Department of Pathology, Neuropathology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA.
Department of Pathology, Molecular Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Acta Neuropathol Commun. 2024 Sep 3;12(1):143. doi: 10.1186/s40478-024-01809-9.
Neuroepithelial tumors with fusion of PLAGL1 or amplification of PLAGL1/PLAGL2 have recently been described often with ependymoma-like or embryonal histology respectively. To further evaluate emerging entities with PLAG-family genetic alterations, the histologic, molecular, clinical, and imaging features are described for 8 clinical cases encountered at St. Jude (EWSR1-PLAGL1 fusion n = 6; PLAGL1 amplification n = 1; PLAGL2 amplification n = 1). A histologic feature observed on initial resection in a subset (4/6) of supratentorial neuroepithelial tumors with EWSR1-PLAGL1 rearrangement was the presence of concurrent ependymal and ganglionic differentiation. This ranged from prominent clusters of ganglion cells within ependymoma/subependymoma-like areas, to interspersed ganglion cells of low to moderate frequency among otherwise ependymal-like histology, or focal areas with a ganglion cell component. When present, the combination of ependymal-like and ganglionic features within a supratentorial neuroepithelial tumor may raise consideration for an EWSR1-PLAGL1 fusion, and prompt initiation of appropriate molecular testing such as RNA sequencing and methylation profiling. One of the EWSR1-PLAGL1 fusion cases showed subclonal INI1 loss in a region containing small clusters of rhabdoid/embryonal cells, and developed a prominent ganglion cell component on recurrence. As such, EWSR1-PLAGL1 neuroepithelial tumors are a tumor type in which acquired inactivation of SMARCB1 and development of AT/RT features may occur and lead to clinical progression. In contrast, the PLAGL2 and PLAGL1 amplified cases showed either embryonal histology or contained an embryonal component with a significant degree of desmin staining, which could also serve to raise consideration for a PLAG entity when present. Continued compilation of associated clinical data and histopathologic findings will be critical for understanding emerging entities with PLAG-family genetic alterations.
具有 PLAGL1 融合或 PLAGL1/PLAGL2 扩增的神经上皮肿瘤最近已被描述，分别具有类似室管膜瘤或胚胎性组织学特征。为了进一步评估具有 PLAG 家族遗传改变的新兴实体，描述了在圣裘德遇到的 8 例临床病例的组织学、分子、临床和影像学特征（EWSR1-PLAGL1 融合 n = 6；PLAGL1 扩增 n = 1；PLAGL2 扩增 n = 1）。在一组（6/6）具有 EWSR1-PLAGL1 重排的幕上神经上皮肿瘤的初始切除标本中观察到一个组织学特征，即同时存在室管膜和神经节细胞分化。这种情况范围从在室管膜瘤/室管膜下瘤样区域内存在明显的神经节细胞簇，到在其他具有室管膜样组织学特征的区域内存在低至中等频率的散在神经节细胞，或存在具有神经节细胞成分的局灶区。当存在时，幕上神经上皮肿瘤中具有室管膜样和神经节细胞特征的组合可能提示存在 EWSR1-PLAGL1 融合，并及时启动适当的分子检测，如 RNA 测序和甲基化分析。在一个 EWSR1-PLAGL1 融合病例中，在包含小群横纹样/胚胎样细胞的区域中显示亚克隆 INI1 缺失，并在复发时出现明显的神经节细胞成分。因此，EWSR1-PLAGL1 神经上皮肿瘤是一种类型的肿瘤，其中可能会获得 SMARCB1 的失活并发展为 AT/RT 特征，从而导致临床进展。相比之下，PLAGL2 和 PLAGL1 扩增病例显示胚胎性组织学或包含具有明显程度的结蛋白染色的胚胎成分，当存在时，这也可能提示存在 PLAG 实体。继续编译相关临床数据和组织病理学发现对于理解具有 PLAG 家族遗传改变的新兴实体将至关重要。
