Essentials of Orthopedic Surgery, third edition / 04-Tumors of the Musculoskeletal System

126 M. Malawer and K. Kellar-Graney

1.The major neurovascular bundle must be free of tumor.

2.Wide resection of the affected bone with a normal muscle cuff in all directions should be done.

3.All previous biopsy sites and all potentially contaminated tissues should be removed en bloc.

4.Bone should be resected 3 to 4 cm beyond abnormal uptake as determined by bone scan. (This is a safe margin to avoid intraosseous tumor extension.)

5.The adjacent joint and joint capsule should be resected.

6.Adequate motor reconstruction must be accomplished by regional muscle transfers.

7.Adequate soft tissue coverage is needed to decrease the risk of skin flap necrosis and secondary infection.

Overall Treatment Strategy

The patient with a primary tumor of the extremity without evidence of metastases requires surgery to control the primary tumor and chemotherapy to control micrometastatic disease. Eighty percent to 90% of all patients with osteosarcoma fall into this category.

Surgery alone results in a 15% to 20% cure rate at best. The choice between amputation and limb-sparing resection must be made by an experienced orthopedic oncologist taking into account tumor location, size or extramedullary extent, the presence or absence of distant metastatic disease, and patient factors such as age, skeletal development, and lifestyle preference that might dictate the suitability of limb salvage or amputation. Routine amputations are no longer performed; all patients should be evaluated for limb-sparing options. Intensive, multiagent chemotherapeutic regimens have provided the best results to date. Patients who are judged unsuitable for limb-sparing options may be candidates for presurgical chemotherapy; those with a good response may then become suitable candidates for limb-sparing operations. The management of these patients mandates close cooperation between chemotherapist and surgeon.

Variants of Osteosarcoma

There are 11 recognizable variants of the classic OS. OS arising in the jaw bones is the most common of all variants. Parosteal and periosteal OS are the most common variants of the classic OS occurring in the extremities. In contrast to classic OS, which arises within a bone (intramedullary), parosteal and periosteal OS arises on the surface (juxtacortical) of the bone. Parosteal osteosarcoma is the most common of the unusual variants, representing about 4% of all osteosarcomas.

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Parosteal Osteosarcoma

Parosteal osteosarcoma (POS) is a distinct variant of conventional osteosarcoma, accounting for 4% of all OS. It arises from the cortex of a bone and generally occurs in older individuals. It has a better prognosis than classical osteosarcoma.

Radiographic Findings

X-rays characteristically show a large, dense, lobulated mass broadly attached to the underlying bone without involvement of the medullary canal. If old enough, the tumor may encircle the bone. The periphery of the lesion is characteristically less mature than the base.

Chondrosarcoma

Chondrosarcoma, the second most-common primary malignant spindle cell tumor of bone, is a heterogeneous group of tumors whose basic neoplastic tissue is cartilaginous without evidence of direct osteoid formation. Bone formation occasionally results from differentiation of cartilage. If there is evidence of direct osteoid or bone production, the lesion is classified as an OS. There are five types of chondrosarcoma: central, peripheral, mesenchymal, differentiated, and clear cell. The classic chondrosarcomas are central (arising within a bone) (Fig. 4-10A) or peripheral (arising from the surface of a bone). The other three are variants and have distinct histologic and clinical characteristics.10

Both central and peripheral chondrosarcomas can arise as a primary tumor or secondary to underlying neoplasm. Seventy-six percent of primary chondrosarcomas arise centrally.10 Secondary chondrosarcomas most often arise from benign cartilage tumors (see Fig. 4-10B). The multiple forms of the benign osteochondromas or enchondromas have a higher rate of malignant transformation than do the corresponding solitary lesions.

Central and Peripheral Chondrosarcomas

Clinical Characteristics and Physical Examination

Half of all chondrosarcomas occur in persons older than 40 years of age. The most common sites are the pelvis, femur, and shoulder girdle. The clinical presentation varies. Peripheral chondrosarcomas may become quite large without causing pain, and local symptoms develop only because of mechanical irritation. Pelvic chondrosarcomas are often large and present with referred pain to the back or thigh, sciatica secondary to sacral plexus irritation, urinary symptoms from bladder neck involvement, unilateral edema resulting from iliac vein obstruction, or as a painless abdominal mass. Conversely, central chondrosarcomas present with dull pain. A mass is rarely present. Pain, which indicates active growth, is an ominous sign of a central cartilage lesion. This sign cannot be overemphasized. An

128 M. Malawer and K. Kellar-Graney

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FIGURE 4-10. Chondrosarcoma. (A) Plain AP radiograph demonstrates a large central calcification of the right ilium, approaching the sacroiliac joint. This patient has a fairly well-defined lytic lesion showing calcification, which is typical of chondrosarcoma. (B) Computed tomography (CT) scan demonstrates secondary chondrosarcoma and a large soft tissue component. Chondrosarcomas are the most common malignancies of the pelvic bones. Large soft tissue components are common. Note the stalk indicating a preexisting exostosis.

