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Year : 2015  |  Volume : 20  |  Issue : 4  |  Page : 165-169

Non-rhabdomyosarcoma soft-tissue sarcomas in children: Contemporary appraisal and experience from a single centre

Department of Pediatric Surgical Oncology, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India

Date of Web Publication2-Sep-2015

Correspondence Address:
Dr. Sajid S Qureshi
Department of Paediatric Surgical Oncology, Tata Memorial Hospital, Ernest Borges Road, Parel, Mumbai - 400 012, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0971-9261.154664

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Nonrhabdmyosarcoma soft tissue sarcomas (NRSTS) include a cluster of different types of soft tissue sarcomas clubbed together due to the rarity of individual subtypes. The diagnostic accuracy is lately reinforced due to the availability of immunohistochemical and molecular markers. Surgery is the central modality of treatment since many of them are insensitive to chemotherapy. With the availability of rational risk stratification system, efforts are in progress to evaluate the role of neoadjuvant chemotherapy and radiotherapy to improve outcomes especially for the locally advanced disease. The survival remains dismal for metastatic disease. This review highlights the current status of NRSTS and also describes the experience from a single centre in treatment of NRSTS.

Keywords: Children, non-rhabdomyosarcoma, soft-tissue sarcoma

How to cite this article:
Qureshi SS, Bhagat M. Non-rhabdomyosarcoma soft-tissue sarcomas in children: Contemporary appraisal and experience from a single centre. J Indian Assoc Pediatr Surg 2015;20:165-9

How to cite this URL:
Qureshi SS, Bhagat M. Non-rhabdomyosarcoma soft-tissue sarcomas in children: Contemporary appraisal and experience from a single centre. J Indian Assoc Pediatr Surg [serial online] 2015 [cited 2023 Feb 2];20:165-9. Available from: https://www.jiaps.com/text.asp?2015/20/4/165/154664

   Introduction Top

Non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) include an assorted group of tumors accounting for 7% of all childhood malignancies and around 50% of all sarcomas in children. [1] The relative infrequency of the different histopathological subtypes precludes performance of clinical trials on a single tumor type, and consequently, NRSTS have been analyzed as a group.

With contemporary treatment, more than 70% of children and adolescents with surgically resected non-metastatic disease are expected to be cured. [2],[3] In contrast, fewer than 10% of patients with metastatic disease are expected to become long-term survivors. [4],[5]


The NRSTS group encompasses several histological variants, including synovial sarcoma, malignant peripheral nerve sheath tumor (MPNST), alveolar soft part sarcoma (ASPS), angiosarcoma, clear cell sarcoma (CCS), fibrosarcoma, ectomesenchymoma, epitheloid hemangioendothelioma, gastrointestinal stromal tumors (GIST), hemangiopericytoma, myxoid chondrosarcoma, spindle cell sarcoma, malignant fibrous histiocytoma (MFH), leiomyosarcoma, epitheloid sarcoma, liposarcoma, dermatofibrosarcoma and poorly differentiated or undifferentiated sarcoma, not otherwise specified. The World Health Organization's (WHO) 2002 revised classification of soft tissue tumors: Intermediate (rarely metastasizing) and malignant tumors, gives a comprehensive list of malignant NRSTS. [6]

Apart from morphology, cytogenetic and molecular genetic abnormalities play an increasing role, both in diagnosis and prognosis of NRSTS. [7] Specific chromosomal translocations have been identified in certain NRSTS which in most instances generate a chimeric fusion protein capable of driving sarcoma genesis. Synovial sarcoma is associated with t (x;18) (p11, q11) (SYT-SSX), alveolar soft parts sarcoma associated with t (X;17) (p11; q25) (ASPLTFE3), and myxoid liposarcoma with t (12;16) (q13; p11) (TLS-CHOP) and t (12;22) (p13; q12) (EWS-CHOP). [8]


NRSTS are usually sporadic however, genetic predisposition is seen in some patients, e. g.  Li-Fraumeni syndrome More Details, hereditary retinoblastoma, Gorlin syndrome, neurofibromatosis type 1, Werner syndrome and familial adenomatous polyposis. [9] With increasing survival in patients with malignancies, especially those who have received radiation or higher doses of anthracyclines and alkylating agents, a higher incidence of secondary sarcomas has been identified. [10] The cellular origin of different types of NRSTS is not reasonably clear however, dedifferentiated mesenchymal cell or progenitor or stem cell have been suggested. [11]

