Musculoskeletal tumors represent approximately 10% of all orthopedic diagnoses and present potential clinical challenges because of their varying presentations and biologic behavior. They may come noted clinically either through incidental discovery or due to direct symptoms.
This chapter places specific emphasis on the initial assessment and evaluation of patients presenting with oncologic processes around the shoulder. We review the salient radiographic and clinical features of the more common lesions, understanding that this document does not represent an entire catalog of all possible oncologic diagnoses that may affect the shoulder. We review the principles of biopsy, surgical resection, and outline the current reconstructive options available.
Surgeons must be acutely aware of the potential functional implications following resection and the reconstructive options available, understanding that concerns for function must never take precedence over obtaining an adequate surgical resection.
Historical review
Sarcoma refers to malignancies of mesenchymal or connective tissue origin. In the early period sarcomas were considered lesions of the extremities and were confused with osteomyelitis and other conditions. Treatment of sarcomas varied greatly during this time. As these lesions began to be recognized as histologically and radiographically distinct entities, management became more targeted. Early surgical management of sarcomas involved wide resection, often consisting of an amputative procedure. Even with these radical resections, survival was quite poor. However, during the 1970s and 1980s, adjuvant treatment with radiotherapy and chemotherapy began to show promise in improved survival, allowing surgeons to begin to shift toward limb-sparing surgery.
With adjuvant treatment, we are now able to perform limb-sparing procedures in the vast majority of cases. With these cases, there is often a need for innovative reconstructive techniques to achieve reasonable functional results, with recent literature focusing on patient-reported outcomes in addition to survival statistics after surgical resection. This chapter briefly discusses the indications for, and assessment of, these procedures in terms of functional results and tumor recurrence.
Anatomy
In the shoulder girdle, anatomic considerations are amplified by the close proximity of critical structures to one another. It has also been suggested that the shoulder is more prone to intra-articular or pericapsular invasion by sarcomas than other joints. This may be due to the thin synovial lining of the shoulder or because the biceps tendon provides a direct route into the joint.
Although an evaluation of musculoskeletal tumors frequently refers to the various anatomic compartments of the region involved, the exact anatomy of the compartments of the shoulder remains poorly defined and often provides little containment to the expansion of tumors. In skeletally immature patients the physis often behaves as a barrier to tumor penetration. It is thought that the avascular environment of the physis as well as the presence of antiangiogenic factors inhibit direct tumoral spread. , Although the vast majority of lesions do not cross the physis, there are a few notable exceptions. These include aneurysmal bone cyst, chondroblastoma, osteogenic sarcoma, and osteomyelitis.
Many anatomic clues are helpful in making the initial diagnosis in patients with an unknown musculoskeletal lesion ( Fig. 12.1 ). For instance, Ewing sarcoma typically develops in the shaft or diaphysis of the humerus; it occurs less frequently in the metaphysis of a long bone. On the other hand, the epicenter of an osteogenic sarcoma is rarely located in the shaft and is usually found in the metaphysis. Primary intra-articular tumors are rare, and an intra-articular lesion is more likely to represent a degenerative, traumatic, or other non-neoplastic diagnosis. Secondary involvement of a joint by an intraosseous malignancy is usually a late phenomenon associated with a longer diagnostic delay or a more aggressive lesion and a worse prognosis (see “Staging and Classification of Tumors” in this chapter). , Intra-articular malignancies require more complex extra-articular resections.
Particularly difficult locations for neoplasms in the shoulder girdle include those of the brachial plexus or lesions that involve the axillary or brachial vessels. Both the plexus and the axillary vessels are contained within their own sheaths, which can eventually be penetrated or infiltrated by an aggressive lesion. Primary tumors of the brachial plexus (malignant peripheral nerve sheath tumors) usually manifest on clinical examination with a nerve deficit or radicular symptoms. Any patient with distinct peripheral nerve symptoms associated with a shoulder mass should be assumed to have nerve involvement until it is demonstrated otherwise. Lesions involving the axillary or brachial vessels require magnetic resonance imaging (MRI) to define the precise extent of involvement.
For optimal function, the shoulder depends on an innervated deltoid and rotator cuff. The deltoid, like most muscle compartments, has anatomic subdivisions (acromial, clavicular, and scapular heads), but grossly it is a well-defined muscle that is easily resectable. However, following resection, reconstruction to restore meaningful function can be extremely challenging, especially in the setting of concomitant resection of the proximal humerus. Perhaps the most important anatomic consideration involved in the treatment of shoulder tumors is the proximity of the tumor to the axillary nerve and the deltoid muscle. Injuries to the axillary nerve during tumor resection or biopsy can result in partial or complete loss of deltoid function. Thus the location of the axillary nerve at the time of biopsy and during resection has great significance. In general, the functional prognosis for tumors of the shoulder girdle is much better if the axillary nerve, deltoid, and rotator cuff are preserved. Reconstruction of the deltoid and/or rotator cuff remains challenging. ,
Classification and staging of tumors
The early classification system for musculoskeletal tumors was popularized by Lichtenstein, who classified tumors according to basic histologic categories. This descriptive histologic system, while useful in identifying general trends in diagnosis and prognosis, had limited significance for guiding treatment.
One of the greatest contributions to today’s improved treatment of sarcomas has been the development of a staging system that assists surgeons in the selection of treatment, assessment of prognosis, and evaluation of results. Such a classification system was introduced by Enneking in 1980, adopted by the Musculoskeletal Tumor Society, and was subsequently accepted, with modifications, by the National Institutes of Health Sarcoma Consensus Study Group as the staging system for all sarcomas. This system is composed of two parts; one for benign lesions and one for malignant lesions. The fundamental basics of the Enneking staging system can be applied to both soft tissue and bone tumors.
Benign tumors of bone
The Enneking staging system relies on radiographic findings to classify lesions. The benign classification uses the Arabic numeral system (1, 2, 3) to identify lesions as latent, active, or aggressive ( Table 12.1 ). A latent lesion, classified as a stage 1 in the Enneking system, is defined as a lesion that is confined within the bone, with minimal or no cortical involvement, and which does not show active growth. A nonossifying fibroma is an example of a latent lesion. An active lesion (stage 2 in the Enneking system) demonstrates progressive growth, limited to the anatomic compartment. These lesions may deform their natural boundaries (cortical bone) but will not penetrate them. Chondroblastomas are considered to be active lesions. An aggressive lesion (stage 3 in the Enneking system) has the potential to penetrate or violate natural boundaries, such as cortical bone or periosteum, and to remain locally destructive without metastasizing. A giant cell tumor (GCT) of bone is an example of an aggressive lesion.
| Stage | Histologic Grade | Description | ||
|---|---|---|---|---|
| Benign | Stage 1 | Latent | ||
| Stage 2 | Active | |||
| Stage 3 | Aggressive | |||
| Malignant | Stage I | IA | Low grade | Intracompartmental |
| IB | Extracompartmental | |||
| Stage II | IIA | High grade | Intracompartmental | |
| IIB | Extracompartmental | |||
| Stage III | Any grade | Metastatic |
Malignant soft tissue and bone tumors
The Enneking system for malignant tumors uses the Roman numeral system (I, II, III) to classify lesions. This system uses a combination of histologic grade (G—low grade or high grade), anatomic extent (T—intracompartmental or extracompartmental), and the presence of metastases (M—includes regional and distant) to define lesions (see Table 12.1 ). Stage I lesions are defined as low-grade tumors that remain localized. Stage II lesions are high-grade tumors that remain localized, and stage III lesions are metastatic and of any histologic grade.
