Musculoskeletal tumors represent approximately 10% of all orthopedic diagnoses and may present a formidable clinical challenge because of their varying presentations and biologic behavior. They may come to clinical attention either through incidental discovery or because of the resulting symptoms.
This chapter places emphasis on the initial assessment and evaluation along with a review of the salient radiographic and clinical features of the more common lesions, although without an in-depth discussion of any particular lesion. Also discussed are the principles of biopsy and surgical resection, the definition and significance of surgical margins, and the classification of resections and reconstructions.
Tumors involving the shoulder girdle are distinguished by the complex functional anatomy, which poses a challenge both to tumor resection and to the preservation of satisfactory function.
Historical Review
The term sarcoma was used by Abernethy in the nineteenth century to describe tumors that have a firm and fleshy feel. Sarcoma refers to malignancies of mesenchymal or connective tissue origin. In the early period sarcomas were lesions of the extremities and were confused with osteomyelitis and other conditions. Even the most accomplished professors of surgery demonstrated little interest in recognizing sarcomas as malignancies distinct from carcinomas, and consequently little work involving classification or treatment was conducted.
An exception was Samuel W. Gross (1837-1884), a well-known surgeon, pathologist, and anatomist at the Jefferson Medical College in Philadelphia, who authored one of the first works that attempted to deal with the classification of various sarcomas, their salient features, indications for treatment, and prognosis. Gross was one of the first to identify sarcomas as a group of tumors distinctly different from carcinomas. With the discovery and development of radiographs (in 1893), various lesions of bone were beginning to attract attention. Gross was one of the first to appropriately identify sarcomas as locally invasive extremity tumors, with frequent metastases to the lungs and that infrequently demonstrated lymphatic or hepatic metastases. In half the cases these unusual lesions were associated with a history of trauma and, according to Gross, they required radical amputation or resection. In retrospect his description of these first cases is remarkable for its clinical accuracy.
The scientific and technical developments in radiology, surgery, and medicine in the early twentieth century resulted in significant advances in orthopedics, which were reflected in improvements in the care of fractures, infections, and tumors. At that time, pathologists and surgeons, such as John Ewing (New York), Ernest A. Codman (Boston), and James Bloodgood (Baltimore), became interested in various tumors of bone. The treatment of sarcomas varied greatly during those early years, but management of these unusual and difficult tumors gradually became more uniform as lesions were recognized histologically and radiographically as distinct entities. The same process of classifying sarcomas into histologic subtypes based on molecular subtype continues today.
Surgical treatment also improved with the developments in pathology and radiology. Aggressive ablative surgery was first recommended by Gross in his classic article on sarcomas and was followed by various innovative surgical techniques. Syme of Edinburgh popularized scapulectomy for malignant tumors in 1856. Boris Linberg’s classic article in 1928 regarding interscapulothoracic resections for malignancies of the shoulder joint reported on aggressive surgery for skeletal tumors with limb salvage. Since these early reports, dramatic advances in imaging, chemotherapy, pathology, and surgical technique have resulted in improved survival and have allowed more limb-sparing surgery.
In the twentieth century Dallas B. Phemister (1882-1951) of the University of Chicago was one of the first surgeons in North America to demonstrate a special interest in limb-sparing surgery, or “limb salvage” as we know it today. Phemister reviewed the American College of Surgeons’ records for osteosarcoma in 1938 and found that only four of 86 extremity cases (4.6%) were treated with a limb-sparing resection. Other reports of limb-sparing surgery at that time described variable results in terms of morbidity and mortality. The popularity of limb-salvage surgery reached its zenith in the 1970s and 1980s with an emphasis on the need for appropriate tumor resection and good functional results.
The specialty of musculoskeletal oncology has crystallized from improvements in radiographic staging studies, chemotherapy, pathology, and surgery. One of the most significant developments involved the evolution of a histologic grading system for sarcomas of bone and soft tissue that allows assessment of a patient’s prognosis according to the stage of the tumor and the proposed treatment. This is one of the only systems that appropriately reflects a patient’s prognosis based on the most significant determinants of that prognosis: the tumor’s mitotic index, histologic subtype, and histologic pleomorphism. This system has demonstrated greater predictability than the previous grading systems. New complementary DNA (cDNA) genotyping of tumors has allowed improved histologic subtyping and the ability to identify molecular defects.
