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Cancer Types   /   Pediatric Cancers   /   Sarcomas: Rhabdomyosarcoma   /   NCI Resources

NCI/PDQ® Health professionals: Childhood Soft Tissue Sarcoma Treatment (PDQ®)

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National Cancer Institute
Last Modified: December 3, 2012

TABLE OF CONTENTS


General Information

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Fortunately, cancer in children and adolescents is rare, although the overall incidence of childhood cancer has been slowly increasing since 1975. 1 Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the primary care physician, pediatric surgical subspecialists, pediatric radiation oncologist, pediatric hematologist/oncologist, rehabilitation specialist, pediatric nurse specialists, social workers, and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life. Refer to the PDQ® Supportive and Palliative Care summaries for specific information about supportive care for children and adolescents with cancer.

Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics. 2 At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate in these trials is offered to most patients/families. Clinical trials for children and adolescents with cancer are generally designed to compare potentially better therapy with therapy that is currently accepted as standard. Most of the progress made in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI Web site.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2002, childhood cancer mortality has decreased by more than 50%. 1 Childhood and adolescent cancer survivors require close follow-up because cancer therapy side effects may persist or develop months or years after treatment. Refer to the PDQ® summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.


Incidence

Pediatric soft tissue sarcomas (STSs) are a heterogenous group of malignant tumors that originate from primitive mesenchymal tissue and account for 7% of all childhood tumors. 3 Multidisciplinary evaluation in centers that have surgical and radiotherapeutic expertise is of critical importance to ensure the best clinical outcome for these patients. Although surgery with or without radiation therapy can be curative for a significant proportion of patients, the addition of chemotherapy might benefit subsets of children with the disease; therefore, enrollment into clinical trials is encouraged.

Rhabdomyosarcoma, a tumor of striated muscle, is the most common STS in children aged 0 to 14 years and accounts for 50% of tumors in this age group. 4 (Refer to the PDQ® summary on Childhood Rhabdomyosarcoma Treatment for more information.) The remaining STSs are commonly referred to as nonrhabdomyosarcomatous STSs and account for about 3% of all childhood tumors. 5 This heterogeneous group of tumors includes neoplasms of: 6

  • Connective tissue (fibrous and adipose).
  • Peripheral nervous system.
  • Smooth muscle (leiomyosarcomas).
  • Vascular tissue (blood and lymphatic vessels).

In children, synovial sarcoma, fibrosarcoma, fibrohistiocytic tumors, and malignant peripheral nerve sheath tumors predominate. 7 8 The distribution of STSs by histology and age, based on the Surveillance Epidemiology and End Results (SEER) information from 1975 to 2008, is depicted in Table 1. The distribution of histologic types by age is shown in Figure 1.


Table 1. Age Distribution of Soft Tissue Sarcomas (STSs) in Children Aged 0 to 19 Years (SEER 19752008)

aDermatofibrosarcoma accounts for 75% of these cases.
  Age <5 y  Age 59 y  Age 1014 y  Age 1519 y  % of the Total Number of STS Cases <20 y 
All soft tissue and other extraosseous sarcomas  1,130  810  1,144  1,573  100 
 
Rhabdomyosarcomas  710  466  364  350  41 
Fibrosarcomas, peripheral nerve, and other fibrous neoplasms  151  64  132  192  12 
  Fibroblastic and myofibroblastic tumors  131  31  57  86    6.5 
  Nerve sheath tumors  19  32  74  104    5 
  Other fibromatous neoplasms  1  1  1  2    0.1 
Kaposi sarcoma  1  2  0  12  0.3 
Other specified soft tissue sarcomas  198  220  512  856  38 
  Ewing tumor and Askin tumor of soft tissue  22  28  57  81    4 
  pPNET of soft tissue  21  19  29  42    2.4 
  Extrarenal rhabdoid tumor  37  3  8  3    1 
  Liposarcomas  5  6  22  66    2 
  Fibrohistiocytic tumorsa  53  69  171  293    12 
  Leiomyosarcomas  13  19  22  57    2.4 
  Synovial sarcomas  12  39  133  204    8.3 
  Blood vessel tumors  15  7  11  33    1.4 
  Osseous and chondromatous neoplasms of soft tissue  1  5  9  16    0.6 
  Alveolar soft parts sarcoma  3  7  19  26    1 
  Miscellaneous soft tissue sarcomas  16  18  31  35    2 
Unspecified soft tissue sarcomas  70  58  136  163  9 
pPNET = peripheral primitive neuroectodermal tumors; SEER = Surveillance Epidemiology and End Results. 
 

