Presentation

A thorough history and physical examination remain the cornerstone for the diagnosis of musculoskeletal malignancy. A patient with a bone tumor may have pain in the extremity, or the tumor may be discovered as an incidental finding. In contrast, patients with soft tissue tumors often present with a painless mass. Elements of the patient’s history that would warrant a higher level of suspicion for malignancy include change in size of a mass, presence of night pain, and constitutional symptoms such as fevers, chills, and night sweats. In the setting of a pathologic fracture, history of antecedent pain may be a clue to a more aggressive process. Although sarcoma metastasis to regional lymph nodes is uncommon, it may be seen in certain subtypes of soft tissue sarcoma. The clinician should always remember that metastases are more common than primary sarcomas, and therefore, history should include asking about common primary carcinoma sources, such as lung, kidney, breast, thyroid, and prostate.

Workup

Diagnostic imaging is a crucial component of the workup of a patient with a musculoskeletal tumor and should proceed in an organized fashion. Initial imaging often includes radiographs in orthogonal planes to localize and characterize a lesion. Although soft tissue lesions may not be seen on plain radiographs, at least 1 set is usually taken to look for calcifications, erosion into adjacent bone, or other features ( Fig. 1 : Soft tissue tumor radiograph and magnetic resonance imaging [MRI]). Bone lesions must be evaluated for location of lesion within the bone, size, margin, zone of transition, periosteal reaction, mineralization, and number of lesions. For lytic bone lesions, the Lodwick classification is commonly used. Lesions may be described as geographic, moth-eaten, or permeative. Geographic lesions with sclerotic or well-defined borders tend to be benign, whereas more aggressive lesions may have a moth-eaten or permeative appearance and a wide zone of transition to normal bone. Cortical destruction, periosteal reaction, and the presence of soft tissue mass are typical of more pathologic processes. Radiographic matrix, when present, may give clues to the diagnosis; for example, fibrous dysplasia has a typical ground-glass appearance, and chondroid matrix may often present with calcified rings, arcs, and stippling.

Radiograph and magnetic resonance imaging (MRI) of soft tissue mass. ( A ) Lateral radiograph of distal radius shows phleboliths in soft tissue volar to distal radius; bone changes include scalloping and sclerosis of volar distal radius cortex. ( B ) Axial T2-weighted MRI of distal radius soft tissue mass in pronator quadratus.

( Courtesy of W. Morrison, MD, Philadelphia, PA.)

Although ultrasonography is generally not used for bone tumors, it may be useful in evaluation of soft tissue mass to determine if a structure is cystic. Clinical scenarios in which ultrasonography might be useful include a superficial soft tissue mass or one adjacent to a joint.

Cross-sectional imaging is able to provide crucial information regarding size, tissue characteristics, and anatomic relationship to other structures of a lesion. Computed tomography (CT) is ideally suited for evaluation of the characteristics of a bony lesion, but may have some usefulness in evaluating soft tissue masses, particularly if there is periosteal reaction or osseous erosions adjacent to the soft tissue mass. MRI of the involved area is useful for both soft tissue and bony lesions and should be performed before any biopsy procedure. The basic imaging sequences used are T1-weighted and T2-weighted images. T1-weighted imaging has a higher signal-to-noise ratio, which makes it useful for defining anatomy and the spatial relationship between the lesion and surrounding tissue, whereas T2-weighted images are fluid sensitive and enable detection of fluid or edema. Fat-suppressed T2-weighted imaging provides improved contrast in detecting edema. For bony lesions, MRI may be helpful in showing extent of marrow replacement or soft tissue mass. Gadolinium may be used as an intravenous contrast agent to determine if a mass is solid with a blood supply.

Whole-body bone scintigraphy can be used to determine if a bony lesion is singular or multifocal. The uptake on bone scintigraphy may also correlate with the aggressiveness of the lesion, except in the case of myeloma, which often has limited bony uptake. For soft tissue tumors, bone scintigraphy may show areas of bony metastases. In the case of multifocal lesions, bone scintigraphy may show a lesion that is more easily accessible for biopsy than the originally detected lesion.

