Chapter 26 Benign/Aggressive Tumors of Bone
The aggressiveness of the lesions described in this chapter is between purely benign and frankly malignant. Although these lesions frequently are treated satisfactorily with intralesional procedures, such as curettage, they are sometimes very aggressive locally and require marginal or wide resection. Systemic involvement, although rare, must be evaluated and treated. Giant cell tumors and chondroblastomas can develop pulmonary metastases and rarely can be fatal. Langerhans cell histiocytosis can involve multiple organ systems in addition to bone involvement and likewise rarely can be fatal. This chapter briefly describes the clinical, radiographic, and pathological features of these lesions. A summary table is provided at the end of the chapter for a quick reference (Table 26-1).
According to a Mayo Clinic series, giant cell tumors represent 5% of neoplasms of bone. They typically occur in patients 20 to 40 years old, and there is a slight female predominance. The most common location for this tumor is the distal femur, followed closely by the proximal tibia. In the distal radius (the third most common location), these tumors frequently are more aggressive. Spinal involvement, other than the sacrum, is rare.
Giant cell tumors usually are solitary lesions; however, 1% to 2% may be synchronously or metachronously multicentric. It is unclear whether multicentric disease represents multiple primary lesions or simply bone metastases from a single primary lesion. Although these tumors typically are benign, pulmonary metastases occur in approximately 3% of patients. Some patients with pulmonary metastases have spontaneous regression or remain asymptomatic for many years. Others may have progressive pulmonary lesions, however, that lead to death despite the fact that the tumors remained histologically benign. The overall mortality rate from disease for patients with pulmonary metastases is approximately 15%. Patients with recurrent lesions or primary lesions that appear aggressive radiographically (stage 3) are at higher risk for pulmonary metastases.
Malignant giant cell tumors represent less than 5% of cases and are classified as primary or secondary. Primary malignant giant cell tumors are extremely rare and are defined as sarcomas that occur within lesions that otherwise are typical of benign giant cell tumors. Secondary malignant giant cell tumors are sarcomas that occur at the sites of giant cell tumors that have been treated, usually with radiation.
Most patients with giant cell tumors have progressive pain that often is related to activity initially and only later becomes evident at rest. The pain is rarely severe, unless a pathological fracture has occurred. In 10% to 30% of patients, pathological fractures are evident at initial examination.
Radiographic findings often are diagnostic. The lesions are eccentrically located in the epiphyses of long bones and usually abut the subchondral bone. Although rare in skeletally immature patients, giant cell tumors arise in the metaphysis in this patient population. One theory suggests that these tumors originate in the metaphysis and later extend into the epiphysis after closure of the physes. Radiographically, the lesions are purely lytic. The zone of transition can be poorly defined on plain radiographs. In less aggressive tumors, a partial rim of reactive bone may be present. The lesion frequently expands or breaks through the cortex; however, intraarticular extension is rare because the subchondral bone usually remains intact. Matrix production usually is not evident within the bone but often is evident if there is soft tissue extension, soft tissue recurrence, or pulmonary metastases. MRI is useful to determine the extent of the lesion within the bone and in the soft tissue. On MRI, the lesion usually is dark on T1-weighted images and bright on T2-weighted images. MRI also may reveal fluid-fluid levels typical of a secondary aneurysmal bone cyst, which occurs in 20% of patients.
Microscopically, giant cell tumors are composed of many multinucleated giant cells (typically 40 to 60 nuclei per cell) in a sea of mononuclear stromal cells. The nuclei of the mononuclear cells are identical to the nuclei of the giant cells, a feature that helps to distinguish giant cell tumors from other tumors that may contain many giant cells. Areas of storiform spindle cell formation, reactive bone formation, or foamy macrophages may be seen. Secondary aneurysmal bone cysts also may be present. Many authors have attempted to grade these tumors histologically, but no grading system has proved to be of prognostic significance.
Giant cell tumors frequently are locally aggressive. Most manifest as stage 2 or stage 3 lesions. Historically, treatment consisted of simple curettage; however, subsequent recurrence rates were greater than 50%. Now, most published series document recurrence rates of 5% to 15%. The decrease in recurrence rates probably can be attributed to several factors. MRI now allows for more accurate assessment of the extent of lesions, and the technique of curettage has improved. It is important to create a cortical window that is at least as large as the lesion to prevent leaving residual tumor cells “around the corner” adjacent to the near-side cortex. Also, use of a power burr to enlarge the cavity 1 to 2 cm in all directions is now considered standard. Care should be taken, however, to avoid perforation through the subchondral bone into the joint. The use of adjuvants, such as liquid nitrogen, phenol, bone cement, electrocautery, or an argon beam coagulator, theoretically help to kill any remaining tumor cells. Also, preliminary studies suggest that bisphosphonates (administered systemically or locally) might help to prevent recurrence.
