What are the pathological features and subtypes of uterine sarcomas?

Pathology of Uterine Sarcomas

Uterine sarcomas are classified into five main histopathologic subtypes based on the 2014 WHO Classification, with uterine leiomyosarcoma being the most common (63%), followed by endometrial stromal sarcomas (21%), and rarer entities including undifferentiated uterine sarcoma, adenosarcoma, and other mesenchymal tumors. 1

Major Histopathologic Subtypes

Low-Grade Endometrial Stromal Sarcoma (LG-ESS)

• Characterized by small cells with low-grade cytology resembling proliferative phase endometrial stromal cells 1
• Mitotic activity is typically low (<5 mitotic figures per 10 high-power fields) 1
• Displays morphologic features of proliferative phase endometrial stroma with any mitotic index 1
• Carries an excellent prognosis with median overall survival not reached in major studies (88% of patients alive at 80 months) 1, 2
• Patients more likely to present with uterine/cervix-confined disease (68% vs 39% for high-grade) 1

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) 1
• Shows pleomorphism or anaplasia greater than proliferative phase endometrial stroma 1
• Can contain areas of conventional low-grade ESS within the tumor 1
• Carries an intermediate prognosis between low-grade ESS and undifferentiated uterine sarcoma, with median overall survival of 16.5-53 months 1, 2
• Presence of residual disease after resection significantly impacts survival negatively 1

Undifferentiated Uterine Sarcoma (UUS)

• Characterized by cells with high-grade cytologic features completely lacking any resemblance to proliferative endometrial stromal cells or any other specific type of differentiation 1
• Mitotic index almost always >10 mitotic figures per 10 high-power fields 1
• Carries the poorest prognosis of all uterine sarcomas regardless of disease stage 1, 2
• Optimal standard treatment options remain unclear 1

Uterine Leiomyosarcoma (uLMS)

• The most common uterine sarcoma subtype, accounting for 63% of cases 1
• Median overall survival of 21 months 1
• Classification excludes smooth muscle tumors of uncertain malignant potential, epithelioid smooth muscle tumors, benign metastasizing leiomyomas, intravenous leiomyomatosis, and diffuse leiomyomatosis 1
• Management may be modified based on specific clinicopathologic prognostic factors:
  • Tumor size (<5 cm vs >5 cm) 1
  • Mitotic activity (<10 vs >10 mitotic figures per 10 high-power fields) 1
  • Patient age (<50 vs >50 years) 1
  • Presence or absence of vascular invasion 1

Rare Uterine Mesenchymal Sarcoma Subtypes

• Adenosarcoma 1
• PEComa (perivascular epithelioid cell neoplasm) 1
• Rhabdomyosarcoma 1

Critical Diagnostic Distinctions

Molecular Analysis

• While molecular studies are not routinely used in pathologic evaluation, molecular analysis (such as identification of characteristic translocations) can help classify difficult cases and provide future therapeutic targets 1
• The distinction between endometrial stromal sarcoma subtypes relies on cytologic grade, mitotic activity, and molecular genetic alterations 2

Important Reclassification

Carcinosarcomas (malignant mixed müllerian tumors) were previously categorized as sarcomas until the mid-2000s but are now considered and treated as high-grade epithelial tumors (carcinomas), not true sarcomas 1

Prognostic Significance

Histopathologic subtype is a significant independent prognostic factor for survival in uterine sarcomas 1, 2:

• Low-grade ESS: Excellent long-term survival (median OS not reached) 1, 2
• High-grade ESS: Intermediate prognosis (median OS 16.5-53 months) 1, 2
• Uterine leiomyosarcoma: Median OS 21 months 1
• Undifferentiated uterine sarcoma: Poorest prognosis regardless of stage 1, 2

Clinical Context

Uterine sarcomas comprise only 3% of all uterine neoplasms, making them rare tumors with limited randomized clinical trial data 1. The rarity and histopathological diversity of these tumors creates challenges in establishing consensus on risk factors and optimal treatment strategies 3.