Clinical presentation

A bimodal age distribution, with increased incidence in infancy that decreases after first year of life is seen in NRSTS. [11] Incidence then increases progressively throughout childhood and adolescence. Commonest presentation includes mass lesions anywhere in the body easily missed or neglected by parents or physicians. [12] The frequent anatomic sites are the extremities, most often in the lower limbs, followed by the trunk, head and neck region and abdomen. [2],[3],[13] The lesions characteristically impersonate a 'benign-looking', well-circumscribed mass, which may mistakenly be observed or excised as a shell-out procedure ('Whoops procedure'). Metastatic disease at presentation is seen in 15%, most commonly to the lungs. The other infrequent sites are the bone, liver, subcutaneous tissue, brain and bone marrow. [4] Lymph nodes involvement is uncommon and is seen in certain NRSTS like epitheloid sarcoma and CCS. [11]

Evaluation and diagnosis

Magnetic resonance imaging (MRI) is considered the imaging modality of choice for the evaluation of local and regional disease as it provides superior soft tissue resolution, multiplanar images, and does not require iodinated contrast agents or ionizing radiation. Malignant lesions are usually larger and display inhomogeneous signal intensity on T2-weighted images. A contrast-enhanced computerized tomography (CT) scan is useful for evaluation of abdominal tumors and pulmonary metastases. Although positron emission tomography (PET) scans have become customary for investigations of many tumors, the role in NRSTS is yet to be clearly defined. [14]

The utility of a biopsy in achieving a diagnosis surpasses any other investigation. The most important consideration is to obtain adequate amount of tissue for diagnosis with minimal disruption of tissue planes. The biopsy incision should be correctly placed since an ill-conceived biopsy may adversely affect the definitive surgical procedure. All incisions, when possible, should be longitudinal on extremities, parallel to the neurovascular structures, to allow easy wide local excision. [15] Core needle biopsies or an open incision biopsy are preferred because they provide the least risk of local contamination. Primary surgical resection is undertaken for small tumor or when wide local resection can be done without risk or functional deformity. Sentinel lymph node mapping may detect occult nodal disease and should be considered in patients at high risk for lymph node metastasis. [16]



Surgery has remained the cornerstone of treatment as many of the NRSTS are considered not enough chemosensitive. Wide local resection is the main objective of surgery for NRSTS. The exact margin of resection that is required to achieve a favourable outcome is unclear. Historically, the standard margin of resection accepted in adults was 2 cm, with recurrence rates of 10-15%. [17] However, a margin of 2 cm is not feasible in the head and neck region, mediastinum, or retroperitoneum as it would require excessive mutilating surgical procedures. Previous reports have recommended a tumor free margin or a margin greater than 1 cm for adequate local control. [18]

Unplanned resections frequently (50%) have microscopic residual disease which is associated with a higher rate of local recurrence. [19] Hence a pre-treatment re-excision (PRE) should be undertaken when the initial operation was not a cancer operation or when malignancy was not suspected preoperatively. The main aim of PRE is to achieve microscopic radicalism prior to other treatment and in appropriate situation avoid irradiation of the tumor bed. It reduces local recurrences and appears to have a positive effect on survival. [20],[21] PRE should be considered as early as possible, although a delay of up to 107 days (median 29 days) has been shown to have no adverse effects. [19] Pulmonary metastatectomy is advocated as an adjunct to combine modality therapy as it improves disease control. [22]


NRSTS are less responsive to radiotherapy than rhabdomyosarcoma and Ewing sarcoma. Adjuvant radiotherapy has been recommended for high grade tumors, in tumors with positive margins of resection or low grade unresectable tumor. [2],[18] The rates of local recurrence significantly decrease with the use of adjuvant radiotherapy in patients with microscopic residual tumor however; local control with radiotherapy alone for unresectable NRSTS is not higher than 25-30%. [23] The use of neoadjuvant radiotherapy with or without chemotherapy is being investigated for achieving significant shrinkage of initially unresectable tumor for facilitating resection. [24] However, the disadvantages include delay in surgical resection, wound healing and loss of information on tumor extent and pathology. In view of the distinct late effects of radiotherapy in very young children, it can be avoided in patients less than 2 years of age. [25] Brachytherapy whenever feasible should be considered as it has the advantage of sparing surrounding normal tissues and the shorter duration of radiation treatment. [26],[27] Newer techniques of radiation delivery like intensity-modulated radiation therapy and proton beam therapy may reduce the toxicity of radiation. [28],[29] For pulmonary metastasis, radiotherapy alone is not effective however, can be used in the multimodal treatment. [4]


The role of adjuvant chemotherapy in the treatment of paediatric NRSTS remains discordant. [5],[30],[31] Chemotherapy is recommended for initially unresectable or metastatic disease. [11] It is also being investigated in tumors more than 5 cm and surgically resected high-grade lesions, since they have high chances of distant metastases. [24] The frequently used drugs are a combination of vincristine, ifosfamide and doxorubicin. Of all the NRSTS, synovial sarcoma has higher response rates with the ifosfamide based regimen. [30]