To fill the defect after curettage, the surgeon has several options, including autograft bone, allograft bone, an artificial bone graft substitute, or methyl methacrylate bone cement. If autograft will be harvested from another site, separate gloves and instruments should be used because cross-contamination could lead to transplantation of tumor cells to the harvest site. Bone graft (or artificial substitute) has the theoretical advantage of restoring normal biomechanics to the joint surface to prevent future degenerative joint disease and restoring bone stock, which may help if future procedures are necessary. There are two main disadvantages, however, to using bone graft: (1) The joint must be protected for an extended time to prevent a pathological fracture, and (2) tumor recurrence often is difficult or impossible to distinguish from graft resorption. These disadvantages may be overcome with the use of bone cement as a filling agent. Bone cement provides immediate stability, which aids in quicker rehabilitation; allows easier detection of recurrence, which is evident as an expanding radiolucency adjacent to the cement mantle; and may kill residual tumor cells through the heat of polymerization.
We treat most giant cell tumors with aggressive, extended curettage followed by argon beam coagulation, which is easy to use, effective, and associated with few complications. We do not use phenol or liquid nitrogen as adjuvant treatment because of potential complications, such as pathological fracture, wound healing problems, and nerve injury. We routinely use bone cement to fill the cavity because of its ease of application, immediate structural support, and ease with which local recurrence can be detected adjacent to the cement mantle. We frequently use screws placed in a crossed (Fig. 26-1) or divergent (Fig. 26-2) pattern to augment the cement mantle. Biomechanical studies performed at our institution have shown this method to significantly increase the strength of the reconstruction.
FIGURE 26-1 Giant cell tumor in 21-year-old man. Patient complained of worsening left knee pain. A and B, Anteroposterior and lateral radiographs of left distal femur show lytic lesion with extension to articular surface. C and D, Coronal and axial MR images show extent of lesion within bone and soft tissue. E, Intraoperative photograph after creation of cortical window. F, Tumor removed and cavity enlarged with power burr. G, After treatment with argon beam coagulator, screws are placed to support cement mantle. H, Placement of screws confirmed by image intensifier. I, Bone cement packed in cavity around screws. J and K, Anteroposterior and lateral postoperative radiographs.
FIGURE 26-2 A and B, Anteroposterior and lateral radiographs of the proximal tibia of a 41-year-old woman with a giant cell tumor. The lesion is radiolucent without a sclerotic rim, eccentric, and abuts subchondral bone. C and D, Anteroposterior and lateral radiographs of the proximal tibia after curettage and placement of cement and divergent screws.
Curettage may not be effective in some stage 3 tumors, and primary resection may be required after biopsy. Around the knee, a hemicondylar osteoarticular allograft reconstruction or a rotating hinge endoprosthesis may be necessary. For aggressive lesions of the distal radius, primary resection and reconstruction with a proximal fibular autograft (either as an arthroplasty or as an arthrodesis) may be indicated (Fig. 26-3). For lesions in expendable bones (e.g., the distal ulna or proximal fibula), primary resection without reconstruction may be indicated. For inoperable lesions in the spine or pelvis, irradiation or embolization (or both) may be used (Fig. 26-4); however, caution is advised because of the risk of sarcomatous change in patients treated by irradiation. In patients with pulmonary metastases, resection should be attempted. Chemotherapy has limited success, and irradiation should be reserved for symptomatic inoperable lesions.
FIGURE 26-3 A and B, Anteroposterior and lateral radiographs of distal radius of 40-year-old woman with pathological fracture through giant cell tumor. C-E, Axial (C), sagittal (D), and coronal (E) MR images of lesion. F, Intraoperative photograph of tumor in situ. G, Tumor has been resected en bloc. H, Contralateral proximal fibular autograft. I, Graft has been secured with wrist fusion plate. J, Photograph of resected specimen. K, Typical microscopic appearance of giant cell tumor. Nuclei of giant cells are identical to nuclei of mononuclear cells. L and M, Anteroposterior and lateral postoperative radiographs.
FIGURE 26-4 Giant cell tumor in 23-year-old woman. Patient had 1-year history of worsening low back pain that radiated down her right leg. A, CT scan. B, Sagittal T2-weighted MR image reveals large lesion in sacrum. CT-guided biopsy confirmed this to be giant cell tumor. Because of morbidity of surgical treatment of lesion in this location, the patient was referred for radiation therapy.
