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Childhood Soft Tissue Sarcoma

Summary Type: Treatment
Summary Audience: Health professionals
Summary Language: English
Summary Description: Expert-reviewed information summary about the treatment of childhood soft tissue sarcomas.


Childhood Soft Tissue Sarcoma

General Information

This cancer treatment information summary provides an overview of the prognosis, diagnosis, classification, and treatment of childhood soft tissue sarcoma.

The National Cancer Institute provides the PDQ pediatric cancer treatment information summaries as a public service to increase the availability of evidence-based cancer information to health professionals, patients, and the public. These summaries are updated regularly according to the latest published research findings by an Editorial Board of pediatric oncology specialists.

Cancer in children and adolescents is rare. 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, 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 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.1 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.

In recent decades, dramatic improvements in survival have been achieved for children and adolescents with cancer. 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 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.

Pediatric soft tissue sarcomas are a group of malignant tumors that originate from primitive mesenchymal tissue and account for 7% of all childhood tumors.2 Rhabdomyosarcomas, tumors of striated muscle, and undifferentiated sarcomas account for more than one half of all cases of soft tissue sarcomas in children. (Refer to the PDQ summary on Childhood Rhabdomyosarcoma Treatment for more information.) The remaining nonrhabdomyosarcomatous soft tissue sarcomas account for approximately 3% of all childhood tumors.3 This heterogeneous group of tumors includes neoplasms of smooth muscle (leiomyosarcoma), connective tissue (fibrous and adipose), vascular tissue (blood and lymphatic vessels), and the peripheral nervous system.4 Synovial sarcomas, fibrosarcomas, and neurofibrosarcomas predominate in pediatric patients.5,6,7,8,9,

Nonrhabdomyosarcomatous soft tissue sarcomas are more common in adults 4 than in children; therefore, much of the information regarding the treatment and natural history of children with these lesions has been on the basis of findings from adult studies. Pediatric nonrhabdomyosarcomatous soft tissue sarcomas (NRSTS), however, are often associated with a better outcome. This difference is most pronounced for infants and young children (younger than 4 years) with fibrosarcoma, whose tumors are locally aggressive but not metastatic. These patients have an excellent prognosis when treated with surgery only and are highly chemosensitive.3,4,10,11 Soft tissue sarcomas in older children and adolescents often behave similarly to those in adult patients.3,4,

Although they can develop in any part of the body, nonrhabdomyosarcomatous soft tissue sarcomas arise most commonly in the trunk and extremities.5,6,12 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.4,

Genetic and environmental factors influence the development of nonrhabdomyosarcomatous soft tissue sarcomas. Heritable cancer-associated changes of the p53 tumor suppressor gene can occur in families with Li-Fraumeni syndrome.13 Members of these families have an increased risk of developing soft tissue tumors, bone sarcomas, breast cancer, brain tumors, and acute leukemia.3 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.4,14,15 Some nonrhabdomyosarcomatous soft tissue sarcomas (particularly malignant fibrous histiocytoma) can develop within a previously irradiated site; others (e.g., leiomyosarcoma) have been linked to Epstein-Barr virus infection in patients with acquired immune deficiency syndrome.3,4,16,

Synovial sarcomas are the most common NRSTS reported in children. The most common location is the lower extremity followed by upper extremity, trunk, abdomen, and head and neck. Approximately 30% of patients with synovial sarcoma are younger than 20 years. The most common site of metastasis is the lung.17 Factors such as stage III/stage IVA (International Union Against Cancer/American Joint Committee on Cancer), tumor necrosis, truncal locations, elevated mitotic rate, age, and histologic grade have been associated with a worse prognosis in adults.18,19,20,

(Refer to the PDQ summary on Childhood Rhabdomyosarcoma Treatment for more information.) (Refer to the PDQ summary on Ewing's Family of Tumors Treatment for more information on extraosseous Ewing’s, peripheral neuroepithelioma, and Askin’s tumor.)

The prognosis and biology of NRSTS tumors vary greatly depending on the age of the patient, the primary site, tumor size, tumor invasiveness, histologic grade, depth of invasion, and extent of disease at diagnosis. 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.6,10,17,21,22,23



1 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.

2 Pappo AS, Pratt CB: Soft tissue sarcomas in children. Cancer Treat Res 91: 205-22, 1997.

3 Miser JS, Triche TJ, Kinsella TJ, et al.: Other soft tissue sarcomas of childhood. In: Pizzo PA, Poplack DG, eds.: Principles and Practice of Pediatric Oncology. 3rd ed. Philadelphia, Pa: Lippincott-Raven, 1997, pp 865-888.

4 Weiss SW, Goldblum JR: Enzinger and Weiss's Soft Tissue Tumors. 4th ed. St. Louis, Mo: Mosby, 2001.

5 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.

6 Rao BN: Nonrhabdomyosarcoma in children: prognostic factors influencing survival. Semin Surg Oncol 9 (6): 524-31, 1993 Nov-Dec.

7 Fletcher CD, Dal Cin P, de Wever I, et al.: Correlation between clinicopathological features and karyotype in spindle cell sarcomas. A report of 130 cases from the CHAMP study group. Am J Pathol 154 (6): 1841-7, 1999.

8 Skytting BT, Bauer HC, Perfekt R, et al.: Clinical course in synovial sarcoma: a Scandinavian sarcoma group study of 104 patients. Acta Orthop Scand 70 (6): 536-42, 1999.

9 Herzog CE: Overview of sarcomas in the adolescent and young adult population. J Pediatr Hematol Oncol 27 (4): 215-8, 2005.

10 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.

11 Neville H, Corpron C, Blakely ML, et al.: Pediatric neurofibrosarcoma. J Pediatr Surg 38 (3): 343-6; discussion 343-6, 2003.

12 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.

13 Chang F, Syrjänen S, Syrjänen K: Implications of the p53 tumor-suppressor gene in clinical oncology. J Clin Oncol 13 (4): 1009-22, 1995.

14 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.

15 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.

16 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.

17 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.

18 Trassard M, Le Doussal V, Hacène K, et al.: Prognostic factors in localized primary synovial sarcoma: a multicenter study of 128 adult patients. J Clin Oncol 19 (2): 525-34, 2001.

19 Guillou L, Benhattar J, Bonichon F, et al.: Histologic grade, but not SYT-SSX fusion type, is an important prognostic factor in patients with synovial sarcoma: a multicenter, retrospective analysis. J Clin Oncol 22 (20): 4040-50, 2004.

20 Ferrari A, Gronchi A, Casanova M, et al.: Synovial sarcoma: a retrospective analysis of 271 patients of all ages treated at a single institution. Cancer 101 (3): 627-34, 2004.

21 Marcus KC, Grier HE, Shamberger RC, et al.: Childhood soft tissue sarcoma: a 20-year experience. J Pediatr 131 (4): 603-7, 1997.

22 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.

23 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.

Cellular Classification

Diagnosis of soft tissue sarcoma in childhood is often difficult. Obtaining adequate tumor tissue is crucial to allow for conventional histology, immunochemistry, and other studies such as cytogenetics, fluorescence in situ hybridization, and molecular pathology. For this reason, open biopsy (or multiple core needle biopsies) is strongly encouraged so that adequate tumor tissue can be obtained to allow all of these crucial studies to be performed.