The extent of disease in the Enneking system is defined by whether the tumor remains intracompartmental or extends extracompartmentally. A tumor is considered intracompartmental if it is limited by natural boundaries, such as fascia, bone, periosteum, or synovial tissue. A tumor is extracompartmental if it penetrates beyond these natural boundaries. It was postulated that the anatomic site (T) was the greatest factor in prognosis because it represents a composite of anatomic site, rate of growth, and time to diagnosis.
Simplicity is both a strength and weakness of the Enneking staging system. By limiting the number of malignant tumor stages (IA, IB, IIA, IIB, and III), this system is simple enough to be used by a wide variety of oncologic and nononcologic specialists alike. Critics of the Enneking system cite the major weaknesses as being the overly simplistic nature of the system, the fact that subcutaneous sarcomas are difficult to define, and the lack of statistical validation of the system.
Additional staging systems are available for use, such as the American Joint Committee on Cancer Staging and the Memorial Sloan-Kettering Cancer Center systems. , , Both of these systems take into account histologic grade, size, location, and the presence of metastases; however, they are each organized differently. These classification systems are more complex than the Enneking system and a complete review is outside the scope of this chapter.
Staging of tumors
Staging involves an assessment with various imaging studies to determine the anatomic extent of the primary disease, as well as to determine if regional or distant metastases have occurred. Typical staging studies include plain radiographs of the affected area, along with an MRI with and without contrast to determine anatomic extent of the lesion ( Fig. 12.2 ). A computed tomography (CT) scan may be helpful to better define the anatomy of bone tumors. A whole-body technetium bone scan or Positron emission tomography/computed tomography (PET/CT) is often obtained to evaluate for distant metastatic disease. CT scanning of the lung is routinely performed to assess for pulmonary metastasis and is more sensitive than plain radiographs for detecting disease.
Molecular biology
The staging systems mentioned previously use grade, anatomic location, size, and tumor extent to predict tumor behavior and, accordingly, patient survival. In the future it is likely that the greatest improvement in predicting the clinical outcome of musculoskeletal tumors will be made with regard to advances in molecular biology. Sarcomas pose a significant challenge because they comprise a rather diverse and heterogeneous group of neoplasms; additionally, chromosomal translocations are often rather complex and inconclusive.
Despite these inherent challenges, some useful information has been gathered that can help improve the understanding of tumor behavior. For example, overexpression of ErbB-2 or the multidrug resistance gene (MDR-1) has been associated with a poor prognosis for patients with osteosarcoma. , A number of translocations are associated with certain types of sarcomas as well ( Table 12.2 ). The characteristic t(11;22)(q24;q12) chromosomal translocation resulting in the EWS-FLI1 transcription factor in Ewing sarcoma has been shown to be a positive predictor of survival independent of tumor site, stage, and size. A gene expression signature has been identified in leiomyosarcomas that can predict the development of metastases. High levels of an apoptosis inhibitor gene, survivin, can portend a poor prognosis for osteosarcoma patients. Findings such as these may allow the clinician to tailor therapy based on the anticipated outcome of the disease in the future. However, today, no widespread targeted therapies based on these genetic variants are available.
| Tumor | Translocation |
|---|---|
| Ewing sarcoma | t(11;22)(q24;q12) |
| Synovial sarcoma | t( x ;18)(p11;q11) |
| Extraskeletal myxoid | t(9;22)(q22;q12) |
| Chondrosarcoma | t(9;17)(q22;q11.2) |
| Clear cell sarcoma | t(12;22)(q13;q12) |
| Myxoid liposarcoma | t(12;16)(q13;p11) |
Classification of tumors
While clinical features such as radiographic findings, location of the tumor, and patient age may suggest a differential diagnosis, a pathologic sample is required for confirmation of an indeterminate lesion. Even though sarcomas are often treated in a similar manner regardless of the histologic classification, this may still have an impact on understanding general tumor tendencies and the unique features displayed by several histologic subtypes. The most common lesions of bone, cartilage, and soft tissue are described below with their histologic, radiographic, and clinical characteristics.
Benign osseous lesions
Osteoid osteoma.
Benign osseous lesions of the shoulder are uncommon. Only 10% to 15% of cases of osteoid osteoma and osteoblastoma occur in the shoulder, and when they do occur, they favor the proximal end of the humerus or glenoid. , Clinically osteoid osteomas typically present in younger patients with a predilection for males. Symptoms of night pain that are temporarily relieved by nonsteroidal antiinflammatories, often within minutes of administration are suggestive of an osteoid osteoma. Radiographically they are characterized by a large area of reactive bone surrounding a small, radiolucent nidus that is often not well visualized on x-rays. Advanced imaging such as technetium bone scans or a CT scan are necessary for diagnosis; on bone scan the area will appear intensely hot, while the CT scan will clearly demonstrate the reactive bone surrounding the nidus. Histologically, this lucent nidus is a well-demarcated, small area of immature woven bone surrounded by reactive bone. The differential diagnosis consists of osteoblastoma, osteomyelitis (Brodie abscess), intraosseous ganglion, stress fracture, and bone island.
The first line of treatment is observation and nonsteroidal antiinflammatory therapy (NSAID), as most osteoid osteomas will involute over time. The average length of NSAID therapy, however, is 3 years. Because of this most patients chose to proceed with surgical intervention. Historically these lesions were curetted out, often leaving a large defect. More recently CT-guided radiofrequency ablation (RFA) has demonstrated efficacy against osteoid osteomas. RFA has been shown to have a 90% success rate and can be repeated for recalcitrant cases. ,
Osteoblastoma.
Some clinicians regard osteoblastoma as a larger version of an osteoid osteoma, but there are several important differences. Clinically these patients have pain that is not typically relieved by NSAID therapy, as is seen with osteoid osteomas. Radiographically the nidus is much larger, often greater than 2 cm in diameter, as opposed to an osteoid osteoma, which usually has a nidus under 1.5 cm. Similar to an osteoid osteoma the nidus is surrounded by a rim of reactive bone and will appear hot on bone scan. The tumor may expand the cortical bone and extend into the soft tissues. The most common locations include the spine, femur, and tibia. Histologically the nidus is similar to an osteoid osteoma with immature osteoid. Treatment is surgical as these lesions do not respond to nonoperative measures. Curettage is the standard of care and is associated with up to a 20% rate of local recurrence, although there are recent reports of success with image-guided RFA and cryoablation. ,
Myositis ossificans.
Myositis ossificans is a benign, reactive, bone-forming process that develops intramuscularly or in the areolar tissues (the tendon, ligament, capsule, and fascia) adjacent to bone. It can occur with or without a history of trauma; without trauma, it may be referred to as pseudomalignant myositis ossificans of the soft parts. Clinically, patients present with pain and decreased range of motion in the affected area. Over time a mass may develop that becomes firm as the bone matures. Radiographically, the tumor appears to have peripheral bone with a central lucent area. This will be highlighted on advanced imaging, such as a CT scan. A bone scan will demonstrate increased uptake around the lesion that diminishes as the bone matures , and is helpful to guide treatment.
Histologically, the periphery is composed of mature lamellar bone with trabeculae, while the center of the tumor is comprised of immature fibroblasts with limited matrix calcification. This histologic pattern is in contrast to osteosarcoma, which demonstrates the most immature area peripherally.
In some patients, myositis ossificans may be confused with osteosarcoma or a soft tissue sarcoma. However, these tumors do not demonstrate the same zonation or peripheral margination phenomenon, nor do they have the same radiographic characteristics. When the proper diagnosis is uncertain, optimal management includes a complete radiographic evaluation and careful clinical observation rather than a hasty or premature excision or biopsy (which can be difficult to interpret due to the presence of immature bone). The radiographic differential diagnosis for myositis ossificans includes: extraosseous or parosteal osteosarcoma, synovial sarcoma, vascular lesions, and calcification of soft tissue secondary to necrosis, inflammation, or infection. Treatment consists of surgical excision. Before excision, a mature lamellar pattern should be seen radiographically with a decrease in intensity on bone scan, which takes approximately 6 to 12 months. Surgery before the bone has matured is associated with a high recurrence rate.
