骨与软组织肉瘤

1 Bone and Soft-tissue Sarcomas: Epidemiology, Radiology, Pathology and Fundamentals of Surgical Treatment Barry Shmookler, Jacob Bickels, James Jelinek, Paul Sugarbaker and Martin M. Malawer OVERVIEW An understanding of the basic biology and pathology of bone and soft-tissue tumors is essential for appropriate planning of their treatment. This chapter reviews the unique biological behavior of soft-tissue and bone sarcomas, which underlies the basis for their staging, resection, and the use of appropriate adjuvant treatment modalities. A detailed description of the clinical, radiographic, and pathological characteristics for the most common sarcomas is presented. Malawer Chapter 01 21/02/2001 14:56 Page 3 BIOLOGY AND NATURAL HISTORY OF BONE AND SOFT-TISSUE TUMORS Soft-tissue and bone sarcomas are a rare and hetero- geneous group of tumors. Although soft tissues and bone comprise 75% of the average body weight, these neoplasms represent less than 1% of all adult and 15% of pediatric malignancies. The annual incidence in the United States, which remains relatively constant, is approximately 6000–7000 soft-tissue and 2500 bone sarcomas. Because these lesions are so rare, few pathol- ogists have sufficient experience to deal comfortably with their diagnosis. This is further compounded by the steady evolution in the classification of soft-tissue and bone tumors, which is based on their biological behavior, ultrastructure, and results of immunohisto- chemical and cytogenetic studies. Risk factors for soft-tissue and bone sarcomas include previous radiation therapy, exposure to chemicals (e.g., vinyl chloride, arsenic), immunodeficiency, prior injury (scars, burns), chronic tissue irritation (foreign-body implants, lymphedema), neurofibromatosis, Paget’s disease, bone infarcts, and genetic cancer syndromes (hereditary retinoblastoma, Li–Fraumeni syndrome, Gardner’s syndrome). In most patients, however, no specific etiology can be identified. Sarcomas originate primarily from elements of the mesodermal embryonic layer. Soft-tissue sarcomas are classified according to the adult tissue that they resem- ble. Similarly, bone sarcomas are usually classified according to the type of matrix production: osteoid- producing sarcomas are classified as osteosarcomas, and chondroid-producing sarcomas are classified as chondrosarcomas. The three most common soft-tissue sarcomas are malignant fibrous histiocytoma (MFH), liposarcoma, and leiomyosarcoma. These tumors are anatomic site-dependent; in the extremities the common subtypes are MFH and liposarcoma, whereas liposarcomas and leiomyosarcoma are the common subtypes in the retroperitoneum and the abdominal cavity. The most common bone sarcomas are osteo- sarcoma, chondrosarcoma, and Ewing’s sarcoma. Although soft-tissue sarcomas can arise anywhere in the body, the lower extremities are the most common site. Incidence is as follows: lower extremities – 46%; trunk – 19%; upper extremities – 13%; retroperitoneum – 12%; head and neck – 9%; other locations – 1%. The presenting symptoms and signs of soft-tissue sarcomas are nonspecific; they commonly present as a painless, slow-growing mass. Diagnosis of sarcomas involving the abdominal and pelvic cavity is subtle; these tumors may progress for long periods without causing overt symptoms. Their location deep within the body precludes palpation of the tumor mass early in the course of the disease; consequently, these tumors often reach tremendous size prior to diagnosis. In the past two decades, survival and the quality of life of patients with soft-tissue and bone sarcomas have dramatically improved as a result of the multimodality treatment approach. Surgery, used in combination with chemotherapy and radiation therapy, can achieve cure in the majority of patients with soft-tissue and bone sarcomas and resection is performed in lieu of amputation in more than 90% of all patients. Principles of chemotherapy and radiation therapy in the treatment of soft-tissue and bone sarcomas are discussed in Chapters 3, 4, and 5. Biological Behavior Tumors arising in bone and soft tissues have charac- teristic patterns of biological behavior because of their common mesenchymal origin and anatomical environ- ment. Those unique patterns form the basis of the staging system and current treatment strategies. Histologically, sarcomas are graded as low, intermediate, or high grade. The grade is based on tumor morphology, extent of pleomorphism, atypia, mitosis, and necrosis. It represents its biological aggressiveness and correlates with the likelihood of metastases. Sarcomas form a solid mass that grows centrifugally with the periphery of the lesion being the least mature. In contradistinction to the true capsule that surrounds benign lesions, which is composed of compressed normal cells, sarcomas are generally enclosed by a reactive zone, or pseudocapsule. This consists of compressed tumor cells and a fibrovascular