Pediatric soft tissue sarcomas are classified histologically according to the soft tissue cell they resemble and include the following:1,

Tumors of fibrous tissue

  • Fibromatoses (desmoid tumors).
  • Adult and infantile fibrosarcoma.
  • Dermatofibrosarcoma.

Fibrohistiocytic tumors

  • Malignant fibrous histiocytoma.

Tumors of adipose tissue

  • Liposarcoma.

Tumors of smooth muscle

  • Leiomyosarcoma.

Tumors of blood and lymph vessels

  • Angiosarcoma.
  • Lymphangiosarcoma.
  • Hemangiopericytoma.
  • Hemangioendothelioma.

Tumors of peripheral nervous system

  • Malignant schwannoma (malignant peripheral nerve sheath tumor).

Tumors of bone and cartilage

  • Extraosseous osteosarcoma.
  • Extraosseous myxoid chondrosarcoma.
  • Extraosseous mesenchymal chondrosarcoma.

Tumors of more than one tissue type

  • Malignant mesenchymoma.
  • Malignant Triton tumor.
  • Malignant ectomesenchymoma.2,

Tumors of unknown histogenesis

  • Alveolar soft part sarcoma (ASPS).
  • Epithelioid sarcoma.
  • Clear cell sarcoma (malignant melanoma of soft parts [MMSP]).
  • Synovial sarcoma.
  • Desmoplastic small round cell tumor.3,

Selected soft tissue sarcomas in children

Alveolar soft part sarcoma

This is a tumor of uncertain histogenesis. A consistent chromosomal translocation t(X;17)(p11.2;q25) juxtaposes the ASP gene with the TFE3 gene.4 Alveolar soft part sarcoma almost never has an objective response to chemotherapy.5 In children, ASPS often presents with metastases 6 and sometimes has a very indolent course. There are single case reports of objective responses to alpha interferon and to bevacizumab.7,8,.

Angiosarcoma

A review of 20 years of experience in the Italian and German Soft Tissue Sarcoma Cooperative Group identified 12 children with angiosarcoma.9 Only one objective response to chemotherapy was observed, and the overall behavior of this tumor was identical to angiosarcoma in adults.

Dermatofibrosarcoma

Dermatofibrosarcoma is a rare tumor, but many of the reported cases arise in children.10 The tumor has a consistent chromosomal translocation t(17;22)(q22;q13) that juxtaposes the COL1A1 gene with the PDGF-beta gene. Most tumors are cured by surgical resection. When surgical resection cannot be accomplished or the tumor is recurrent, treatment with imatinib has been effective.11,

Leiomyosarcoma

A retrospective analysis of the Italian cooperative group identified one child with leiomyosarcoma over a 24-year period.12 A retrospective analysis of the St. Jude Children’s Research Hospital experience from 1962 to 1996 identified 40 children with nonrhabdomyosarcomatous soft tissue sarcomas; none had leiomyosarcoma.13 Among 43 children with HIV/AIDS who developed tumors, 8 developed Epstein-Barr virus–associated leiomyosarcoma.14,

Liposarcoma

A retrospective analysis of the Italian cooperative group identified 2 children with liposarcoma over a 24-year period.12 The tumors did not respond to chemotherapy. Outcomes were the same as those observed for adults with liposarcoma.

Malignant fibrous histiocytoma

At one time, malignant fibrous histiocytoma (MFH) was the single most common histiotype among adults with soft tissue sarcomas. Since it was first recognized in the early 1960s, however, MFH has been plagued by controversy in terms of both its histogenesis and its validity as a clinicopathologic entity. The latest World Health Organization classification includes MFH no longer as a distinct diagnostic category but rather as subtypes of an undifferentiated pleomorphic sarcoma.15,

Malignant peripheral nerve sheath tumor

Malignant peripheral nerve sheath tumor arises in children with type 1 neurofibromatosis (NF1) and sporadically.16 Features with favorable prognosis have been reported to include absence of NF1, less invasiveness, lower stage, and extremity as primary site.16,.

Nonrhabdomyosarcomatous soft tissue tumors are fairly readily distinguished from rhabdomyosarcoma or Ewing’s family of tumors. To distinguish between various nonrhabdomyosarcomatous lesions, tumor samples should be carefully evaluated by using immunocytochemical tests as well as light and electron microscopy.1,17 Many nonrhabdomyosarcomatous soft tissue sarcomas are characterized by chromosomal abnormalities. Some of these chromosomal translocations lead to fusion of 2 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 1. Patients with undifferentiated sarcoma have been eligible for participation in rhabdomyosarcoma trials coordinated by the Intergroup Rhabdomyosarcoma Study Group and the Children’s Oncology Group. The rationale for this inclusion was the observation that patients with undifferentiated sarcoma have similar sites of disease and outcome to those with alveolar rhabdomyosarcoma. In therapeutic trials for adults with soft tissue sarcoma, patients with undifferentiated sarcoma are included with all other histologies and treated in a similar manner. Contemporary treatment for adult soft tissue sarcoma utilizes ifosfamide and doxorubicin, sometimes with the addition of other chemotherapy agents, surgery, and radiation therapy. No data are available to compare these 2 approaches. (Refer to the PDQ summary on Childhood Rhabdomyosarcoma Treatment for more information.)

Table 1. Frequent Aberrations Seen In Nonrhabdomyosarcomatous Soft Tissue Tumors*

HistologyChromosomal aberrations Genes involved* Adapted from 18,** Malignant melanoma of soft partsAlveolar soft part sarcomat(x;17)(p11.2;q25)ASPL/TFE3 4,19,Clear cell sarcoma (MMSP**)t(12;22)(q13;q12)ATF1/EWSDermatofibrosarcoma t(17;22)(q22;q13)COL1A1/PDGFBDesmoplastic small round cell tumorst(11;22)(p13;q12)WT1/EWS 3,Extraskeletal myxoid chondrosarcomat(9;22)(q22;q12)EWS-CHNHemangiopericytomat(12;19)(q13;q13.3) and t(13;22)(q22;q13.3)Infantile fibrosarcomat(12;15);+11; also +8,+17,+20ETVG(TEL)/NTRK3Leiomyosarcomat(12;14)Low-grade fibromyxoid sarcomat(7;16)(q33;p11)FUS/BBF2H7Malignant fibrous histiocytoma 19p+, ring chromosomeMyxoid liposarcoma t(12;16)(q13;p11)FUS/CHOPNeurofibrosarcoma Deletion 17q11.2Synovial sarcomat(x;18)(p11.2;q11.2) SYT/SSX

Diagnosis of synovial sarcoma is made by immunohistochemical analysis, ultrastructural findings, and demonstration of the specific chromosomal translocation t(x;18)(p11.2;q11.2). This abnormality is specific for synovial sarcoma and is found in all morphologic subtypes. Synovial sarcoma results in rearrangement of the SYT gene on chromosome 18 with one of the subtypes (1, 2, or 4) of the SSX gene on chromosome X.20 Synovial sarcoma can be subclassified as monophasic fibrous type, biphasic type with distinct epithelial and spindle cell components, or poorly differentiated. Poorly differentiated synovial sarcoma has features of monophasic or biphasic synovial sarcoma but also a variable proportion of poorly differentiated areas characterized by high cellularity, pleomorphism, and polygonal or small round-cell morphology, numerous mitoses, and often necrosis.21,

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 process known as grading. This process is used to improve the correlation between histologic findings and clinical outcome.22 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.17,22,23,

Grade 1 lesions

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

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 5 mitotic figures per 10 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

  • Pleomorphic or round cell liposarcoma.
  • Mesenchymal chondrosarcoma.
  • Extraosseous osteosarcoma.
  • Triton tumor (malignant peripheral nerve sheath tumor with rhabdomyosarcomatous elements).
  • Alveolar soft part sarcoma.
  • Synovial sarcoma.
  • Epithelioid sarcoma.
  • Clear cell sarcoma (MMSP).