Prognostic factors

Tumor size of more than 5 cm, high grade tumors, unresectability and the presence of metastases are predominant poor prognostic factors. [2],[3],[32] Based on these factors, risk stratification has been suggested. [11] High-risk category indicates metastatic disease with approximately 15% survival. Intermediate risk indicates an unresectable tumor or a tumor that is both high grade and more than 5 cm in maximal diameter. The survival in this group is approximately 50%. Low-risk tumors are resectable tumors that are both high grade and less than 5 cm in diameter or low grade of any size. The survival is approximately 90%. This stratification has been utilised in the ongoing Children's Oncology Group (COG) study. [24] Surgical margins, visceral sites and older age are other prognostic factors. [2],[3]

Tata memorial hopsital (TMH) experience

A total of 102 patients with NRSTS were offered curative treatment between January 2006 and April 2014. Of these 102 patients, 16 had a recurrent tumor and one had a second malignancy following successful treatment for hepatoblastoma 3 years earlier. The remaining 85 patients with primary NRSTS were included in this analysis. All patients had a comprehensive clinical evaluation and a core biopsy performed for confirmation of the diagnosis. Lesions were considered unresectable if a wide, non-mutilating resection was not feasible on the basis of clinical and radiological evaluation due to its size or location. These patients received neoadjuvant chemotherapy and/or radiotherapy.

The median age of patients was 10 years (range 2 months-18 years) with 59 males and 26 females. The most common site was the extremity (N = 41). The other sites included the trunk (N = 10), head and neck (N = 15), intra-abdominal (N = 15), intra-thoracic (N = 2) and genitourinary (N = 2). Regional lymph node metastasis was present in eight patients.


Upfront surgery was performed in 61 patients, of whom 32 were PRE; 21 patients received neoadjuvant chemotherapy, two patients received both chemotherapy and radiotherapy and one patient received radiotherapy prior to surgery. Amputations were required in four patients and wide excision was achieved in the remaining patients. Vascularised flap was used for reconstruction in eight patients, polypropylene mesh in two patients and skin graft in one patient. The median duration of surgery was two hours (range 20 minutes to 7.30 hours) and the median blood loss was 100 ml (range 10-2400 ml). The median postoperative hospital stay was seven days (range 1-35 days). There was no postoperative mortality.

Postoperative radiotherapy was administered to 50 patients; 11 of these patients received interstitial brachytherapy. Adjuvant chemotherapy was offered to 36 patients, which was along with radiotherapy in 25.


The predominant histological types were synovial sarcoma (N = 28), ASPS (N = 8), myofibroblastic sarcoma (N = 8), infantile fibrosarcoma (N = 6), spindle cell sarcoma (N = 4), epitheloid sarcoma (N = 3), clear cell sarcoma (N = 3), rhabdoid tumor (N = 3) and MPNST (N = 3). Residual tumor was noted in 17 patients (53%) who had a PRE. Surgical margins were positive in 4/70 patients.


Wound infection occurred in nine patients, transient nerve paresis in two patients, intestinal obstruction, chyle leak and flap necrosis in one each.

Outcome and survival

The median follow-up was 32 months (range, 2-106 months). There were 22 relapses or progression (26%). The relapses were local only in five, both local and distant in one, regional and distant in one and distant only in 13 patients. Two patients had progression of pulmonary metastases on treatment. The sites of metastases were lungs in 11 patients, abdominal cavity in three and both lungs and bone in one patient. Surgery was offered to 11 patients either alone or with chemotherapy and/or radiotherapy. Radiotherapy or chemotherapy alone was offered to six patients and five patients received best supportive care. Eleven patients died after relapse and three are alive with disease. The projected 5 year overall survival (OS), event free survival (EFS) and local control (LC) were 79%, 62% and 88%.

Prognostic factors

On univariate analysis tumor size of less than 5 cm, resectable disease, depth, presence of metastases and margin status were significant prognostic factors for both OS and EFS. Tumor grade was significant for EFS only. Age, gender, site of tumor and invasiveness was not found to be significant. On multivariate analysis presence of metastases and resectable disease were significant for OS. The tumor size had a borderline significance (P = 0.052). The risk of death in patients with resectable disease was 83% less compared to unresectable disease (P = 0.002). The hazard ratio of death for metastatic disease was 4.4 fold (P = 0.017) as compared to non-metastatic disease. Tumor size, grade, margin status and metastatic disease remained significant for EFS on multivariate analysis.

   Conclusion Top

NRSTS incorporates varied soft tissue sarcoma which is essential due the rarity of individual tumor subtypes. Surgery is the cornerstone of treatment however newer approaches are being evaluated for improving outcomes. Survival is influenced by the presence of metastases and surgically unresectable disease.

   Acknowledgement Top

We wish to thank Mr. Mehboob Shah for meticulous data collection and retrieving follow-up of patients defaulting after completion of treatment.

   References Top

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