Figure 1. The distribution of nonrhabdomyosarcomatous soft tissue sarcomas in children aged 0 to 19 years, as reported by the Surveillance Epidemiology and End Results program from 1975 to 2008.

Nonrhabdomyosarcomatous STSs are more common in adolescents and adults, 6 and most of the information regarding treatment and natural history of the disease in younger patients has been based on adult studies.


Risk Factors

Some genetic and environmental factors have been associated with the development of nonrhabdomyosarcomatous STS:

  • Genetic factors:
    • Li-Fraumeni syndrome: Patients with Li-Fraumeni syndrome (usually due to heritable cancer-associated changes of the p53 tumor suppressor gene) have an increased risk of developing soft tissue tumors (mostly nonrhabdomyosarcomatous STSs), bone sarcomas, breast cancer, brain tumors, and acute leukemia. 5 9
    • Neurofibromatosis type 1: Approximately 4% of patients with neurofibromatosis type 1 develop malignant peripheral nerve sheath tumors, which usually develop after a long latency; some patients develop multiple lesions. 10 11 12
    • Familial adenomatous polyposis: Patients with familial adenomatous polyposis are at increased risk of developing desmoid tumors. 13
    • Werner syndrome: Werner syndrome is characterized by spontaneous chromosomal instability, resulting in increased susceptibility to cancer and premature aging. An excess of STSs has been reported in patients with Werner syndrome. 14
    • Retinoblastoma gene: Germline mutations of the retinoblastoma gene have been associated with an increased risk of developing STSs, particularly leiomyosarcoma. 15

  • Environmental factors:
    • Radiation: Some nonrhabdomyosarcomatous STSs (particularly malignant fibrous histiocytoma) can develop within a previously irradiated site. 5 16
    • Epstein-Barr virus infection in patients with AIDS: Some nonrhabdomyosarcomatous STSs (e.g., leiomyosarcoma) have been linked to Epstein-Barr virus infection in patients with AIDS. 5 17


Clinical Presentation

Although nonrhabdomyosarcomatous STSs can develop in any part of the body, they arise most commonly in the trunk and extremities. 7 18 19 These neoplasms can present initially as an asymptomatic solid mass, or they may be symptomatic because of local invasion of adjacent anatomical structures.

Systemic symptoms (e.g., fever, weight loss, and night sweats) are rare. Hypoglycemia and hypophosphatemic rickets have been reported in cases of hemangiopericytoma, whereas hyperglycemia has been noted in patients with fibrosarcoma of the lung. 20


Diagnosis

When a suspicious lesion is identified, it is crucial that a complete workup, followed by adequate biopsy be performed. Generally, it is better to image the lesion prior to any interventions. Plain films can be used to rule out bone involvement and detect calcifications that may be seen in soft tissue tumors such as extraskeletal osteosarcoma or synovial sarcoma. Chest radiography and computed tomography (CT) of chest are essential to assess the presence of metastases. CT can be used to image intraabdominal tumors, such as liposarcoma, and magnetic resonance imaging (MRI) can be used for extremity lesions.