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 5 mitotic figures per 10 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.



1 Weiss SW, Goldblum JR: Enzinger and Weiss's Soft Tissue Tumors. 4th ed. St. Louis, Mo: Mosby, 2001.

2 Oppenheimer O, Athanasian E, Meyers P, et al.: Malignant ectomesenchymoma in the wrist of a child: case report and review of the literature. Int J Surg Pathol 13 (1): 113-6, 2005.

3 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.

4 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.

5 Reichardt P, Lindner T, Pink D, et al.: Chemotherapy in alveolar soft part sarcomas. What do we know? Eur J Cancer 39 (11): 1511-6, 2003.

6 Kayton ML, Meyers P, Wexler LH, et al.: Clinical presentation, treatment, and outcome of alveolar soft part sarcoma in children, adolescents, and young adults. J Pediatr Surg 41 (1): 187-93, 2006.

7 Roozendaal KJ, de Valk B, ten Velden JJ, et al.: Alveolar soft-part sarcoma responding to interferon alpha-2b. Br J Cancer 89 (2): 243-5, 2003.

8 Azizi AA, Haberler C, Czech T, et al.: Vascular-endothelial-growth-factor (VEGF) expression and possible response to angiogenesis inhibitor bevacizumab in metastatic alveolar soft part sarcoma. Lancet Oncol 7 (6): 521-3, 2006.

9 Ferrari A, Casanova M, Bisogno G, et al.: Malignant vascular tumors in children and adolescents: a report from the Italian and German Soft Tissue Sarcoma Cooperative Group. Med Pediatr Oncol 39 (2): 109-14, 2002.

10 Buckley PG, Mantripragada KK, Benetkiewicz M, et al.: A full-coverage, high-resolution human chromosome 22 genomic microarray for clinical and research applications. Hum Mol Genet 11 (25): 3221-9, 2002.

11 Price VE, Fletcher JA, Zielenska M, et al.: Imatinib mesylate: an attractive alternative in young children with large, surgically challenging dermatofibrosarcoma protuberans. Pediatr Blood Cancer 44 (5): 511-5, 2005.

12 Cecchetto G, Alaggio R, Dall'Igna P, et al.: Localized unresectable non-rhabdo soft tissue sarcomas of the extremities in pediatric age: results from the Italian studies. Cancer 104 (9): 2006-12, 2005.

13 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.

14 Pollock BH, Jenson HB, Leach CT, et al.: Risk factors for pediatric human immunodeficiency virus-related malignancy. JAMA 289 (18): 2393-9, 2003.

15 Randall RL, Albritton KH, Ferney BJ, et al.: Malignant fibrous histiocytoma of soft tissue: an abandoned diagnosis. Am J Orthop 33 (12): 602-8, 2004.

16 Carli M, Ferrari A, Mattke A, et al.: Pediatric malignant peripheral nerve sheath tumor: the Italian and German soft tissue sarcoma cooperative group. J Clin Oncol 23 (33): 8422-30, 2005.

17 Recommendations for the reporting of soft tissue sarcomas. Association of Directors of Anatomic and Surgical Pathology. Mod Pathol 11 (12): 1257-61, 1998.

18 Sandberg AA: Translocations in malignant tumors. Am J Pathol 159 (6): 1979-80, 2001.

19 Ladanyi M: The emerging molecular genetics of sarcoma translocations. Diagn Mol Pathol 4 (3): 162-73, 1995.

20 van de Rijn M, Barr FG, Collins MH, et al.: Absence of SYT-SSX fusion products in soft tissue tumors other than synovial sarcoma. Am J Clin Pathol 112 (1): 43-9, 1999.

21 van de Rijn M, Barr FG, Xiong QB, et al.: Poorly differentiated synovial sarcoma: an analysis of clinical, pathologic, and molecular genetic features. Am J Surg Pathol 23 (1): 106-12, 1999.

22 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.

23 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.

Stage Information

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 that is used for adults has not been validated in pediatric studies.1 Two systems are currently in use for staging pediatric nonrhabdomyosarcomatous soft tissue 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.
  • 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 disease

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

The other schema typically used to stage pediatric soft tissue tumors is the tumor-node-metastases system of the International Union Against Cancer.3 In this staging system, T1 lesions are those that are confined to the organ of origin, and T2 lesions invade adjacent organs. These categories can be subclassified to reflect the maximum tumor diameter (a: ≤5 cm; b: >5 cm). Nodal involvement is indicated by N1 (N0: no nodal involvement), and the presence of distant metastases at the time of diagnosis is indicated by the M1 (vs. M0) designation. 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.

These 2 staging systems have proven to be of prognostic significance in pediatric and adult nonrhabdomyosarcomatous soft tissue sarcomas.4,5,6,7,8 In a review of a large adult series of nonrhabdomyosarcomas, 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.9



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.

3 Harmer MH, ed.: TNM Classification of Pediatric Tumors. Geneva: UICC, 1982.

4 Rao BN: Nonrhabdomyosarcoma in children: prognostic factors influencing survival. Semin Surg Oncol 9 (6): 524-31, 1993 Nov-Dec.

5 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.

6 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.

7 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.

8 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.

9 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.

Treatment Option Overview

Because of the rarity of pediatric nonrhabdomyosarcomatous soft tissue sarcomas, all children, adolescents, and young adults with these tumors should have their treatment planned by a multidisciplinary team composed of pediatric oncologists, surgeons, and radiotherapists. To better define the natural history and response to therapy of the tumors, children with rare neoplasms should be considered for entry into national or institutional treatment protocols.