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adult with a plain radiograph suggestive of a “benign” cartilage tumor but who is experiencing pain most likely has a chondrosarcoma.

Radiographic Findings

Central chondrosarcomas have two distinct radiologic patterns. One is a small, well-defined lytic lesion with a narrow zone of transition and surrounding sclerosis with faint calcification; this is the most common malignant bone tumor that may appear radiographically benign (Fig. 4-11). The second type has no sclerotic border and is difficult to localize. The key sign of malignancy is endosteal scalloping. This type is difficult to diagnose on plain radiographs and may go undetected for a long period of time. In contrast, peripheral chondrosarcoma is easily recognized as a large mass of characteristic calcification protruding from a bone. Correlation of the clinical, radiographic, and histologic data is essential for accurate diagnosis and evaluation of the aggressiveness of cartilage tumor. In general, proximal or axial location, skeletal maturity, and pain point toward malignancy, even though the cartilage may appear benign.

FIGURE 4-11. Low-grade chondrosarcoma of the distal femur. AP radiograph of a small, lowgrade, well-defined central chondrosarcoma arising from the distal femur. Some endosteal scalloping is noted in this view, and some cortical thinning has occurred on the lateral side. Endosteal scalloping is typical in lowgrade chondrosarcomas.

130 M. Malawer and K. Kellar-Graney

Grading and Prognosis

Chondrosarcomas are graded I, II, and III; the majority are either grade I or grade II. The metastatic rate of moderate grade versus high grade is 15% to 40% versus 75%.1 Grade III lesions have the same metastatic potential as osteosarcomas.

In general, peripheral chondrosarcomas are a lower grade than central lesions. Ten-year survival rates among those with peripheral lesions are

77% compared with 32% among those with central lesions. Secondary chondrosarcomas arising from osteochondromas (see Fig. 4-10B) also have a low malignant potential; 85% are grade 1. The multiple forms of benign osteochondromas or enchondromas have a higher rate of malignant transformation than the corresponding solitary lesions.

Microscopic Characteristics

The histologic spectrum of this neoplasm varies tremendously: high-grade examples can be easily identified, whereas certain low-grade tumors are exceedingly difficult to distinguish from chondromas. Correlation of the histologic features with both the clinical setting and the radiographic changes is therefore of utmost importance in avoiding serious diagnostic error. The grade of malignant cartilaginous tumors correlates with clinical behavior. Grade I tumors are characterized by an increased number of chondrocytes set in a matrix that is chondroid to focally myxoid.

Areas of increased cellularity with more marked variation in cell size, significant nuclear atypia, and frequent pleomorphic forms define a grade II lesion. Binuclear forms are more common in this group.

Grade III chondrosarcomas, which are relatively uncommon, show even greater cellularity, often with spindle cell areas, and reveal prominent mitotic activity. Chondrocytes may contain large, bizarre nuclei. Areas of myxoid change are common.

Treatment

The treatment of chondrosarcoma is surgical removal. Guidelines for resection for high-grade chondrosarcomas are similar to those for OS. The sites of origin and the fact that chondrosarcomas tend to be low grade make them amenable to limb-sparing procedures. The four most common sites are the pelvis, proximal femur, shoulder girdle, and diaphyseal portions of long bones.

Variants of Chondrosarcoma

There are three less common variants of classic chondrosarcoma. Each is briefly described next.

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Clear Cell Chondrosarcoma

Clear cell chondrosarcoma, the rarest form of chondrosarcoma, is a slowgrowing, locally recurrent tumor resembling a chondroblastoma but with some malignant potential that typically occurs in adults. The most difficult clinical problem is early recognition; it is often confused with chondroblastoma. Metastases occur only after multiple local recurrences. Primary treatment is wide excision. Systemic therapy is not required.

