Endometrial Carcinoma: Pathology, Molecular Profiling, and Surgical Staging

1. POLE-mutated: These tumors are identified by pathogenic mutations in the exonuclease domain of the POLE gene. They generally carry an excellent prognosis.
2. MSI-H/dMMR: This group is characterized by microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR). These are often assessed via immunohistochemical (IHC) staining or polymerase chain reaction (PCR).
3. NSMP (No Specific Molecular Profile): These tumors do not fall into the other three categories.
4. p53 aberrant: These are characterized by an aberrant or mutant pattern on IHC staining.

Comprehensive molecular profiling is a cornerstone of modern care. Additionally, ancillary testing is recommended for specific scenarios: HER2 IHC is recommended for all p53 aberrant carcinomas and for all metastatic/recurrent disease. For advanced stages, testing for ER/PR (estrogen and progesterone receptors) may also be indicated.

Surgical Staging Principles

For disease confined to the uterus, the standard surgical treatment is Total Hysterectomy and Bilateral Salpingo-Oophorectomy (TH/BSO).

Surgical Considerations

To minimize the risk of spreading tumor cells throughout the abdomen, tumors should be removed en bloc rather than using intraperitoneal morcellation. While peritoneal cytology is often obtained during surgery, it does not independently affect the FIGO staging. In cases of Stage II disease, a Radical Hysterectomy (RH) may be required to ensure negative surgical margins.

Sentinel Lymph Node (SLN) Mapping

For patients with apparent uterine-confined disease, Sentinel Lymph Node (SLN) mapping is preferred over systemic lymphadenectomy for staging. This technique uses dyes such as Indocyanine green (ICG) or Technetium-99m injected into the cervix to identify the high-risk nodes most likely to harbor metastasis.

A critical component of this process is ultrastaging. To detect low-volume disease, SLNs undergo thin serial sectioning with H&E and potentially cytokeratin IHC. The results are classified as follows:

• $pN0(i+)$: This classification is used when lymph nodes contain only isolated tumor cells. Importantly, these nodes do not upstage the patient, but they are vital for informing discussions regarding adjuvant therapy.

Imaging and Preoperative Workup

Before surgery, imaging is used to assess the extent of the disease and guide surgical planning. Common modalities include:

• Pelvic MRI: Often used for local staging and assessing myometrial invasion.
• Computed Tomography (CT): Useful for evaluating distant spread.
• Fluorodeoxyglucose (FDG)-PET/CT: May be utilized in specific clinical contexts to identify metastatic sites.

The integration of these pathologic, molecular, and surgical principles ensures that each patient receives a treatment plan tailored to their specific tumor biology and stage.