Every attempt should be made to resect the primary tumor with negative margins before or after chemotherapy. The timing of surgery depends on an assessment of the feasibility and morbidity of surgery. Involvement of a surgeon with special expertise in the resection of soft tissue sarcomas in the decision is highly desirable. Sentinel lymph node mapping is employed at some centers to identify the regional nodes that are the most likely to be involved, though its contribution has not been clearly defined.1,2 If the original operation failed to achieve pathologically negative tissue margins, a second procedure should be performed to obtain clear, but not necessarily wide margins.3,4,5,6,7 When the initial operation was done without the knowledge that cancer was present, a re-excision of the affected region should always be considered, even in the absence of a mass on magnetic resonance imaging.8 When there is concern about the adequacy of the surgical margin, radiation therapy is indicated.9 This is particularly important in high-grade tumors with tumor margins less than 1 cm.10,11 Thus, by using these 2 treatment modalities, local control of the primary tumor can be achieved in more than 80% of patients.12,13 Although combined surgery and radiation therapy have dramatically improved outcome in adults and children with soft tissue sarcomas over the past 20 years,9 the morbidity of high-dose radiation therapy is of concern in infants and young children with these tumors.14 Brachytherapy and intraoperative radiation may be applicable in select situations.13,15,16 Preoperative radiation therapy has been associated with excellent local control rates 17,18,19 but has been associated with an increased rate of wound complications in adults.20 Patients in the pediatric age group with unresected nonrhabdomyosarcomatous soft tissue sarcoma have a poor outcome. Only about one third of patients treated with multimodality therapy remain disease-free.20,21,

Therapeutic strategies for children and adolescents with soft tissue tumors are similar to those for adult patients, though there are important differences. For example, the biology of the pediatric form of the neoplasm may differ dramatically from that of the adult lesion. Limb-sparing procedures are more difficult to perform in pediatric patients. In addition, the morbidity of radiation therapy in young children may be much greater than that observed in adults. Lastly, the concern regarding potential long-term side effects of combined modality therapy (radiation, surgery, and chemotherapy) is greater for children, whose survival may be much longer than that of adults. Therefore, to maximize tumor control and minimize long-term morbidity, treatment must be individualized for children and adolescents with nonrhabdomyosarcomatous soft tissue tumors. These patients should be enrolled in prospective studies that accurately assess any potential complications.22,

The role of adjuvant (postoperative) chemotherapy remains controversial. A meta-analysis of updated data from adult soft tissue sarcoma patients from all available randomized trials concluded that recurrence-free survival was better with adjuvant chemotherapy.23 The largest prospective pediatric trial failed to demonstrate any benefit with adjuvant vincristine, dactinomycin, cyclophosphamide, and doxorubicin.12 Synovial sarcoma appears to be more sensitive to chemotherapy than many other soft tissue sarcomas, and children with synovial sarcoma seem to have a better prognosis.24,25,26,27 A German trial suggested a benefit for adjuvant chemotherapy in children with synovial sarcoma.28 A meta-analysis also suggested that chemotherapy may provide benefit.29 Many treatment centers advocate adjuvant chemotherapy following resection of synovial sarcoma in children and young adults; unequivocal proof of the value of this strategy from prospective, randomized clinical trials is lacking.



1 Neville HL, Andrassy RJ, Lally KP, et al.: Lymphatic mapping with sentinel node biopsy in pediatric patients. J Pediatr Surg 35 (6): 961-4, 2000.

2 Neville HL, Raney RB, Andrassy RJ, et al.: Multidisciplinary management of pediatric soft-tissue sarcoma. Oncology (Huntingt) 14 (10): 1471-81; discussion 1482-6, 1489-90, 2000.

3 Okcu MF, Despa S, Choroszy M, et al.: Synovial sarcoma in children and adolescents: thirty three years of experience with multimodal therapy. Med Pediatr Oncol 37 (2): 90-6, 2001.

4 Sugiura H, Takahashi M, Katagiri H, et al.: Additional wide resection of malignant soft tissue tumors. Clin Orthop (394): 201-10, 2002.

5 Cecchetto G, Guglielmi M, Inserra A, et al.: Primary re-excision: the Italian experience in patients with localized soft-tissue sarcomas. Pediatr Surg Int 17 (7): 532-4, 2001.

6 Chui CH, Spunt SL, Liu T, et al.: Is reexcision in pediatric nonrhabdomyosarcoma soft tissue sarcoma necessary after an initial unplanned resection? J Pediatr Surg 37 (10): 1424-9, 2002.

7 Paulino AC, Ritchie J, Wen BC: The value of postoperative radiotherapy in childhood nonrhabdomyosarcoma soft tissue sarcoma. Pediatr Blood Cancer 43 (5): 587-93, 2004.

8 Kaste SC, Hill A, Conley L, et al.: Magnetic resonance imaging after incomplete resection of soft tissue sarcoma. Clin Orthop (397): 204-11, 2002.

9 Marcus KC, Grier HE, Shamberger RC, et al.: Childhood soft tissue sarcoma: a 20-year experience. J Pediatr 131 (4): 603-7, 1997.

10 Blakely ML, Spurbeck WW, Pappo AS, et al.: The impact of margin of resection on outcome in pediatric nonrhabdomyosarcoma soft tissue sarcoma. J Pediatr Surg 34 (5): 672-5, 1999.

11 Skytting B: Synovial sarcoma. A Scandinavian Sarcoma Group project. Acta Orthop Scand Suppl 291: 1-28, 2000.

12 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.

13 Merchant TE, Parsh N, del Valle PL, et al.: Brachytherapy for pediatric soft-tissue sarcoma. Int J Radiat Oncol Biol Phys 46 (2): 427-32, 2000.

14 Suit H, Spiro I: Radiation as a therapeutic modality in sarcomas of the soft tissue. Hematol Oncol Clin North Am 9 (4): 733-46, 1995.

15 Schomberg PJ, Gunderson LL, Moir CR, et al.: Intraoperative electron irradiation in the management of pediatric malignancies. Cancer 79 (11): 2251-6, 1997.

16 Nag S, Shasha D, Janjan N, et al.: The American Brachytherapy Society recommendations for brachytherapy of soft tissue sarcomas. Int J Radiat Oncol Biol Phys 49 (4): 1033-43, 2001.

17 Sadoski C, Suit HD, Rosenberg A, et al.: Preoperative radiation, surgical margins, and local control of extremity sarcomas of soft tissues. J Surg Oncol 52 (4): 223-30, 1993.

18 Virkus WW, Mollabashy A, Reith JD, et al.: Preoperative radiotherapy in the treatment of soft tissue sarcomas. Clin Orthop (397): 177-89, 2002.

19 Zagars GK, Ballo MT, Pisters PW, et al.: Preoperative vs. postoperative radiation therapy for soft tissue sarcoma: a retrospective comparative evaluation of disease outcome. Int J Radiat Oncol Biol Phys 56 (2): 482-8, 2003.

20 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.

21 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.

22 Miser JS, Triche TJ, Kinsella TJ, et al.: Other soft tissue sarcomas of childhood. In: Pizzo PA, Poplack DG, eds.: Principles and Practice of Pediatric Oncology. 3rd ed. Philadelphia, Pa: Lippincott-Raven, 1997, pp 865-888.

23 Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data. Sarcoma Meta-analysis Collaboration. Lancet 350 (9092): 1647-54, 1997.

24 McGrory JE, Pritchard DJ, Arndt CA, et al.: Nonrhabdomyosarcoma soft tissue sarcomas in children. The Mayo Clinic experience. Clin Orthop (374): 247-58, 2000.

25 Ferrari A, Gronchi A, Casanova M, et al.: Synovial sarcoma: a retrospective analysis of 271 patients of all ages treated at a single institution. Cancer 101 (3): 627-34, 2004.

