Endometrial Stromal Sarcoma: An Update

Abstract

Endometrial stromal sarcoma (ESS) is a rare malignant tumor of uterine mesenchyme, accounting for 15-20% of uterine sarcomas. It is classified into low-grade (LG-ESS) and high-grade (HG-ESS) subtypes, each defined by distinct histopathological and molecular features. LG-ESS exhibits slow progression, resembling proliferative-phase endometrial stroma, with genetic alterations like JAZF1-SUZ12 fusions. HG-ESS is more aggressive, characterized by high mitotic activity, necrosis, and genetic markers such as BCOR internal tandem duplication, often leading to advanced-stage diagnosis. Surgical resection is the cornerstone for managing early-stage ESS. A total hysterectomy with bilateral salpingo-oophorectomy (BSO) is recommended to prevent recurrence. Fertility-preserving approaches may be considered in LG-ESS but are associated with high recurrence rates. Lymphadenectomy is not routinely performed, given its limited prognostic value. HG-ESS, due to its aggressiveness, often requires additional treatment, including chemotherapy. Adjuvant therapy varies by subtype. LG-ESS responds well to hormonal treatments such as aromatase inhibitors and progestins, while tamoxifen is contraindicated. HG-ESS, lacking hormonal receptor expression, is managed with chemotherapy, often incorporating doxorubicin-based regimens. Radiotherapy may improve local control in select cases but shows limited impact on overall survival. Advanced-stage ESS treatment focuses on complete cytoreduction, supplemented by systemic therapies. Hormonal therapy remains the standard for advanced LG-ESS, whereas HG-ESS relies on chemotherapy. Prognosis depends on the subtype and stage. LG-ESS has favorable outcomes, with five-year survival exceeding 90% in early stages, but recurrent disease remains common. HG-ESS is associated with poorer survival due to its aggressive nature. Advances in molecular profiling offer promising avenues for personalized therapies, integrating genomic insights with targeted treatments to improve outcomes in this rare malignancy.

Keywords: endometrial stromal sarcoma; gynecologic oncology; uterine sarcoma.

Figure 1

(A) Axial pelvic MRI image showing a hypointense endometrial mass with infiltrative margins in a patient with low-grade ESS (LG-ESS). (B) Sagittal pelvic MRI image highlighting endometrial thickening and myometrial infiltration in LG-ESS. (C) Axial MRI scan demonstrating extensive myometrial invasion and central necrosis in a case of high-grade ESS (HG-ESS). (D) Coronal MRI image depicting heterogeneous signal intensity with hemorrhagic and necrotic areas in HG-ESS. (E) PET-CT scan showing elevated FDG uptake in a metabolically active HG-ESS lesion. All figures are original and created by the authors.

Figure 2

(A) Low-grade ESS (LG-ESS) showing proliferation of uniform oval to spindle-shaped cells with minimal cytologic atypia and low mitotic activity (H&E, ×20). (B) Fluorescence in situ hybridization (FISH) for JAZF1 gene rearrangement in LG-ESS: split signals of 3′ (red) and 5′ (green) probes indicate gene rearrangement; yellow dot represents normal spot without gene rearrangement. (C) High-grade ESS (HG-ESS) with BCOR internal tandem duplication: proliferation of oval to spindle-shaped cells with high mitotic index (H&E, ×20). (D) Diffuse nuclear BCOR immunoreactivity in HG-ESS. (E) Strong and diffuse nuclear staining for cyclin D1 in HG-ESS. (F) CD10 expression is absent or markedly reduced in HG ESS with BCOR alterations. All figures are original and created by the authors.

Figure 3

Summary of the morphological and immunohistochemical characteristics of endometrial stromal sarcoma subtypes. All figures are original and created by the authors.

Figure 4

Kaplan–Meier survival curves comparing progression-free survival (A) and overall survival (B) between low-grade endometrial stromal sarcoma (LG-ESS) and high-grade endometrial stromal sarcoma (HG-ESS), adapted from Wang et al., BMC Cancer, 2022 [87]. LG-ESS shows significantly improved prognosis over HG-ESS (log-rank p < 0.001 for both outcomes).