FNCLCC Grading System for Soft Tissue Sarcomas
The FNCLCC (Fédération Nationale des Centres de Lutte Contre le Cancer) grading system is the standard method for grading soft tissue sarcomas, distinguishing three malignancy grades (1,2, and 3) based on three scored parameters: tumor differentiation, necrosis extent, and mitotic count. 1, 2
The Three-Parameter Scoring System
The FNCLCC system evaluates each of the following parameters and assigns numerical scores 1, 2:
Tumor Differentiation
- Score 1: Well-differentiated tumors that closely resemble normal tissue 1, 2
- Score 2: Moderately differentiated tumors with intermediate features 1
- Score 3: Poorly differentiated tumors with minimal resemblance to tissue of origin 1, 2
Necrosis Assessment
- Score 0: No necrosis present 1, 2
- Score 1: Less than 50% tumor necrosis 1, 2
- Score 2: 50% or greater tumor necrosis 1, 2
Mitotic Count (per 10 high-power fields)
Final Grade Calculation
Sum the three parameter scores to determine the final malignancy grade 1, 2:
- Grade 1 (Low-grade): Total score of 2 or 3 1
- Grade 2 (Intermediate-grade): Total score of 4 or 5 1
- Grade 3 (High-grade): Total score of 6,7, or 8 1
Clinical Application and Prognostic Significance
Histologic grading using the FNCLCC system is the single most important prognostic factor in soft tissue sarcomas, serving as the primary determinant for metastatic risk assessment and adjuvant treatment decisions. 2 The FNCLCC system demonstrates superior prognostic value compared to other grading systems, with higher predictive weight assigned in multivariate analysis for metastasis development and tumor mortality 3.
Practical Implementation Algorithm
Obtain adequate tissue: Use multiple core needle biopsies under imaging guidance, avoiding frozen sections which prevent complete diagnosis 1, 2
Ensure expert pathology review: Pathological expert validation is required when the original diagnosis was made outside a reference center 1, 2
Score all three parameters: Apply the FNCLCC system systematically, calculating the total score 2
Report mitotic rate independently: Provide the actual mitotic count separately whenever possible, as mitotic index is a key prognostic parameter 2, 4
Integrate with staging: Combine grade with tumor size, depth, and site for comprehensive risk assessment 2
Critical Limitations and Pitfalls
Core Needle Biopsy Underestimation
Core biopsies may underestimate tumor malignancy grade in up to 12% of cases. 1 When preoperative treatment is planned, radiological imaging showing necrosis provides additional information to estimate malignancy grade 1. Modified grading systems incorporating Ki-67 immunoexpression and radiological necrosis assessment improve accuracy to 91.2% versus 87.9% with conventional methods 5.
Myxoid Tumor Discrepancies
Many discrepant cases where core biopsy underestimates grade involve myxoid tumors (myxofibrosarcomas or myxoid liposarcomas), leiomyosarcomas, or undifferentiated pleomorphic sarcomas 5. A higher than expected Ki-67 score in a low-grade sarcoma on core biopsy should raise concern that a higher-grade component was not sampled. 5
Post-Treatment Grading Prohibition
Grading cannot be reliably assigned after preoperative medical treatment, as tumor tissue undergoes major therapy-related changes that prevent standard malignancy grading. 1, 6 This includes the presence of non-treatment-related necrosis, hemorrhage, and heterogeneity of post-treatment changes 1.
Histotype-Specific Considerations
FNCLCC grading has no prognostic significance in certain tumor types such as malignant peripheral nerve sheath tumors (MPNST) and angiosarcomas 7. The system was developed primarily in adult cohorts, though it demonstrates adequate prognostic utility in pediatric nonrhabdomyosarcoma soft tissue sarcomas 4.
Quality Assurance Requirements
The mitotic rate should be recorded with improved reliability, and external quality assurance programs are strongly encouraged for laboratories performing grading assessments. 2 Pathological assessment must be made in collaboration with the surgeon and discussed at specialized sarcoma multidisciplinary team meetings 2. Correlation of all clinicopathological and radiological findings at multidisciplinary meetings is essential to assess histological grade on core biopsy as accurately as possible 5.