Chapter 34 Bone Tumors
Orthopedic oncology is a complex surgical discipline that involves the care and management of individuals with primary and secondary neoplasms of the musculoskeletal system. The neoplasms may be benign or malignant. This chapter deals with bone tumors only.
Management of bone tumors is more difficult than treatment of neoplasms in other organ sites because of the need for skeletal stability. Adequate oncologic resection must be followed by skeletal reconstruction and restoration of function. With benign lesions, the process of reconstruction may be facilitated by bone’s unique property of regenerating, even in adults. For malignant lesions, bone cannot be relied on to heal and aggressive unconventional reconstruction is required. Care must be taken, from biopsy to definitive treatment. An inappropriately placed skeletal biopsy may result in a fracture. Bone biopsy may be extensive and require cement along with internal fixation to prevent an iatrogenic fracture.
Biopsy is a complex cognitive skill in the skeleton. Fine-needle, core, or surgical biopsy tracts harbor malignant cells. Therefore, definitive surgical resection of cancer requires removing the biopsy tract, all iatrogenic contamination, and the bone tumor in an en bloc resection. This requires extensive exposure with wide flaps and mobilization of neurovascular structures. Inappropriately placed biopsy or needle puncture sites can complicate placement of the definitive surgical incision or require multiple incisions, thereby jeopardizing limb salvage. Key structures may be contaminated by the biopsy tract. It has been conclusively shown in several studies that surgeons inexperienced in musculoskeletal oncology principles have a three to four times increased rate of complications from a poorly placed biopsy site.1–3 Unfortunately, this results in unnecessarily complex revision surgery and, in some cases, amputation instead of limb salvage.
Staging of skeletal sarcomas is straightforward and has remained relatively unchanged since its original description by Enneking and colleagues.4 Roman numeral I refers to a low-grade skeletal sarcoma as interpreted by the pathologist. Roman numeral II is high grade. Roman numeral III signifies metastasis, whether regional or distant. The letter A refers to intracompartmental tumor localization, whereas the letter B refers to extracompartmental growth of the primary skeletal sarcoma. A bone tumor that begins in the femur and grows into the quadriceps musculature is extracompartmental because it has grown out of its original compartment into another. Pathologic fractures can be thought of as extracompartmental tumors. The Enneking system has five stages, IA, IB, IIA, IIB, and III. Stage IIB tumors are high risk. Stage III represents metastases of any type. The staging system of the American Joint Committee on Cancer has not been universally adopted for skeletal sarcomas.
Bone tumor management can best be summarized by three factors. The first is the adequacy of oncologic resection. The second is the type and extent of skeletal reconstruction. The third is the functional outcome anticipated by the specific type of skeletal reconstruction. All three factors must be weighed and discussed with the patient and caregivers to decide on the optimal management for a particular individual. Adequacy of the surgical oncologic margin is not always the prime consideration; surgical resection for palliation is often important.
There are four types of surgical resection, each of which is defined by their margin. The margin represents the surgical dissection plane relative to the pseudocapsule and the neoplasm itself. Intralesional resections are exemplified by curettage. The surgical dissection plane goes through the tumor itself and potentially leaves gross tumor behind. Marginal resections generate a dissection plane at the periphery of the tumor through its pseudocapsule (e.g., subperiosteal long bone dissection). Theoretically, microscopic tumor may be left behind. Wide surgical margins have a dissection plane through a cuff of normal tissue. The cuff of normal tissue may be 1 cm or 1 m distant to the tumor. Theoretically, only satellite malignant cells may be left behind. With radical resection margins, the entire compartment in which the tumor resides is resected. For example, a tumor that originates in the distal end of the femur would undergo radical resection if the entire femur were removed, from the hip joint to the knee joint. Local recurrence rates are inversely proportional to how radical the surgical procedure is. It is common for a limb salvage procedure to achieve a more radical margin than amputation. For example, limb salvage resection of a distal femoral sarcoma can achieve a wide surgical margin that spares the popliteal vessels and most of the extensor mechanism and calf musculature. In contrast, an amputation that goes through the tumor of a distal femoral sarcoma achieves only an intralesional resection margin.
The skeleton is a dynamic organ that receives 20% of the cardiac output and can often heal itself. Surgical care and preparation of the resection bed optimize the chance for skeletal regeneration. Children regenerate bone at a higher rate than adults. Small bone defects of approximately 5 cm or smaller are often bone-grafted with autogenous bone obtained from the iliac crest, allograft bone obtained from bone banks, or a combination. Growth factors such as bone morphogenetic protein 2 (BMP2) and BMP7 are being used to potentiate osteoinduction. Demineralized bone matrix is a commercially derived allograft product that retains the noncellular protein constituents of normal bone and may facilitate osteogenesis.
Larger skeletal defects require more complex reconstruction strategies. If a joint is close by, reconstruction often involves the use of an arthroplasty or arthrodesis. These two options frequently require the application of a metal or structural bone allograft spacer. Occasionally, a vascularized autograft such as a fibula may be used by itself or in conjunction with skeletal reconstruction. An intercalary segmental defect involves the shaft of a long bone and does not require joint reconstruction. In these cases, structural bone allografts and metal spacers are used along with internal fixation, such as intramedullary rods or plates and screws.