Because bone and soft tissue sarcomas have a tendency to metastasize to the lungs, CT of the thorax is imperative in the evaluation of these patients, although it does not need to be performed before biopsy. In the case of a metastatic lesion from an unknown source, chest, abdomen, and pelvis CT should be obtained in addition to common laboratory studies ( Table 1 ). Approximately 85% of skeletal metastases of unknown origin may be identified with inclusion of these imaging modalities.

Positron emission tomography (PET) is an imaging modality that detects localization of radiolabeled tracers, such as fluorodeoxyglucose (FDG), and is commonly used for evaluation of metastases of carcinomas and lymphomas. In a recent meta-analysis, FDG-PET has been shown to have high sensitivity and specificity for diagnosis of soft tissue or mixed soft tissue and osseous lesions and may be able to differentiate between benign and malignant lesions. However, its role in the routine staging of soft tissue and osseous sarcomas continues to be investigated.

Biopsy

Often the clinical history, patient age, and radiographic features of a bony lesion are helpful in determining a differential diagnosis for bone tumors, and in the case of lesions that are benign and appear latent, they may obviate biopsy. However, in aggressive appearing bone lesions and most soft tissue masses, a histologic specimen should be obtained for diagnosis. The importance of obtaining a biopsy in the appropriate manner cannot be overemphasized, because of the potential for compromising the definitive surgical treatment as well as patient outcome. For this reason, suspected primary malignancies should be referred to the surgeon who will be providing definitive management. Soft tissue masses that are larger than 5 cm or deep to the investing fascia have a high increased chance of being a sarcoma and should be referred on to an orthopedic oncologist before obtaining biopsy.

Biopsy may be performed by either open or closed technique. Closed techniques such as fine-needle aspiration and core needle biopsy have the advantage of being performed outside an operating room, but in some cases, they may not yield sufficient tissue. Open biopsy has the advantage of providing more tissue for pathology evaluation and should be performed in accordance with standard principles ( Table 2 ).

Grading and Staging

Current grading and staging systems for musculoskeletal tumors are designed to guide treatment, provide prognostic information for patients, and standardize research. Tumor grade refers to the histologic appearance of a tumor and is determined based on cellular anaplasia, mitotic activity, presence or absence of abnormal mitotic figures, amount of necrosis, and growth pattern. Low-grade lesions are generally well differentiated and show few mitoses and a moderate cellular atypia, whereas high-grade lesions may show a higher mitotic activity, poorly differentiated cells, evidence of microvascular invasion, and increased cellularity.

Staging incorporates the tumor grade along with factors such as tumor size, depth, and presence or absence of regional or distant metastases to better define a patient’s prognosis. For malignant tumors, Enneking and colleagues proposed a staging system, which was later adopted by the Musculoskeletal Tumor Society (MSTS), which is based on 3 factors: low or high tissue grade, whether or not the tumor is confined to an anatomic compartment, and presence or absence of metastasis ( Table 3 ). Benign bone tumors are staged separately, based on the biological activity of the tumor ( Table 4 ). Stage 1 benign bone tumors, such as nonossifying fibroma, are termed latent and remain static or are replaced spontaneously. Stage 2 benign lesions, such as an aneurysmal bone cyst or chondroblastoma, are termed active and show progressive growth but are limited by anatomic barriers. Stage 3 benign lesions, such as giant cell tumor of bone, are termed aggressive and show progressive growth not limited by anatomic barriers and may have potential for systemic metastases.

For soft tissue sarcomas, staging systems that use tumor size and depth as opposed to intracompartmental or extracompartmental status have been suggested to be more useful for prediction of systemic recurrence and death from sarcoma. The Fifth edition of the American Joint Committee on Cancer (AJCC) staging system is 1 such staging system used for soft tissue sarcomas ( Table 5 ).

