Soft tissue sarcomas

Diagnosis and management of sarcomas

♦ Any enlarging mass, deep to deep fascia should be regarded as a potential sarcoma.

♦ Tissue for histology should be obtained by cutting needle (e.g. Trucut), not incisional biopsy. The biggest surgical problems are caused by injudicious incisions.

♦ Incision biopsy should never be performed—this disseminates the tumour and is never curative. Surgery should be preceded by appropriate CT or MRI.

♦ Multidisciplinary care of sarcomas is best carried out in centres with appropriate expertise—including surgery, pathology, radiotherapy, and chemotherapy.

Rhabdomyosarcoma (RMS)

The commonest soft tissue tumour in childhood and adolescence. More than half the cases occur in children under 10 years and is rare in adults over 40. Male to female ratio is approximately 1.3:1. Arises from primitive mesenchymal cells with the capacity for rhabdomyoblastic development. Commonest sites of origin are:

♦ Genitourinary tract

♦ Retroperitoneum

♦ Extremities

Disease may spread locally (e.g. from the orbit to the meninges and central nervous system) and disseminates to lymph nodes, lungs, bones, marrow, and brain. An aggressive disease requiring multi-modality treatment. Outlook depends on the disease site and histolog-ical subtype.

Pleomorphic RMS is a rather rare adult soft tissue tumour, which behaves in a similar fashion to other adult soft tissue tumours in that while it may be curable if localized it is not as chemosensitive as the childhood variety and carries a poor prognosis once metastatic.


Presents with swelling or other local symptoms such as displacement of the eye, vaginal bleeding, dysuria, etc. In establishing a histological diagnosis it is currently advisable to obtain fresh tissue for chromosomal studies.

Embryonal RMS

Accounts for about 60% of cases. Occurs mainly in children under 15, most commonly affecting:

♦ Head and neck, including orbit

♦ Genitourinary tract

♦ Retroperitoneum

'Embryonal' refers to the spectrum of cell type, from primitive round cells to rhabdomyoblasts, which may be thought to mimic the stages in muscle embryogenesis. Botryoid RMS is a subtype characterized by polypoid growth, like a 'bunch of grapes', and is usually found in hollow organs such as the vagina, bladder, and nasopharyngeal sinuses.

Alveolar RMS

Characterized by poorly differentiated round or oval cells forming irregular spaces and separated by fibrous septae, giving the appearance of'alveoli'. Sometimes this appearance is absent but the uniform appearance of the cells is distinct from that of the embryonal variety. Multinucleate giant cells may be observed. Alveolar RMS has a significantly worse prognosis than embryonal.

If fresh tissue is available, the diagnosis may be confirmed by the presence of a t(2;13) (q37;q14) or variant t(1;13) (p36;q14) chromosomal translocation. The result is fusion of PAX3 or PAX7 genes respectively with the FKHR gene, producing a chimeric protein. Translocation may be identified by fluorescence in situ hybridization (FISH) or reverse transcriptase polymerase chain reaction (RT-PCR) methods that require little tumour tissue. Translocation may be detected in about half of cases and, where present, reliably distinguishes alveolar from embryonal RMS.


Staging should include MRI or CT of the primary site, CT scan of the thorax, isotope bone scan, and bone marrow aspirate and trephine. The stage is usually assigned using the SIOP-UICC TNM (tumour, nodes, metastases) staging system which is useful in determining appropriate therapy.

Prognostic factors

The prognosis in RMS depends on site, size, extent of spread (i.e. stage, histology, sex, in that the outlook is somewhat worse in girls), and response to chemotherapy.


Treatment usually begins with combination chemotherapy, followed by local treatment i.e. complete surgical resection where possible plus radiotherapy if excision incomplete, or radiotherapy alone if resection

Table 28.1 Prognostic factors in rhabdomyosarcoma



Orbit, paratesticular, vagina

Parameningeal, retroperitoneal,


Localized to tissue of origin

Contiguous spread, nodal or metastatic


Complete resection feasible


Embryonal histology

Alveolar histology

Infant or child


Complete response to chemotherapy

Poor response to chemotherapy

is not feasible. Patients with embryonal histology may be treated with vincristine plus actinomycin D; treatment is intensified with the addition of ifosfamide, doxorubicin, and other drugs for worse staging histology. Additional drugs such as etoposide and carboplatin and high-dose alkylating agent therapy, with peripheral blood progenitor cell rescue, may improve the outlook for some patients with metastatic disease, but the prognosis remains grave for alveolar RMS.

RMS is highly sensitive to radiotherapy. In combination with chemotherapy, doses of 40-50 Gy will usually ensure local disease control. However, there are serious long-term sequelae associated with the combined modality treatment in children. These include:

♦ Damage to sensitive organs, such as bladder, eye, brain, testis, ovary, and thyroid

♦ Risk of second malignancy

♦ Imbalanced bone growth, especially where epiphyses are included in the field

In infants and children with localized tumours and favourably histology, such as embryonal RMS of the orbit, it may be possible to omit radiotherapy. Extremity tumours, alveolar histology, and para-meningeal tumours require radiotherapy.