Mesenchymal Chondrosarcoma

Mesenchymal chondrosarcoma is a rare, aggressive variant of chondrosarcoma characterized by a biphasic histologic pattern, that is, small, compact cells intermixed with islands of cartilaginous matrix. This tumor has a predilection for flat bones; long tubular bones are rarely affected. It tends to occur in the younger age group and has a high metastatic potential. The 10-year survival rate is 28%. This entity responds favorably to radiotherapy.

Dedifferentiated Chondrosarcoma

Approximately 10% of chondrosarcomas may dedifferentiate into either a fibrosarcoma or an OS.1,2 They occur in older individuals and are often fatal. Surgical treatment is similar to that described for other high-grade sarcomas. Adjuvant therapy is warranted.

Giant Cell Tumor of Bone

Giant cell tumor of bone (GCT) is an aggressive, locally recurrent tumor with a low metastatic potential (4%–8%). Giant cell sarcoma of bone refers to a de novo, malignant GCT, not to the tumor that arises from the transformation of a GCT previously thought to be benign. These two lesions are separate clinical entities.

Clinical Characteristics and Physical Examination

GCTs occur slightly more often in females than in males. Eighty percent of GCTs in the long bones occur after skeletal maturity; 75% of these develop around the knee joint. A joint effusion or pathologic fracture, uncommon with other sarcomas, is common with GCT. GCTs occasionally occur in the vertebrae (2%–5%) and the sacrum (10%).1

Natural History and Potential Malignancy

Although GCTs are rarely malignant de novo (2%–8%), they may undergo transformation and demonstrate malignant potential histologically and clinically after multiple local recurrences. Between 8% and 22% of known

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GCTs become malignant following local recurrence.1 This rate decreases to less than 10% if patients who have undergone radiotherapy are excluded. Approximately 40% of malignant GCTs become malignant at the first recurrence. The remainder typically become malignant by the second or third recurrence; thus, each recurrence increases the risk of malignant transformation. A recurrence after 5 years is extremely suspicious for a malignancy. Primary malignant GCT generally has a better prognosis than secondary malignant transformation of typical GCT does, especially if the transformation occurs after radiation therapy. Local recurrence of a GCT is determined by the adequacy of surgical removal rather than by histologic grade.

Radiographic and Clinical Evaluation

GCTs are eccentric lytic lesions without matrix production occurring at the end of long bones. About 10% are axial. They have poorly defined borders with a wide area of transition. They are juxtaepiphyseal with a metaphyseal component. Although the cortex is expanded and appears destroyed, at surgery it is usually found to be attenuated but intact. Periosteal elevation is rare; soft tissue extension is common (Fig. 4-12). In the skeletally immature patient, aneurysmal bone cyst must be differentiated, although both lesions are closely related. GCTs are classified as type I, II, or III (Enneking staging system).

Microscopic Characteristics

Two basic cell types constitute the typical GCT. The stroma is characterized by polygonal to somewhat spindled cells containing central round nuclei. Scattered diffusely throughout the stroma are benign, multinucleated giant cells. Small foci of osteoid matrix, produced by the benign stroma cells, can be observed; however, chondroid matrix never occurs.

Treatment

Treatment of GCT of bone is surgical removal. In general, curettage of the bony cavity with “cleaning” of the walls with a high-speed burr drill and the use of a physical adjuvant kills any cells remaining within the cavity wall. The author prefers the combined use of cryosurgery (either liquid nitrogen or a closed system of argon/helium) to obtain temperatures of − 40°C. The cavity is then reconstructed with bone graft, polymethyl acrylate (PMMA), and internal fixation devices, which permit early mobilization.

Cryosurgery

Cryosurgery has been used more successfully for GCT than for any other type of bone tumor. Cryosurgery is effective in eradicating the tumor while

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FIGURE 4-12. Giant cell tumor. (A) Plain lateral photograph demonstrates a giant cell tumor (GCT) of the distal femur; this is an aggressive expansile, lytic lesion that has thinned the cortex on the anterior portion of the bone. GCTs typically arise from the metaphyseal–epiphyseal junction in skeletally mature patients. This radiograph shows no evidence of matrix formation, as would be expected for an osteosarcoma, which frequently arises from the same location. The distal femur is the most common site for GCTs. (B) CT scan of the distal femur demonstrates a GCT of the distal femoral condyle. The cortices are thin, although there is no evidence of pathologic fracture or soft tissue extension.