Common Bone-Forming Tumors

Osteoid osteomas represent approximately 10% of all benign bone tumors and may be found in the upper extremity in 19% to 31% of cases. These lesions commonly present with well-localized pain in the second to third decade of life. History of night pain and pain relief with use of aspirin or nonsteroidal antiinflammatory medications is common. From a radiographic perspective, there is a characteristic intracortical radiolucent nidus surrounded by a rim of dense reactive bone, which may be best appreciated on CT scan. Bone scan can show intense isotope uptake in these lesions. Although some cases are self-limiting, surgical treatment options include radiofrequency ablation or intralesional curettage. Radiofrequency ablation can be performed in the forearm, arm, and shoulder, but may be technically difficult in the hand and wrist because of proximity to neurovascular structures. The recurrence rates after intralesional curettage may be as high as 25% in some studies.

Osteosarcoma is a primary malignant tumor of mesenchymal origin characterized by its production of immature neoplastic osteoid. When the upper extremity is affected, the humerus is the most common location, followed by lesions in the radius, ulna, metacarpals, and phalanges. Treatment involves neoadjuvant chemotherapy, wide resection or amputation, and postoperative chemotherapy based on tumor margins and tumor response to chemotherapy. Tumors involving the phalanges and metacarpals can be successfully treated with ray resection, whereas limb salvage surgery is generally indicated for most proximal lesions.

Prognostic factors for survival include tumor size and location, presence of systemic or skip metastases at the time of presentation, and response to neoadjuvant chemotherapy. Increase of serum markers such as lactate dehydrogenase and alkaline phosphatase are also associated with risk of relapse. Local recurrence is dependent on a clean tumor margin and tumor response to chemotherapy.

The addition of adjuvant chemotherapy has greatly improved the survival rate of nonmetastatic osteosarcoma, with rates of disease-free survival at 2 years improving from 17% to 66% in 1 randomized controlled trial. Tumor location within the extremity (proximal vs distal) may have an effect on outcome, with some investigators reporting worse outcomes for proximal humerus lesions, whereas others have reported good outcomes with 74% disease-free survival at 5-year. Osteosarcomas arising in the hand may behave less aggressively than those in other locations, with a higher proportion of low-grade tumors and surface lesions and favorable outcomes, despite longer times between symptom onset and treatment.

Common Cartilage Tumors

A spectrum of cartilage-forming tumors may present in the upper extremity. Enchondromas are one of the most common primary bone tumors in the upper extremity and typically arise in the diaphysis of the metacarpals or proximal or middle phalanges. They may occur solitarily or may be multiple in certain conditions such as Ollier disease (multiple enchondromatosis) or Maffuci syndrome (multiple enchondromatosis associated with soft tissue hemangiomas). They typically are asymptomatic. Pain may be related to impending fracture or be a sign of malignant degeneration to chondrosarcoma. Radiographically, the lesions can be expansile and lobular with endosteal scalloping and cortical thinning. MRI shows areas of multilobulated increased signal on T2-weighted imaging, interspersed with foci of low signal, representing matrix calcification. Features suggestive of malignant degeneration include progressive cortical destruction, loss of matrix mineralization, and an adjacent soft tissue mass. In certain locations, in particular the small bones of the fingers and the proximal fibula, radiographic features may appear slightly more aggressive without representing malignancy. Treatment of enchondromas is dependent on symptoms and concern for malignancy. Asymptomatic lesions may be observed with serial radiographs. Pathologic fractures are generally managed with immobilization while the fracture heals, followed by biopsy and intralesional curettage with or without augmentation, such as bone graft and bone cement.

Other benign cartilaginous tumors include extraskeletal chondroma, periosteal chondroma, osteochondroma, and chondroblastoma. Extraskeletal chondroma is a chondroma arising in the soft tissue and not in association with a joint, which distinguishes it from synovial chondromatosis. Periosteal chondromas arise adjacent to the bone within the periosteum and may result in scalloping of the outer cortex. MRI may confirm the characteristic appearance of cartilage in both of these lesions, and treatment with marginal excision is appropriate. Osteochondroma, as it occurs at other sites, is characterized by a bony prominence with medullary continuity to the affected bone, topped with a cartilaginous cap. Growth of the osteochondroma ceases when patients reach skeletal maturity. Multiple osteochondromas may be associated with multiple hereditary exostosis. The lesions may be observed or treated with marginal excision if symptomatic. Rarely, malignant degeneration of the cartilaginous cap may occur.