26 Van Glabbeke M, van Oosterom AT, Oosterhuis JW, et al.: Prognostic factors for the outcome of chemotherapy in advanced soft tissue sarcoma: an analysis of 2,185 patients treated with anthracycline-containing first-line regimens--a European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol 17 (1): 150-7, 1999.

27 Koscielniak E, Harms D, Henze G, et al.: Results of treatment for soft tissue sarcoma in childhood and adolescence: a final report of the German Cooperative Soft Tissue Sarcoma Study CWS-86. J Clin Oncol 17 (12): 3706-19, 1999.

28 Ladenstein R, Treuner J, Koscielniak E, et al.: Synovial sarcoma of childhood and adolescence. Report of the German CWS-81 study. Cancer 71 (11): 3647-55, 1993.

29 Okcu MF, Munsell M, Treuner J, et al.: Synovial sarcoma of childhood and adolescence: a multicenter, multivariate analysis of outcome. J Clin Oncol 21 (8): 1602-11, 2003.

Nonmetastatic Childhood Soft Tissue Sarcoma

Treatment options by soft tissue sarcoma type

For nonmetastatic pediatric nonrhabdomyosarcomatous soft tissue sarcomas, treatment with surgery alone is often curative.1,2,3,4,5,6 If the initial surgery was performed without suspicion of malignancy, re-excision by a surgeon experienced in the treatment of soft tissue sarcoma is essential, even if imaging studies do not suggest the presence of residual tumor. Postoperatively, tumor-free margins must be confirmed through pathologic evaluation, and re-excision must be performed if the margins are positive. If further resection is not feasible, postoperative radiation therapy, or if possible, brachytherapy should be used.7,8 For patients with local recurrence, re-excision of the mass is indicated.

  1. Tumors with low potential for metastasis:

    Fibrosarcomas and hemangiopericytomas are tumors with low potential for metastasis in infants and young children; desmoid tumors, aggressive fibromatosis, dermatofibrosarcoma, and angiomatoid malignant fibrous histiocytomas typically are also clinically less aggressive, rarely metastasize, and can often be treated successfully with surgery alone.1,9,10,11 In children with infantile fibrosarcoma, preoperative chemotherapy has made possible a more conservative surgical approach; agents active in this setting include vincristine, dactinomycin, cyclophosphamide, and ifosfamide.1,12 Responses to presurgical chemotherapy with similar agents have been reported in cases of infantile hemangiopericytoma.1,

    Desmoid tumors are well-differentiated fibrous lesions that rarely metastasize, but they have a significant potential for local invasiveness and recurrence. The treatment of choice is resection to achieve clear margins. If postoperative margins are positive, 70% of patients will have a recurrence of disease. When complete surgical excision is not feasible and the tumor poses significant potential for mortality or morbidity, preoperative strategies that include external-beam radiation therapy, postoperative interstitial iridium192, nonsteroidal anti-inflammatory agents, antiestrogens, vinblastine, and methotrexate should be considered.13,14 Evaluation of the benefit of chemotherapy for treatment of desmoid tumors has been extremely difficult because desmoid tumors have a highly variable natural history. Large adult series and a single pediatric series have reported long periods of disease stabilization and even regression without systemic therapy.15,16 Partially excised or recurrent lesions that do not pose a significant danger to vital organs may be monitored closely if other treatment alternatives are not available.16,17,18,19,20 Whenever possible, however, the treatment of choice is complete resection.

    Treatment option under clinical evaluation:

    The following treatment option is currently under investigation in national and/or institutional clinical trials. For more information about clinical trials, please see the NCI Web site.

    • Imatinib mesylate used as a treatment in recurrent soft tissue, bone sarcomas, and primary desmoid tumors.
  2. The pediatric neoplasms listed below exhibit similar biologic behavior to those lesions in adults, and a discussion of their treatment follows.
    • Fibrosarcoma in older children and adolescents.
    • Malignant peripheral nerve sheath tumor.
    • Liposarcoma.
    • Synovial sarcoma.
    • Hemangiopericytoma in older children and young adults.
    • Extraosseous osteosarcoma.
    • Extraosseous chondrosarcoma.
    • Malignant fibrous histiocytoma.
    • Leiomyosarcoma.
    • Epithelioid sarcoma.

    Standard treatment options:

    Every attempt should be made to resect the primary tumor locally with negative margins.21,22 If the original operation failed to achieve pathologically negative tissue margins, a second surgery may be indicated.2 Although combined surgery and radiation therapy have dramatically improved outcome in adults and children with soft tissue sarcomas over the past 20 years,7 the morbidity of high-dose radiation therapy should be taken into consideration in infants and young children with these tumors.23 The use of brachytherapy and intraoperative radiation therapy is under study.8,24 Preoperative radiation therapy has been associated with excellent local control rates in adults;25 this approach has not been used extensively in pediatric patients.

    The role of adjuvant (postoperative) chemotherapy remains controversial. Virtually all trials of adjuvant chemotherapy in adults with soft tissue sarcoma report the results of treatment for all patients in aggregate. This may obscure important differences in chemosensitivity among histologic subtypes of soft tissue sarcoma. A retrospective analysis of neoadjuvant chemotherapy in adults with soft tissue sarcoma suggested a benefit for patients with larger tumors.26 The largest prospective pediatric trial failed to document any benefit of adjuvant chemotherapy with vincristine, dactinomycin, cyclophosphamide, and doxorubicin in children with grossly resected tumors.27 This trial also reported results in aggregate for a variety of soft tissue sarcomas. In patients with unresectable or metastatic disease treated with vincristine, dactinomycin, and cyclophosphamide, the overall and disease-free survival rates were 31% and 10%, respectively.28 It is possible to achieve complete responses after aggressive chemotherapy, radiation therapy, and surgery in most patients with more advanced nonrhabdomyosarcomatous soft tissue sarcoma.29,

    Chemotherapy for extraosseous osteosarcoma has not been well studied. Treatment has previously been recommended to follow soft tissue sarcoma guidelines rather than guidelines for osteosarcoma of bone.30 Extraosseous osteosarcoma may be more chemosensitive in young patients than in adults.30 A retrospective analysis of the German Cooperative Osteosarcoma Study identified a favorable outcome for extraskeletal osteosarcoma treated with surgery and conventional osteosarcoma chemotherapy.31 (Refer to the PDQ summary on Osteosarcoma/Malignant Fibrous Histiocytoma of Bone for more information.)

    Synovial sarcoma appears to be more sensitive to chemotherapy than many other soft tissue sarcomas, and children with synovial sarcoma seem to have a better prognosis.32,33 A German randomized trial suggested a benefit for adjuvant chemotherapy in children with synovial sarcoma.34 A meta-analysis also suggested that chemotherapy may provide benefit.22 Many treatment centers advocate adjuvant chemotherapy following resection of synovial sarcoma in children and young adults; unequivocal proof of the value of this strategy from prospective, randomized clinical trials is lacking.