Malignant osseous lesions
Osteosarcoma.
Osteosarcoma is the most common malignant primary bone tumor after myeloma. It is the most common primary sarcoma occurring in the shoulder, followed by Ewing sarcoma and chondrosarcoma. Osteosarcoma demonstrates a bimodal age distribution, with the highest peak occurring in the teenage years (representing primary tumors) and a second peak in the seventh decade (representing secondary tumors).
Classic osteosarcoma is a high-grade, aggressive tumor that develops in metaphyseal bone, typically as a stage IIB lesion with an extraosseous soft tissue component present at initial evaluation. , , Many patients present with pain, with or without a palpable mass. The typical patient experiences intrinsic bone pain at night that is typically unrelated to activity ( Box 12.1 ). The average duration of symptoms at initial assessment is 3 to 6 months, reflecting the subtle nature of the preliminary symptoms and the need for early recognition of intraosseous pain and night pain as warning symptoms. ,
Approximately 10% to 15% of all osteosarcomas occur in the proximal part of the humerus, whereas 1% to 2% develop in the scapula or clavicle. , , , The typical radiograph for osteosarcoma has a sunburst pattern with periosteal reaction and possible penetration of the adjacent cortex ( Fig. 12.3 A). Differential diagnosis includes Ewing sarcoma, eosinophilic granuloma, osteoblastoma, GCT, and metastatic disease in older patients. Osteosarcomas usually have increased activity on bone scan ( Fig. 12.3 B), and a soft tissue mass as seen on CT scan ( Fig. 12.3 C) or MRI ( Fig. 12.3 D). Arteriography is no longer the technique of choice for evaluating soft tissue involvement, but it may be performed to evaluate major vessel involvement or the response to intra-arterial chemotherapy ( Fig. 12.3 E). In addition to the classic type, variants of osteosarcoma include telangiectatic (vascular) osteosarcoma, secondary osteosarcoma (Paget disease or radiation-induced), and various low-grade lesions, such as periosteal and parosteal osteosarcoma. , , The histologic criterion for the diagnosis of osteosarcoma includes a malignant spindle cell stroma that produces osteoid. , , The overall survival rate at 5 years for patients with osteosarcoma is approximately 70% with appropriate chemotherapy and surgery but decreases drastically with recurrence or metastatic disease. Prognostic factors for survival include age, the stage at presentation, and the degree of histologic necrosis at resection (following neoadjuvant chemotherapy). Treatment remains multi-agent chemotherapy and wide surgical resection.
Benign cartilaginous lesions
Osteochondroma.
The incidence of cartilaginous tumors in the shoulder is second only to those occurring about the pelvis. A solitary osteochondroma is the most common benign tumor of the shoulder; approximately one-fourth of all osteochondromas occur along the proximal humerus. Osteochondromas are thought to be a developmental abnormality arising from the perichondral ring and typically enlarge during skeletal growth. A plain radiograph is usually diagnostic in demonstrating a smooth excrescence of metaphyseal cancellous bone that is confluent and continuous with normal metaphyseal bone ( Fig. 12.4 ).
Osteochondromas may form as pedunculated lesions with a stalk, or as a sessile lesion with a broad base of attachment to the underlying bone. A CT scan will demonstrate corticomedullary continuity with the underlying bone, which is diagnostic of an osteochondroma and helps differentiate this from a parosteal osteosarcoma.
Many lesions are asymptomatic. If an osteochondroma is large, a patient may present with a mechanical block to motion or symptoms of compression of adjacent neurovascular structures, especially around the shoulder. Treatment consists of simple excision through the stalk with removal of the cartilaginous cap in order to reduce recurrence. Excision is often delayed until skeletal maturity in young patients to avoid damage to the growth plate.
Concern regarding a possible secondary chondrosarcoma can arise in patients with pain and enlargement of the mass after skeletal maturity. Secondary chondrosarcoma forms from the cartilage cap and is diagnosed based on thickening of the cartilage cap greater than 2 cm on advanced imaging (MRI). A biopsy is usually not helpful as the secondary chondrosarcoma is often low grade and often difficult to differentiate from normal tissue for the pathologists. The risk of a secondary chondrosarcoma arising out of an osteochondroma is less than 1% per lesion, although rates as high as 10% to 30% have been reported regarding secondary malignancy in patients with multiple hereditary exostoses. ,
Chondroblastoma.
Chondroblastoma is an unusual, benign cartilaginous tumor that most commonly occurs in skeletally immature patients. It is often located in the epiphysis, although it may cross the physis. These tumors typically are classified as an active lesion (stage 2), although a more aggressive (stage 3) form has been reported. In very rare cases, metastasis to the lungs has occurred.
Chondroblastomas are more common in the lower extremity, but when they do occur in the upper extremity they are often located in the proximal humeral epiphysis (25% of cases). These lesions often present with pain at the tumor site. Radiographically, these appear as round or oval well-circumscribed lesions with a rim of reactive bone. The lesion will demonstrate stippled calcifications consistent with its chondroid matrix. An MRI will show increased bony edema surrounding the lesion ( Fig. 12.5 ). Histologically the chondroblasts are arranged in a cobblestone pattern with a chicken-wire calcification.
The differential diagnosis is dependent on the patient’s age and includes: other benign bone tumors in children, GCT, chondrosarcoma, or metastatic adenocarcinoma in adults. Treatment usually involves extensive intralesional curettage, which results in a large subchondral defect of the humeral head, often requiring bone graft to prevent subchondral collapse. An adjuvant agent such as hydrogen peroxide or cryotherapy can help reduce local recurrence rates, which have been reported as high as 10% to 35%. ,
Periosteal chondroma.
Periosteal chondroma is another benign cartilaginous lesion of the proximal humeral metaphysis, usually located just proximal to the deltoid insertion. It typically presents with minimal symptoms, although tendon irritation may occur. The mass is located under the periosteum, and as the lesion grows periosteal elevation may be observed. Radiographs will demonstrate scalloping of the underlying bone. As there is minimal reactive bone, a bone scan will only show slight uptake. Histologic specimens will demonstrate cartilage similar to an enchondroma, although more cellularity and malignant-appearing cells may be seen with a periosteal chondroma.
The differential diagnosis includes periosteal osteosarcoma, which does not have the well-defined underlying sclerotic cortex. Periosteal osteosarcoma is a more aggressive malignant lesion that can extend into the medullary canal in a small percentage of cases.
Treatment is with marginal excision of the lesion, historically with removal of the underlying cortex to prevent recurrence. Adjuvant treatment with cryotherapy has also been reported to help reduce the recurrence rate. , Bone grafting of the defect may be necessary following removal.
Enchondroma.
Enchondroma is a benign, central cartilaginous lesion that is most commonly found in the small tubular bones of the hand, but also occurs in the proximal end of the humerus in 10% to 15% of cases. , , Enchondromas are usually solitary, but multiple lesions with extensive deformity can be seen in Ollier disease (enchondromatosis) ( Fig. 12.6 ) or Maffucci syndrome (enchondromatosis with multiple hemangiomas of skin or viscera, or both). It is common for enchondromas of the proximal humerus to be encountered incidentally during a workup for unrelated shoulder pain. When an enchondroma occurs adjacent to a joint that is symptomatic for degenerative reasons, clinical assessment of pain related to the enchondroma may be difficult. This scenario is not uncommon, and it makes the initial evaluation of intraosseous cartilage tumors difficult. As enchondromas are rarely symptomatic, every effort should be made to rule out other sources of pain prior to treating the enchondroma ( Fig. 12.7 ).