Nonrhabdomyosarcomatous soft tissue tumors are fairly readily distinguished pathologically from rhabdomyosarcoma and Ewing sarcoma; however, classification of childhood nonrhabdomyosarcomatous STS type is often difficult. A core-needle biopsy or small incisional biopsy that obtains adequate tumor tissue is crucial to allow for conventional histology, immunocytochemical analysis, and other studies such as light and electron microscopy, cytogenetics, fluorescence in situ hybridization, and molecular pathology, 21 22 given the diagnostic importance of translocations. Needle biopsy techniques must obtain an adequate tissue sample and usually require obtaining multiple cores of tissue. Image guidance using ultrasound, CT scan, or MRI may be necessary to ensure a representative biopsy. 23 Incisional biopsies are acceptable but should not compromise subsequent wide local excision, and excisional biopsy of the lesion must be avoided. Transverse extremity incisions should be avoided to reduce skin loss, as should extensive surgical procedures prior to definitive diagnosis. For these reasons, open biopsy or multiple core-needle biopsies are strongly encouraged so that adequate tumor tissue can be obtained to allow for crucial studies to be performed and to avoid limiting future treatment options.

A single-institution analysis of adolescents and adults compared patients with unplanned excision of STS to stage-matched controls. In this retrospective analysis, unplanned initial excision of STS resulted in increased risk for local recurrence, metastasis, and death, and this increase was greatest for high-grade tumors. 24[Level of evidence: 3iiA]

Many nonrhabdomyosarcomatous STSs are characterized by chromosomal abnormalities. Some of these chromosomal translocations lead to a fusion of two disparate genes. The resulting fusion transcript can be readily detected by using polymerase chain reaction-based techniques, thus facilitating the diagnosis of those neoplasms that have translocations. Some of the most frequent aberrations seen in nonrhabdomyosarcomatous soft tissue tumors are listed in Table 2.


Table 2. Frequent Chromosomal Aberrations Seen in Nonrhabdomyosarcomatous STSa

aAdapted from Sandberg, Slater et al., Mertens et al., and Romeo.
Histology  Chromosomal Aberrations   Genes Involved 
Alveolar soft part sarcoma  t(x;17)(p11.2;q25)  ASPL/TFE3  
Angiomatoid fibrous histiocytoma  t(12;16)(q13;p11), t(2;22)(q33;q12), t(12;22)(q13;q12)  FUS/ATF1, EWSR1/CREB1, EWS/ATF1 
Clear cell sarcoma  t(12;22)(q13;q12), t(2;22)(q33;q12)  ATF1/EWS, EWSR1/CREB1 
Congenital (infantile) fibrosarcoma/mesoblastic nephroma  t(12;15)(p13,q25)   ETV-NTRK3  
Dermatofibrosarcoma protuberans  t(17;22)(q22;q13)  COL1A1/PDGFB 
Desmoid fibromatosis  Trisomy 8 or 20, loss of 5q21  CTNNB1 or APC mutations 
Desmoplastic small round cell tumors  t(11;22)(p13;q12)  EWS/WT1  
Epithelioid hemangioendothelioma  t(1;3)(p36;q25)   WWTR1/CAMTA1 
Epithelioid sarcoma  Inactivation SMARCB1  SMARCB1 
Extraskeletal myxoid chondrosarcoma  t(9;22)(q22;q12), t(9:17)(q22;q11), t(9;15)(q22;q21), t(3;9)(q11;q22)  EWSR1/NR4A3, TAF2N/NR4A3, TCF12/NR4A3, TGF/NR4A3 
Hemangiopericytoma  t(12;19)(q13;q13.3) and t(13;22)(q22;q13.3)   
Inflammatory myofibroblastic tumor  t(1;2)(q23;q23), t(2;19)(q23;q13), t(2;17)(q23;q23), t(2;2)(p23;q13), t(2;11)(p23;p15)   TPM3/ALK, TPM4/ALK, CLTC/ALK, RANBP2/ALK, CARS/ALK 
Low-grade fibromyxoid sarcoma  t(7;16)(q33;p11), t(11;16)(p11;p11)  FUS/CREB3L2, FUS/CREB3L1 
Malignant peripheral nerve sheath tumor  17q11.2, loss or rearrangement 10p, 11q, 17q, 22q  NF1 
Myxoid/round cell liposarcoma   t(12;16)(q13;p11), t(12;22)(q13;q12)  FUS/DD1T3, EWSR/DD1T3 
Rhabdoid tumor   Inactivation SMARCB1  SMARCB1 
Synovial sarcoma  t(x;18)(p11.2;q11.2)   SYT/SSX 
Tenosynovial giant cell tumor  t(1;2)(p13;q35)   CSF1 
STS = soft tissue sarcoma. 
25 26 27 28 