    A large retrospective analysis of the German and Italian experience with malignant peripheral nerve sheath tumor identified incomplete resection, large tumor size, tumor invasiveness, non-extremity primary site, and clinical diagnosis of neurofibromatosis as unfavorable prognostic findings.21 There was a trend for improved outcome with adjuvant radiation therapy. While 65% of measurable tumors had objective responses to ifosfamide-containing chemotherapy regimens, the analysis did not conclusively demonstrate improved survival for chemotherapy.21,

    Treatment options under clinical evaluation:

    • None at present.
  3. Alveolar soft part sarcoma is a tumor of uncertain histogenesis characterized by an x/17 translocation.35 Pediatric alveolar soft part sarcoma seems to have a better outcome than its adult counterpart.36 In a series of 19 treated patients, one group reported a 5-year overall survival (OS) rate of 80%, a 91% OS rate for patients with localized disease, a 100% OS rate for patients with tumors 5 cm or smaller, and a 31% OS rate for patients with tumors larger than 5 cm.6 A subset of renal tumors found in young people was previously considered to be renal cell carcinoma, but the subset now appears to be genetically related to alveolar soft part sarcoma.37,

    Standard treatment options:

    The standard approach is complete resection of the primary lesion.6, If complete excision is not feasible, radiation therapy should be administered. The value of adjuvant chemotherapy in completely resected alveolar soft part sarcomas remains unproven, particularly because patients with unresected or metastatic tumors failed to respond to chemotherapeutic agents frequently used to treat soft tissue sarcomas.38 Patients with alveolar soft part sarcomas may relapse several years after a prolonged period of apparent remission.39,

    Treatment options under clinical evaluation:

    • The role of adjuvant chemotherapy in children with this malignancy has not been tested. Because these tumors are rare, all children with alveolar soft part sarcoma should be enrolled in prospective clinical trials.
  4. Desmoplastic small round cell tumor is a primitive sarcoma that most frequently involves the abdomen, pelvis, or tissues around the testes.40,41 The tumor occurs mainly in males and invades locally but may spread to the lungs and elsewhere. Cytogenetic studies of these tumors have demonstrated the recurrent translocation t(11;22)(p13;q12), which has been characterized as a fusion of the WT1 and EWS genes.42,

    Standard treatment options:

    Complete resection of this tumor is rarely possible, thus effective treatment must rely on chemotherapy and radiation therapy. Treatment for individuals with desmoplastic small round cell tumor following surgery requires aggressive chemotherapy with the agents that are used for the treatment of sarcoma combined with appropriate radiation treatment. Prognosis is dependent on the extent and aggressiveness of the tumor and its treatment.40,41,43, Whole abdominopelvic radiotherapy is feasible but has not significantly improved the outcome for this diagnosis.44,

    Treatment options under clinical evaluation:

    • None at present.
  5. Clear cell sarcoma (malignant melanoma) of soft parts (also called clear cell sarcoma of tendons and aponeuroses) is somewhat similar to cutaneous malignant melanoma but is cytogenetically distinct; most cases have a t(12;22)(q13;q12) translocation that has not been reported in melanoma.45 Patients with small, localized tumors fare best; treatment is primarily surgical with radiation therapy for uncertain or involved margins. Antisarcoma chemotherapy is rarely effective.46,
  6. Hemangioendotheliomas are tumors found in infants that arise within the liver or elsewhere and usually remain benign.47 The tumors are sometimes associated with consumptive coagulopathy, also known as the Kasabach-Merritt syndrome (or phenomenon).48,49,50 In older children and adults, hemangioendotheliomas may occur elsewhere in the body and can metastasize to lungs, lymph nodes, bones, and within the pleural or peritoneal cavities. The preferred pathologic designation for these lesions in older persons is epithelioid hemangioendothelioma, which connotes the possibility of distant spread. These latter lesions are considered of intermediate malignant potential, between benign hemangioma and angiosarcoma.51,52 Treatment of the asymptomatic liver hemangioendothelioma of a child younger than 1 year may consist of close observation, because some will regress. Symptomatic lesions require urgent medical or surgical management, especially if coagulopathy is present.47,48,49,50 Epithelioid hemangioendothelioma of the liver should be managed surgically; some patients may need orthotopic liver transplantation because this disease does not respond to radiation therapy or chemotherapy.51,
  7. Vascular tumors vary from hemangiomas, which are considered always benign, to angiosarcomas, which are highly malignant.53 Complete surgical excision appears to be crucial for angiosarcomas and lymphangiosarcomas despite evidence of tumor shrinkage in some patients in response to local therapy.54,55,56,


1 Miser JS, Pappo AS, Triche TJ: Other soft tissue sarcomas of childhood. In: Pizzo PA, Poplack DG, eds.: Principles and Practice of Pediatric Oncology. 4th ed. Philadelphia, Pa: Lippincott, Williams and Wilkins, 2002, pp 1017-1050.

2 Rao BN: Nonrhabdomyosarcoma in children: prognostic factors influencing survival. Semin Surg Oncol 9 (6): 524-31, 1993 Nov-Dec.

3 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.

4 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.

5 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.

6 Casanova M, Ferrari A, Bisogno G, et al.: Alveolar soft part sarcoma in children and adolescents: A report from the Soft-Tissue Sarcoma Italian Cooperative Group. Ann Oncol 11 (11): 1445-9, 2000.

7 Marcus KC, Grier HE, Shamberger RC, et al.: Childhood soft tissue sarcoma: a 20-year experience. J Pediatr 131 (4): 603-7, 1997.

8 Merchant TE, Parsh N, del Valle PL, et al.: Brachytherapy for pediatric soft-tissue sarcoma. Int J Radiat Oncol Biol Phys 46 (2): 427-32, 2000.

9 Ferrari A, Casanova M, Bisogno G, et al.: Hemangiopericytoma in pediatric ages: a report from the Italian and German Soft Tissue Sarcoma Cooperative Group. Cancer 92 (10): 2692-8, 2001.

10 Cecchetto G, Carli M, Alaggio R, et al.: Fibrosarcoma in pediatric patients: results of the Italian Cooperative Group studies (1979-1995). J Surg Oncol 78 (4): 225-31, 2001.

11 Buitendijk S, van de Ven CP, Dumans TG, et al.: Pediatric aggressive fibromatosis: a retrospective analysis of 13 patients and review of literature. Cancer 104 (5): 1090-9, 2005.

12 Loh ML, Ahn P, Perez-Atayde AR, et al.: Treatment of infantile fibrosarcoma with chemotherapy and surgery: results from the Dana-Farber Cancer Institute and Children's Hospital, Boston. J Pediatr Hematol Oncol 24 (9): 722-6, 2002.

13 Skapek SX, Hawk BJ, Hoffer FA, et al.: Combination chemotherapy using vinblastine and methotrexate for the treatment of progressive desmoid tumor in children. J Clin Oncol 16 (9): 3021-7, 1998.

14 Gandhi MM, Nathan PC, Weitzman S, et al.: Successful treatment of life-threatening generalized infantile myofibromatosis using low-dose chemotherapy. J Pediatr Hematol Oncol 25 (9): 750-4, 2003.

15 Merchant NB, Lewis JJ, Woodruff JM, et al.: Extremity and trunk desmoid tumors: a multifactorial analysis of outcome. Cancer 86 (10): 2045-52, 1999.

16 Faulkner LB, Hajdu SI, Kher U, et al.: Pediatric desmoid tumor: retrospective analysis of 63 cases. J Clin Oncol 13 (11): 2813-8, 1995.