The risk of malignant transformation of solitary lesions is extremely small. By contrast, the risk of malignant transformation is 25% to 30% in Ollier disease and even higher in Maffucci syndrome. Malignant degeneration is usually heralded by increased or new pain, or by an increase in tumor size.
The typical radiographic appearance of an enchondroma is that of a central lucent lesion with a well-defined bony margin and intralesional punctate calcifications. There will be minimal endosteal scalloping. Cortical perforation or a soft tissue mass is concerning for malignant degeneration. Enchondromas represent incomplete endochondral ossification, as such they are composed of hyaline cartilage.
The differential for an enchondroma includes a bone infarct or chondrosarcoma. A chondrosarcoma is distinguished from an enchondroma by endosteal scalloping with cortical perforation and possible periosteal reaction with a soft tissue mass, although sometimes this is difficult, especially for low-grade lesions.
Treatment of an enchondroma is based on a thorough assessment of the presence of pain and the risk of fracture. Lesions that are painless can be observed with serial radiographs. If a patient develops pain or there is evidence of radiographic progression, then reevaluation is essential. Intralesional curettage and bone grafting are often sufficient, although wide resection should be performed in cases of suspected malignant degeneration.
Malignant cartilaginous lesions
Chondrosarcoma.
Primary chondrosarcoma is more commonly seen in the middle to later decades of life, and its incidence in the shoulder is second only to the pelvis/hip joint. , It is also the most common primary bone malignancy to arise in the coracoid process.
Secondary chondrosarcoma accounts for approximately 25% of all chondrosarcomas and may be found in patients with a preexisting enchondroma, osteochondroma, multiple enchondromatosis (Ollier disease), , , or multiple hereditary exostoses.
Chondrosarcomas typically manifest as intraosseous lesions with poorly defined margins and faint intrinsic calcifications. Low-grade chondrosarcomas may be difficult to distinguish from enchondromas; these will typically present with endosteal scalloping with possible cortical perforation and/or periosteal reaction. An MRI is useful to demonstrate the extent of the intraosseous lesion and soft tissue expansion ( Fig. 12.8 ). Technetium bone scans are typically moderately hot for both enchondromas and low-grade chondrosarcomas and are not helpful in distinguishing one from the other.
The histologic differentiation between enchondroma and low-grade chondrosarcoma is difficult and often requires radiographic and clinical correlation. Characteristics that suggest malignancy include increased cellularity, pleomorphism, and evidence of mitotic activity. These findings are subtle and often require review by a pathologist adept in sarcomas. , High-grade lesions are easier to diagnose as they are more invasive, have a higher metastatic rate, and usually occur in long-standing enchondromas as a dedifferentiated chondrosarcoma. ,
The differential diagnosis for chondrosarcoma includes enchondroma, osteosarcoma, and metastases. Less commonly, a primary chondrosarcoma arises from the surface of a bone or joint. Its clinical and radiographic appearance is very subtle, and a diagnostic delay of 6 to 12 months is not uncommon.
Chondrosarcomas are relatively resistant to radiation and chemotherapy, and surgical management is therefore the mainstay of treatment. High-grade lesions require wide surgical resection in order to decrease the risk of recurrence. Low-grade chondrosarcomas, on the other hand, have a lower risk of metastases. This decreased risk has led some to label these as “low-grade cartilaginous neoplasms” or “atypical cartilaginous tumors” rather than a chondrosarcoma in order to avoid the stigma of a sarcoma diagnosis. These authors recommend intralesional curettage in the appendicular skeleton rather than wide resection.
Synovial dysplasias.
Cartilaginous loose bodies typically arise out of a proliferative synovium in a reactive metaplastic process known as synovial chondromatosis (or osteochondromatosis). This process most commonly affects large joints (the knee, elbow, shoulder, and hip) in young adults and results in multiple small, cartilaginous, intra-articular loose bodies as the process matures. In the few cases in which the nodules form a compact mass of cartilage, this may be confused with a low-grade, periarticular or juxta-articular chondrosarcoma. An intra-articular location favors the benign diagnosis of synovial chondromatosis; consequently, sometimes one of the preoperative goals is to determine whether the location is intra-articular or extra-articular. In such cases MRI or CT scan with or without arthrography might pinpoint the exact site of involvement. Synovial chondromatosis is typically a slowly progressive, degenerative disease that ultimately leads to joint destruction. It requires aggressive total synovectomy to prevent persistence or recurrence, and in older patients with degenerative disease, it is well treated with joint excision and replacement. A few reports have associated malignant transformation with long-standing synovial chondromatosis. ,
Another disease associated with proliferating synovium is pigmented villonodular synovitis. It is generally associated with a boggy, inflammatory synovitis, with or without bony erosions in adolescents or young adults. Histologically, it is a benign, aggressive synovial-histiocytic process that is thought to be of neoplastic origin, with new literature demonstrating chromosomal translocations. Treatment for the diffuse form of the disease requires aggressive complete synovectomy, often with an open approach, while nodular synovitis may be removed arthroscopically with good results. Various forms of radiation therapy have been used in some centers, although this is less common with today’s treatment options. Occasionally, joint degeneration is severe and arthroplasty is recommended.
Miscellaneous intraosseous tumors
Simple bone cyst.
Simple bone cysts, or unicameral bone cysts, occur most commonly in children between the ages of 4 and 12 years. Simple bone cysts are well-defined, central radiolucent lesions arising in the metaphysis adjacent to the physis (active) and, with maturation, migrate distally into the diaphysis (latent). , Occasionally, a fragment of the cyst wall breaks off and floats into the fluid-filled cyst cavity. Radiographically, this appearance is known as the fallen-leaf sign. Simple bone cysts typically involve the proximal part of the humerus (in 50% of cases) and contain straw-colored fluid; they may be confused with an aneurysmal bone cyst or, less often, with fibrous dysplasia.
There is a wide spectrum of treatment options available for unicameral bone cysts. Some authors recommend initial observation of the lesion while others argue for aspiration and injection with either steroid or demineralized bone matrix with autogenous bone marrow. The result is complete healing of the cystic area in approximately 50% of cases and partial healing in 45%. A comparison of injection of steroids versus autologous bone marrow versus allogeneic bone graft has yielded similar success rates; however, multiple steroid injections are often necessary to achieve healing. ,
Surgical options are also highly varied, with authors reporting on drainage screws, elastic nails, or curettage with bone grafting. Recurrence or persistence of the cyst after treatment is not uncommon, often requiring additional procedures. Some diagnostic overlap occurs between aneurysmal and simple cysts in children because some simple cysts can have hemorrhagic fluid and yet do not contain aneurysmal tissue. In general, if a cyst fractures, it is advisable to allow sufficient time for fracture healing as there may be partial or complete resolution of the cyst following the injury.
Fig. 12.9 A shows a simple cyst with a healing pathologic fracture in the humerus of an 8-year-old boy. The patient remained symptomatic after fracture healing and underwent percutaneous aspiration and injection of autogenous bone marrow and demineralized bone matrix, resulting in complete resolution of the cyst ( Fig. 12.9 B).
Aneurysmal bone cyst.
