Table 2.
Diagnostic revisions based on WGS analysis.
| Study Nr | Suspected Diagnosis | Localization | Molecular Diagnostic Test Performed | Diagnostic Revision | Based on |
|---|---|---|---|---|---|
| 8 | Adenocarcinoma of unknown primary | Head/neck | IHC, SISH (HER2), NGS panel | Synovial sarcoma | SS18—SSX1 fusion |
| 44 | Alveolar rhabdomyosarcoma | Head/neck | IHC, RT-PCR, fusion analysis | Spindle-cell/sclerosing rhabdomyosarcoma | MYOD1 p.Leu122Arg |
| 45 | Embryonal rhabdomyosarcoma | Head/neck | IHC, FISH, methylation assay, fusion analysis | Spindle cell/sclerosing rhabdomyosarcoma | MYOD1 p.Leu122Arg |
| 46 | Osteosarcoma, undifferentiated pleiomorphic sarcoma of bone | Head/neck | IHC | Spindle cell/sclerosing rhabdomyosarcoma | FUS—TFCP2 fusion |
| 47 | Sarcomatoid mesothelioma vs. sarcoma | Intrathoracic/mediastinal | IHC, fusion analysis | Sarcoma NOS | Complete genomic profile, including lack of NF2 and BAP1 driver events |
| 54 | Wild-type GIST | Intra-abdominal | IHC, NGS panel (2×), fusion analysis | KIT mutated GIST | KIT exon 11 deletion (51 nucleotides) |
| 57 | Ewing sarcoma | Trunk | IHC, fusion analysis, RT-PCR (EWS1), FISH | Myoepithelial carcinoma | EWSR1—POU5F1 fusion |
| 63 | Dedifferentiated liposarcoma (recurrence) | Trunk | - | Radiotherapy-associated second primary | Lack of MDM2/CDK4 co-amplification |
| 80 | Carcinoma of unknown primary | Intra-abdominal | IHC | Desmoplastic Small-Round-Cell Tumor | EWSR1—WT1 fusion |
| 81 | Malignant peripheral nerve sheath tumor | Head/neck | IHC, fusion analysis | Melanoma | High ML/UV-signature, TERT promoter mutation |
| 82 | Melanoma vs. sarcoma | Extremity | IHC, fusion analysis | Melanoma | High ML/UV-signature, TERT promoter mutation |
| 83 | Interdigitating dendritic cell sarcoma | Extremity | IHC, NGS panel (2×), FISH | Melanoma | High ML/UV-signature, TERT promoter mutation |
IHC = immunohistochemistry, SISH = silver in situ hybridization, FISH = fluorescence in situ hybridization, RT-PCR = reverse transcription polymerase chain reaction, NGS = next-generation sequencing. Morphology and information on IHC can be found in Supplementary Figure S1. Detailed information on genes included in NGS panels and fusion analysis can be found in Supplementary Table S5.