Soft tissue masses are frequently seen in children. Although most are benign or reactive, soft tissue sarcomas (STS)-both rhabdomyosarcoma (most common) and non-rhabdo STS, do occur in the extremities. Appropriate evaluation of extremity soft tissue tumors often includes a biopsy as the clinical and imaging features may not be enough to establish a definitive diagnosis. Much needs to be done for improving the treatment of these rare but often devastating sarcomas. Given the small numbers of these cases seen at various centers, collaborative efforts should be made to further our understanding and improve the management of these challenging cases.
Key points
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Soft tissue sarcomas (STS) in children are rare and may have overlapping clinical and imaging features with more common benign tumors and reactive processes, thus making them a diagnostic challenge.
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Soft tissue sarcomas, unlike bone sarcomas, often present as painless masses.
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Soft tissue sarcomas grow in a centrifugal fashion and usually have well defined margins, thus making the differentiation from benign soft tissue lesions challenging.
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Many STS have characteristic chromosomal abnormalities.
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Rhabdomyosarcomas (RMS) are the most common pediatric soft tissue sarcoma in the 0 to 14 age group and account for more than 50% of STS in this age group.
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Alveolar RMS and non-RMS STS are more common in the extremities.
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Treatment of RMS is a combination of chemotherapy, surgery, and radiation (as needed), whereas treatment of non-RMS STS is primarily surgery.
Introduction
Soft tissue masses in children include the more common reactive and benign soft tissue masses but also include the rare and much more serious soft tissue sarcomas (STS). These sarcomas are a heterogeneous group of malignancies that arise from a mesenchymal cell of origin. Each year in the United States approximately 850 to 900 children and adolescents (age 20 years or less) are diagnosed with a STS. Of these, approximately 350 are rhabdomyosarcomas (RMS). The incidence of STS in this age group is 11 per million and these make up 7.4% of all cancers in this age group. Boys are affected slightly more frequently and in the adolescent population, African Americans are slightly more frequently affected.
Imaging findings in soft tissue masses are frequently nonspecific and biopsy, therefore, is an important component of the diagnostic workup of soft tissue tumors. Familiarity with the clinical and imaging appearance of STS may help the treating surgeon devise an appropriate evaluation and management strategy. Treatment of pediatric soft tissue sarcoma often involves chemotherapy and surgery. Radiation is used with caution in young children, especially for tumors close to growth plates. This review covers some of the essential concepts for making the diagnosis and understanding treatment principles of malignant soft tissue tumors in children. Also highlighted are some of the recent advances in imaging, diagnostic pathology.
Introduction
Soft tissue masses in children include the more common reactive and benign soft tissue masses but also include the rare and much more serious soft tissue sarcomas (STS). These sarcomas are a heterogeneous group of malignancies that arise from a mesenchymal cell of origin. Each year in the United States approximately 850 to 900 children and adolescents (age 20 years or less) are diagnosed with a STS. Of these, approximately 350 are rhabdomyosarcomas (RMS). The incidence of STS in this age group is 11 per million and these make up 7.4% of all cancers in this age group. Boys are affected slightly more frequently and in the adolescent population, African Americans are slightly more frequently affected.
Imaging findings in soft tissue masses are frequently nonspecific and biopsy, therefore, is an important component of the diagnostic workup of soft tissue tumors. Familiarity with the clinical and imaging appearance of STS may help the treating surgeon devise an appropriate evaluation and management strategy. Treatment of pediatric soft tissue sarcoma often involves chemotherapy and surgery. Radiation is used with caution in young children, especially for tumors close to growth plates. This review covers some of the essential concepts for making the diagnosis and understanding treatment principles of malignant soft tissue tumors in children. Also highlighted are some of the recent advances in imaging, diagnostic pathology.
Diagnostic strategy
A primary care physician is often faced with the initial evaluation of a soft tissue mass in the child and they often send these children on to a general surgeon or an orthopedist for further evaluation. The differential diagnosis in this situation may be extremely broad. A complete history and the rapidly disappearing art of physical examination are extremely important in narrowing this down to a more appropriate list of differential diagnoses. Pain is not a reliable indicator of malignant potential. Solid (noncystic) lesions in children (and adults) need to be worked up further and this may include imaging (ultrasound for small superficial lesions and magnetic resonance imaging [MRI] for larger, deeper lesions). A high index of suspicion should be maintained in patients with premalignant conditions or cancer predisposition syndromes ( Table 1 ). A biopsy is warranted in cases where the clinical and imaging findings are insufficient to clinch the diagnosis.
