Undifferentiated Pleomorphic Sarcoma / Malignant Fibrous Histiocytoma (MFH)

Overview

Undifferentiated pleomorphic sarcoma (UPS), historically termed malignant fibrous histiocytoma (MFH), is a high-grade soft tissue sarcoma classified under SOFT_TISSUE in the OncoTree hierarchy. It can arise de novo or as a radiation-associated sarcoma.

Cohorts in the corpus

• sarcoma_msk_2023: 14 RT-UPS patients and 273 sporadic UPS controls, sequenced on MSK-IMPACT PMID:37350195.

Recurrent alterations

• TP53 LOF mutations/deletions in 43% of RT-UPS vs 57% sporadic UPS PMID:37350195.
• CDKN2A/CDKN2B deletions in 29% of RT-UPS vs 20% sporadic UPS PMID:37350195.
• KMT2D truncating/missense mutations in 21% of RT-UPS vs 4% sporadic UPS PMID:37350195.
• RB1 truncating mutations/deletions in 14% of RT-UPS vs 19% sporadic UPS PMID:37350195.
• NOTCH3 missense mutations in 14% of RT-UPS vs 4% sporadic UPS PMID:37350195.
• RT-UPS had the highest insertion:SNV and deletion:SNV ratios among RT-sarcomas (adjusted P < 0.05) PMID:37350195.
• FGA of 25% in RT-UPS PMID:37350195.

Subtypes

• Radiation-associated UPS (RT-UPS): Enriched for KMT2D and NOTCH3 alterations compared to sporadic UPS. Longest median latency from radiation to diagnosis among RT-sarcomas: 18.5 years PMID:37350195.
• Sporadic UPS: Higher rates of TP53 (57%) and RB1 (19%) alterations PMID:37350195.

Therapeutic landscape

• Treatment follows histotype-specific approaches; the genomic landscape of RT-UPS supports treating based on histology rather than RT status PMID:37350195.

Sources

• PMID:37350195 — Dermawan JK et al., J Pathol 2023. Comparative genomic analysis of 82 RT-sarcomas including 14 RT-UPS.

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