Endometrial stromal sarcomas are uncommon malignancies arising from the specialized stroma unique to the uterine endometrium. Low-grade and high-grade endometrial stromal sarcomas differ in both cellular appearance and in their underlying molecular alterations.

This slide demonstrates a diffuse neoplasm that effaces virtually the entire myometrium. On intermediate power the tumor has a vaguely nested-appearing architecture due to the presence of fine, branching capillaries. The neoplasm is composed of cells that vary in size and shape (spindled, epithelioid, and polygonal) with a variable amount of cytoplasm, though generally the nucleus-to-cytoplasm ratio is high. Cells do not resemble typical proliferative-phase endometrial stroma. The nuclei show little pleomorphism and do not have prominent nucleoli. Necrosis is not seen. These features are characteristic of a high-grade endometrial stromal sarcoma.

High-grade endometrial stromal sarcoma can be difficult to distinguish from other uterine sarcomas, particularly smooth muscle tumours. In this case, the tumour was reactive for Cyclin D1, CD10 (weakly), and desmin, but negative for caldesmon, keratins, and HMB-45. The immunoprofile of uterine mesenchymal tumours can overlap significantly. On molecular testing, this tumour showed the characteristic t(10;17) translocation producing a YWHAE-FAM22 fusion-gene.