Aneurysmal bone cysts are not uncommon in the proximal end of the humerus, but because of their widespread occurrence as a secondary lesion engrafted on other tumors (simple cysts, GCTs, chondroblastomas, or osteoblastomas), the true incidence is unknown. The molecular biology of aneurysmal bone cysts has been elucidated and appears to involve upregulation of oncogenes. The radiographic hallmark is that of a lucent, expansile metaphyseal lesion. MRI shows the presence of fluid-fluid levels ( Fig. 12.10 ), although this may also be seen with hemorrhage into a simple bone cyst. Treatment includes curettage plus bone grafting, which in isolation is associated with a recurrence rate of 20% to 30%. Modern treatment options add adjuvant therapy, such as argon beam coagulation or cryotherapy to help reduce the recurrence rate. Open growth plates and young age are associated with a higher recurrence risk.
Aneurysmal bone cysts can have an aggressive appearance, and a careful biopsy should be performed before curettage to exclude the possibility of telangiectatic osteosarcoma. It may be extremely difficult to distinguish these two entities on frozen section alone. In such cases definitive treatment should be delayed until a final diagnosis is rendered.
Fibrous dysplasia.
Fibrous dysplasia is a dysplasia of bone that often presents as a painful lesion secondary to a pathologic fracture, repeated microfractures, or intrinsic structural weakness resulting from the pathologic bone. It is monostotic in 80% of cases and polyostotic in 20%. It is thought to be caused by a GS alpha protein activating mutation and may be associated with McCune Albright syndrome or Mazabraud syndrome.
Radiographs will show a well-defined lesion that has a reactive rim of tissue with a “ground-glass” appearance. Fig. 12.11 shows the plain radiograph and CT scan, respectively, of the humerus of a 20-year-old woman with severe polyostotic fibrous dysplasia. She had a history of chronic pseudarthroses (see Fig. 12.11 A) that had persisted despite bracing. Histologically there is a proliferation of fibroblastic tissue with surrounding woven bone that has been described as “Chinese letters.”
When associated with symptoms or a pathologic fracture, diaphyseal involvement usually requires intramedullary fixation rather than bone grafting because cancellous bone graft is consistently consumed by the dysplastic process and is ineffective in resolving the weakened bone. Studies suggest that there may be a role for medical therapy, namely bisphosphonates, in alleviating pain. Newer reports are evaluating denosumab therapy; however, this is not currently recommended outside of specialized centers. ,
Nonossifying fibroma.
Nonossifying fibroma is a benign fibrous lesion that appears radiographically as an eccentric, well-defined, lucent lesion with a scalloped border abutting the adjacent cortex ( Fig. 12.12 ). It is found more commonly in the lower than the upper extremity. When the lesion is smaller than 4 cm, it may be referred to as a fibrous cortical defect. When longer than 5 cm or occupying more than half the transverse diameter of the bone, these lesions are at risk for pathologic fracture. The majority of nonossifying fibromas heal spontaneously and require no treatment. Treatment is reserved for lesions with atypical radiographs (which require biopsy) or for symptomatic or larger lesions that require treatment to prevent a pathologic fracture.
Giant cell tumor.
GCT of bone is a locally aggressive lesion. Although classically considered benign, in rare cases GCT of bone has the potential for metastatic pulmonary spread. GCT of bone is a common lesion in people between 20 and 40 years of age and develops primarily in the distal end of the femur or proximal part of the tibia (in 60% to 70% of cases). It can also occur in the proximal end of the humerus in 5% to 10% of cases.
GCT is a radiolucent, epiphyseal-metaphyseal tumor that most commonly has a distinct bony margin and is often associated with extensive subchondral bone erosion. There can be bony expansion, cortical destruction, or frank extension of the tumor mass into the soft tissues. Periosteal reaction is uncommon unless there has been a prior pathologic fracture. Although most cases involve solitary lesions, the rare diagnosis of multifocal GCT of bone is usually associated with hand lesions and a slightly younger population. The radiographic differential diagnosis in an adult includes aneurysmal bone cyst, brown tumor of hyperparathyroidism, metastatic adenocarcinoma, lymphoma, chondrosarcoma, intraosseous ganglion, and osteomyelitis. Serum levels of parathyroid hormone, calcium, and phosphate should be checked to differentiate brown tumors from multifocal GCT.
The local recurrence rate after curettage alone is 20% to 30% for active lesions. This has prompted authors to recommend adjuvant treatment, such as burring and argon beam coagulation. With these adjuvant treatments the recurrence rate is reduced and is the current recommendation for most surgically accessible tumors. ,
Radiotherapy can be considered for GCTs in difficult or inoperable locations; however, there are cases of reported malignant transformation following radiation, prompting some to recommend against this option except in rare circumstances.
Systemic therapy with bisphosphonates, and more recently, denosumab, has demonstrated good local control. Currently the National Comprehensive Cancer Network recommends systemic therapy for unresectable lesions, or if the anticipated resection would result in excessive morbidity.
Reticuloendothelial tumors
Tumors of reticuloendothelial origin include a category of intraosseous lesions that arise from marrow stem cells and lesions of similar histology. They are also referred to as round cell or small, blue cell tumors. This category of tumors or abnormalities includes diagnoses, such as leukemia, lymphoma, neuroblastoma, histiocytosis, rhabdomyosarcoma, Ewing sarcoma, infection, and, in adults, multiple myeloma and metastatic adenocarcinoma.
Multiple myeloma.
Multiple myeloma is the most common primary malignancy of bone and typically occurs in the middle decades of life; the shoulder girdle is involved in 5% to 10% of cases. , The most common site of involvement is the axial skeleton, but multiple distinct lesions develop in the extremities in a significant number of patients and can require surgical stabilization to prevent impending fracture if medical treatment has failed. In patients with a solitary intraosseous myeloma or plasmacytoma of the shoulder at initial evaluation, biopsy is indicated for diagnostic reasons. Multiple myeloma may occur initially in the humerus, scapula, or glenoid as an innocent-appearing bone cyst in a mature adult.
Elevated serum calcium levels, anemia, serum protein electrophoresis, or a distinctly cold bone scan may suggest the diagnosis of myeloma before biopsy in a patient with a solitary lesion or unknown diagnosis. Patients with myeloma are typically treated with radiation, chemotherapy, and possible autologous stem cell transplant. , Additionally, bisphosphonates have had a positive effect in reducing skeletal events and bone pain. Surgical management is often palliative in nature, aimed at pathologic fractures or impending pathologic fractures. Prior to surgery it is often helpful to embolize the tumor in order to reduce the bleeding risk.
Fig. 12.13 A shows the plain radiograph of a 42-year-old man in apparent good health but experiencing shoulder pain. Coronal ( Fig. 12.13 B) and transverse ( Fig. 12.13 C) MRI views demonstrate a suprascapular soft tissue lesion that extends anteriorly and posteriorly to the scapula. Open biopsy was diagnostic for multiple myeloma with extensive bone disease. The patient died suddenly 1 week after the biopsy, with an undocumented serum calcium level. All patients with the diagnosis of myeloma need to undergo careful evaluation of their serum electrolytes for the possibility of hypercalcemia, which is usually heralded by altered mental status, fatigue, weakness, or nausea.
Ewing sarcoma.
The second most common intraosseous malignancy in adolescence is Ewing sarcoma, an aggressive marrow cell tumor that appears as a permeative diaphyseal tumor that is poorly marginated and typically associated with a large soft tissue mass. , Differential diagnosis consists of osteomyelitis, osteosarcoma, lymphoma, eosinophilic granuloma, other round cell tumors, and neuroblastoma, especially in children younger than 2 years.
Fig. 12.14 A shows such a permeative lesion in the humeral diaphysis of a 16-year-old with a typically hot bone scan ( Fig. 12.14 B) and an associated soft tissue mass ( Fig. 12.14 C). Although plain radiography is useful for diagnostic purposes, it is not reliable for determining the extent of intramedullary disease. For this reason, an MRI is mandatory before surgery to accurately determine the resection margins. Ewing sarcoma today is primarily treated with aggressive chemotherapy and surgical resection or radiation therapy, depending on the size and location of the primary lesion.