Prognosis

The prognosis of nonrhabdomyosarcomatous STS tumors varies greatly depending on the histologic grade, invasiveness, tumor size, resectability, use of radiation therapy, site of primary tumor, and presence of metastases. 36 37 38 Some pediatric nonrhabdomyosarcomatous STSs are associated with a better outcome. For instance, infantile fibrosarcoma, presenting in infants and children younger than 4 years, has an excellent prognosis given that the tumor is highly chemosensitive and surgery alone can cure a significant number of these patients. 5

Soft tissue sarcomas in older children and adolescents often behave similarly to those in adult patients. 5 21

Pediatric patients with unresected localized nonrhabdomyosarcomatous STSs have a poor outcome. Only about one-third of patients treated with multimodality therapy remain disease free. 36 39; 40 41[Level of evidence: 3iiiA]

In a pooled analysis from U.S. and European pediatric centers, outcome was better for patients who received radiation therapy than for patients who did not, and outcome was better for patients whose tumor-removal procedure was deemed complete than for patients whose tumor removal was incomplete. 40[Level of evidence: 3iiiA]

Because long-term related morbidity must be minimized while disease-free survival is maximized, the ideal therapy for each patient must be carefully and individually determined utilizing these prognostic factors before initiating therapy for these patients. 18 42 43 44 45 46


Related Disease Summaries

Refer to the following PDQ® summaries for information about other types of sarcoma:

References:

  1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010. [PUBMED Abstract]
  2. Guidelines for the pediatric cancer center and role of such centers in diagnosis and treatment. American Academy of Pediatrics Section Statement Section on Hematology/Oncology. Pediatrics 99 (1): 139-41, 1997. [PUBMED Abstract]
  3. Pappo AS, Pratt CB: Soft tissue sarcomas in children. Cancer Treat Res 91: 205-22, 1997. [PUBMED Abstract]
  4. Ries LA, Smith MA, Gurney JG, et al., eds.: Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. Bethesda, Md: National Cancer Institute, SEER Program, 1999. NIH Pub.No. 99-4649. Also available online. [PUBMED Abstract]
  5. Okcu MF, Pappo AS, Hicks J, et al.: The nonrhabdomyosarcoma soft tissue sarcomas. In: Pizzo PA, Poplack DG: Principles and Practice of Pediatric Oncology. 6th ed. Philadelphia, Pa: Lippincott Williams and Wilkins, 2010, pp 954-86. [PUBMED Abstract]
  6. Weiss SW, Goldblum JR: General considerations. In: Weiss SW, Goldblum JR: Enzinger and Weiss's Soft Tissue Tumors. 5th ed. St. Louis, Mo: Mosby, 2008, pp 1-14. [PUBMED Abstract]
  7. Dillon P, Maurer H, Jenkins J, et al.: A prospective study of nonrhabdomyosarcoma soft tissue sarcomas in the pediatric age group. J Pediatr Surg 27 (2): 241-4; discussion 244-5, 1992. [PUBMED Abstract]
  8. Herzog CE: Overview of sarcomas in the adolescent and young adult population. J Pediatr Hematol Oncol 27 (4): 215-8, 2005. [PUBMED Abstract]
  9. Chang F, Syrjínen S, Syrjínen K: Implications of the p53 tumor-suppressor gene in clinical oncology. J Clin Oncol 13 (4): 1009-22, 1995. [PUBMED Abstract]
  10. Weiss SW, Goldblum JR: Benign tumors of peripheral nerves. In: Weiss SW, Goldblum JR: Enzinger and Weiss's Soft Tissue Tumors. 5th ed. St. Louis, Mo: Mosby, 2008, pp 825-901. [PUBMED Abstract]
  11. deCou JM, Rao BN, Parham DM, et al.: Malignant peripheral nerve sheath tumors: the St. Jude Children's Research Hospital experience. Ann Surg Oncol 2 (6): 524-9, 1995. [PUBMED Abstract]
  12. Stark AM, Buhl R, Hugo HH, et al.: Malignant peripheral nerve sheath tumours--report of 8 cases and review of the literature. Acta Neurochir (Wien) 143 (4): 357-63; discussion 363-4, 2001. [PUBMED Abstract]
  13. Groen EJ, Roos A, Muntinghe FL, et al.: Extra-intestinal manifestations of familial adenomatous polyposis. Ann Surg Oncol 15 (9): 2439-50, 2008. [PUBMED Abstract]
  14. Goto M, Miller RW, Ishikawa Y, et al.: Excess of rare cancers in Werner syndrome (adult progeria). Cancer Epidemiol Biomarkers Prev 5 (4): 239-46, 1996. [PUBMED Abstract]
  15. Kleinerman RA, Tucker MA, Abramson DH, et al.: Risk of soft tissue sarcomas by individual subtype in survivors of hereditary retinoblastoma. J Natl Cancer Inst 99 (1): 24-31, 2007. [PUBMED Abstract]
  16. Weiss SW, Goldblum JR: Malignant fibrous histiocytoma (pleomorphic undifferentiated sarcoma). In: Weiss SW, Goldblum JR: Enzinger and Weiss's Soft Tissue Tumors. 5th ed. St. Louis, Mo: Mosby, 2008, pp 403-27. [PUBMED Abstract]
  17. McClain KL, Leach CT, Jenson HB, et al.: Association of Epstein-Barr virus with leiomyosarcomas in children with AIDS. N Engl J Med 332 (1): 12-8, 1995. [PUBMED Abstract]
  18. Rao BN: Nonrhabdomyosarcoma in children: prognostic factors influencing survival. Semin Surg Oncol 9 (6): 524-31, 1993 Nov-Dec. [PUBMED Abstract]
  19. Zeytoonjian T, Mankin HJ, Gebhardt MC, et al.: Distal lower extremity sarcomas: frequency of occurrence and patient survival rate. Foot Ankle Int 25 (5): 325-30, 2004. [PUBMED Abstract]
  20. Weiss SW, Goldblum JR: Miscellaneous tumors of intermediate malignancy. In: Weiss SW, Goldblum JR: Enzinger and Weiss's Soft Tissue Tumors. 5th ed. St. Louis, Mo: Mosby, 2008, pp 1093-1160. [PUBMED Abstract]
  21. Weiss SW, Goldblum JR: Enzinger and Weiss's Soft Tissue Tumors. 4th ed. St. Louis, Mo: Mosby, 2001. [PUBMED Abstract]
  22. 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]
  23. Chowdhury T, Barnacle A, Haque S, et al.: Ultrasound-guided core needle biopsy for the diagnosis of rhabdomyosarcoma in childhood. Pediatr Blood Cancer 53 (3): 356-60, 2009. [PUBMED Abstract]