17 Merchant TE, Nguyen D, Walter AW, et al.: Long-term results with radiation therapy for pediatric desmoid tumors. Int J Radiat Oncol Biol Phys 47 (5): 1267-71, 2000.

18 Zelefsky MJ, Harrison LB, Shiu MH, et al.: Combined surgical resection and iridium 192 implantation for locally advanced and recurrent desmoid tumors. Cancer 67 (2): 380-4, 1991.

19 Weiss AJ, Lackman RD: Low-dose chemotherapy of desmoid tumors. Cancer 64 (6): 1192-4, 1989.

20 Klein WA, Miller HH, Anderson M, et al.: The use of indomethacin, sulindac, and tamoxifen for the treatment of desmoid tumors associated with familial polyposis. Cancer 60 (12): 2863-8, 1987.

21 Carli M, Ferrari A, Mattke A, et al.: Pediatric malignant peripheral nerve sheath tumor: the Italian and German soft tissue sarcoma cooperative group. J Clin Oncol 23 (33): 8422-30, 2005.

22 Okcu MF, Munsell M, Treuner J, et al.: Synovial sarcoma of childhood and adolescence: a multicenter, multivariate analysis of outcome. J Clin Oncol 21 (8): 1602-11, 2003.

23 Suit H, Spiro I: Radiation as a therapeutic modality in sarcomas of the soft tissue. Hematol Oncol Clin North Am 9 (4): 733-46, 1995.

24 Schomberg PJ, Gunderson LL, Moir CR, et al.: Intraoperative electron irradiation in the management of pediatric malignancies. Cancer 79 (11): 2251-6, 1997.

25 Sadoski C, Suit HD, Rosenberg A, et al.: Preoperative radiation, surgical margins, and local control of extremity sarcomas of soft tissues. J Surg Oncol 52 (4): 223-30, 1993.

26 Grobmyer SR, Maki RG, Demetri GD, et al.: Neo-adjuvant chemotherapy for primary high-grade extremity soft tissue sarcoma. Ann Oncol 15 (11): 1667-72, 2004.

27 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.

28 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.

29 Nathan PC, Tsokos M, Long L, et al.: Adjuvant chemotherapy for the treatment of advanced pediatric nonrhabdomyosarcoma soft tissue sarcoma: the National Cancer Institute experience. Pediatr Blood Cancer 44 (5): 449-54, 2005.

30 Wodowski K, Hill DA, Pappo AS, et al.: A chemosensitive pediatric extraosseous osteosarcoma: case report and review of the literature. J Pediatr Hematol Oncol 25 (1): 73-7, 2003.

31 Goldstein-Jackson SY, Gosheger G, Delling G, et al.: Extraskeletal osteosarcoma has a favourable prognosis when treated like conventional osteosarcoma. J Cancer Res Clin Oncol 131 (8): 520-6, 2005.

32 McGrory JE, Pritchard DJ, Arndt CA, et al.: Nonrhabdomyosarcoma soft tissue sarcomas in children. The Mayo Clinic experience. Clin Orthop (374): 247-58, 2000.

33 Ferrari A, Gronchi A, Casanova M, et al.: Synovial sarcoma: a retrospective analysis of 271 patients of all ages treated at a single institution. Cancer 101 (3): 627-34, 2004.

34 Ladenstein R, Treuner J, Koscielniak E, et al.: Synovial sarcoma of childhood and adolescence. Report of the German CWS-81 study. Cancer 71 (11): 3647-55, 1993.

35 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.

36 Fanburg-Smith JC, Miettinen M, Folpe AL, et al.: Lingual alveolar soft part sarcoma; 14 cases: novel clinical and morphological observations. Histopathology 45 (5): 526-37, 2004.

37 Argani P, Antonescu CR, Illei PB, et al.: Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma: a distinctive tumor entity previously included among renal cell carcinomas of children and adolescents. Am J Pathol 159 (1): 179-92, 2001.

38 Ogose A, Yazawa Y, Ueda T, et al.: Alveolar soft part sarcoma in Japan: multi-institutional study of 57 patients from the Japanese Musculoskeletal Oncology Group. Oncology 65 (1): 7-13, 2003.

39 Lieberman PH, Brennan MF, Kimmel M, et al.: Alveolar soft-part sarcoma. A clinico-pathologic study of half a century. Cancer 63 (1): 1-13, 1989.

40 Leuschner I, Radig K, Harms D: Desmoplastic small round cell tumor. Semin Diagn Pathol 13 (3): 204-12, 1996.

41 Kushner BH, LaQuaglia MP, Wollner N, et al.: Desmoplastic small round-cell tumor: prolonged progression-free survival with aggressive multimodality therapy. J Clin Oncol 14 (5): 1526-31, 1996.

42 Gerald WL, Ladanyi M, de Alava E, et al.: Clinical, pathologic, and molecular spectrum of tumors associated with t(11;22)(p13;q12): desmoplastic small round-cell tumor and its variants. J Clin Oncol 16 (9): 3028-36, 1998.

43 Schwarz RE, Gerald WL, Kushner BH, et al.: Desmoplastic small round cell tumors: prognostic indicators and results of surgical management. Ann Surg Oncol 5 (5): 416-22, 1998 Jul-Aug.

44 Goodman KA, Wolden SL, La Quaglia MP, et al.: Whole abdominopelvic radiotherapy for desmoplastic small round-cell tumor. Int J Radiat Oncol Biol Phys 54 (1): 170-6, 2002.

45 Speleman F, Delattre O, Peter M, et al.: Malignant melanoma of the soft parts (clear-cell sarcoma): confirmation of EWS and ATF-1 gene fusion caused by a t(12;22) translocation. Mod Pathol 10 (5): 496-9, 1997.

46 Ferrari A, Casanova M, Bisogno G, et al.: Clear cell sarcoma of tendons and aponeuroses in pediatric patients: a report from the Italian and German Soft Tissue Sarcoma Cooperative Group. Cancer 94 (12): 3269-76, 2002.

47 Daller JA, Bueno J, Gutierrez J, et al.: Hepatic hemangioendothelioma: clinical experience and management strategy. J Pediatr Surg 34 (1): 98-105; discussion 105-6, 1999.

48 Lyons LL, North PE, Mac-Moune Lai F, et al.: Kaposiform hemangioendothelioma: a study of 33 cases emphasizing its pathologic, immunophenotypic, and biologic uniqueness from juvenile hemangioma. Am J Surg Pathol 28 (5): 559-68, 2004.

49 Hu B, Lachman R, Phillips J, et al.: Kasabach-Merritt syndrome-associated kaposiform hemangioendothelioma successfully treated with cyclophosphamide, vincristine, and actinomycin D. J Pediatr Hematol Oncol 20 (6): 567-9, 1998 Nov-Dec.

50 Deb G, Jenkner A, De Sio L, et al.: Spindle cell (Kaposiform) hemangioendothelioma with Kasabach-Merritt syndrome in an infant: successful treatment with alpha-2A interferon. Med Pediatr Oncol 28 (5): 358-61, 1997.

51 Makhlouf HR, Ishak KG, Goodman ZD: Epithelioid hemangioendothelioma of the liver: a clinicopathologic study of 137 cases. Cancer 85 (3): 562-82, 1999.

