- Always include nodular fasciitis in the differential of rapidly growing soft-tissue masses—even in deep, intraneural, or juxta-articular sites where it may mimic sarcoma.
- Clinical and radiologic features are often misleading: ~2/3 of cases lacked suspicion pre-operatively and were frequently worked up as nerve sheath tumors or malignancy.
- Molecular confirmation is critical in atypical cases: USP6 rearrangement is a hallmark; FISH is useful but can be false-negative—NGS should be used when results are equivocal.
- Histology can appear “alarming” (high cellularity, atypia) but does not imply malignancy—recognition prevents overtreatment.
- Rare USP6 fusion partners may correlate with distinctive features (e.g., higher cellularity, giant cells, younger patients), suggesting biological heterogeneity but not necessarily aggressive behavior.
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