Abstract
75 Pediatric and Young Adult NSD3::NUTM1 Sarcomas: True Rhabdomyosarcomas or Extensive Rhabdomyoblastic Differentiation?
Laboratory investigation, Vol.106(3 Supplement), 104353
03/2026
DOI: 10.1016/j.labinv.2025.104353
Abstract
Background
NUTM1-rearranged neoplasms comprise an expanding group that includes classic BRD4/3-driven NUT carcinoma and emerging mesenchymal tumors with non-BRD fusion partners. More recently, NUTM1 rearrangements are recognized in a broader spectrum of neoplasms, including undifferentiated high-grade sarcomas collectively termed NUTM1-rearranged sarcomas, which often harbor fusions involving MAX and MAD family genes. Most reported cases have occurred in adults, with few pediatric examples. We report 3 pediatric and young adult NSD3::NUTM1 sarcomas and highlight their morphologic/immunophenotypic overlap with rhabdomyosarcoma, a previously unreported finding.
Design
3 NSD3::NUTM1-fused sarcomas were identified from 2 large pediatric institutions. Available pathology material, including IHC, was reviewed. DNA and RNA sequencing was performed for molecular characterization. Clinical data was extracted from medical records.
Results
Patients were 1 month (Fig. 1), 22 months (Fig. 2; Case 2), and 22 years old (Fig. 2; Case 3), all males. Tumors arose in anterior chest wall, forehead, and upper arm (sizes 4.5–7 cm). The youngest patient’s tumor was congenital. Histologically, all were poorly differentiated, with sheets and nests of round to spindle cells with coarse chromatin, prominent nucleoli, frequent mitoses, necrosis, and variable rhabdomyoblastic differentiation. Desmin was diffuse in 2 tumors and negative in one; Myogenin and MyoD1 ranged from strong/diffuse (n=2) to negative (n=1). SMA and CK were variably expressed, and 1 case showed nuclear p63 with negative p40. NSD3::NUTM1 fusions were confirmed by NGS. 2 cases were initially diagnosed as rhabdomyosarcoma and one as a NUTM1-rearranged sarcoma. Clinically, all presented with rapidly enlarging soft-tissue masses. 2 patients died within 5–11 months complicated with extensive metastases; one remains alive with disease at 4 months.
Conclusions
NSD3::NUTM1 sarcomas can occur in pediatrics and young adults and may exhibit striking rhabdomyoblastic differentiation overlapping with rhabdomyosarcoma. Recognition of this entity is essential, as it likely represents a distinct molecular subset with aggressive behavior. Comprehensive pathologic and molecular evaluation is required for accurate diagnosis. Methylation and epigenomic studies are needed to clarify the relationship between these tumors and rhabdomyosarcomas.
Details
- Title: Subtitle
- 75 Pediatric and Young Adult NSD3::NUTM1 Sarcomas: True Rhabdomyosarcomas or Extensive Rhabdomyoblastic Differentiation?
- Creators
- Muhammad Shaheen - Cincinnati Children's Hospital Medical CenterSimone HettmerSomak Roy - Cincinnati Children's Hospital Medical CenterErin Rudzinski - Indiana University School of MedicineMegan Zilla - Cincinnati Children's Hospital Medical CenterArchana Shenoy - Cincinnati Children's Hospital Medical CenterSara Szabo - Cincinnati Children's Hospital Medical CenterOscar Lopez-Nunez - Cincinnati Children's Hospital Medical Center
- Resource Type
- Abstract
- Publication Details
- Laboratory investigation, Vol.106(3 Supplement), 104353
- DOI
- 10.1016/j.labinv.2025.104353
- ISSN
- 0023-6837
- eISSN
- 1530-0307
- Publisher
- Elsevier
- Language
- English
- Date published
- 03/2026
- Academic Unit
- Pathology
- Record Identifier
- 9985217814402771
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