Stage Information

Nonmetastatic Disease
Metastatic Disease
Recurrent/Progressive Disease
TNM Stage Information
Soft Tissue Sarcoma Tumor Pathological Grading System
        Grade 1 lesions
        Grade 2 lesions
        Grade 3 lesions
Prognostic Significance of Tumor Staging

Clinical staging has an important role in predicting the clinical outcome and determining the most effective therapy for pediatric soft tissue sarcomas. As yet, there is no well-accepted staging system that is applicable to all childhood sarcomas; the system from the American Joint Commission for Cancer (AJCC) that is used for adults has not been validated in pediatric studies, however, the current Children's Oncology Group (COG) trial is using the AJCC staging system (see Tables 2–5 below) to facilitate comparison of results with other pediatric and adult soft tissue sarcoma trials.[1] Two systems are currently in use for staging pediatric nonrhabdomyosarcomatous soft tissue sarcoma (NRSTS) tumors. The surgicopathologic staging system used by the Intergroup Rhabdomyosarcoma Study (see below) is based on the amount of tumor that remains after initial surgery and whether the disease has metastasized.[2]

Nonmetastatic Disease

• Group I: Tumor completely resected with histologically negative margins.
• Group II: Grossly resected tumor with microscopic residual tumor.
  • IIA: Grossly resected tumor with microscopic residual disease.
  • IIB: Regional disease with involved nodes completely resected with no microscopic disease.
  • IIC: Regional disease with involved nodes grossly resected but with evidence of residual microscopic disease and/or histologic involvement of the most distal regional lymph node in the dissection.
• Group III: Incomplete resection or biopsy with gross residual tumor.

Metastatic Disease

• Group IV: Any localized or regional tumor with distant metastases present at the time of diagnosis.

Recurrent/Progressive Disease

• Any soft tissue sarcoma that recurs after initial treatment or progresses after radiation therapy, chemotherapy, or initial surgery.

The other schema typically used to stage pediatric soft tissue tumors is the TNM system of the International Union Against Cancer.[3] In this staging system, T1 lesions are 5 cm or less in greatest dimension, and T2 lesions are more than 5 cm in greatest dimension. These categories can be subclassified to reflect the maximum tumor depth (a: superficial tumor; b: deep tumor). Regional nodal involvement is indicated by the N1 (N0: no regional nodal involvement) designation and the presence of distant metastases at the time of diagnosis is indicated by the M1 (M0: no metastatic involvement) designation.

TNM Stage Information

The American Joint Committee on Cancer (AJCC) has designated staging by the four criteria of tumor size, nodal status, grade ¹, and metastasis (TNGM).[4]

Table 2. Primary Tumor (T)^a

TX	Primary tumor cannot be assessed.
T0	No evidence of primary tumor.
T1	Tumor ≤5 cm in greatest dimension.b
T1a	Superficial tumor.
T1b	Deep tumor.
T2	Tumor >5 cm in greatest dimension.b
T2a	Superficial tumor.
T2b	Deep tumor.

aReprinted with permission from AJCC: Soft tissue sarcoma. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 291-8.

bSuperficial tumor is located exclusively above the superficial fascia without invasion of the fascia; deep tumor is located either exclusively beneath the superficial fascia, superficial to the fascia with invasion of or through the fascia, or both superficial yet beneath the fascia.

Table 3. Regional Lymph Nodes (N)^a

NX	Regional lymph nodes cannot be assessed.
N0	No regional lymph node metastasis.
N1b	Regional lymph node metastasis.

aReprinted with permission from AJCC: Soft tissue sarcoma. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 291-8.

bPresence of positive nodes (N1) in M0 tumors is considered Stage III.

Table 4. Distant Metastasis (M)^a

aReprinted with permission from AJCC: Soft tissue sarcoma. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 291-8.
M0	No distant metastasis.
M1	Distant metastasis.

