Management of Uterine Neoplasms and Sarcomas

Uterine Sarcomas

Uterine sarcomas are malignant mesenchymal tumors categorized by their histologic and molecular characteristics. Unlike carcinosarcomas, which are treated as high-grade epithelial carcinomas, true sarcomas require specific mesenchymal-directed management.

Key Subtypes

Endometrial Stromal Sarcoma (ESS)

ESS is divided into two main categories:

1. Low-grade ESS: Often characterized by $JAZF1$, $PHF1$, or $EPC1$ gene fusions.
2. High-grade ESS: May harbor $YWHAE::FAM22A/B$ or $BCOR$ alterations.

Uterine Leiomyosarcoma (uLMS)

The most common subtype (63%), uLMS typically presents as spindle cell tumors. Diagnosis is supported by IHC markers such as desmin and SMA (smooth muscle actin).

Undifferentiated Uterine Sarcoma (UUS)

UUS is a diagnosis of exclusion for aggressive tumors that do not meet other criteria. A specific subset is SMARCA4-deficient uterine sarcoma (SDUS), which is characterized by the biallelic inactivation of the $SMARCA4$ gene.

Rhabdomyosarcoma (RMS)

An aggressive group (including alveolar, embryonal, and pleiomorphic types) that expresses myogenic biomarkers like myogenin and MyoD1.

Müllerian Adenosarcoma

This is a biphasic tumor. A critical prognostic factor is sarcomatous overgrowth (SO), defined as the sarcoma component comprising $\ge 25\%$ of the total tumor volume.

Other Rare Mesenchymal Tumors

• PEComa: Perivascular epithelioid cell tumors.
• UTROSCT: Uterine Tumor Resembling Ovarian Sex Cord Tumor.

Clinical Management and Staging

Diagnosis and Surgical Principles

Diagnosis often occurs post-hysterectomy, making expert pathology review and molecular analysis (e.g., NGS, FISH) critical.

Warning: Intraperitoneal morcellation is strictly contraindicated in patients with suspected uterine malignancy due to the risk of upstaging the disease.

For medically operable patients, the standard is hysterectomy with or without BSO and en bloc tumor resection. Staging follows the FIGO/AJCC systems to determine the extent of disease.

Adjuvant and Systemic Therapy for Sarcomas

Management varies significantly by subtype and stage:

• Low-grade ESS/Adenosarcoma (without SO): For Stage I, BSO is preferred or observation if the patient is menopausal. For advanced stages (II–IV), management includes BSO, systemic endocrine therapy (such as aromatase inhibitors or progestins), and potentially EBRT.
• High-grade/Advanced Sarcomas:
  • EBRT: May be used for stages II, III, or IVA.
  • Systemic Therapy: For advanced or recurrent disease, options include chemotherapy or biomarker-directed therapies. For example, patients with $CDK4$ amplification may be candidates for Palbociclib.