| Beckwith Wiedemann syndrome | 11p15 | RMS, Wilms tumor |
| Noonan syndrome | 12q24 | RMS |
| Costello syndrome | 12p12.1 | RMS |
| Li-Fraumeni syndrome | 17p13.1 (LFS 1); 1q23 (LFS3) | RMS, LPS |
| Hereditary retinoblastoma | 13q14.2 | LMS, Osteosarcoma |
| Neurofibromatosis type 1 | 17q11.2 | MPNST |
| Adenomatous polyposis coli | 5q21-q22 | Desmoid tumors |
Biopsy
With imaging being less specific in soft tissue compared with bone tumors, biopsy is an extremely important component to making the diagnosis. This biopsy may be excisional (typically for small, superficial lesions or those with characteristic clinical and imaging findings) or incisional (especially in masses close to neurovascular structures, such as in the popliteal fossa or axilla). Needle (core and fine-needle aspiration) biopsies are especially useful in deep soft tissue masses and are often used with image (ultrasound, computed tomography [CT], MR) guidance. Obtaining adequate lesional tissue is paramount, as is a discussion of the clinical and radiographic information with the pathologist before the biopsy. This discussion helps to prepare for appropriate sample processing and further testing. Samples are best sent to the laboratory fresh on a moist nonadherent pad, so that the pathologist can obtain the appropriate tests, for example, flow cytometry cannot be performed on formalinized samples. Principles of biopsy of musculoskeletal lesions are detailed in Box 1 . The importance of an appropriately planned and performed biopsy cannot be overemphasized ( Fig. 1 ). The hematoxylin and eosin appearance of the biopsied tissue is frequently diagnostic. With improving technology, pathologists now frequently use various adjuncts to confirm their diagnosis and also further subclassify tumors and give prognostic information. These include the following.
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Review the clinical and radiographic findings with the radiologist and pathologist before the biopsy.
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The biopsy should be performed at the site of definitive treatment by appropriately trained personnel or in consultation with them, if the former not feasible.
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Use a tourniquet whenever possible. Avoid expressive exsanguination (Eschmarck bandage).
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Shortest possible incision, longitudinally placed, along the line of the eventual resection.
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Minimum soft tissue dissection and contamination of tissue planes. Dissection through and not in between muscles to minimize contamination and need for eventual resection.
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Choose the best site for the biopsy: usually the advancing edge of the tumor and not the central portion, which may often be necrotic. A thorough analysis of the MR images helps in planning this.
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Obtain adequate amount of tissue for diagnosis and ancillary tests. Minimal distortion of the specimen and send it down fresh to the pathologist for appropriate tests.
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Achieve hemostasis and use a drain (brought out in line with the incision and close to it), if needed.
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Sutures placed close to the wound edges to minimize the amount of skin to be excised at the time of definitive resection.
Immunohistochemistry
Immunohistochemistry is a technique that uses antibodies to identify specific molecules on different kinds of tissue. These molecules not only help to identify different histologic tissue types but may also help to understand how cells grow and differentiate, thereby helping to understand some of the pathways involved in pathogenesis of these tumors. There are more than 200 immunohistochemical stains available and this number is growing exponentially. Some of the commonly used immunohistochemical stains and the tissues that these are associated with are shown in Table 2 .
| Marker | Tumor Type |
|---|---|
| S-100 | Neurogenic tumors mostly, but fairly nonspecific |
| Cytokeratin, epithelial membrane antigen | Carcinomas, synovial sarcoma, epithelioid sarcoma, myoepithelial tumors |
| CD 31, CD 34 | Vascular lesions, CD 34 also in DFSP, spindle cell lipoma |
| Myogenin (more specific) and MyoD1 | Skeletal muscle, rhabdomyosarcoma |
| Smooth muscle actin | Leiomyosarcoma, myofibroblastic lesions |
| Caldesmon | Smooth muscles, GIST, glomus tumor |
| Podoplanin 2 | Lymphatic malformations, Kaposi sarcoma |
| TLE1 (transducin-like enhancer of split 1) | Synovial sarcoma |
| Ki-67 | Marker of proliferation |
Cytogenetics
The use of cytogenetics has resulted in increased recognition of chromosomal abnormalities associated with various tumors. Various cytogenetic techniques include karyotyping, fluorescent in situ hybridization, comparative genomic hybridization, and chromosome microdissection. The cytogenetic abnormalities associated with soft tissue tumors include a wide spectrum from gains to losses of chromosomal material (trisomies, deletions, translocations). Translocation associated STS are commonly seen in the younger population (and frequently involve the EWS gene) compared with adults who frequently have nonspecific or complex aberrations. Detection of these genetic changes has added another diagnostic weapon to our armamentarium, especially in borderline cases. Some of the more frequent cytogenetic changes are listed in Table 3 .
| Tumor | Cytogenetic Abnormality |
|---|---|
| Myxoid LPS | t(12;16)(q13;11) and t(2;22)(q13;q12) |
| Infantile fibrosarcoma | t(12;15)(p13;q25) |
| Embryonal rhabdomyosarcoma | Loss of heterozygosity at 11p15 |
| Alveolar rhabdomyosarcoma | t(2;13)(q35;q14) or t(1;13)(q36;q14) or 25%–40% cases without either |
| Angiomatoid fibrous histiocytoma | t(12;16)(q13;11) or t(2;22)(q13;12) |
| Synovial sarcoma | t(X;18)(p11;q11) |
| Epithelioid sarcoma-proximal | 22q11.2 alterations |
| Alveolar soft part sarcoma | der(17)t(x;17)(p11.2;q25) |
| Extraskeletal myxoid chondrosarcoma | t(9;22)(q22;q12) or t(9;17)(q22;q12) or t(9;15)(q22;q21) |
| Extraskeletal EWS | t(11;22)(q24;q12) and other less common variants |
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