Table 5. Anatomic Stage/Prognostic Groups^a

Stage	T	N	M	Grade
aReprinted with permission from AJCC: Soft tissue sarcoma. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 291-8.
IA	T1a	N0	M0	G1, GX
	T1b	N0	M0	G1, GX
IB	T2a	N0	M0	G1, GX
	T2b	N0	M0	G1, GX
IIA	T1a	N0	M0	G2, G3
	T1b	N0	M0	G2, G3
IIB	T2a	N0	M0	G2
	T2b	N0	M0	G2
III	T2a, T2b	N0	M0	G3
	Any T	N1	M0	Any G
IV	Any T	Any N	M1	Any G

Soft Tissue Sarcoma Tumor Pathological Grading System

In most cases, accurate histopathologic classification of soft tissue sarcomas alone does not yield optimal information about their clinical behavior. Therefore, several histologic parameters, including degree of cellularity, cellular pleomorphism, mitotic activity, degree of necrosis, and invasive growth, are evaluated in the grading process. This process is used to improve the correlation between histologic findings and clinical outcome.[5] In children, grading of soft tissue sarcomas is compromised by the good prognosis of certain tumors such as infantile fibrosarcoma. In addition, testing of a grading system within the pediatric population is difficult because of the rarity of these neoplasms. In March 1986, the Pediatric Oncology Group conducted a prospective study on pediatric soft tissue sarcomas other than rhabdomyosarcoma and devised the grading system that is shown below. Analysis of outcome for patients with localized soft tissue sarcomas other than rhabdomyosarcoma demonstrated that patients with grade 3 tumors fared significantly worse than did those with grade 1 or grade 2 lesions. This finding suggests that this system can accurately predict the clinical behavior of nonrhabdomyosarcomatous soft tissue tumors in children.[5-7] The current COG protocol, (COG-ARST0332 ⁶), is evaluating the grading systems developed by the COG (see below) and the French Federation of Cancer Centers Sarcoma Group.[8]

Grade 1 lesions

• Angiomatoid malignant fibrous histiocytoma.
• Deep-seated dermatofibrosarcoma protuberans.
• Extraosseous myxoid chondrosarcoma.
• Myxoid and well-differentiated liposarcoma.
• Well-differentiated malignant peripheral nerve sheath tumor.
• Well-differentiated or infantile (patient age 4 years or younger) fibrosarcoma.
• Well-differentiated or infantile (patient age 4 years or younger) hemangiopericytoma.

Grade 2 lesions

In grade 2 lesions, which are soft tissue sarcomas not included in grade 1 and grade 3 lesions, less than 15% of the surface area shows necrosis, and there are fewer than five mitotic figures per ten high-power fields (40X objective). As secondary criteria of grade 2 tumors, the incidence of nuclear atypia is not marked, and the tumor is not markedly cellular.

Grade 3 lesions

• Alveolar soft part sarcoma.
• Clear cell sarcoma (MMSP).
• Desmoplastic small round cell tumor.
• Epithelioid sarcoma.
• Extraosseous osteosarcoma.
• Mesenchymal chondrosarcoma.[9]
• Pleomorphic or round cell liposarcoma.
• Synovial sarcoma.
• Triton tumor (MPNST with rhabdomyosarcomatous elements).
• Undifferentiated soft tissue sarcoma.

Any other sarcoma not included in grade 1 in which more than 15% of the surface area is necrotic or in which there are more than five mitotic figures per ten high-power fields (40X objective) is considered a grade 3 lesion. Marked atypia and cellularity are less predictive but may assist in placing tumors in this category.

Although a standardized staging system for pediatric NRSTS does not exist, the current COG trial is using the sixth edition AJCC staging system for soft tissue sarcomas (with central pathology review).[10]

Prognostic Significance of Tumor Staging

These two staging systems have proven to be of prognostic significance in pediatric and adult NRSTSs.[11-15] In a review of a large adult series of NRSTSs, superficial extremity sarcomas have a better prognosis than deep tumors. Thus, in addition to grade and size, the depth of invasion of the tumor should be considered.[16]

Several adult and pediatric series have shown that patients with large or invasive tumors have a significantly worse prognosis than do those with small, noninvasive tumors. A retrospective review of soft tissue sarcomas in children and adolescents suggests that the 5 cm cutoff used for adults with soft tissue sarcoma may not be ideal for smaller children, especially infants. The review identified an interaction between tumor diameter and body surface area.[17] This relationship requires further study to determine the therapeutic implications of the observation.

