KAT6B::KANSL1 fusion-positive uterine mesenchymal neoplasm with hybrid endometrial stromal and smooth muscle features: a case report

KAT6B/A::KANSL1 fusion-positive uterine mesenchymal neoplasms are rare and may show overlapping endometrial stromal and smooth muscle features. We report a 47-year-old woman with regular menses, no dysmenorrhea, and a 7-year history of a presumed uterine fibroid. She underwent laparoscopic myomectomy at an outside hospital in November 2024. The fragmented specimen was interpreted as an endometrial stromal tumor with smooth muscle differentiation, but the tumor–myometrium interface could not be assessed, and an endometrial stromal nodule could not be distinguished from low-grade endometrial stromal sarcoma. Subsequent pelvic magnetic resonance imaging showed postoperative changes, possible residual leiomyomas, and heterogeneous enhancement at the uterine fundus. Pelvic computed tomography showed heterogeneous uterine enhancement without definite extrauterine disease. Because the original specimen was fragmented and a potentially malignant uterine mesenchymal neoplasm could not be excluded, completion hysterectomy with bilateral salpingo-oophorectomy was performed. The hysterectomy specimen contained multiple residual intramyometrial nodules with marked regional heterogeneity. One component showed fascicular smooth muscle morphology and diffuse desmin and h-caldesmon expression, whereas other nodules showed tongue-like myometrial infiltration, focal intravascular growth, spiral arteriole-like vessels, and diffuse ER, PR, CD10, and SMA expression. Whole-transcriptome sequencing identified an in-frame KAT6B::KANSL1 fusion involving KAT6B exon 3 and KANSL1 exon 11. Because the tumor expressed ER and PR, postoperative letrozole was administered for 30 days, after which surveillance was selected following review of the final pathologic and molecular findings. At 8 months after completion surgery, no clinical or radiologic recurrence was detected; this limited follow-up does not permit conclusions regarding long-term biological behavior or endocrine treatment benefit.