Soft tissue sarcomas approx 1% of all new cancer diagnoses.

Almost half pts eventually die as a result of the cancer. Soft tissue sarcomas can occur anywhere in the body, but most originate in an extremity (59%), the trunk (19%), the retroperitoneum (15%), or the head and neck (9%). Soft tissue sarcomas originate from a wide variety of mesenchymal cell types and include malignant fibrous histiocytoma, liposarcoma, rhabdomyosarcoma, leiomyosarcoma, and desmoid tumors. While the histopathology of these tumors is highly variable, with some exceptions they tend to behave in a fashion dictated by tumor grade rather than the cell of origin. Most soft tissue sarcomas arise de novo, and rarely do they result from malignant degeneration of a benign lesion. Familial syndromes genetically predisposed to the formation of soft tissue sarcomas, including LiFraumeni syndrome, Recklinghausen disease, and Gardner syndrome. Other proven risk factors exist that may increase the chances of sarcoma formation. External radiation therapy can increase the incidence of sarcomas by 8-fold to 50-fold. Chronic extremity lymphedema also increases the risk for lymphangiosarcoma. A classic example is the development of upper extremity lymphangiosarcomas in the lymphedematous arm of women treated for breast cancer (Stewart-Treves syndrome). Other less clear associations link chronic tissue trauma and occupational chemical exposures with an increased risk for sarcoma formation. The major features of the staging system for soft tissue sarcomas are the grade of the tumor, its size, and the presence of metastatic disease. Although the site of the tumor is not considered in staging, patients with retroperitoneal tumors tend to have a worse prognosis. Sarcomas generally metastasize by the hematogenous route, and the metastatic sites of sarcomas are related to the location of the primary tumor. The vast majority of metastases from extremity sarcomas are to the lung, while the majority of retroperitoneal tumors metastasize to the liver. Lymph node involvement is rare with most soft tissue sarcomas, although it may occur with epithelioid sarcoma, clear cell sarcoma, angiosarcoma, rhabdomyosarcoma, or synovial sarcoma.

Grading is based on the cellular architecture and invasive nature of the tumor, FNAB is not a typically useful biopsy technique for the initial diagnosis of a sarcoma. If a tumor is small (< 3 cm) and superficial, excisional biopsy should be performed. All extremity biopsy incisions should be oriented longitudinally, as the biopsy incision scar should be excised in a subsequent definitive resection of the tumor. Core needle biopsies may be performed for large, palpable superficial tumors. For large, deep tumors or those adjacent to vital structures, incisional biopsy is usually the diagnostic method of choice. The incision should be centered over the mass, tissue flaps should not be raised, and meticulous hemostasis should be ensured, all to prevent the dissemination of tumor cells into adjacent tissue planes.

Treatment of Extremity Sarcomas

MRI is the imaging modality of choice for any suspected extremity sarcoma because it is most accurate in defining the extent of the tumor and invasion of surrounding structures. MRI is also used for follow-up imaging to assess response in patients undergoing therapy, as well as for local and regional recurrence. A chest x-ray or chest CT should be obtained in order to evaluate for pulmonary metastases in patients with high-grade tumors. Surgery remains the primary therapy for localized extremity sarcomas, but multimodality therapy is recommended to minimize the likelihood of recurrence or the need for amputation. Historically, amputation was the only form of curative surgical therapy for large extremity sarcomas, but multimodality therapy has allowed for a high rate of limb preservation. Today, fewer than 5% of