Miscellaneous dysplasias
Gaucher disease.
Gaucher disease is an uncommon metabolic disorder of the reticuloendothelial system and glucocerebroside-glycolipid metabolism that affects the liver, spleen, and bone marrow. The disease has a higher incidence in the Jewish population and presents most commonly in the first three decades of life, with equal incidence in both sexes. Patients typically present with cytopenia, hepatosplenomegaly, and bone pain. The bone pain is secondary to vascular thrombosis and most commonly occurs in the femoral head, with a high degree of bilaterality.
The disease in many ways represents a form of avascular necrosis of the bone. The humeral head is the second most common site of involvement, and radiographic changes include osteopenia, diaphyseal or medullary expansion, and cortical erosions. The differential diagnosis includes osteomyelitis in the acute setting and round cell tumors in the nonacute setting. Surgical treatment involves internal fixation for fracture prophylaxis or treatment of deformity, joint replacement in adults when indicated, and appropriate management of femoral head necrosis in children. Enzyme replacement is the mainstay of systemic therapy and has been shown to greatly reduce skeletal morbidity.
Paget disease.
Paget disease (also known as osteitis deformans) occurs after the fourth decade and has a slight preponderance in men. It is the second most common metabolic bone disorder in people older than 50 years. Geographically, it appears to have a higher incidence in Great Britain, Western Europe, Australia, and the United States, whereas it is relatively rare in India, Asia, and Africa. Paget disease develops most commonly in the pelvis, skull, lumbosacral spine, femur, and humerus. It can occur in a polyostotic or a monostotic form and is usually evident at the time of initial evaluation. The typical radiographic picture shows cortical thickening, bony enlargement, trabecular thickening, and mixed areas of lysis and sclerosis. This is followed by pathologic microfracture and diaphyseal bowing. The differential diagnosis in an adult includes metastatic adenocarcinoma, osteosarcoma, and osteomyelitis. Patients should be assessed by evaluation of serum alkaline phosphatase and urinary hydroxyproline levels, a total body bone scan, and a CT scan or MRI.
Most patients with Paget disease do not require surgical management. The minority of patients who do require surgery usually have musculoskeletal complaints related to deformity, fracture, or altered joint mechanics. Patients with Paget disease undergoing orthopedic surgery should, in general, be pretreated to reduce bleeding associated with the hypervascularity of the bone. Paget disease itself is best managed medically with bisphosphonates or calcitonin.
Sarcoma arising out of Paget disease is characterized by a history of progressive pain and a lytic lesion with a soft tissue mass ( Fig. 12.15 ). Radiographically, Paget sarcoma of the scapulohumeral area is characterized by predominantly lytic changes in the humerus and purely sclerotic changes in the scapula. Pagetoid sarcoma is a rare variant of osteosarcoma with a very poor prognosis regardless of its site or stage at presentation. Paget sarcoma is best managed by ensuring a radical surgical margin because of the diffuse nature of the disease and the difficulty of assessing the extent of sarcomatous changes.
Fig. 12.16 A–B present early and late radiographs of Paget disease in the proximal humerus. The lytic lesion, combined with a history of increasing arm pain, served notice of an early secondary osteosarcoma that worsened on 3-month radiographs ( Fig. 12.16 C). Paget disease affected the full humerus, and the bone scan ( Fig. 12.16 D) was of little help in demarcating bony margins or osseous involvement of the secondary sarcoma. MRI and CT scans again demonstrate the soft tissue and bony extent of disease in the proximal part of the humerus ( Fig. 12.16 E–F).
Benign soft tissue tumors
Ganglion.
A ganglion is a common soft tissue tumor often confused with other cystic lesions. Ganglia have a thin lining but no true synovial capsule. They are filled with a characteristic gelatinous material. In the shoulder they are often associated with degenerative conditions or a labral tear. MRI is the study of choice for evaluating these lesions and for determining their precise anatomic location. Typically, the MRI shows a rounded or lobular fluid signal mass with low signal on T1-weighted images and high signal on T2-weighted images. When located in the spinoglenoid notch, a ganglion may produce suprascapular nerve palsy secondary to nerve entrapment.
Lipoma.
Lipomas can occur intramuscularly or within normal fat planes of the axilla, or in the subscapular or other perivascular spaces. They present as soft, nontender masses. A minority of lipomas are tender or firm and may have an equivocal history of a change in size. On MRI or CT scan a benign lipoma usually has a uniform, fatty consistency that is diagnostic without a biopsy ( Fig. 12.17 ). Alternatively, a liposarcoma has a firmer consistency than that of a lipoma. Additionally, liposarcomas appear vastly different on MRI than a lipoma, often demonstrating a heterogeneous makeup. If an MRI demonstrates these findings, then a biopsy of the area in question should be performed to exclude the possibility of a liposarcoma. Whereas lipomas may undergo an intralesional or marginal excision, liposarcomas require wide surgical margins and may be treated with radiation and chemotherapy to help reduce the risk of recurrence.
Hemangioma.
Hemangiomas typically appear as enlarging intramuscular lesions in a child or young adult. They are best visualized by MRI and typically have a serpiginous configuration of vessels. These lesions do not usually pose diagnostic or surgical problems, with the exception of large hemangiomas or hemangiomatosis of skeletal muscle. These are aggressive, congenital lesions that are often unresectable because of extensive neurovascular and soft tissue involvement. , Many of these extensive lesions result in amputations because of painful, dysvascular, or infected extremities. Most of these lesions are best diagnosed by open biopsy after MRI, CT scan with contrast, or arteriography. Well-localized lesions are more easily resected than the more extensive congenital lesions. Embolization and interferon treatment have had mixed results in halting the progression of disease.
Fibromatosis.
Fibromatosis (desmoid tumor) is a locally aggressive (stage 2 or 3) lesion found in young children, teenagers, and young adults. These lesions have a firm consistency on clinical examination and may be associated with osseous erosions or invasion of a neurovascular bundle. Considerable confusion and contradiction is found in the literature regarding the natural history and treatment of fibromatosis. Historically these were treated with surgical resection, with a 30% to 40% rate of local recurrence. More recently these are treated with radiation and/or systemic therapies. Spontaneous regression has also been described. Because of this, observation is now a reasonable approach to newly diagnosed asymptomatic tumors.
The congenital form of the disease is referred to as congenital fibrosarcoma , primarily because of its very impressive histologic cellularity. The adolescent version is best referred to as aggressive fibromatosis and behaves as an active or aggressive lesion. Preoperative and postoperative MRI studies are mandatory in these patients to fully assess the soft tissue involvement. Treatment should involve a multidisciplinary team.
Soft tissue sarcomas
Soft tissue sarcomas occur in the upper extremity in approximately one-third of all cases. Delays in diagnosis are common. , Moreover, soft tissue sarcomas are often misdiagnosed as benign, and patients undergo a contaminated marginal resection of these lesions before definitive biopsy. Soft tissue sarcomas are characterized by four fairly typical clinical characteristics. They generally have a firm consistency and are deep to the superficial muscular fascia, larger than 5 cm, and nontender (see Box 12.1 ). Adequate staging before biopsy is important for soft tissue sarcomas, just as it is for bone sarcomas ( Fig. 12.18 ). Staging usually consists of advanced imaging of the site in question (MRI with and without contrast) as well as a chest CT scan with a possible whole-body PET/CT or bone scan.