Limb-sparing procedures, when properly executed, involve innovative reconstructive techniques to achieve reasonably functional results. This chapter briefly discusses the indications for, and assessment of, these procedures in terms of functional results and tumor recurrence.
Sarcomas are unusual tumors that require complex treatment. Their rarity and heterogeneity have been major reasons for their haphazard treatment in the past. The difficulties associated with assigning specific subtypes to sarcomas are evidenced by the fact that even among expert pathologists, the agreement rate for subtype is only 61% to 75%, with the level of agreement varying by subtype. Recent advances in the molecular phenotyping of these tumors and their corresponding grade and molecular imaging have allowed greater accuracy in tumor subtyping and have facilitated treatment decisions.
Anatomy
In the shoulder girdle, anatomic considerations are amplified by the proximity of the brachial plexus and major vessels of the upper extremity to the humerus, scapula, and chest wall. It has also been suggested that the shoulder is more prone to intra-articular or pericapsular invasion by sarcomas than are other joints. This may be due to the relatively small joint size or 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. These compartments include the deltoid compartment, the posterior scapular compartment (supraspinatus, infraspinatus, teres minor, and teres major), the subscapular compartment (subscapularis), the anterior pectoral compartment (pectoralis minor and major), the anterior humeral compartment (biceps and coracobrachialis), the lateral humeral compartment (brachialis), the posterior humeral compartment (medial, lateral, and long head of the triceps), and the intra-articular compartment of the glenohumeral joint ( Fig. 22-1 ). Little work has been done on the true containment or integrity of these compartments, and their boundaries are theoretical.
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 tumor 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. 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 nonneoplastic 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 as a brachial plexus nerve deficit. 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.
To function normally, the shoulder depends on a well-innervated deltoid and rotator cuff in addition to adequate glenohumeral stability. The deltoid, like most muscle compartments, has anatomic subdivisions (acromial, clavicular, and scapular), but grossly it is a well-defined muscle that is easily resectable, although extremely difficult to reconstruct functionally after proximal humeral resections for bone tumors.
Perhaps the most important anatomic consideration involved in the treatment of shoulder tumors is the anatomy of the axillary nerve and its relationship to the deltoid and surgical exposure. 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. Glenohumeral joint mechanics can be replaced by shoulder arthroplasty, whereas reconstruction of the deltoid or rotator cuff is significantly more difficult.
Staging and Classification 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 was useful in identifying general trends in diagnosis and prognosis, but it had limited significance for determining adjuvant treatment (such as chemotherapy or radiation therapy) and prognosis. Today, most staging systems attempt to describe the anatomic extent of the disease as well as the presence or absence of metastases. They allow clinicians to compare clinical information in a clear and consistent manner, and the stage of the tumor enables the physician to provide prognostic information to the patient.
Benign Tumors of Bone
One system that stages benign tumors relies on the radiographic findings and uses an Arabic numeral system (as opposed to the Roman numeral system used for staging malignant disease). Benign disease is denoted as stage 1, 2, or 3, depending on whether the tumor is latent, active, or aggressive. A latent benign lesion does not show active growth and is confined to bone, with minimal or no cortical involvement. A classic example is a nonossifying fibroma. An active lesion shows active growth but is confined within the compartment defined by the surrounding natural boundaries. There may be extensive cortical damage. Aneurysmal bone cysts and chondroblastomas are typically considered to be active lesions. An aggressive lesion has the potential to penetrate or violate natural boundaries, such as cortical bone or periosteum, and to remain locally aggressive without metastasizing. A giant cell tumor of bone is an ideal example. Campanacci has applied this staging system specifically to giant cell tumors in an effort to guide treatment.