The long-term functional outcome after skeletal reconstruction is directly related to the durability of the implant. Metallic implants offer good immediate function, but suffer from metal fatigue after millions of repetitive loading cycles, and long-term failure eventually occurs. In contrast, bone autografts or allografts provide short-term partial stability (protected weight bearing) but have the potential long-term advantage of permanent osteogenic ingrowth along with revascularization, leading to intact viable bone. The weight-bearing needs of the lower extremities are different from those of the high-demand, non–weight-bearing functions of the upper extremities. The axial skeleton has a mixture of high-demand and load-bearing requirements. Skeletal reconstruction in children requires calculation for limb growth. The more complicated the reconstruction, the higher the infection rate. Infections of metallic endoprostheses or large structural allografts can often be devastating and result in amputation. Terminal cancer patients who require skeletal reconstruction have different functional needs, immediate functional use with inconsequential long-term demands.
Alterations in DNA by inheritance, carcinogen exposure, sporadic replication or housekeeping error, mutation, chromosomal rearrangement, amplification, deletion, or change in expression can be oncogenic. Neoplastic cells that acquire such a genetic change may begin a multistep process that confers a potential growth advantage. Further genetic change leads to more mutations and the creation of clones of cells that acquire malignant characteristics.
Benign and malignant skeletal neoplasms have a host of DNA alterations catalogued by the absence or presence of suppressor genes, oncogenes, translocations, and chromosome gains or losses. Table 34-1 lists these genetic alterations for some selected bone tumors5; this table is meant to be a summary rather than an exhaustive list.
In contrast, skeletal metastases (e.g., carcinomas) manipulate the normal bone microenvironment to create osteolytic bone destruction while promoting the growth and spread of cancer cells.6,7 Cell adhesion molecules are used for both cell to cell and cell to matrix binding. Deregulation of matrix metalloproteinases disrupts the delicate balance of matrix homeostasis by increasing proteolytic activity. Degradation of the extracellular matrix results in cancer cell invasion. Angiogenesis stimulators such as vascular endothelial growth factor, fibroblast growth factor, and transforming growth factor-β are triggered by cancer cells to promote their own growth. Parathyroid hormone–related protein is released by certain tumor cells acting on the same receptors for parathyroid hormones to promote osteoclast-mediated bone resorption. Osteoclastogenesis is also promoted by interleukin-6, interleukin-8, and RANKL (receptor activator of nuclear factor κB ligand). There is a complex interaction among many cell receptors, cytokines, growth factors, and proteases in the metastatic bone microenvironment.
The incidence of benign bone tumors far exceeds that of skeletal sarcomas. In our clinical experience, there are at least five benign bone tumors for every primary malignant bone neoplasm. Unni and Inwards8 have found that approximately 54% of benign bone tumors are chondrogenic. Osteochondroma and enchondroma are the most common benign tumors. Both can be polyostotic. Osteochondromas are surface neoplasms of bone, whereas enchondromas are located intraosseously. The true prevalence of these tumors is unknown because many go undetected and unreported.
The significance of benign bone tumors is that they occur more frequently in the pediatric population than in adults. Fractures are often the initial mode of expression. A pathologic fracture may occur during running or other activities, with pain being the initial symptom. Frequently, benign bone tumors are detected in the pediatric or adult population as an incidental radiographic discovery. A patient with rotator cuff tendinitis may complain of shoulder pain and a plain radiograph identifies an incidental abnormality in the proximal humeral metaphysis, which by itself is asymptomatic. Benign bone tumors grow with the child and generally stop growing when the child reaches skeletal maturity. In children and adults, surgical indications include deformity (angular or limb length inequality), pain, pathologic fracture, and malignant transformation.
Most benign bone tumors can be resected safely with an intralesional resection margin. These procedures typically consist of intralesional curettage. The goal is a local recurrence rate between 10% and 20%. In the skeletally immature patient, physeal injury must be avoided.
Reconstruction of benign bone tumors after curettage is often accomplished with a combination of bone grafting and stabilization of impending or completed fractures. Bone grafting can be performed with autogenous bone or allograft. Many allograft preparations are commercially available, including demineralized bone matrix from an American Association of Tissue Banks–approved bone bank.9 Adequate curettage demands a large bone portal to access the intraosseous cavity, which, however, severely compromises the biomechanical integrity of the bone and requires operative stabilization. Stabilization can be done extracorporeally, such as with a cast or splint. Internal bone stabilization can be accomplished with a combination of rods, plates, pins, or screws. The goal is to achieve osteogenesis, preserve skeletal growth, and gain strength within weeks.
The functional outcome after intralesional resection, fixation, and bone grafting, especially in a child, is excellent. Limb length inequalities, especially overgrowth, may occur when the procedure is performed in a young child. The younger the child, the more conservative are the internal fixation techniques. Casting is preferred because joint stiffness is seldom a problem in this patient population.
Enchondroma (Fig. 34-1) is a benign proliferation of hyaline cartilage typically found in long bones, but it may also occur in the axial skeleton. Cartilage anlage or islands retain chondroid features and continue to grow until skeletal maturity, when they begin to undergo calcification. Their long-term physiologic activity is why they remain scintigraphically active decades later on a bone scan. An enchondroma typically begins in the metaphysis and extends into the diaphysis. It seldom occurs in the epiphysis of long bones. Polyostotic syndromes may occur, often with unilateral predominance. Ollier’s disease is the eponym associated with multiple skeletal enchondromas. Maffucci’s syndrome is Ollier’s disease associated with multiple subcutaneous hemangiomas. In the pediatric population, management involves maintaining a strong, straight, and symmetrical bone of appropriate length. After skeletal maturity, malignant transformation is rare. However, the greater the tumor burden, the greater the late malignant transformation rate. Therefore, patients with Ollier’s disease often have a higher incidence of chondrosarcoma formation than those with solitary disease. The more axially located tumors of the pelvis, spine, and scapula have the worst prognosis. Interestingly, individuals with Maffucci’s syndrome have the same elevated incidence of chondrosarcoma formation; however, this unique patient population frequently succumbs to the development of occult carcinomas.10