Table 2 Molecular and histologic features of neuroepithelial tumors with PLAG-family genetic alterations
Patient | Methylation profiling (DKFZ 12.5) | RNA sequencing | Copy number profile | DNA sequencing mutations | Histologic appearance | Mitotic index | Ki-67 LI | Necrosis | MVP | IHC |
|---|---|---|---|---|---|---|---|---|---|---|
#1 | Neuroepithelial tumour, PLAGL1-fused, 0.99 | EWSR1-PLAGL1 fusion | Focal loss on 6q | None detected | 1st: regionally ependymal-like, cellular 2nd: ependymal-like with occasional dysmorphic appearing ganglionic cells 3rd: regionally ependymal-like with foci of ganglionic cells | 1st: 12/10 hpf | ~ 40–60% | Multifocal nonpalisading necrosis | No | GFAP: positive in a subset, areas of absent staining OLIG2: positive in a smaller subset of neoplastic cells EMA: negative Synaptophysin: patchy positivity within the neoplasm p53: nuclear positivity in the vast majority of neoplastic cells |
#2 | Neuroepithelial tumour, PLAGL1-fused, 0.99 | EWSR1-PLAGL1 fusion | Focal gains/losses on 6q loss of 22q with focal interstitial gain | SMARCB1 p.R53* 34% allelic frequency | 1st: large ependymal-like areas, subclonal INI1 loss in region with small clusters of rhabdoid/embryonal cells 2nd: leptomeningeal disease with frequent ganglion cells and INI1 loss | 1st: 19/10 hpf in ependymal area 22/10 hpf in area of INI1 loss | ~ 40% | Present in first resection nonpalisading | Yes | GFAP: patchy positivity within ependymal-like areas OLIG2: nuclear positivity in a smaller subset of neoplastic cells EMA: rare/focal paranuclear dot-like staining Neurofilament: supports a solid growth pattern Synaptophysin: patchy positivity within ependymal-like areas L1CAM: patchy weak staining Desmin: positive in an intermediate percentage of cells/processes in INI1 retained area INI1: subclonal loss in a region containing small rhabdoid/embryonal clusters |
#3 | Neuroepithelial tumour, PLAGL1-fused, 0.99 | EWSR1-PLAGL1 fusion | Focal loss on 6q | None detected | 1st, 2nd: concurrent ependymal and ganglionic features 3rd: ependymal-like with focal ganglion cells | Variable in first resection, low in subsequent resections 1st: 8/10 hpf in cellular area, low in areas of decreased cellularity 3rd: 3/10 hpf | Variable in first resection, low in subsequent resections 1st: 15–25% in cellular areas, 4–8% in less cellular areas 3rd: predominantly 4–8%, focally up to 15% | Focally present in first resection nonpalisading | No | GFAP: variably positive within the neoplasm OLIG2/SOX10: negative EMA: rare/focal paranuclear dot-like staining Neurofilament: solid and infiltrative pattern in first resection, predominantly solid subsequently Synaptophysin/NeuN: highlights ganglionic cells L1CAM: patchy positivity Desmin: rare filamentous staining |
#4 | Neuroepithelial tumour, PLAGL1-fused, 0.99 | EWSR1-PLAGL1 fusion | Focal loss on 6q focal loss on 22q | None detected | Concurrent ependymal and ganglionic features | Low | 5–8% | No | Small foci | GFAP: positive throughout the neoplasm OLIG2/SOX10: negative EMA: patchy paranuclear dot-like staining Neurofilament: predominantly solid, with areas of infiltration Synaptophysin: highlights areas of ganglionic differentiation L1CAM: negative in majority of the neoplasm, regional positivity Desmin: negative |
#5 | Neuroepithelial tumour, PLAGL1-fused, 0.99 | EWSR1-PLAGL1 fusion | Focal loss on 6q | None detected | Subtle concurrent ependymal and ganglionic features | Low | 8–10% | No | No | GFAP: positive within the neoplasm OLIG2/SOX10: negative EMA: negative Neurofilament: highlights neuronal processes and areas of infiltration Synaptophysin: highlights ganglionic differentiation, and areas of infiltration L1CAM: patchy positivity Desmin: rare positive cells and filaments |
#6 | Neuroepithelial tumour, PLAGL1-fused, 0.99 | EWSR1-PLAGL1 fusion | Noisy copy number signal on 6q | None detected | Ependymal features with focal areas of ganglionic cells | 16/10 hpf | 20–30% | Large areas of nonpalisading necrosis | Focal | GFAP: positive in majority of neoplasm, with areas of absent staining OLIG2: negative in vast majority of tumor cells SOX10: negative EMA: essentially negative Neurofilament: supports a solid growth pattern Synaptophysin: no significant staining Desmin: positive in a smaller percentage of neoplastic cells |
#7 | CNS Embryonal tumour with PLAG-family amplification, 0.99 | No recurrent fusion transcripts | PLAGL2 amplification gain of 2, 3, 7, 8, 11, 12, 19, 21 loss of 10, 22 | None detected | Embryonal, vaguely perivascular arrangement | 19/10 hpf | ~ 35% | Focal | No | GFAP: positive in a smaller subset of neoplastic cells Synaptophysin: focally positive, no significant staining Desmin: positive in a significant percentage of neoplastic cells YAP1: positive GAB1: negative beta-catenin: cytoplasmic |
#8 | CNS Embryonal tumour with PLAG-family amplification, 0.99 | No recurrent fusion transcripts | PLAGL1 amplification, gain 7, loss 17p | NCOR2 p.V862fs 16% allelic frequency present in third resection, not detected in second resection | Divergent differentiation with prominent embryonal component, glial elements, and myogenic differentiation | 16/10 hpf in primitive component | ~ 70% in highest areas, while 8–20% in other areas | Present nonpalisading | Incipient | GFAP: positive regions, with occasional positive cells in other areas Synaptophysin: multiple areas of strong staining, and positive small clusters Desmin: positive in a significant percentage of neoplastic cells Cytokeratin CAM 5.2: focal area with positivity in majority of cells |