Cancer Grading is Based on Cell Differentiation
Cancer grading is fundamentally based on cell differentiation—the degree to which cancer cells resemble normal, mature cells of the tissue from which they originated. 1
Understanding the Grading System
The histologic grade of a tumor evaluates how much cancer cells differ from their normal counterparts under microscopic examination. This assessment is distinct from staging, which measures tumor size, local invasion, and metastasis. 2
Key Grading Principles
Well-differentiated tumors (Grade 1) show cells that closely resemble normal tissue architecture and cellular features, indicating slower growth and better prognosis 1
Moderately differentiated tumors (Grade 2) demonstrate intermediate characteristics between normal and abnormal cellular appearance 1
Poorly differentiated tumors (Grade 3) contain cells that look markedly abnormal compared to normal tissue, with loss of organized structure and increased aggressive behavior 1
Specific Grading Systems by Cancer Type
Sarcomas (FNCLCC System)
The Federation Nationale des Centres de Lutte Contre le Cancer grading system evaluates three parameters to determine malignancy grade: 1
- Tumor differentiation (scored 1-3: well, moderate, poor)
- Necrosis (scored 0-2: absent, <50%, ≥50%)
- Mitotic count (scored 1-3: <10-19, ≥20 per 10 high-power fields)
The sum of these scores determines the final grade (Grade 1: 2-3 points; Grade 2: 4-5 points; Grade 3: 6-8 points). 1
Prostate Cancer (Gleason Score)
The Gleason score specifically measures the degree of glandular differentiation, adding the two most common histologic patterns (each scored 1-5) to create a final score of 6-10. 1, 3, 4
- Gleason 6 (3+3): Well-differentiated with organized gland formation 1, 3
- Gleason 7: Moderately differentiated with intermediate features 1, 3
- Gleason 8-10: Poorly differentiated with minimal to no gland formation 1, 3
Colorectal Cancer
Histological grading traditionally assesses the percentage of gland formation, though newer systems evaluate poorly differentiated clusters for improved reproducibility and prognostic accuracy. 1, 5, 6, 7
Renal Cell Carcinoma
The International Society of Urological Pathology (ISUP) grading system for clear-cell and papillary RCC is based on nucleolar size and prominence, which reflects cellular differentiation. 1
Why Differentiation Matters Clinically
Poorly differentiated tumors pursue more aggressive courses than well-differentiated counterparts, independent of tumor size or extent of spread. 2 This makes grading a critical prognostic indicator that:
- Separates patients into distinct risk subgroups within the same stage 2
- Guides treatment intensity decisions 1, 3, 4
- Provides prognostic information beyond what staging alone offers 2
Important Clinical Caveat
Grading cannot be reliably assigned after preoperative chemotherapy or radiation, as treatment-induced changes alter cellular morphology and obscure the original differentiation pattern. 1 In these cases, pre-treatment biopsy grading must be used for clinical decision-making.
Distinguishing Grading from Staging
While tumor size, local invasion, and metastasis are components of staging (TNM classification), they do not define grading. 1 Grading specifically evaluates cellular and architectural features that reflect how abnormal the cancer cells appear compared to normal tissue—a direct measure of differentiation. 1, 2