patients with extremity soft tissue sarcoma require amputation, generally reserved for patients whose tumors do not respond to preoperative therapy and cannot be resected adequately, have no evidence of metastatic disease, and have a good prognosis for rehabilitation. A pseudocapsule composed of tumor cells surrounds sarcomas, and local invasion along fascial planes and neurovascular structures is common. It is important not to dissect along the pseudocapsule, which is associated with high local recurrence rates, but rather obtain a wide (2-cm) margin of normal tissue. This may need to be compromised in the immediate vicinity of functionally important neurovascular structures. If the tumor involves these structures, nerve grafts and arterial reconstruction with autologous or prosthetic conduits may be required. Large soft tissue defects often require the construction of myocutaneous flaps to improve function and cosmesis. Soft tissue sarcomas rarely invade bone or skin, and wide resections of these structures are infrequently necessary. Following wide local excision, metal clips should be placed at all margins of the resection in order to guide subsequent radiotherapy. For patients with T1 tumors located superficially in an area where it is not difficult to obtain widely negative margins, postoperative radiation therapy may not be necessary. For most other lesions, postoperative radiation is almost always recommended, with either external beam radiation or brachytherapy. Radiation should be started 48 weeks after surgery, as delay can result in a lower local control rate. Preoperative radiotherapy may have some advantages in patients with large tumors. Lower doses can be delivered to an undisturbed tumor bed, which may also have better oxygenation, and larger tumors may decrease in size, allowing for limb-sparing procedures. Preoperative radiation is associated with an increase in short-term wound complications but a decrease in long-term tissue fibrosis and edema. The optimal mode and sequence for treatment has yet to be defined and often requires a multidisciplinary approach. Adjuvant chemotherapy remains controversial. Chemotherapy can be given either preoperatively or postoperatively. The three drugs most effective in sarcoma are doxorubicin, dacarbazine, and ifosfamide. Preoperative chemotherapy is sometimes recommended because in addition to the early treatment of micrometastatic disease, it allows for assessment of tumor response, which helps avoid prolonged therapy in patients not responding. However, while disease-free survival may be improved, there are conflicting data on overall survival. A recent meta-analysis of randomized trials suggested there may be a small survival benefit for extremity sarcomas, and so its use has increased. The vast majority of localized recurrences in soft tissue sarcomas occur in the first 2 years after resection, necessitating close follow-up during that period. A local recurrence is not indicative of systemic disease and, in the absence of evidence of metastases, should be treated aggressively in the same manner as a primary tumor. The resection of pulmonary metastases should be considered in patients who have fewer than four radiographically detectable lesions and who have achieved apparent local control following resection of the primary tumor. In such circumstances, disease-free survival can approach 2535%.

Treatment of Retroperitoneal Sarcomas

Retroperitoneal sarcomas comprise approximately 15% of all soft tissue sarcomas, with liposarcoma, malignant fibrous histiocytoma, and leiomyosarcoma the three most common types. They usually present as a large abdominal mass. Nearly half are over 20 cm in size at diagnosis. Once they compress or invade contiguous structures, they can cause symptoms such as abdominal pain or nausea and vomiting. Workup should include CT of the abdomen and pelvis to evaluate the mass as well as CT of the lung and liver to look for metastases. CT-guided core biopsy is the sampling technique of choice, with open or laparoscopic incisional biopsy reserved for inconclusive core biopsies.

As with extremity sarcomas, surgery represents the primary treatment, with the goal being en bloc resection with a rim of normal tissue. Although retroperitoneal tumors are generally large at presentation and often invade vital structures, the majority of these tumors are resectable. Retroperitoneal sarcomas rarely invade surrounding organs, but an intense desmoplastic reaction makes it difficult to assess the extent of tumor, so often these organs need to be resected rather than risk positive margins. The kidney, colon, pancreas, and spleen are the most commonly resected organs. While adjuvant radiation therapy is standard in extremity sarcoma, evidence supporting its use in retroperitoneal sarcoma is less convincing. Because of the low tolerance to radiation of the abdominal and retroperitoneal organs, delivery of adequate radiotherapy is often difficult. There is encouraging evidence for intraoperative radiation therapy to the tumor bed, but this technique is still considered investigational and can be performed only in select centers. Although complex, preoperative radiation may be beneficial because it uses lower radiation doses, is less injurious to the small bowel, and can increase respectability by shrinking the tumor and creating a thickened capsular structure around the lesion.