Endometrial stromal sarcomas with unusual histologic features: a report of 24 primary and metastatic tumors emphasizing fibroblastic and smooth muscle differentiation.

We report the clinicopathologic features of 24 uterine primary and metastatic endometrial stromal sarcomas with fibromyxoid features (ESS-F) and smooth muscle differentiation (ESS-SM) (endometrial stromal sarcoma variants). Two groups of tumors were retrieved from the surgical pathology files at Memorial Sloan-Kettering Cancer Center: 1) gynecologic mesenchymal neoplasms with striking smooth muscle or fibroblastic differentiation that did not meet the clinical or histologic criteria for leiomyosarcoma or other established neoplasms containing smooth muscle; and 2) metastatic lesions showing ovoid and spindle cell morphology, involving lung, originally diagnosed as low-grade leiomyosarcoma, low-grade smooth muscle neoplasm, intravenous leiomyomatosis, fibrous hamartoma, and benign metastasizing leiomyoma. We identified 12 patients with 30 tumors; 24 were available for review. The mean age was 51 years (range 21-74 years). Follow-up >1 year was available for eight patients, with a mean time of 8.5 years. Each patient had a uterine primary and 10 experienced metastases. Mean time to recurrence was 6.8 years. Sites of metastasis included lung, retroperitoneum, right atrium/inferior vena cava, colon, and ovaries. No patient died of disease, but in many cases the follow-up period ended with the discovery of a metastasis. Four patients were originally diagnosed with endometrial stromal sarcoma, but other presenting diagnoses included benign metastasizing leiomyoma, fibroleiomyomatous tumor of lung, smooth muscle tumor of uncertain or low malignant potential, and intravascular leiomyomatosis. On review each patient had at least one tumor (primary and/or metastasis) that was determined to be an endometrial stromal sarcoma variant. Review diagnoses were as follows: endometrial stromal sarcoma (nonvariant), ESS-F, and ESS-SM. Eight of 10 primary tumors with available slides were endometrial stomal sarcoma variants (six ESS-F and two ESS-SM). When these variant features were present, they comprised between 50% and 100% of the neoplasm. The variant histology tumors exhibited prominent spiral arterioles, perivascular edema, and stromal cell condensation around blood vessels. All metastases but one were variant tumors; eight were ESS-F and five were ESS-SM. Four metastases did not resemble the uterine primary. Desmin marked smooth muscle mostly but not specifically. h-Caldesmon marked smooth muscle exclusively. Endometrial stromal cells as well as some fibroblasts and smooth muscle cells expressed CD10. We conclude that the presence of even focal endometrial stromal differentiation in an invasive uterine mesenchymal lesion with a predominant low-grade smooth muscle, fibroblastic, and/or myxoid phenotype should permit classification as low-grade sarcoma-they should be considered endometrial stromal sarcomas.