Grading of Sarcoma: Prognostic and Treatment Implications

Introduction to Sarcoma Grading

The European Society for Medical Oncology recommends that histologic grading is the single most important prognostic factor in soft tissue sarcomas, serving as the primary determinant for metastatic risk assessment and adjuvant treatment decisions 1, 2
The European Society for Medical Oncology suggests that grading must be provided in all feasible cases because it has both prognostic and predictive meaning that directly influences treatment intensity 1, 3

The Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system is the standard grading method and distinguishes three malignancy grades based on three parameters, as recommended by the European Society for Medical Oncology 1, 3, 4
The FNCLCC system evaluates tumor differentiation, with scores ranging from 1 (well-differentiated) to 3 (poorly differentiated), as suggested by the European Society for Medical Oncology 4, 5
The FNCLCC system assesses necrosis, with scores ranging from 0 (absent) to 2 (≥50%), as recommended by the European Society for Medical Oncology 5, 6
The FNCLCC system evaluates mitotic count, with scores ranging from 1 (<10 mitoses) to 3 (≥20 mitoses), as suggested by the European Society for Medical Oncology 2, 5, 6

The Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) staging system emphasizes histologic grade as the primary determinant, combined with tumor size, depth, and presence of metastases, as recommended by the European Society for Medical Oncology 1, 2, 3
The UICC/AJCC staging system places grade above size and depth in prognostic importance, as suggested by the European Society for Medical Oncology 2

The European Society for Medical Oncology recommends obtaining adequate tissue through multiple core needle biopsies under imaging guidance 2
The European Society for Medical Oncology suggests ensuring expert pathology review, with pathological expert validation required when the original diagnosis was made outside a reference center 1, 3
The European Society for Medical Oncology recommends applying the FNCLCC grading system, scoring all three parameters and calculating the total 1, 3
The European Society for Medical Oncology suggests reporting the mitotic rate independently, whenever possible, and providing the actual mitotic count separately 1, 6
The European Society for Medical Oncology recommends integrating grade with tumor size, depth, and site for comprehensive risk assessment, and using nomograms for treatment decisions, particularly for adjuvant/neoadjuvant therapy selection 1, 2, 5

The European Society for Medical Oncology recommends that the mitotic rate should be recorded with improved reliability, and external quality assurance programs are strongly encouraged for laboratories performing grading assessments 1, 6
The European Society for Medical Oncology suggests that the pathological assessment should be made in collaboration with the surgeon and discussed at specialized sarcoma multidisciplinary team meetings 2, 5

The Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grading system is the standard method for grading soft‑tissue sarcomas, distinguishing three malignancy grades (1, 2, 3) based on tumor differentiation, necrosis extent, and mitotic count. 7

Tumor differentiation – Score 1 for well‑differentiated tumors, Score 2 for moderately differentiated tumors, and Score 3 for poorly differentiated tumors. 7
Necrosis extent – Score 0 when no necrosis is present, Score 1 when necrosis involves < 50 % of the tumor, and Score 2 when necrosis involves ≥ 50 % of the tumor. 7
Mitotic count (per 10 high‑power fields) – Score 1 for < 10 mitoses, Score 2 for 10–19 mitoses, and Score 3 for ≥ 20 mitoses. 7

The three parameter scores are summed to obtain the final grade:
- Grade 1 (low‑grade) – total score 2–3
- Grade 2 (intermediate‑grade) – total score 4–5
- Grade 3 (high‑grade) – total score 6–8
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Adequate tissue acquisition requires multiple core‑needle biopsies performed under imaging guidance; frozen sections should be avoided because they may prevent a complete diagnosis. 7
Expert pathology review is mandatory when the initial diagnosis was made outside a specialized sarcoma reference center. 7

Core‑needle biopsies can underestimate the true malignancy grade in up to 12 % of cases. 7
When pre‑operative treatment is planned, radiological imaging that demonstrates necrosis provides additional information to help estimate the malignancy grade. 7
Grading cannot be reliably assigned after pre‑operative medical therapy because therapy‑related changes (e.g., necrosis, hemorrhage, heterogeneous tissue alterations) obscure the standard histologic criteria. 7