References

1. Weiss SW, Goldblum JR: Enzinger and Weiss's Soft Tissue Tumors. 4th ed. St. Louis, Mo: Mosby, 2001. 
   
   
2. Maurer HM, Beltangady M, Gehan EA, et al.: The Intergroup Rhabdomyosarcoma Study-I. A final report. Cancer 61 (2): 209-20, 1988.  [PUBMED Abstract]
   
   
3. Harmer MH, ed.: TNM Classification of Pediatric Tumors. Geneva: UICC, 1982. 
   
   
4. Soft tissue sarcoma. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 291-6. 
   
   
5. Parham DM, Webber BL, Jenkins JJ 3rd, et al.: Nonrhabdomyosarcomatous soft tissue sarcomas of childhood: formulation of a simplified system for grading. Mod Pathol 8 (7): 705-10, 1995.  [PUBMED Abstract]
   
   
6. Recommendations for the reporting of soft tissue sarcomas. Association of Directors of Anatomic and Surgical Pathology. Mod Pathol 11 (12): 1257-61, 1998.  [PUBMED Abstract]
   
   
7. Skytting B, Meis-Kindblom JM, Larsson O, et al.: Synovial sarcoma--identification of favorable and unfavorable histologic types: a Scandinavian sarcoma group study of 104 cases. Acta Orthop Scand 70 (6): 543-54, 1999.  [PUBMED Abstract]
   
   
8. Coindre JM, Terrier P, Guillou L, et al.: Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: a study of 1240 patients from the French Federation of Cancer Centers Sarcoma Group. Cancer 91 (10): 1914-26, 2001.  [PUBMED Abstract]
   
   
9. Dantonello TM, Int-Veen C, Leuschner I, et al.: Mesenchymal chondrosarcoma of soft tissues and bone in children, adolescents, and young adults: experiences of the CWS and COSS study groups. Cancer 112 (11): 2424-31, 2008.  [PUBMED Abstract]
   
   
10. American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002. 
    
    
11. Rao BN: Nonrhabdomyosarcoma in children: prognostic factors influencing survival. Semin Surg Oncol 9 (6): 524-31, 1993 Nov-Dec.  [PUBMED Abstract]
    
    
12. Pisters PW, Leung DH, Woodruff J, et al.: Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol 14 (5): 1679-89, 1996.  [PUBMED Abstract]
    
    
13. Coindre JM, Terrier P, Bui NB, et al.: Prognostic factors in adult patients with locally controlled soft tissue sarcoma. A study of 546 patients from the French Federation of Cancer Centers Sarcoma Group. J Clin Oncol 14 (3): 869-77, 1996.  [PUBMED Abstract]
    
    
14. Pappo AS, Fontanesi J, Luo X, et al.: Synovial sarcoma in children and adolescents: the St Jude Children's Research Hospital experience. J Clin Oncol 12 (11): 2360-6, 1994.  [PUBMED Abstract]
    
    
15. Pratt CB, Maurer HM, Gieser P, et al.: Treatment of unresectable or metastatic pediatric soft tissue sarcomas with surgery, irradiation, and chemotherapy: a Pediatric Oncology Group study. Med Pediatr Oncol 30 (4): 201-9, 1998.  [PUBMED Abstract]
    
    
16. Brooks AD, Heslin MJ, Leung DH, et al.: Superficial extremity soft tissue sarcoma: an analysis of prognostic factors. Ann Surg Oncol 5 (1): 41-7, 1998 Jan-Feb.  [PUBMED Abstract]
    
    
17. Ferrari A, Miceli R, Meazza C, et al.: Soft tissue sarcomas of childhood and adolescence: the prognostic role of tumor size in relation to patient body size. J Clin Oncol 27 (3): 371-6, 2009.  [PUBMED Abstract]