52 Pinet C, Magnan A, Garbe L, et al.: Aggressive form of pleural epithelioid haemangioendothelioma: complete response after chemotherapy. Eur Respir J 14 (1): 237-8, 1999.

53 Coffin CM, Dehner LP: Vascular tumors in children and adolescents: a clinicopathologic study of 228 tumors in 222 patients. Pathol Annu 28 Pt 1: 97-120, 1993.

54 Lezama-del Valle P, Gerald WL, Tsai J, et al.: Malignant vascular tumors in young patients. Cancer 83 (8): 1634-9, 1998.

55 Fata F, O'Reilly E, Ilson D, et al.: Paclitaxel in the treatment of patients with angiosarcoma of the scalp or face. Cancer 86 (10): 2034-7, 1999.

56 Ferrari A, Casanova M, Bisogno G, et al.: Malignant vascular tumors in children and adolescents: a report from the Italian and German Soft Tissue Sarcoma Cooperative Group. Med Pediatr Oncol 39 (2): 109-14, 2002.

Metastatic Childhood Soft Tissue Sarcoma

The prognosis for children with metastatic soft tissue sarcomas is poor,1,2,3,4,5,6, and these children should receive combined treatment with chemotherapy, radiation therapy, and surgical resection of pulmonary metastases. In a prospective randomized trial, chemotherapy with vincristine, dactinomycin, doxorubicin, and cyclophosphamide with or without dacarbazine led to tumor responses in one third of the patients with unresectable or metastatic disease. The estimated 4-year survival rate, however, was poor, with fewer than one third of the children surviving.6,7,8,

Standard treatment options

Children with isolated pulmonary metastases should undergo exploratory thoracotomy in an attempt to resect all gross disease. The estimated 5-year survival rate after thoracotomy for pulmonary metastasectomy has ranged from 10% to 58% in adult studies. Formal segmentectomy, lobectomy, and mediastinal lymph node dissection are unnecessary.9,

Treatment options under clinical evaluation

Vincristine, doxorubicin, and ifosfamide with granulocyte colony-stimulating factor have been used in patients with unresected or metastatic tumors. The Pediatric Oncology Group evaluated the combination of doxorubicin and ifosfamide in children with unresected or metastatic soft tissue sarcomas because several adult trials have suggested that ifosfamide-based regimens may be superior to other chemotherapeutic regimens for soft tissue sarcomas.10,



1 Demetri GD, Elias AD: Results of single-agent and combination chemotherapy for advanced soft tissue sarcomas. Implications for decision making in the clinic. Hematol Oncol Clin North Am 9 (4): 765-85, 1995.

2 Elias A, Ryan L, Sulkes A, et al.: Response to mesna, doxorubicin, ifosfamide, and dacarbazine in 108 patients with metastatic or unresectable sarcoma and no prior chemotherapy. J Clin Oncol 7 (9): 1208-16, 1989.

3 Edmonson JH, Ryan LM, Blum RH, et al.: Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J Clin Oncol 11 (7): 1269-75, 1993.

4 Rao BN: Nonrhabdomyosarcoma in children: prognostic factors influencing survival. Semin Surg Oncol 9 (6): 524-31, 1993 Nov-Dec.

5 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.

6 Pappo AS, Rao BN, Jenkins JJ, et al.: Metastatic nonrhabdomyosarcomatous soft-tissue sarcomas in children and adolescents: the St. Jude Children's Research Hospital experience. Med Pediatr Oncol 33 (2): 76-82, 1999.

7 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.

8 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.

9 Putnam JB Jr, Roth JA: Surgical treatment for pulmonary metastases from sarcoma. Hematol Oncol Clin North Am 9 (4): 869-87, 1995.

10 Walter AW, Shearer PD, Pappo AS, et al.: A pilot study of vincristine, ifosfamide, and doxorubicin in the treatment of pediatric non-rhabdomyosarcoma soft tissue sarcomas. Med Pediatr Oncol 30 (4): 210-6, 1998.

Recurrent Childhood Soft Tissue Sarcoma

With the possible exception of infants with congenital fibrosarcoma, the prognosis for patients with recurrent or progressive disease is poor. The selection of further treatment depends on many factors, including the site of recurrence, prior therapy, and individual patient considerations. Local recurrence or isolated pulmonary recurrence should be treated with complete resection. All patients with recurrent tumors should be offered enrollment in current drug studies.

Standard treatment options

Resection is the standard treatment for recurrent pediatric nonrhabdomyosarcomatous soft tissue sarcomas. If the patient has not yet received radiation therapy, adjuvant radiation should be considered after local excision of the recurrent tumor. Limb-sparing procedures with adjuvant brachytherapy has been evaluated in adults but has not been studied extensively in children. For some children with extremity sarcomas who have received previous radiation therapy, amputation may be the only therapeutic option. No prospective trial has been able to prove that enhanced local control of pediatric soft tissue sarcomas will ultimately improve survival. Therefore, treatment should be individualized for the site of recurrence and biologic characteristics (e.g., grade, invasiveness, and size) of the tumor. All patients should be considered for enrollment in clinical trials. Pulmonary metastasectomy may achieve prolonged disease control for some patients.1 A large, retrospective analysis of patients with recurrent soft tissue sarcoma showed that isolated local relapse had a better prognosis and that resection of pulmonary metastases improved the probability of survival.2

Treatment options under clinical evaluation

Phase I and II trials of chemotherapy.



1 Belal A, Salah E, Hajjar W, et al.: Pulmonary metastatectomy for soft tissue sarcomas: is it valuable? J Cardiovasc Surg (Torino) 42 (6): 835-40, 2001.

2 Zagars GK, Ballo MT, Pisters PW, et al.: Prognostic factors for disease-specific survival after first relapse of soft-tissue sarcoma: analysis of 402 patients with disease relapse after initial conservative surgery and radiotherapy. Int J Radiat Oncol Biol Phys 57 (3): 739-47, 2003.

Changes to This Summary (1/04/2007)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Editorial changes were made to this summary.

More Information

About PDQ

  • PDQ® - NCI's Comprehensive Cancer Database.
    • Full description of the NCI PDQ database.

Additional PDQ Summaries

  • PDQ® Cancer Information Summaries: Adult Treatment
    • Treatment options for adult cancers.
  • PDQ® Cancer Information Summaries: Pediatric Treatment
    • Treatment options for childhood cancers.
  • PDQ® Cancer Information Summaries: Supportive Care
    • Side effects of cancer treatment, management of cancer-related complications and pain, and psychosocial concerns.
  • PDQ® Cancer Information Summaries: Screening/Detection (Testing for Cancer)
    • Tests or procedures that detect specific types of cancer.
  • PDQ® Cancer Information Summaries: Prevention
    • Risk factors and methods to increase chances of preventing specific types of cancer.
  • PDQ® Cancer Information Summaries: Genetics
    • Genetics of specific cancers and inherited cancer syndromes, and ethical, legal, and social concerns.
  • PDQ® Cancer Information Summaries: Complementary and Alternative Medicine
    • Information about complementary and alternative forms of treatment for patients with cancer.

Important:

This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237) .

2007-01-04







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