Chondrosarcomas can occur primarily or secondarily after malignant degeneration of an enchondroma or osteochondroma. These slow-growing tumors are locally aggressive but have low metastatic potential and are not sensitive to adjuvant radiation or chemotherapy. Radiographic differentiation from enchondroma is difficult but may show significant endosteal scalloping, cortical destruction, and a soft tissue mass. Although chondrosarcoma represents one of the most common primary malignant bone tumors of the hands, its incidence is low compared with other sites such as the pelvis, femur, and humerus ( Fig. 2 ). Histologic differentiation between low-grade chondrosarcoma and enchondroma may be difficult and often relies on correlation with clinical history and radiologic appearance.

Chondrosarcoma of proximal humerus. ( A ) Anteroposterior view of proximal humerus lesion with ring and arc calcifications; aggressive appearance with destruction of bony cortices. ( B ) Axial CT view of bony destruction of proximal humeral lesion; arrow points to area of cortical destruction and extracompartmental extension of tumor. ( C ) Axial T2 MRI view of proximal humeral lesion with lobulated appearance. Increased signal intensity and erosion through overlying cortex.

( Courtesy of W. Morrison, MD, Philadelphia, PA.)

Humeral lesions may be effectively treated with wide excision and limb-sparing surgery, with allograft or endoprosthetic reconstruction. However, functional limitations in shoulder range of motion are common to both reconstructive options. Compared with chondrosarcoma at other locations, the reported overall survival for humeral lesions was better than occurrences in the pelvis or femur and equivalent to those in the tibia, with 96% survival at an average 16-year follow-up. The treatment of lesions in the hand is dependent on histologic grade. Grade 1 lesions in the hand may be treated with curettage and grafting or wide excision, with similar low rate of local recurrence. However, higher-grade lesions have an increased chance of local recurrence, and wide excision or amputation may be preferable. Compared with high-grade lesions found in other anatomic sites, hand lesions have a lower rate of metastases.

Benign but Locally Aggressive Lesions

Giant cell tumor of bone

Giant cell tumor of bone is a locally destructive neoplasm with a high recurrence rate and a small potential for distant pulmonary metastases. It more commonly affects the distal femur and proximal tibia, but when it affects the upper extremity, it may involve the distal radius and proximal humerus. Radiographically, it appears as an eccentric metaphyseal or epiphyseal lucency with cortical thinning. The Campanacci radiographic grading system is often used and describes the aggressiveness of the lesion. Stage I (calm) lesions do not distort the overlying cortex; stage II (active) lesions cause cortical expansion and thinning but do not perforate the overlying cortex; stage III (aggressive) lesions perforate the cortex and extend into the adjacent soft tissues. MRI is useful in assessing the soft tissue component of a lesion ( Fig. 3 ). The treatment of these lesions ranges from curettage and bone grafting with or without adjuvant treatments used for low-grade lesions to marginal or wide resection with autograft or allograft reconstruction for more aggressive lesions.

MRI of giant cell tumor. ( A ) Coronal T2 MRI of giant cell tumor shows perforation of radial cortex; arrow points to area of cortical destruction and extension of tumor into soft tissue envelope. ( B ) Axial T1 MRI of giant cell tumor shows volar extension of tumor mass.

( Courtesy of W. Morrison, MD, Philadelphia, PA.)

General Surgical Considerations

The goal of any surgical intervention for musculoskeletal tumors is local control. Before the 1970s, amputation was a common surgical procedure for malignant extremity tumors. Improvements in tumor imaging, adjunctive chemotherapy, radiation therapy, soft tissue coverage procedures, and reconstructive options have enabled limb salvage to be performed in 90% to 95% of upper extremity malignancies. The optimal surgical intervention is determined based on information obtained through tumor grading and staging and tumor imaging. Enneking and colleagues delineated the 4 types of surgical margins that may be achieved by excision or amputation based on the relationship of the plane of dissection to the tumor and surrounding structures. Intralesional procedures are those that dissect directly through tumor bed and result in gross contamination of the surgical field. This procedure may be acceptable for incisional biopsy or for definitive treatment of some benign tumors. Marginal procedures are those that dissect through a tumor pseudocapsule, which leaves behind residual microscopic disease. Wide excision procedures are those that avoid violating the tumor or its pseudocapsule by dissecting through a cuff of normal tissue around the tumor. Radical excision involves removing the entire bone or muscle compartment that is affected by tumor. The use of this classification for level of tumor resection facilitates comparisons in outcomes of tumor treatment among studies.