Patients diagnosed with giant cell tumors require long-term follow-up. Most local recurrences and pulmonary metastases occur within 3 years but have been reported to occur 20 years later. Chest radiographs should be obtained at the time of diagnosis to stage the lesion. We routinely obtain a chest CT scan as a baseline study at this time as well. At minimum, patients should have radiographs of the primary tumor site and the chest at 3- to 4-month intervals for 2 years, at 6-month intervals for the following year, and annually thereafter. An abnormality on the chest radiograph should be evaluated further with CT. Bone recurrence usually is evident as an expanding lucency on the radiograph. Soft tissue recurrences may be apparent as ossification or may be evident only as a palpable mass, in which case MRI is indicated.
Chondroblastoma, a rare neoplasm, typically occurs in patients 10 to 25 years old, with a 2 : 1 male predominance. According to the Mayo Clinic series, this tumor represents 1% of all bone tumors. The distal femur, proximal humerus, and proximal tibia are the most common sites of occurrence. In older patients, chondroblastoma has a tendency to occur in flat bones. Multicentric disease is exceedingly rare. Most patients complain of progressive pain that may mimic a chronic synovitis or other intraarticular pathological conditions.
Radiographic findings usually are characteristic. This well-circumscribed lesion usually is centered in an epiphysis of a long bone; however, it also may be located in an apophysis, such as the greater tuberosity (Fig. 26-5) or the greater trochanter (Fig. 26-6). Often it has a surrounding rim of reactive bone (Fig. 26-7), and 30% to 50% exhibit matrix calcification. CT can be helpful to detect subtle areas of calcification that may or may not be detectable on plain radiographs. MRI frequently demonstrates abundant surrounding edema. Soft tissue extension is extremely rare. In children, a well-circumscribed epiphyseal lesion that crosses an open growth plate is highly suggestive of chondroblastoma but could also represent an infectious process. For adults, differential diagnoses for an epiphyseal lesion include giant cell tumor and clear cell chondrosarcoma. In contrast to chondroblastomas, however, giant cell tumors usually do not have a rim of sclerotic bone or intralesional calcification and may have a soft tissue component.
FIGURE 26-5 Chondroblastoma in 16-year-old boy. Patient had left shoulder pain for 1 year. A, Anteroposterior radiograph of left shoulder reveals lytic lesion in proximal left humerus extending across open physis. B, CT scan shows calcification of lesion. C and D, MR images show fluid-fluid level. Incision biopsy confirmed diagnosis of chondroblastoma with secondary aneurysmal bone cyst. E, Anteroposterior radiograph after curettage and bone grafting. F, Typical microscopic appearance of chondroblastoma.
FIGURE 26-6 Chondroblastoma in 12-year-old boy. Patient complained of worsening right hip pain for several months. A and B, Anteroposterior and lateral radiographs of right hip show radiolucent lesion in greater trochanter. C, Coronal MR image shows lesion in greater trochanter with surrounding edema. D, Postoperative radiograph after curettage and grafting with allograft cancellous bone chips and demineralized bone matrix.
FIGURE 26-7 A and B, Anteroposterior radiograph and CT scan of a 16-year-old girl with a chondroblastoma of the femoral head. The lesion is epiphyseal and has a narrow zone of transition with a thin rim of reactive bone and a small amount of matrix mineralization. C, MR image demonstrates the lesion with extensive surrounding edema as well as an effusion. D, Extended curettage was performed through an anterior approach followed by placement of a bone graft substitute (E).
Microscopically, chondroblastoma consists of sheets of chondroblasts usually with a background of chondroid matrix. The cells are polygonal with distinct cytoplasmic outlines. Dystrophic calcification is frequently present and may surround individual cells, giving the classic “chicken wire” appearance. Multinucleated giant cells are abundant, and secondary aneurysmal bone cysts are present in 20% of patients. Histological grading is of no prognostic significance.
Chondroblastomas usually present as stage 2 and, more rarely, as stage 3 lesions. Although they typically are not as aggressive as giant cell tumors, surgical management is warranted for almost all chondroblastomas owing to the slowly progressive nature of the disease. Treatment consists of extended curettage and bone grafting or placement of bone cement. Adequate curettage always should take precedence over sparing the physis (Fig. 26-8).
FIGURE 26-8 A, Anteroposterior radiograph demonstrates a chondroblastoma in the proximal tibial epiphysis of a 15-year-old boy. B and C, Coronal and sagittal MR images more clearly demonstrate the lesion as well as extensive surrounding edema. D and E, Lesion is treated with extended curettage with a power burr and argon beam coagulation.