Sarcomas - Bone And Soft Tissue Malignancies

Introduction

Sarcomas of the bone and soft tissue are rare. When they do occur, they can develop in virtually any area of the body and affect all age groups and races. The diagnosis and treatment of such lesions is often complex, and firm guidelines are not established given the disparity of presentations and relative rarity of individual sarcoma subtypes. A multidisciplinary approach is essential to appropriate management of sarcomas, incorporating the role of the oncologists, radiologists, pathologists, thoracic and orthopedic surgeons, physical therapists and prosthetists, amongst others.
Bone sarcomas include osteosarcomas, which are the most common, chondrosarcomas, Ewing's sarcomas, and, very rarely, fibrosarcomas. Soft tissue tumors include malignant fibrous histiocytomas, leiomyosarcomas, liposarcomas and rhabdomyosarcomas, to name a few. Each of these sarcomas present in different ways, exhibit different behaviors and prognoses, and present unique therapeutic challenges.

Epidemiology and Etiology

• Incidence of primary bone and soft tissue tumors is remarkably low, with an estimated 3,970 new primary bone cancers and 13,590 new soft tissue cancers expected in the US annually. Mortality rates are about 2,050 from bone cancers and 5,200 from soft tissue tumors.
• Etiology of these tumors is unknown, though some can present as second malignancies in patients treated with radiotherapy for previous cancers.
• Hereditary links are suggested by evidence of a familial tendency in bone cancers derived from siblings with osteosarcoma, Ewing's sarcoma and chondrosarcoma. Molecular genetics are a top area of current research, and some sarcomas exhibit characteristic translocations (for example, t(11:22) seen in Ewing's sarcoma).
• Risk factors are not well identified, but may include
  • Slight predominance seen in adolescents and males
  • Prior exposures to high-dose irradiation for cancer treatment or agents such as alkylating drugs, immunosuppression and neurofibromatosis type I (neurofibrosarcoma)
  • Hyperparathyroidism, chronic osteomyelitis, old bone infarction and pre-existing bone conditions like Paget's disease for bone tumors

Screening Recommendations

• Considering the relatively low incidence of these malignancies, no screening tests are available for the general population.
• Those with a personal or family history of predisposing conditions should have individualized screening by their physicians with attention to areas at risk. Routine radiographic tests are not generally recommended.

Clinical Presentation

• History: Bone tumors usually cause pain of gradual onset and worsening severity, sometimes radicular and in presence of a pathological fracture; soft tissue tumors often present as painless masses unless there is nerve impingement
• Physical exam: Careful inspection and palpation of area of pain and/or swelling, noting dimensions and presence of dilated surface veins; lymph and musculoskeletal exams especially vital
• Lab studies: Individualized based on suspected entity, areas of involvement and planned therapy. May include serum alkaline phosphatase levels with osteosarcoma and LDH with Ewing's sarcoma.
• Radiologic studies: Useful for staging, surgical and radiotherapeutic treatment planning. Studies of potential use include plain radiographs, bone scans, arteriography, CT scans, ultrasound and MRI, which is considered to be superior to CT in demonstrating tumor extent and detecting recurrence.
  • For bone, three basic radiographic patterns of tumor destruction having diagnostic and prognostic implications discussed below are:
    • Geographic large, well-defined hole with edge of intact bone adjacent to edge of destroyed bone
    • Moth-eaten multiple holes that tend to join (prognosis poorer)
    • Permeative multiple small holes in cortical bone that decrease in size and number as you move to periphery
• Diagnostic studies: Biopsy is essential; open or incisional biopsy, including frozen sections, is the most common method used as it yields a large tissue volume for study. Closed or needle biopsy can be employed for patients with metastatic disease or deep lesions and is about 80% accurate [1].

Natural Course and Pathology

Prognosis depends on the size of the tumor (large is generally worse), the tumor grade, and the location. Patients with distant metastases generally have a poor prognosis.