zone of reactive tissue with a variable inflammatory component that interacts with the surrounding normal tissues. The thickness of the reactive zone varies with the histogenic type and grade of malignancy. High- grade sarcomas have a poorly defined reactive zone that may be locally invaded by the tumor (Figure 1.1). Musculoskeletal Cancer Surgery4 Figure 1.1 A pseudocapsule of a high-grade soft-tissue sar- coma (arrows). It is composed of compressed tumor cells and a fibrovascular zone of reactive inflammatory response. Malawer Chapter 01 21/02/2001 14:56 Page 4 In addition, they may break through the pseudo- capsule to form metastases, termed “skip metastases”, within the same anatomic compartment in which the lesion is located. By definition, these are locoregional micrometastases that have not passed through the circulation (Figure 1.2). This phenomenon may be responsible for local recurrences that develop in spite of apparently negative margins after a resection. Although low-grade sarcomas regularly interdigitate into the reactive zone, they rarely form tumor skip nodules beyond that area. Sarcomas respect anatomical borders. Local anatomy influences tumor growth by setting natural barriers to extension. In general, sarcomas take the path of least resistance and initially grow within the anatomical compartment in which they arose. In a later stage the walls of that compartment are violated (either the cortex of a bone or aponeurosis of a muscle), and the tumor breaks into a surrounding compartment (Figure 1.3). Most bone sarcomas are bicompartmental at the time of presentation; they destroy the overlying cortex and extend directly into the adjacent soft tissues (Figures 1.4, 1.5). Soft-tissue sarcomas may arise between compartments (extracompartmental) or in an anatomical site that is not walled off by anatomical barriers such as the intermuscular or subcutaneous planes. In the latter case they remain extracompart- mental and only in a later stage break into the adjacent compartment. Carcinomas, on the other hand, directly invade the surrounding tissues, irrespective of compartmental borders (Figure 1.6). Bone and Soft-tissue Sarcomas 5 Figure 1.2 High-grade sarcomas may break through the pseudocapsule to form “skip” metastases within the same anatomical compartment. They are occasionally found with low-grade sarcomas. Skip nodules are tumor foci not in continuity with the main tumor mass that form outside the pseudocapsule. “Satellite"” nodules, by contrast, form within the pseudocapsule. (A) Multiple satellite nodules (arrows) associated with a high-grade MFH. Note the normal intervening tissue. (B) “Skip” metastases (arrows) from an osteosarcoma of the distal femur. This finding is preoperatively documented in less than 5% of patients. A B Malawer Chapter 01 21/02/2001 14:56 Page 5 Musculoskeletal Cancer Surgery6 A B Figure 1.3 (A) Sagittal section of a high-grade osteosar- coma of the distal femur. The growth plate, although not invaded by the tumor in this case, is not considered an anatomical barrier to tumor extension. This is probably because of the numerous vascular channels that pass through the growth plate to the epiphysis. However, the articular cartilage is an anatomical barrier to tumor extension and very rarely is directly violated by a tumor. (B) Coronal section of a high-grade osteosarcoma of the distal femur. Although gross involvement of the epiphysis and medial cortical breakthrough and soft-tissue extension are evident, the articular cartilage is intact. This phenomenon allows intra-articular resection of high-grade sarcomas of the distal femur in most cases. Thick fascial planes are barriers to tumor extension. (C) axial MRI, showing a high-grade leiomyosarcoma of the vastus lateralis and vastus inter- medius muscles. The tumor does not penetrate (clockwise) the lateral intermuscular septum, adductor compartment, and the aponeuroses of the sartorius and rectus femoris muscles. C Malawer Chapter 01 21/02/2001 14:56 Page 6 Joint Involvement Direct tumor extension through the articular cartilage is rare and usually occurs as the result of a pathological fracture with seeding of the joint cavity or by peri- capsular extension (Figure 1.7). Occasionally, structures that pass through the joint (e.g., the cruciate ligaments) act as a conduit for tumor growth (Figures 1.8, 1.9). Transcapsular skip nodules are demonstrated in 1% of all osteosarcomas. Metastatic Pattern Unlike carcinomas, bone and soft-tissue sarcomas disseminate almost exclusively through the blood. Hematogenous spread of extremity sarcomas is mani- fested by pulmonary involvement in the early stages and by bony involvement in later stages (Figure 1.10). Abdominal and pelvic soft-tissue sarcomas, on the other hand, typically metastasize to the liver and lungs. Low-grade soft-tissue sarcomas have a low (< 15%) rate of subsequent metastasis while high-grade lesions have a significantly higher (> 15%) rate of metastasis. Metastases from sarcomas to regional lymph nodes are infrequent; the condition is observed in only 13% of patients with soft-tissue sarcomas and 7% of bone sarcomas at initial presentation. The prognosis associated with such an event is similar to that of distant metastasis. Most patients with high-grade primary bone sarcomas, unlike soft-tissue sarcomas, have distant micrometastases at presentation; an estimated 80% of patients with osteosarcomas have micrometastatic lung disease at the time of diagnosis. For that reason, in most Bone and Soft-tissue Sarcomas 7 A B Figure 1.4 (A) Ewing’s sarcoma of the distal two-thirds of the femur, and (B) osteosarcoma of the proximal tibia. Note the extraosseous component of the tumor. Most high-grade bone sarcomas are bicompartmental at the time of presentation (i.e., they involve the bone of origin as well as the adjacent soft tissues). Tumors at that extent are staged as IIB tumors (see staging of malignant bone tumors: Enneking’s classification). Malawer Chapter 01 21/02/2001 14:56 Page 7 cases, cure of a high-grade primary bone sarcoma can be achieved only with systemic chemotherapy and surgery. As mentioned, high-grade soft-tissue sarcomas have a smaller metastatic potential. Because of that difference in metastatic capability the role of chemo- therapy in the treatment of soft-tissue sarcomas and its impact on survival are still a matter of controversy. STAGING OF MUSCULOSKELETAL TUMORS Staging is the process of classifying a tumor, especially a malignant tumor, with respect to its degree of differentiation, as well its local and distant extent, in order to plan the treatment and estimate the prognosis. Staging allows the surgeon to determine the type and the extent of the operation that is necessary for a specific type of tumor in a particular anatomic location, as well as the indication for neoadjuvant treatment modalities. Staging of a musculoskeletal tumor is based on the findings of the physical examination and the results of imaging studies. Biopsy and histopathological evaluation is an essential component of staging, but should always be the final step. The concept and practice of biopsy of musculoskeletal tumors is discussed in Chapter 2. Plain radiographs remain the key imaging modality in the evaluation of bone tumors. Based on medical history, physical examination, and plain radiographs, accurate diagnosis of bone tumors can be made in more than 80% of cases. Because of the fine trabecular detail revealed by plain radiographs, bone lesions of the extremities can be detected at a very early stage; lesions of the spine and pelvis, by contrast, are not diagnosed until a large volume of bone has been destroyed. Once a bone lesion is found, computerized tomography (CT) is the imaging modality of choice to evaluate the extent of bone destruction. Magnetic resonance imaging (MRI) has been proven to be superior to CT in the evaluation of the intramedullary and extraosseous, soft-tissue extent of bone tumors (Figure 1.11). In their early stages, soft-tissue tumors are hard to detect due to the lack of bone involvement. Occasionally, distortion of fat planes in plain radio- graphs implies the presence of a soft-tissue mass. CT should be performed on a helical scanner that enables improved two-dimensional images and three- dimensional reconstruction capability. The field of view should be small enough to allow adequate resolution, particularly of the lesion and the adjacent neuro- vascular bundle and muscle groups. The slice thickness should be designed in order to allow at least 10–15 slices through the tumor. Intravenous contrast dye should be employed in the evaluation of soft-tissue tumors unless a clear contraindication for its use exists. On the other hand, contrast dye is of little value in the evaluation of bone tumors. MRI is a valuable tool in the evaluation of soft-tissue tumors and of the medullary and soft-tissue com- ponents of bone tumors. The signal intensity of a tumor is assessed by comparing it with that of the adjacent soft tissues, specifically skeletal muscle and subcu- taneous fat. MRI also enables one to view a lesion in all three planes (axial, sagittal, and coronal). Contrast- Musculoskeletal Cancer Surgery8 Figure 1.5 Biologic behavior of bone and soft-tissue sarcomas. Unique features are formation of reactive zone, intracompartmental growth, and, rarely, the presence of skip metastases. Malawer Chapter 01 21/02/2001 14:56 Page 8 enhanced MRI is useful in evaluating the relationship of a tumor to the adjacent blood vessels and in charac- terizing cystic lesions. The presence of orthopedic hardware or surgical clips is not a contraindication to the performance of MRI; however, if a lesion is immediately adjacent to the location of the hardware, the local field may be distorted. Although the purpose of MRI is to evaluate the anatomical extent of a lesion, it also can accurately diag- nose