  24. Qureshi YA, Huddy JR, Miller JD, et al.: Unplanned excision of soft tissue sarcoma results in increased rates of local recurrence despite full further oncological treatment. Ann Surg Oncol 19 (3): 871-7, 2012. [PUBMED Abstract]
  25. Sandberg AA: Translocations in malignant tumors. Am J Pathol 159 (6): 1979-80, 2001. [PUBMED Abstract]
  26. Slater O, Shipley J: Clinical relevance of molecular genetics to paediatric sarcomas. J Clin Pathol 60 (11): 1187-94, 2007. [PUBMED Abstract]
  27. Mertens F, Antonescu CR, Hohenberger P, et al.: Translocation-related sarcomas. Semin Oncol 36 (4): 312-23, 2009. [PUBMED Abstract]
  28. Romeo S, Dei Tos AP: Clinical application of molecular pathology in sarcomas. Curr Opin Oncol 23 (4): 379-84, 2011. [PUBMED Abstract]
  29. Ladanyi M, Lui MY, Antonescu CR, et al.: The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25. Oncogene 20 (1): 48-57, 2001. [PUBMED Abstract]
  30. Ladanyi M: The emerging molecular genetics of sarcoma translocations. Diagn Mol Pathol 4 (3): 162-73, 1995. [PUBMED Abstract]
  31. Williams A, Bartle G, Sumathi VP, et al.: Detection of ASPL/TFE3 fusion transcripts and the TFE3 antigen in formalin-fixed, paraffin-embedded tissue in a series of 18 cases of alveolar soft part sarcoma: useful diagnostic tools in cases with unusual histological features. Virchows Arch 458 (3): 291-300, 2011. [PUBMED Abstract]
  32. Antonescu CR, Dal Cin P, Nafa K, et al.: EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma. Genes Chromosomes Cancer 46 (12): 1051-60, 2007. [PUBMED Abstract]
  33. Barnoud R, Sabourin JC, Pasquier D, et al.: Immunohistochemical expression of WT1 by desmoplastic small round cell tumor: a comparative study with other small round cell tumors. Am J Surg Pathol 24 (6): 830-6, 2000. [PUBMED Abstract]
  34. Errani C, Zhang L, Sung YS, et al.: A novel WWTR1-CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites. Genes Chromosomes Cancer 50 (8): 644-53, 2011. [PUBMED Abstract]
  35. Jain S, Xu R, Prieto VG, et al.: Molecular classification of soft tissue sarcomas and its clinical applications. Int J Clin Exp Pathol 3 (4): 416-28, 2010. [PUBMED Abstract]
  36. Spunt SL, Hill DA, Motosue AM, et al.: Clinical features and outcome of initially unresected nonmetastatic pediatric nonrhabdomyosarcoma soft tissue sarcoma. J Clin Oncol 20 (15): 3225-35, 2002. [PUBMED Abstract]
  37. Spunt SL, Poquette CA, Hurt YS, et al.: Prognostic factors for children and adolescents with surgically resected nonrhabdomyosarcoma soft tissue sarcoma: an analysis of 121 patients treated at St Jude Children's Research Hospital. J Clin Oncol 17 (12): 3697-705, 1999. [PUBMED Abstract]
  38. Ferrari A, Casanova M, Collini P, et al.: Adult-type soft tissue sarcomas in pediatric-age patients: experience at the Istituto Nazionale Tumori in Milan. J Clin Oncol 23 (18): 4021-30, 2005. [PUBMED Abstract]
  39. O'Sullivan B, Davis AM, Turcotte R, et al.: Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet 359 (9325): 2235-41, 2002. [PUBMED Abstract]
  40. Ferrari A, Miceli R, Rey A, et al.: Non-metastatic unresected paediatric non-rhabdomyosarcoma soft tissue sarcomas: results of a pooled analysis from United States and European groups. Eur J Cancer 47 (5): 724-31, 2011. [PUBMED Abstract]
  41. Smith KB, Indelicato DJ, Knapik JA, et al.: Definitive radiotherapy for unresectable pediatric and young adult nonrhabdomyosarcoma soft tissue sarcoma. Pediatr Blood Cancer 57 (2): 247-51, 2011. [PUBMED Abstract]
  42. Dillon PW, Whalen TV, Azizkhan RG, et al.: Neonatal soft tissue sarcomas: the influence of pathology on treatment and survival. Children's Cancer Group Surgical Committee. J Pediatr Surg 30 (7): 1038-41, 1995. [PUBMED Abstract]
  43. 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]
  44. Marcus KC, Grier HE, Shamberger RC, et al.: Childhood soft tissue sarcoma: a 20-year experience. J Pediatr 131 (4): 603-7, 1997. [PUBMED Abstract]
  45. Pratt CB, Pappo AS, Gieser P, et al.: Role of adjuvant chemotherapy in the treatment of surgically resected pediatric nonrhabdomyosarcomatous soft tissue sarcomas: A Pediatric Oncology Group Study. J Clin Oncol 17 (4): 1219, 1999. [PUBMED Abstract]
  46. 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]