There are many varieties of soft tissue sarcomas. The most common soft tissue sarcoma in adults is undifferentiated pleomorphic sarcoma (previously termed malignant fibrous histiocytoma), which occurs most often in older adults (aged 50 to 70 years). , , Liposarcoma, on the other hand, typically occurs in the lower extremities in young adults as a large lesion with a histology ranging from low grade to high grade or pleomorphic. , , Synovial sarcoma is a less common lesion associated with faint soft tissue calcifications, a juxta-articular location, and a high metastatic rate. Fibrosarcoma, rhabdomyosarcoma, leiomyosarcoma, clear cell sarcoma, and epithelioid lesions are other, less common soft tissue malignancies.
Regardless of the tissue type, the grade of the lesion and the anatomic location of the primary tumor are the most significant factors determining prognosis and treatment. Most soft tissue sarcomas are treated with preoperative (neoadjuvant) or postoperative (adjuvant) radiation with possible concomitant chemotherapy. Surgical resection with a wide margin remains the mainstay for curative treatment.
While most soft tissue sarcomas spread via hematogenous routes, synovial sarcoma, epithelioid sarcoma, and rhabdomyosarcoma are characterized by a high incidence (10% to 20%) of regional lymph node metastasis and a poor prognosis. Survival with these tumors is generally recognized as being closely related to the histologic grade and size of the mass. ,
Incidence of neoplasms
Malignant tumors arising within the musculoskeletal system are rare and account for 0.5% to 0.7% of all malignancies. They are relatively more common in children, in whom they represent 6.5% of all cancers. Although the incidence of soft tissue sarcomas has little apparent sexual or racial predilection, osteosarcoma and Ewing sarcoma have demonstrated a slight male preference (1.3:1.0). , Various sources have estimated that 1000 to 2000 new cases of osteosarcoma occur annually in the United States. , , The true incidence of most of these tumors remains somewhat speculative, largely due to the methods of reporting.
The most common malignancy of the adult musculoskeletal system is metastatic adenocarcinoma, most often from the kidney, lung, breast, or prostate. The most common primary malignancy of bone is multiple myeloma, a plasma cell malignancy usually diagnosed by the medical oncologist rather than the orthopedic surgeon. Multiple myeloma has an incidence that is approximately twice that of osteosarcoma. Excluding multiple myeloma, the most common primary malignant tumor of bone is osteosarcoma. If both benign and malignant primary lesions of the musculoskeletal system are included, cartilaginous tumors are the most common primary lesion (both benign and malignant) of the skeletal system.
Age is a highly important characteristic in the occurrence and distribution of tumors. The overall distribution of tumors by age in decades ( Figs. 12.19 and 12.20 ) demonstrates a preponderance of benign tumors in the skeletons of growing children, with 58% of all benign lesions occurring in the second and third decades. Malignant tumors of the skeleton have a peak incidence in adolescents and middle-aged adults. , , Osteosarcoma and Ewing sarcoma are the most common malignant bone tumors in adolescents. In adults osteosarcoma and chondrosarcoma occur with an incidence second only to multiple myeloma and metastatic adenocarcinoma. Osteosarcoma accounts for approximately 40% of all primary malignancies of bone, chondrosarcoma for 20%, and Ewing sarcoma for 12.5%. , ,
The incidence of tumors by anatomic location is best estimated by a review of the works of Enneking and Dahlin. The overall incidence of primary sarcomas in the shoulder is approximately 15%. , The shoulder is the third most common overall site for sarcomas, behind the hip-pelvis (first) and the distal femoral and proximal tibial areas of the knee (second). In general, one-third of all sarcomas affect the upper extremity. Most shoulder tumors (68.6% to 71.5%) develop in the proximal part of the humerus ( Fig. 12.21 ). Tumors of the shoulder girdle occur in the clavicle (6% to 10% of all cases) and in the scapula (18% to 24%). ,
Clinical features
Despite refinements and developments in the field of musculoskeletal oncology, patients with musculoskeletal malignancies generally experience a 3- to 6-month history of symptoms before an accurate diagnosis is made. The challenge for the general practitioner is to make the diagnosis based on the initial history, physical examination, and plain radiographs. Most of these lesions have a subtle onset, and their initial diagnosis requires attention to certain details and an understanding of a few hallmark signs. The patient’s initial assessment remains a crucial step to a successful evaluation and treatment plan. In 70% to 80% of cases it is possible to correctly diagnose and recognize most malignancies based on the initial history, physical examination, and plain radiographs.
Patients with an intraosseous malignancy almost always have pain. The challenge to the physician is to distinguish between the pain of malignancy and the other more common types of musculoskeletal pain. Concerning, red-flag symptoms of a malignancy are pain at night or pain at rest (see Box 12.1 ). Any patient who experiences a symptom of significant pain at night should be carefully assessed radiographically at the time of the first evaluation. As night pain can be a prominent complaint of patients with rotator cuff pathology, evaluation of shoulder symptoms may prove challenging in the presence of an underlying bone lesion.
Other pertinent findings in the history that may be helpful include a personal history of cancer in the patient or a strong family history of malignancy. Weight loss and general malaise may be significant symptoms for metastatic disease, and the physician should initiate a workup to further evaluate the patient’s general health. It is unusual, however, for a patient to have generalized symptoms as the initial symptom of a sarcoma.
Musculoskeletal neoplasms present a clinical challenge to the orthopedist in determining whether a patient has intraosseous pain or intra-articular pain. This distinction is not readily apparent in the early diagnosis of most intraosseous tumors. A careful physical examination can sometimes elicit findings consistent with joint tenderness, impingement, or weakness, suggesting some sort of intra-articular process. It is unusual for sarcomas to extend into a joint, and the presence of joint findings or symptoms is more consistent with trauma, degenerative disease, or some other nonneoplastic process. In general, intra-articular processes are exacerbated by physical activities and joint motion (see the section on physical examination). Similarly, some patients have referred pain that can lead to an erroneous diagnosis of shoulder pain that actually originated from the cervical spine.
In addition to a specific examination to evaluate patients for a possible neoplasm, all patients should have a complete general musculoskeletal examination to evaluate for joint range of motion, strength, and stability. Regional adenopathy should be routinely sought on examination and will be found with many tumors. It is usually an inflammatory phenomenon, reactive to the tumor. However, lymph node adenopathy larger than 1 cm should be evaluated further by MRI and biopsy performed before a definitive resection of the primary tumor is attempted.
All soft tissue lesions should be carefully evaluated for the four characteristics of a soft tissue sarcoma: nontender mass, firm consistency, deep or subfascial location, and a size greater than 5 cm (see Box 12.1 ). Exceptions occur, but as a general rule these guidelines are reliable in the initial evaluation of various soft tissue lesions, and if present, a biopsy should be performed prior to attempted removal.
The most reliable clinical sign for a soft tissue sarcoma is the consistency or density of the lesion. For instance, the most common soft tissue tumor in an adult is a lipoma, which may be large, deep in location, and nontender; however, its consistency usually indicates whether it is malignant. Lipomas are typically very soft, with the consistency of normal fat, whereas liposarcomas are usually firm. The ability to distinguish the consistency of a soft tissue mass can be a somewhat subtle, but important finding. Anything with a consistency more dense than normal fat should be evaluated carefully by MRI.
Routine clinical follow-up for a patient with a malignancy is important for detecting progressive disease at an early stage. After the immediate postoperative evaluation, patients with sarcomas are generally monitored at routine intervals, with most institutions having their own standardized protocol. Evaluation is typically performed with an MRI (with and without contrast) of the surgical site and a chest CT to evaluate for lung metastases.
