Molecular genetic analysis of a case report of undifferentiated pleomorphic sarcoma with rhabdomyosarcomatous differentiation: insights from whole-exome sequencing and literature review.

BACKGROUND

Undifferentiated pleomorphic sarcoma (UPS) is one of the most common high-grade soft tissue sarcomas in adults, accounting for approximately 20-25% of all soft tissue sarcomas. However, the subtype with rhabdomyosarcomatous differentiation is exceedingly rare (<1%), and its clinicopathological and molecular features remain poorly defined.

CASE DESCRIPTION: A 47-year-old woman presented with a 10-day history of abdominal pain, nausea, and vomiting. Imaging revealed an ill-defined cystic-solid mass measuring approximately 80 mm × 64 mm posterior and to the right of the uterus, with indistinct margins from the uterus and adjacent bowel loops, right lower abdominal peritoneal thickening, and pelvic effusion. The patient underwent laparoscopic total hysterectomy with bilateral salpingo-oophorectomy. Histopathological examination showed a high-grade pleomorphic spindle cell neoplasm with scattered rhabdomyoblasts. Immunohistochemistry (IHC) demonstrated focal nuclear positivity for MyoD1 and myogenin, confirming rhabdomyosarcomatous differentiation; desmin was positive, and the Ki-67 proliferation index was approximately 40%. Whole-exome sequencing (WES) identified 5,778 somatic mutations, including seven somatic missense mutations in TP53, ALK, NCOR2, GNAS, GOPC, PLEC, and STIP1, with a moderate tumor mutational burden (TMB) of 9.13 mutations/Mb.

CONCLUSIONS

This case expands the pathological and molecular spectrum of UPS with rhabdomyosarcomatous differentiation. Increased clinical awareness, thorough immunohistochemical evaluation, and molecular profiling are essential to avoid misdiagnosis and to guide the management of this rare, aggressive sarcoma.