Intralesional Procedures

An intralesional procedure such as curettage and bone grafting with or without adjuvant treatments may be appropriate for aneurysmal bone cysts and giant cell tumors without soft tissue extension. The local recurrence rate of aneurysmal bone cysts treated by simple curettage with or without bone grafting varies between 10% and 60%. Marginal resection may be considered in expendable bones to decrease the rate of local recurrence. Alternatives to marginal resection include an intralesional procedure with adjuvants such as cryosurgery with liquid nitrogen, phenol, high-speed burring, and cementation with methylmethacrylate after curettage of the lesion. The use of cryosurgery after curettage of aneurysmal bone cyst has been associated with a decreased recurrence rate between 5% and 16%. Gibbs and colleagues have advocated for high-speed burring instead of cryosurgery and had only 12% local recurrence with this technique. However, as highlighted by Athanasian, cryosurgery may be technically demanding within the small bones of the hand and carries with it risks of fracture, premature physeal closure, and joint collapse.

Wide Resection

Wide resection is indicated for malignant tumors and benign but locally aggressive tumors with soft tissue extension. Although surgical resection of the tumor and secondary limb reconstruction procedures are intertwined, the primary goal of surgical intervention is to obtain local control of the tumor. Preservation of limb function should not compromise resection margins. In the preoperative planning, careful assessment of tumor involvement of neurovascular structures is critical, because this may necessitate nerve or vessel reconstruction or preclude the possibility of limb salvage. For example, the clinical triad of intractable pain, motor deficit, and venography showing obliteration of the axillary vein has been postulated as being predictive of brachial plexus involvement. During the planning for surgical resection, consideration should be given to the reconstruction of the bony, neurovascular, and soft tissue defects after tumor resection.

Nerve or Vascular Involvement

Preoperative evaluation must assess tumor involvement of peripheral neurovascular structures, because this has an impact on the feasibility of performing limb salvage surgery, reconstructive options, expected postoperative function, and potential complications. Cross-sectional imaging with MRI may show whether tumor is adjacent to or encasing nerves or vessels. Advances in microsurgery have enabled tumor resection to be carried out within the adventitial or epineural planes if tumor is lying adjacent to these critical structures. However, if tumor arises from or is encasing nerves or vessels, then, they must be sacrificed at the time of resection. In general, if tumor involves 2 or more major nerves in the upper extremity or if anticipated function of the distal limb after tumor resection is predicted to be poor, then, amputation may be preferable. Resection and replantation may be an alternative to amputation if tumor-free margins may be obtained. The technique involves segmental resection of the proximal portion of the limb, including bone, soft tissue, and skin, and in some cases, nerves or vessels, with reimplantation of the distal limb to the body similar to rotationplasty described in the lower extremity.

Arterial resection can often be managed well with bypass grafting using vein autografts or synthetic grafts. Although not specific to the upper extremity, outcomes of limb salvage surgery in the lower extremity that required arterial reconstruction have shown higher rates of requirement of soft tissue coverage, wound complications, deep vein thrombosis, and limb edema compared with surgeries without need for vascular reconstruction. In addition, the risk of progression to requiring amputation is higher when vascular reconstruction is needed. The requirement for postoperative therapeutic anticoagulation to prevent graft thrombosis may be related to the increased risk of wound complications.

In cases of single peripheral nerve resections in which motor and sensory deficits are expected, restoration of motor function has traditionally been achieved through tendon transfers. Although more commonly used in brachial plexus injuries, nerve transfers may be a promising alternative for restoring distal motor or sensory function after nerve resection. Ozkan and colleagues reported restoration of 10-mm 2-point discrimination in 15 of 25 hands with sensory deficits attributable to a variety of causes. To prevent contamination of the donor surgical site, tendon transfers should be performed in a delayed fashion, once negative tumor margins have been confirmed. The specific tendon transfers to be used are dependent on the expected functional deficit expected after nerve resection and should be individualized to the patient.