Soft tissue Ewing's sarcoma and primitive neuroectodermal tumour (PNET)

Ewing's tumours are the second commonest bone malignancy in children. These are small round cell tumours of neuroectodermal origin and are characterized by chromosomal translocations involving the EWS gene, located at chromosome 22q12, fused with FL11 [t(11;22) (q24;q12)] or, more rarely, ERG [t(21;22) (a22;q12)]. Genetic analysis with FISH or RT-PCR methods may aid diagnosis. Soft tissue Ewing's sarcoma or PNET most commonly involves the extremities, chest wall (Askin's tumour), or pelvis.

In terms of treatment, much of the management of RMS applies to the Ewing's family of tumours. Prognosis with surgery alone is dismal (<10% cure) because of the frequency of systemic spread. Pre- and post-operative combination chemotherapy (doxorubicin, actino-mycin D, ifosfamide, vincristine) is of crucial importance. Surgery is the preferred primary local treatment but radiotherapy is required after incomplete resection or where surgery is not feasible. Tumour bulk and response to chemotherapy are the two most important prognostic factors. The outlook is worse for those patients with tumours larger than 200 ml or with lung metastases, worse still in the case of bone metastases at diagnosis. Site is also important—axial primaries fare worse through a combination of late presentation and problems achieving local control of disease. Five-year survival rates are about 60% overall—80% for good-risk cases, falling to 20% in metastatic or larger tumours.

Adult sarcomas

Soft tissue sarcomas (STS) are rare tumours, accounting for 1% of adult malignancies and 6% of those in childhood. There are about 1200 new cases in the UK annually. Many histopathological varieties of STS are described, the most common being leiomyosarcoma, malignant fibrous histiocytoma, and liposarcoma. Classification of an individual tumour is based on morphology and immunohisto-chemistry.

Certain types of adult STS, such as clear cell, epithelioid, and synovial, always behave in an aggressive fashion. For those tumours that are more variable in their behaviour, such as liposarcoma, grade is more important than subtype since grade, tumour size, and resecta-bility are key prognostic factors.

Low-grade, well-differentiated tumours may recur locally but rarely metastasize. Alveolar soft part sarcoma may behave in an indolent fashion but nevertheless does metastasize, and the prognosis is poor.

Disease pattern and prognosis

♦ 50% have high-grade sarcomas

♦ 50% of high-grade sarcomas die from metastases

♦ Metastases—rare with primary tumour <5 cms

—common with primary tumour >15 cms

♦ Superficial tumours have better prognosis

♦ Extremity tumours spread to lung

♦ RMS, clear cell, epithelioid sarcomas spread to nodes

♦ Angiosarcomas, synovial sarcomas spread to bone

♦ Retroperitoneal sarcomas spread to liver

♦ Gynaecological sarcomas—diagnosed late, bad prognosis

♦ Older patients—worse prognosis

♦ Liposarcoma—better prognosis

♦ Synovial sarcoma is chemosensitive


Radical surgery for the primary STS offers the only hope of cure. Complete compartmental resection for extremity tumours is no longer advocated since it is known that sarcomas rarely cross fascial boundaries. If possible, some muscle in the compartment should be spared. Sarcomas do, however, spread longitudinally. It is for this reason that careful pre-operative planning is required using MRI or CT scan to delineate the tumour extent and relationship to major vessels or nerves that may indicate the need for reconstructive surgery. If required, in the case of diagnostic difficulty the surgeon performing the definitive operation should carry out further biopsies. There needs to be close collaboration between surgeon and radiotherapist.

Preservation of function should be a priority, and amputation is rarely necessary. For high-grade tumours and any locally recurrent tumour, adjuvant radiotherapy is advised. This may be delivered pre-or post-operatively. Doses in the range of 55-65 Gy are recommended.

Retroperitoneal tumours are rarely radically resectable and recurrence is common, especially for higher-grade tumours. While radiotherapy may reduce local recurrence, it is likely to do little to influence prognosis, and the dose which can be safely delivered to the abdomen (40-50 Gy) will be insufficient to control the majority of STS.

Advanced disease

Metastases may be surgically removed in the case of limited relapse in the lungs. Any benefit increases with the relapse-free interval and if metastases are few in number. Chemotherapy for resectable locally recurrent or metastatic disease is palliative.

Ifosfamide and doxorubicin are the most active agents, but reported response rates are still disappointing (15-30%). There is clear evidence for a dose-response relationship with both drugs. Combination chemotherapy may produce higher response rates but is more toxic. Synovial sarcoma is chemosensitive and complete responses are observed. Low-grade tumours and especially gastrointestinal stromal tumours are generally unresponsive to conventional chemotherapy.

The role of adjuvant chemotherapy remains unclear but a recent meta-analysis of primary data from all published randomized trials showed significantly improved progression-free survival and a small improvement in overall survival, amounting to 4% at 10 years, which failed to reach statistical significance. There remains an urgent need for more effective systemic therapy in this group of diseases.

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