Histopathological Classification

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World Health Organization (WHO) Classification of Soft Tissue Sarcomas (STSs)

The WHO lists the following cell types in its classification of STSs: 1 2

This summary focuses on high-grade sarcomas and low-grade tumors that present special problems in the pediatric and adolescent population, including desmoid tumor and infantile fibrosarcoma. For many low-grade STSs, surgical resection is curative and there is no need for additional therapy.

  • Adipocytic tumors.
    • Liposarcomamyxoid or well-differentiated.

  • Chondro-osseous tumors.
    • Extraskeletal chondrosarcoma (mesenchymal and other variants). 3
    • Extraskeletal osteosarcoma.

  • Fibroblastic/myofibroblastic tumors.
    • Desmoid tumor (also called aggressive fibromatosis).a
    • Fibrosarcoma.b 4
    • Inflammatory myofibroblastic tumor.a
    • Low-grade fibromyxoid sarcoma. 5
    • Myxofibrosarcoma, low grade.
    • Sclerosing epithelioid fibrosarcoma.

  • Skeletal muscle tumors.

  • Smooth muscle tumors.
    • Leiomyosarcoma.

  • So-called fibrohistiocytic tumors.
    • Plexiform fibrohistiocytic tumor.a
    • Undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma (including pleomorphic, giant cell, myxoid/high-grade myxofibrosarcoma, and inflammatory forms).

  • Tumors of peripheral nerves.
    • Malignant peripheral nerve sheath tumor.

  • Tumors of uncertain differentiation.
    • Alveolar soft part sarcoma.
    • Clear cell sarcoma of soft tissue.
    • Desmoplastic small round cell tumor. 6
    • Epithelioid sarcoma.
    • Extrarenal rhabdoid tumor.
    • Extraskeletal myxoid chondrosarcoma.
    • Primitive neuroectodermal tumor (PNET)/extraskeletal Ewing tumor.
    • Synovial sarcoma.
    • Undifferentiated sarcoma; sarcoma, not otherwise specified (NOS). 7

  • Vascular tumors.
    • Angiosarcoma, deep.c
    • Epithelioid hemangioendothelioma.
    • Hemangiopericytoma (infantile).

[Note: aNot a high-grade tumor; bThe category of fibrosarcoma can be inclusive of fibrosarcomatous differentiation in dermatofibrosarcoma protuberans; cCutaneous angiosarcoma may be difficult to stage using the American Joint Committee on Cancer system.]