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preserving joint motion and avoiding the need for resection or amputation. Liquid nitrogen is a very effective physical adjuvant and is recommended following curettage resection. Curettage alone is not recommended because of the associated high rate of local recurrence.

Malignant Fibrous Histiocytoma

Clinical Characteristics

Malignant Fibrous Histiocytoma (MFH) is a high-grade bone tumor histologically similar to its soft tissue counterpart. Osteoid production is absent. It is a disease of adulthood. The most common sites are the metaphyseal ends of long bones, especially around the knee. Alkaline phosphatase values are normal, helping rule out an osteosarcoma or fibrosarcoma. Pathologic fracture is common. MFH disseminates rapidly. Lymphatic involvement, although rare for other bone sarcomas, has been reported.

Radiographic Characteristics

MFH is an osteolytic lesion associated with marked cortical disruption, minimal cortical or periosteal reaction, and no evidence of matrix formation. The extent of the tumor routinely exceeds plain radiographic signs. MFH may be multicentric (10%) and associated with bone infarcts (10%).

Treatment

Treatment is similar to that of other high-grade sarcomas. Adjuvant chemotherapy has similar results to that seen in the treatment of osteosarcoma.

Fibrosarcoma of Bone

Clinical Characteristics

Fibrosarcoma of bone is a rare entity, accounting for only 1% of bone tumors. It is characterized by interlacing bundles of collagen fibers (herringbone pattern) without any evidence of tumor bone or osteoid formation. Fibrosarcoma occurs in middle age. The long bones are most affected. Fibrosarcomas occasionally arise secondarily in conjunction with an underlying disease such as fibrous dysplasia, Paget’s disease, bone infarcts, osteomyelitis, postirradiation bone, and GCT. Fibrosarcoma may be either central or cortical (termed periosteal). The histologic grade is a good prognosticator of metastatic potential. Overall survival rate is 27% and 52% for central and peripheral lesions, respectively. Late metastases do occur, and 10and 15-year survival rates vary. In general, periosteal tumors have a better prognosis than do central lesions.

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Radiographic Features

Fibrosarcoma is a radiolucent lesion that shows minimal periosteal and cortical reaction. The radiographic appearance closely correlates with the histologic grade of the tumor. Low-grade tumors are well defined, whereas high-grade lesions demonstrate indistinct margins and bone destruction similar to those of osteolytic OS. Plain radiographs often underestimate the extent of the lesion. Pathologic fracture is common (30%) because of the lack of matrix formation. Differential diagnosis includes GCT, aneurysmal bone cyst, MFH, and osteolytic OS.

Ewing’s Sarcoma and Other Small Round Cell Sarcomas

of Bone

Round cell sarcomas of bone behave differently and require different therapeutic management than do spindle cell sarcomas. Round cell sarcomas of bone consist of poorly differentiated small cells without matrix production. They present radiographically as osteolytic lesions. These lesions are best treated with radiation and chemotherapy; surgery is reserved for special situations. Non-Hodgkin’s lymphoma and Ewing’s sarcoma are the most common small cell sarcomas. The differential diagnosis of round cell sarcomas includes metastatic neuroblastoma, metastatic undifferentiated carcinoma, histiocytosis, small cell OS, osteomyelitis, and multiple myeloma.

Ewing’s Sarcoma

Ewing’s sarcoma is the second most common bone sarcoma of childhood; it is approximately one-half as frequent as OS. The lesion is characterized by poorly differentiated, small, round cells with marked homogeneity. The exact cell of origin is unknown. The clinical and biologic behavior is significantly different from that of spindle cell sarcomas. Within the past two decades, the prognosis of patients with Ewing’s sarcomas has dramatically been improved by the combination of adjuvant chemotherapy, improved radiotherapy techniques, and the select use of limited surgical resection.

Clinical Characteristics and Physical Examination

Ewing’s sarcomas tend to occur in young children, although rarely in those below the age of 5 years. Characteristically the flat and axial bones (50%–

60%) are involved. When a long (tubular) bone is involved, it is most often the proximal or diaphyseal area. In contrast, OS occur in adolescence (average age, 15), most often around the knees, and involve the metaphysis of long bones. Another unique finding with Ewing’s sarcomas is systemic signs, such as fever, anorexia, weight loss, leukocytosis, and anemia.1 All