Table 1.
Biomarkers and genetic signatures for distinguishing DSRCTs, Ewing sarcoma, and alveolar rhabdomyosarcoma.
| IHC Markers and Genetic Signatures | DSRCT | Ewing Sarcoma | Alveolar Rhabdomyosarcoma |
|---|---|---|---|
| EMA and keratins [31] | Variable (distinctive dot-like cytoplasmic expression occasionally) | Negative (but diffuse in adamantinoma-like variant [32]) | Variable (may show focal keratin positivity) |
| Desmin | Distinct dot-like and perinuclear cytoplasmic staining pattern) [27] | Negative | Positive |
| Vimentin | Distinctive dot-like cytoplasmic expression occasionally [11] | Positive in 80–90% | Negative |
| WT1 (C terminus) | Positive in 65–90% [33] but negative for WT1 (N terminus) | Negative | Negative |
| NSE, neurofilament, and synaptophysin (NE markers) | Variable [34,35] | Variable | Variable |
| Actin | Variable | Negative | Positive |
| Myogenin [36,37] | Negative | Negative | Positive |
| MyoD1 [36] | Negative | Negative | Positive |
| CD99 | Negative | Positive (membranous; up to 95%) [38] | Positive |
| FLI1 | Negative | Positive (nuclear with EWSR1::FLI1 fusion; up to 90%) [39] | Negative |
| ERG | Negative | Positive (nuclear with EWSR1::ERG fusion) [40] | Negative |
| NKX2.2 | Negative | Positive (nuclear; up to 93%) [41] | Negative |
| S100 protein [11] | Negative | Negative | Negative |
| Genetic signatures | EWSR1::WT1 gene fusion | EWSR1 rearrangements: EWSR1::FLI1, EWSR1::ERG, EWSR1::FEV, EWSR1::ETV1, EWSR1::E1AF, EWSR1::ZSG, or FUS::ERG gene fusions | t(2;13) or t(1;13) involving FOXO1 and PAX3 or PAX7: PAX3::FOXO1, PAX7::FOXO1, or PAX3::AFX gene fusions |
Abbreviations: AFX: forkhead transcription factor gene; DSRCT: desmoplastic small round cell tumor; E1AF: adenovirus E1A enhancer-binding gene; EMA: epithelial membrane antigen; ERG: ETS-related gene; ETV1: ETS variant transcription factor 1 gene; EWSR1: Ewing sarcoma breakpoint region 1; FEV: human fifth Ewing variant gene; FLI1: friend leukemia integration 1 gene; FOXO1: forkhead box protein O1 gene; FUS: fused in sarcoma gene; IHC: immunohistochemistry; MyoD1: myogenic differentiation 1; NE: neuroendocrine; NSE: neuron-specific enolase; PAX3: paired box 3 gene; PAX7: paired box 7 gene; WT1: Wilms tumor protein 1; ZSG: zinc finger sarcoma gene.