Grading vs. Staging of Endometrial Carcinoma
Grading describes the tumor's histological differentiation and cellular aggressiveness, while staging defines the anatomical extent of disease spread—grading predicts biological behavior, staging determines treatment strategy.
Grading: Histological Differentiation Assessment
Grading evaluates the microscopic architecture and cellular characteristics of the tumor itself. 1
FIGO Grading System for Endometrioid Carcinoma
The degree of histological differentiation is assessed by measuring the proportion of solid (non-squamous, non-morular) growth pattern 1, 2:
- Grade 1 (G1): ≤5% solid growth pattern 1, 2
- Grade 2 (G2): 5–50% solid growth pattern 1, 2
- Grade 3 (G3): >50% solid growth pattern 1, 2
Critical caveat: Notable nuclear atypia that is inappropriate for the architectural grade automatically upgrades a Grade 1 or 2 tumor by one grade level 1, 2. This rule prevents under-treatment of biologically aggressive tumors that would otherwise appear well-differentiated architecturally 2.
Grading Limitations
- Preoperative grading based on endometrial sampling changes at final pathology in up to 25% of cases 1, 2
- Interobserver reproducibility of FIGO grading is suboptimal, particularly for distinguishing Grade 1 from Grade 2 tumors 3, 4
- Grading applies primarily to endometrioid histology; serous, clear cell, and undifferentiated carcinomas are automatically considered high-grade regardless of architecture 1
Staging: Anatomical Extent of Disease
Staging defines where the cancer has spread anatomically and is determined surgically. 1
FIGO 2009 Staging System
The most widely used classification endorsed by FIGO 1, 2:
Stage I—Confined to the uterus:
- Ia: Tumor limited to the endometrium or invading <50% of myometrium 1, 2
- Ib: Invasion ≥50% of myometrium 1, 2
Stage II—Extension to the cervix:
Stage III—Extension beyond the uterus:
- IIIa: Tumor invades serosa and/or adnexa, and/or positive peritoneal cytology 1, 2
- IIIb: Vaginal involvement 1, 2
- IIIc: Metastasis to pelvic or para-aortic lymph nodes 1, 2
Stage IV—Invasion of neighboring organs or distant metastases:
- IVa: Tumor invasion of bladder and/or bowel mucosa 1, 2
- IVb: Distant metastases including intra-abdominal or inguinal lymph nodes 1, 2
Staging Requirements
Surgical staging must include total hysterectomy with bilateral salpingo-oophorectomy, peritoneal washings, thorough abdominal exploration, and assessment of pelvic and para-aortic lymph nodes 2, 5. For high-risk histologies (Grade 3 or non-endometrioid types), retroperitoneal lymph node dissection and omentectomy (particularly for serous carcinoma) are recommended 1, 2.
Integration: Risk Stratification Combines Both
Both grading and staging are independent prognostic factors that together determine treatment. 1, 2
Approximately 75% of patients present with Stage I disease, which is subdivided into risk categories based on both stage and grade 1, 2:
- Low-risk: Stage Ia/Ib, Grade 1–2, endometrioid histology—no adjuvant therapy required 1, 2, 5
- Intermediate-risk: Stage Ic Grade 1–2 OR Stage Ia/Ib Grade 3, endometrioid histology—consider adjuvant radiotherapy 1, 2
- High-risk: Stage Ic Grade 3 OR any stage with serous, clear cell, small cell, or undifferentiated histology—requires combined chemotherapy and radiotherapy 1, 2
Additional Prognostic Factors
Beyond grade and stage, established independent prognostic factors include depth of myometrial invasion, histological type, tumor diameter, lymphovascular space involvement, endocervical stromal invasion, and patient age 1, 2. These factors refine risk assessment when grade and stage alone are insufficient for treatment decisions 1.
Common Pitfalls
Frozen section assessment is unreliable for determining final grade or stage intraoperatively—decisions regarding lymphadenectomy should rely on preoperative risk assessment rather than frozen section findings 1, 2. The preoperative diagnosis changes at final pathology in up to 25% of cases, making definitive surgical planning challenging 1, 2.
Serous and clear cell carcinomas are automatically high-risk regardless of stage or grade and require aggressive treatment with chemotherapy 1, 2, 6. Do not be misled by low stage or favorable architecture in these histologic subtypes 6.