What is the difference between FIGO grade and FIGO stage in endometrial cancer?

FIGO Grade vs FIGO Stage in Endometrial Cancer

FIGO grade measures the degree of tumor differentiation based on architectural pattern and nuclear atypia, while FIGO stage describes the anatomic extent of disease spread determined through surgical and pathologic assessment.

FIGO Grading System

FIGO grading is a histologic assessment of tumor differentiation that evaluates the microscopic appearance of cancer cells 1:

• Grade 1 (G1): Well-differentiated tumor with ≤5% non-squamous, non-morula solid growth pattern 1
• Grade 2 (G2): Moderately differentiated tumor with 5-50% solid growth pattern 1
• Grade 3 (G3): Poorly differentiated tumor with >50% solid growth pattern 1

Nuclear atypia can upgrade the grade: If notable nuclear atypia is present that is inappropriate for the architectural grade, a Grade 1 or 2 tumor is raised by one grade level 1. Marked nuclear atypia is defined as significant nuclear pleomorphism identifiable at 10× magnification or enlarged nuclei (1.5-2× normal size) with irregular nuclear contours, dispersed chromatin, and prominent nucleoli 2.

Key Grading Principles

• Grading is determined from endometrial biopsy or final surgical pathology 1
• For serous adenocarcinomas, clear cell adenocarcinomas, and squamous cell carcinomas, nuclear grading takes precedence over architectural patterns 3
• Adenocarcinomas with squamous differentiation are graded according to the nuclear grade of the glandular component 3

FIGO Staging System

FIGO staging is a surgical-pathologic system that describes the anatomic extent of disease spread 1, 4. The 2009 FIGO system (current standard) replaced the outdated 1970 clinical staging system, which was inaccurate in 15-20% of patients 1, 4.

Current FIGO 2009 Staging Definitions

Stage I - Confined to the uterus:

• IA: Tumor with <50% myometrial invasion 1, 5
• IB: Tumor with ≥50% myometrial invasion 1, 5

Stage II: Tumor invades cervical stroma but does not extend beyond the uterus 1, 5. Endocervical glandular involvement without stromal invasion remains Stage I 1, 4.

Stage III - Local/regional spread:

• IIIA: Tumor invades serosa and/or adnexa 5, 4
• IIIB: Vaginal and/or parametrial involvement 5, 4
• IIIC1: Positive pelvic lymph nodes only 1, 5
• IIIC2: Positive para-aortic lymph nodes with or without pelvic nodes 1, 5

Stage IV - Distant spread:

• IVA: Tumor invasion of bladder and/or bowel mucosa 5
• IVB: Distant metastases including intra-abdominal or inguinal lymph nodes 5

Critical Staging Principles

Surgical staging is mandatory and includes total hysterectomy with bilateral salpingo-oophorectomy, peritoneal washings, thorough abdominal exploration, and assessment of myometrial invasion depth 1, 5. The 2009 FIGO system emphasizes thorough surgical/pathologic assessment of histologic grade, myometrial invasion, and extent of extrauterine spread 1, 4.

Positive peritoneal cytology no longer upstages disease in the 2009 FIGO system, though it remains an independent risk factor 1, 4.

How Grade and Stage Work Together

Both grade and stage are independent prognostic factors that work synergistically to determine risk stratification and treatment planning 1, 6. Approximately 75% of patients present with Stage I disease, which is subdivided into risk categories based on both stage and grade 1, 5:

• Low risk: Stage IA, Grade 1-2, endometrioid histology 1, 5
• Intermediate risk: Stage IB Grade 1-2, or Stage IA Grade 3, endometrioid histology 1, 5
• High risk: Stage IB Grade 3, or any stage with serous/clear cell/undifferentiated histology 1, 5

Multivariate analysis confirms that FIGO stage, grade, age, and depth of myometrial invasion are independent predictors of outcome 6. The surgical staging system better predicts outcome compared with clinical staging alone 6.

Common Pitfalls to Avoid

• Do not confuse preoperative biopsy grade with final pathologic grade: The preoperative histological diagnosis (type and grade) changes at final evaluation in up to 25% of cases 1
• Do not upstage based solely on positive peritoneal cytology, as this is no longer part of the 2009 staging criteria 1, 4
• Do not classify endocervical glandular involvement without stromal invasion as Stage II; these patients remain Stage I 1, 4
• Recognize that Grade 2 tumors defined by nuclear atypia alone (with <5% solid growth) have similar myoinvasion rates (89%) as architecturally-defined Grade 2 tumors, validating the nuclear upgrade rule 2