What is an endometrial stromal neoplasm?

Endometrial Stromal Neoplasm: Definition and Classification

Endometrial stromal neoplasms are rare uterine mesenchymal tumors that histologically resemble the stromal cells of proliferative phase endometrium, comprising less than 10% of all uterine mesenchymal neoplasms. 1, 2

Classification System

The NCCN Guidelines, aligned with the 2014 WHO Classification, recognize distinct categories of endometrial stromal tumors based on morphology, molecular features, and prognosis 3:

Low-Grade Endometrial Stromal Sarcoma (LG-ESS)

• Characterized by small cells with low-grade cytology that resemble stromal cells in proliferative endometrium 3
• Mitotic activity is typically low (<5 mitotic figures per 10 high-power fields) 3
• Most commonly harbor the JAZF1-SUZ12 gene fusion 1, 4
• Usually express estrogen and progesterone receptors 1
• Excellent prognosis with 5-year overall survival of 80-100% 1
• Median overall survival not reached in major studies (88% of patients alive at 80 months) 3

High-Grade Endometrial Stromal Sarcoma (HG-ESS)

• Characterized by small cells with high-grade cytology, frequent necrosis, and brisk mitotic activity (>10 mitotic figures per 10 high-power fields) 3
• Shows pleomorphism or anaplasia greater than proliferative phase endometrial stroma 3
• May contain areas of conventional LG-ESS 3
• Associated with YWHAE-FAM22 translocation or BCOR gene abnormalities 1, 4
• Intermediate prognosis between LG-ESS and undifferentiated uterine sarcoma, with median overall survival of 16.5-53 months 3

Undifferentiated Uterine Sarcoma (UUS)

• Characterized by cells with high-grade cytologic features lacking any resemblance to proliferative endometrial stromal cells 3
• Lacks specific genetic abnormalities that characterize other stromal tumors 1
• Poor prognosis with median overall survival of 12-23 months 1

Endometrial Stromal Nodule (ESN)

• Benign counterpart with well-circumscribed borders 4, 5
• May harbor JAZF1-SUZ12 fusion similar to LG-ESS 4

Key Diagnostic Features

The critical distinction between these entities relies on three factors: cytologic grade, mitotic activity, and molecular genetic alterations 3, 4:

• Cytologic features: Low-grade tumors resemble normal proliferative endometrial stroma, while high-grade tumors show pleomorphism and anaplasia 3
• Mitotic index: <5 mitotic figures per 10 HPF suggests low-grade; >10 suggests high-grade 3
• Molecular markers: JAZF1-SUZ12 fusion identifies most LG-ESS; YWHAE-FAM22 translocation identifies HG-ESS 1, 4

Clinical Presentation

Endometrial stromal neoplasms primarily affect peri- or postmenopausal women with an annual incidence of approximately 0.30 per 100,000 women 1:

• LG-ESS patients are significantly more likely to present with uterine/cervix-confined disease (68% vs 39% for high-grade) 3
• HG-ESS and UUS present with stage III-IV disease in approximately 70% of cases at diagnosis 1

Prognostic Significance

Histopathologic subtype is a significant independent prognostic factor for survival 3:

• LG-ESS: Indolent behavior with excellent long-term survival 1
• HG-ESS: Intermediate prognosis, significantly worse than LG-ESS but better than UUS 3
• UUS: Poorest prognosis regardless of disease stage 3
• Presence of residual disease after resection has significant negative impact on overall survival for high-grade but not low-grade ESS 3

Important Clinical Caveat

Despite the generally favorable prognosis of low-grade ESS, rare cases may behave aggressively with direct spread to retroperitoneum or distant metastases, emphasizing the need for complete surgical staging and long-term surveillance 6.