• Osteosarcoma Most common osseous malignancy; arises from primitive bone-forming mesenchyma in the medullary cavity of the bony metaphysis. Most common primary tumor sites are distal femur, proximal tibia and proximal humerus, the latter two with better prognosis [1].
  • Most cases of osteosarcoma are in young adults ages 10-30, but 10% are in adults over 60.
  • Histologic pattern highly variable mixture of bone, cartilage and stroma
  • Radiologic pattern of "sunburst" representing new periosteal bone formation is classic finding and can be virtually diagnostic
  • Metastatic spread occurs hematogenously, most commonly to lung
  • In presence of pulmonary metastases at time of diagnosis, five-year survival rate after surgery with or without irradiation is 24%; the overall survival rate is 59% at 5 years [2].
• Chondrosarcoma 14% of malignant bone tumors, arises from cartilage with absence of osteoid tissue [1].
  • Most common sites are pelvic bone, long bones, scapula and ribs
  • Histologic pattern of many cartilage cells with plump nuclei
  • Radiologic pattern is lobular with possible calcification
  • Metastatic spread does not tend to occur early, as tumor is slow-growing and locally invasive
  • Advanced cases metastasize via venous channels to lungs and heart.
  • Five-year survival rate after surgery is 79%, far better than osteosarcoma [1].
• Fibrosarcoma 7% of malignant bone tumors, arises from malignant fibroblasts [1].
  • Most common sites are femur and tibia
  • Histologic findings range from low to high grade
  • Radiologic pattern varies depending on aggressiveness of tumor
  • Metastasis occurs primarily to lungs
  • Five- survival is between 40-60%[3]. Owing to advances in treatment approaches, many patients can be cured with a combination of local and systemic treatment.
• Ewing's Sarcoma 6% of malignant bone tumors, arises from mesenchymal connective tissue of diaphyseal bone marrow and rarely involves epiphyses [1].
  • Most common sites are pelvis and long bone, but no one site predominates
  • Histologic pattern of packed, uniform cells with indistinct borders, prominent nuclei and finely divided chromatin.
  • Radiologic pattern of "onion" layers representing new, laminated subperiosteal bone
  • Metastasis occurs early and frequently involves the lungs
  • Five-year survival rate following surgery and radiotherapy is highly variable depending on local extent, location and presence of metastatic disease. Overall survival about 39% if metastatic disease is present, and 82% with localized disease [4].
• Soft Tissue Sarcomas Most often occur in extremities, the remainder located in head and neck and retroperitoneum
  • Histological subtypes include malignant fibrous histiocytoma, liposarcoma, fibrosarcoma, synovial sarcoma, rhabdomyosarcoma and leiomyosarcoma.
  • Nodal metastases are common in synovial, epithelioid and rhabdomyo-sarcomas
  • Poor prognosis with lymph node involvement and high histologic grade. Prognosis tends to be more favorable in children and adolescents.
  • The overall survival rate is 65% at five years, but only 18% if disease has distant metastasis at the time of diagnosis. Survival is highly variable amongst different types of soft tissue sarcomas; five-year survival rate ranging from 30% for retroperitoneal lesions to 95% for some trunk sarcomas and subsets of rhabdomyosarcomas [1].
  • Prognosis tends to be higher in children and adolescents than in adults.

Treatment

• Osteosarcoma
  • Surgery and adjuvant chemotherapy given pre- and postoperatively results in markedly increased five-year survival rate and disease-free interval, making limb salvage resections possible. In metastatic disease, surgery and postoperative chemotherapy achieve 2-year survival rates of up to 40% [2].
  • Radiation is reserved for palliative or inoperable cases.
• Chondrosarcoma
  • Surgery ranging from wide resection with reconstruction to amputation.
  • Refractory to chemotherapy given poor blood supply, but role of adjuvant chemotherapy with surgery is under investigation. 
  • Radiation (possibly with neutrons) has limited role in palliative or inoperable cases.
• Ewing's Sarcoma
  • Primary chemotherapy for 6-12 months integrated with surgery and/or radiation is regimen of choice.
• Fibrosarcoma
  • Surgery is the mainstay of treatment.
  • Adjuvant chemotherapy regimens under study for use in metastases.
  • Radioresistant tumors in general.
• Soft Tissue Sarcomas
  • Surgery with or without pre- and post-operative radiation, based on size of tumor and degree of local structural involvement.
  • Role of adjuvant chemotherapy is not clearly defined, and continues to be topic of clinical research.