References:

  1. 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. [PUBMED Abstract]
  2. Brodowicz T, Schwameis E, Widder J, et al.: Intensified Adjuvant IFADIC Chemotherapy for Adult Soft Tissue Sarcoma: A Prospective Randomized Feasibility Trial. Sarcoma 4 (4): 151-60, 2000. [PUBMED Abstract]
  3. 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]
  4. Steelman C, Katzenstein H, Parham D, et al.: Unusual presentation of congenital infantile fibrosarcoma in seven infants with molecular-genetic analysis. Fetal Pediatr Pathol 30 (5): 329-37, 2011. [PUBMED Abstract]
  5. Evans HL: Low-grade fibromyxoid sarcoma: a clinicopathologic study of 33 cases with long-term follow-up. Am J Surg Pathol 35 (10): 1450-62, 2011. [PUBMED Abstract]
  6. Barnoud R, Sabourin JC, Pasquier D, et al.: Immunohistochemical expression of WT1 by desmoplastic small round cell tumor: a comparative study with other small round cell tumors. Am J Surg Pathol 24 (6): 830-6, 2000. [PUBMED Abstract]
  7. Alaggio R, Collini P, Randall RL, et al.: Undifferentiated high-grade pleomorphic sarcomas in children: a clinicopathologic study of 10 cases and review of literature. Pediatr Dev Pathol 13 (3): 209-17, 2010 May-Jun. [PUBMED Abstract]


Staging and Grading Systems for Childhood Soft Tissue Sarcoma

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Clinical staging has an important role in predicting the clinical outcome and determining the most effective therapy for pediatric soft tissue sarcomas (STSs). As yet, there is no well-accepted staging system that is applicable to all childhood sarcomas. The system from the American Joint Committee on Cancer (AJCC) that is used for adults has not been validated in pediatric studies.

Although a standardized staging system for pediatric nonrhabdomyosarcomatous STS does not exist, the last Children's Oncology Group (COG) trial used the sixth edition AJCC cancer staging manual for STSs (with central pathology review) (see Tables 36 below). 1

Two systems are currently in use for staging pediatric nonrhabdomyosarcomatous STS tumors.

  • Surgico-pathologic staging system: The surgico-pathologic staging system used by the Intergroup Rhabdomyosarcoma Study (see below) is based on the amount, or extent, of tumor that remains after initial surgery and whether the disease has metastasized. 2
  • TNM staging system: The other system typically used to stage pediatric soft tissue tumors is the TNM system of the International Union Against Cancer. Staging is based on the extent of the tumor (T), the extent of spread to the lymph nodes (N), and the presence of metastasis (M). 3


Intergroup Rhabdomyosarcoma Study Staging System


Nonmetastatic disease

  • Group I: Localized tumor, completely resected with histologically negative margins.
  • Group II: Grossly resected tumor with microscopic residual tumor at the margin(s) and/or extension into regional lymph nodes.
    • IIA: Localized, grossly resected tumor with microscopic residual disease.
    • IIB: Regional disease with involved nodes completely resected with no microscopic disease. The most proximal (to the patient, most distal to the tumor) regional lymph node must be negative.
    • IIC: Regional disease with involved nodes grossly resected but with evidence of residual microscopic disease at the primary site and/or histologic involvement of the most proximal regional lymph node in the dissection.

  • Group III: Localized tumor, incompletely resected, or biopsy only, with gross residual tumor.


Metastatic disease

  • Group IV: Any localized or regional tumor with distant metastases present at the time of diagnosis. This includes the presence of malignant cells in effusions (pleural, peritoneal) and/or cerebrospinal fluid (rare).


Recurrent/progressive disease

  • Any STS that recurs after initial treatment or progresses after radiation therapy, chemotherapy, or initial surgery.


TNM Staging System

The AJCC has designated staging by the four criteria of tumor size, nodal status, histologic grade, and metastasis. 4


Table 3. Primary Tumor (T)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. 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.
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. 
 
 


Table 4. Regional Lymph Nodes (N)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.bPresence of positive nodes (N1) in M0 tumors is considered Stage III.
NX  Regional lymph nodes cannot be assessed. 
N0  No regional lymph node metastasis. 
N1b  Regional lymph node metastasis. 
 
 


Table 5. 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.

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M0  No distant metastasis. 
M1  Distant metastasis.