a variety of soft-tissue tumors, including lipomas, liposarcomas, synovial cysts, pigmented villonodular synovitis, hemangiomas, and fibromatoses. Hematomas frequently have a characteristic appear- ance in MRI; however, high-grade sarcomas that have undergone significant intratumoral hemorrhage may resemble hematomas. For this reason the diagnosis of a simple hematoma should be made cautiously and, once it is made, close clinical monitoring must be made until the condition has been resolved. The general guidelines regarding narrowing of the field and recommended number of slices per tumor are similar to those of CT. Bone scintigraphy was traditionally used to assess the medullary extension of a primary bone sarcoma. As a rule the bone was cut approximately 6 cm proximal to the margin of the increased uptake. MRI allows more accurate determination of the medullary tumor extent; as a result, safer resections in narrower margins can be performed. Bone scan is currently used to determine the presence of metastatic and polystotic bone disease and the involvement of a bone by an adjacent soft- tissue sarcoma. In addition, the appearance of a bone lesion in the flow and pool phases of a three-phase bone scan reflects its biological activity and may be helpful in its diagnosis. It is also used as an indirect means of evaluating tumor response to chemotherapy. Angiography is essential prior to surgery because vascular displacement is common in tumors that have a large extraosseous component. Blood vessels are likely Bone and Soft-tissue Sarcomas 9 Figure 1.6 (A) Axial MRI, showing metastatic bladder carcinoma to the posterior thigh. (B) Plain radiograph of the proximal femur revealed direct invasion through the cortical bone with a pathological fracture of the lesser trochanter (arrows). (C) In surgery, exploration of the sciatic nerve revealed direct tumor involvement with extension under the epineural sheath. A B C Malawer Chapter 01 21/02/2001 14:56 Page 9 to be distorted or, less commonly, directly incorporated to the tumor mass. Angiography provides information that helps the surgeon plan the anatomical approach and gauge the likelihood that a major blood vessel has to be resected en-bloc with the tumor. It can also detect vascular anomalies (Figure 1.12) and establish patency of collateral vessels. Proximal femur resection, for example, frequently necessitates ligation of the profun- dus femoral artery (PFA). A patent superficial femoral artery (SFA) must be documented by angiography prior to surgery, otherwise the extremity will suffer severe ischemia following ligation of the PFA. Preoperative embolization may be useful in preparation for resection of metastatic vascular carcinomas if an intralesional procedure is anticipated. Metastatic hypernephroma is an extreme example of a vascular lesion that may bleed extensively and cause exsanguination upon the execu- tion of an intralesional procedure without prior embolization. Intra-arterial administration of chemotherapy allows the use of another type of information that can obtained from angiographs; reduction in tumor vascularity. As revealed by serial angiographs, such reduction was shown to be indicative of good response to preoperative chemotherapy. Figure 1.13 summarizes the use of the various imaging modalities in the staging process of a primary bone sarcoma. There is no single universally accepted staging system for soft-tissue and bone sarcomas. Some systems are valuable in the determination of the operative strategy, whereas others may be more useful in the estimation of the prognosis. An important variable in any staging system for musculoskeletal tumors, unlike a staging Musculoskeletal Cancer Surgery10 Figure 1.7 Pericapsular extension of an osteosarcoma of the proximal humerus (arrows). Figure 1.8 Extension of an osteosarcoma of the distal femur to the knee joint along the cruciate ligaments (arrow points to tumor); the articular cartilage is intact. Knee joint extension of a high-grade sarcoma of the distal femur is a rare event, necessitating extra-articular resection (i.e., en- bloc resection of the distal femur, knee joint, and a component of the proximal tibia), as shown in this figure. Figure 1.9 The five major mechanisms of joint involve- ment by a bone sarcoma. The most common mechanisms are pathologic fracture and pericapsular extension. Malawer Chapter 01 21/02/2001 14:56 Page 10 system for carcinomas, is the grade of the tumor. The system that is most commonly used for the staging of soft-tissue sarcomas is that of the American Joint Committee on Cancer (Table 1.1).1 It is based primarily on the Memorial–Sloan Kettering staging system and does not apply to rhabdomyosarcoma. Critics of this system point out that it is based largely on single- institution studies that were not subjected to multi- institutional tests of validity. The Musculoskeletal Tumor Society adopted staging systems that were originally