Bone Reconstruction

The options for reconstruction of bony defects after tumor resection may be categorized based on location (diaphysis vs epiphysis) and, in the case of juxta-articular lesions, motion-preserving or arthrodesis procedures. Diaphyseal bone defects can be effectively managed with fibular bone graft. Epiphyseal bone defects of the distal radius and proximal humerus can also be managed with proximal fibular bone grafts, osteoarticular allograft, or endoprosthetic reconstruction.

Fibula Autograft

Vascularized and nonvascularized fibular autografts have a wide range of usefulness in reconstructive procedures of the upper extremity and may be used for diaphyseal defects of the humerus, radius, and ulna or as osteoarticular reconstructions of the proximal humerus, distal radius, or distal ulna. Maruthainar and colleagues reported good outcomes of 12 nonvascularized fibular autografts for reconstruction of distal radius defects. Excluding 3 patients who required forearm amputation for tumor recurrence, functional range of motion was preserved with few complications. In the proximal humerus, fibular autografts may be prone to fracture, which has been reported to occur in up to 36% of patients. Despite this complication, which may be treated nonoperatively in some patients, quality of life and functional scores were marginally higher than in patients treated with an endoprosthesis in 1 series. Hsu and colleagues reviewed 30 vascularized fibula autografts for reconstruction after a variety of upper extremity and lower extremity sarcoma resections. Union rate was 90% in this series, with a 10% rate of infection and 10% rate of stress fracture. Gebert and colleagues reported a higher complication rate in a series of 21 patients in whom vascularized fibula autograft was used for upper extremity reconstructions: graft fracture and pseudoarthrosis occurred in 24% and 19% of patients, respectively.

Soft Tissue Reconstruction

The importance of soft tissue reconstruction as part of the overall limb salvage procedure is critical and may involve several techniques. The spectrum of soft tissue reconstruction includes primary closure, split-thickness and full-thickness skin grafts, local or regional flaps, and free-tissue transfer. The choice of technique is dependent on tumor-related factors such as defect size, location, and involvement of neurovascular structures as well as patient-related factors such as age, health status, and functional status.

The plan for soft tissue coverage should already be in place when skin incisions are made for tumor resection to prevent compromise of later reconstructive options. When primary closure would result in undue skin tension, skin grafts may be used. Full-thickness grafts are often preferable, because they do not contract and wear better than split-thickness skin grafts. Skin grafts should not be placed directly over exposed hardware, tendon, or bone and require a clean healthy wound bed to support neovascularization.

In 1 large series of 100 sarcoma resections of the upper extremity, flap coverage was required in 29% of patients. In the arm and forearm, tumor sizes of 5 cm or greater are associated with need for soft tissue flap reconstruction, whereas in the hand, the tumor sizes of 2.5 cm or greater often require these complex closures. Regional flaps commonly used in the upper extremity include the radial forearm flap, lateral arm flap, latissimus dorsi flap, and posterior interosseous flap. Fillet flaps using the spare parts after tumor resection may be used frequently for hand lesions and can obviate other regional flaps.

The radial forearm flap may be used as a free flap or pedicled reverse flap, which may reach as far distally as the webspaces and provides approximately 12 × 17 cm of tissue. It requires sacrifice of the radial artery and may be harvested as either a fascial, fasciocutaneous, or osteocutaneous flap, although fracture is a common complication if of the osteocutaneous variant. The lateral arm flap may be harvested as a fasciocutaneous flap with dimensions of 8 × 15 cm and can be used to cover the shoulder or turned down to cover the elbow. The latissimus dorsi flap, based off the thoracodorsal artery, may be used as a large (25 × 35 cm) myocutaneous flap for coverage of the shoulder, arm, and elbow. A functional reconstruction may be performed in which the latissimus dorsi is transferred to provide elbow flexion or extension in addition to soft tissue coverage. The gracilis may be harvested as a free myocutaneous flap to cover small and medium-sized defects. Its use as a functional free-tissue transfer to the arm and forearm has been described.