Intraosseous lesions that appear benign on plain radiographs, or lesions that are discovered incidentally, can be monitored if the plain radiographs are well demarcated and the lesions are obviously benign. If the initial plain radiographs are equivocal, a bone scan and CT or MRI are indicated to determine whether the lesion is active and requires a biopsy or whether it can be monitored clinically. For instance, most low-grade, calcified, or cartilaginous intraosseous lesions can be safely monitored at 6-month intervals.
Radiographic and laboratory evaluation
The interpretation of the initial plain radiographs is an important step in the early diagnosis of most musculoskeletal tumors. When dealing with skeletal lesions, the orthopedist should have a system for evaluating the initial plain radiographs and formulating a differential diagnosis. Every bone lesion has a characteristic location, margin, and density that typify it radiographically. These three radiographic characteristics are important in describing a lesion’s growth rate and intrinsic density. These concepts originated in a different format from that of Jaffe, who, when evaluating radiographs, first posed the questions “What is the lesion’s density?,” “What is it doing to bone?,” “What is the bone doing to it?,” and “What is its location?” This approach helps focus attention on the lesion’s growth rate and degree of activity and thus on its malignant potential. With these three characteristics in mind, the initial plain radiographs can be interpreted with the correct diagnosis in most cases.
Location
Where is the lesion located? Is it in the epiphysis, metaphysis, or diaphysis? Are there multiple metastatic sites or one primary site of involvement? For example, an aggressive metaphyseal tumor in an adolescent is very likely to be an osteosarcoma, whereas a diaphyseal lesion is much more likely to be Ewing sarcoma. Whether the lesion is central or eccentric within the bone is also important information. Nonossifying fibroma is almost always eccentric, whereas cartilaginous lesions (enchondromas) are usually centrally located.
Margin
The margin of the lesion on plain radiographs is the best reflection of that lesion’s growth rate at the time of the initial evaluation. It refers to the interface between the lesion and surrounding normal bone. If a tumor is slow-growing it will have a distinct or sclerotic margin that demonstrates the ability of the surrounding normal bone to react to it, thus marginating, or walling off, that lesion. A sclerotic or distinct peripheral bony margin indicates a slow-growing or benign lesion and is not generally seen with malignant or aggressive benign tumors. This type of margin reflects the ability of bone to respond adequately to a slowly growing tumor.
At the other end of the spectrum is a lesion that is not well marginated and does not have a distinct rim of reactive bone around it. This pattern reflects a more rapidly growing tumor that enlarges at a rate faster than normal bone can react to it. The best examples of an aggressive lesion that infiltrates or percolates through bone are the permeative lesion of Ewing sarcoma or any intramedullary round cell tumor or small blue cell tumor of bone.
Density
The intrinsic density of a lesion within bone or soft tissue is another piece of information contributing to the initial diagnosis. Is the lesion made of bone, cartilage (calcifications), fibrous dysplasia (ground-glass density), or soft tissue (clear)? A truly cystic (or fluid-filled) lesion is most likely to be a benign or infectious lesion in bone or soft tissue, and this cystic nature may be determined clinically or demonstrated by imaging studies.
Evaluation
Complete assessment of a patient with a musculoskeletal lesion involves a careful evaluation of both the clinical and radiographic findings. The complex anatomy and the frequency of referred pain make many diagnoses in the shoulder a challenge.
Appropriate initial radiographs for evaluating most patients include a well-exposed, properly positioned film. It is essential that a well-exposed radiograph of the shoulder be obtained in all patients, especially those with persistent symptoms who may be failing conservative treatment for what is believed to be an intra-articular glenohumeral problem.
For abnormalities noted on plain radiographs, a bone scan is often helpful in determining the activity of the lesion. A whole-body bone scan can also determine the presence of other bony lesions.
A CT scan is a valuable procedure for investigating bony detail. This modality is useful for evaluating the characteristics of bony lesions and the extent of cortical involvement from intraosseous or soft tissue lesions adjacent to the cortex. CT scan of the chest (along with plain radiographs) is used to evaluate the presence of metastases, which is important for a newly diagnosed or suspected malignancy. CT scan of the chest, abdomen, and pelvis is an excellent screening tool for an unknown primary tumor when a bone lesion is suspicious for metastatic disease.
MRI provides the greatest detail of soft tissue and bone marrow involvement. It also allows a detailed analysis of a tumor or related abnormality (such as an abscess or hematoma), particularly when used with intravenous gadolinium contrast. MRI is useful for analyzing exact anatomic location and relationship to other important anatomic structures.
Possible tumor involvement of the neurovascular bundle and brachial plexus is best assessed on MRI, whereas arteriography is now reserved specifically for lesions located adjacent to a major vessel.
PET/CT has continued to gain acceptance in clinical practice, replacing bone scans in some centers as the imaging modality of choice to determine presence and location of metastatic disease. Additional research has shown that prognostic information is able to be gleaned from a change in standardized uptake values before and after treatment.
Laboratory
In general, laboratory studies for sarcomas are not of great assistance in making the initial diagnosis. The most common exception is serum alkaline phosphatase, which is often elevated in osteosarcoma or Paget disease. Urinalysis (microscopic hematuria) and the measurement of serum acid phosphatase or prostate-specific antigen levels are helpful in the evaluation of possible malignancies of the prostate or kidney. A hematocrit is useful in evaluating for anemia (which is frequently present in multiple myeloma). White blood cell count, erythrocyte sedimentation rate, and C-reactive protein are often helpful in the diagnosis of infection, although all may be normal in the types of subacute infections that are likely to be confused with neoplasms. Any patient who has multiple myeloma as the differential diagnosis should get serum calcium checked preoperatively to detect hypercalcemia. In addition, these patients should undergo a serum and urine protein electrophoresis study to evaluate their immunoglobulin profile. Lactate dehydrogenase may have prognostic value for osteosarcoma. Abnormalities in electrolytes, blood urea nitrogen, creatinine, and liver function tests may provide clues to the possibility of underlying systemic diseases, some of which can manifest with bone and soft tissue abnormalities.
Complications of tumors
One of the most significant complications of a musculoskeletal tumor is pathologic fracture; the majority of these fractures are secondary to metastatic adenocarcinoma. Approximately one-third of all diagnosed cases of breast, pulmonary, thyroid, renal, and prostatic carcinoma involve skeletal metastases. Although the most common site for metastasis is the axial skeleton, approximately 25% of all metastases are located in the shoulder girdle.
Surgery may be indicated to obtain a primary diagnosis by open biopsy or to achieve internal fixation for fracture prophylaxis. Patients with an established tumor diagnosis and lytic lesions that represent bone metastases should, in general, be treated first with chemotherapy and radiation therapy if the evidence indicates that the particular lesion is likely to respond to such treatment and is not at immediate risk of fracture. Metastatic lesions that are generally considered to be resistant to radiation therapy or chemotherapy (such as renal cell carcinoma) and lesions that have failed similar previous treatment should be treated surgically. Surgical stabilization is indicated in any patient with an impending or completed pathologic fracture who can tolerate a general anesthetic and who has a life expectancy that is projected to be longer than the estimated time to recover from surgery. Closed management, usually with a coaptation splint or Sarmiento brace, is relatively poor at relieving fracture symptoms in the humerus because of persistent rotational instability. Healing is generally unpredictable and pain relief is inadequate.
Fig. 12.22 demonstrates a pathologic fracture through the proximal humerus in a 77-year-old patient with extensive metastatic hepatocellular carcinoma. He was treated with plating and cementation of the defect. His poor medical status and limited life expectancy (several months) dictated this more conservative surgical procedure rather than the usual treatment of hemiarthroplasty. Even patients with widespread metastatic disease can benefit greatly from a careful but aggressive approach to the management of pathologic fractures and impending fractures. At last follow-up (7 months) the patient continued to have good pain control and function of the arm.