Theoretically, only malignant tumors (by definition) can metastasize; however, a counterexample to this is presented by the ability of some histologically “benign” giant cell tumors to “metastasize” to the lung in a few cases. Other aggressive benign tumors (chondroblastoma) have also demonstrated lung metastases in a small number of cases. Stage 2 and 3 lesions account for the vast majority of cases seen in clinical practice.
Although this staging system allows clinicians to characterize typical benign bone lesions, interobserver disagreement diminishes the clinical usefulness of the system in everyday practice.
Malignant Soft Tissue and Bone Tumors
The most commonly cited staging systems for soft tissue sarcomas are the Memorial Sloan-Kettering Cancer Center (MSK) system, the American Joint Committee on Cancer Staging System (AJCC), and the system of Enneking and colleagues. The MSK and AJCC systems both take into account histologic grade, size, location, and the presence of metastases, but they are organized differently. The highest category in both of these systems denotes the presence of metastases and therefore the worst prognosis. Critics of the AJCC system point out that the system has not been subjected to multiinstitution scrutiny and is based on an inordinate number of nonextremity tumors.
One of the greatest contributions to today’s improved treatment of sarcomas has been the development of a staging system that assists 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 subsequently accepted, with modifications, by the National Institutes of Health Sarcoma Consensus Study Group as the staging system for all sarcomas. It represents a combined assessment of the histologic, or surgical, grade (G), the anatomic site of primary disease (T), and the presence or absence of metastases (M). Surgical grading is based on histologic assessment, with a lesion identified as benign (G0), low-grade malignant (G1), or high-grade malignant (G2) ( Tables 22-1 and 22-2 ). The fundamental basics of the system can be applied to both soft tissue and bone sarcomas.
| Stage | Tumor | Nodes | Metastasis | Grade | Stage Grouping |
|---|---|---|---|---|---|
| IA | T1 | N0 | M0 | G1,2 | Low grade |
| IB | T2 | N0 | M0 | G1,2 | Low grade |
| IIA | T1 | N0 | M0 | G3,4 | High grade |
| IIB | T2 | N0 | M0 | G3,4 | High grade |
| III | T3 | N0 | M0 | Any G | — |
| IVA | Any T | N0 | M1a | Any G | — |
| IVB | Any T | N1 | Any M | Any G | — |
| IVB | Any T | Any N | M1b | Any G | — |
| Stage | Tumor | Node | Metastasis | Grade | Grade | Stage Grouping |
|---|---|---|---|---|---|---|
| I | T1a | N0 | M0 | G1-2 | G1 | Low |
| I | T1b | N0 | M0 | G1-2 | G1 | Low |
| I | T2a | N0 | M0 | G1-2 | G1 | Low |
| I | T2b | N0 | M0 | G1-2 | G1 | Low |
| II | T1A | N0 | M0 | G3-4 | G2-3 | High |
| II | T1b | N0 | M0 | G3-4 | G2-3 | High |
| II | T2a | N0 | M0 | G3-4 | G2-3 | High |
| III | T2b | N0 | M0 | G3-4 | G2-3 | High |
| IV | Any T | N1 | M0 | Any G | Any G | High or low |
| IV | Any T | N0 | M1 | Any G | Any G | High or low |
The original concept of the staging system as devised by Enneking represented a departure from the staging system of the American Joint Committee for Cancer Staging and End Results, originally designed for evaluating various carcinomas. Enneking thought that the AJCC system correlated poorly with the natural history of sarcomas. He described the salient features of sarcomas with reference to their distinction from carcinomas and the significance of those features regarding staging.
In contrast to carcinomas, most sarcomas were described as having a similar natural history, one of progressive local invasion and eventual hematogenous pulmonary metastasis. The surgical treatment of sarcomas of the extremities is significantly different from that of lesions of the head and neck, retroperitoneum, trunk, and abdomen. Appropriate surgery with or without adjuvant radiation and chemotherapy remains the definitive treatment of the primary disease for most sarcomas.
The extent of disease in the Enneking system is defined by the anatomic setting. Compartmentalization, or compartmental escape, is an important characteristic of sarcomas, in contrast to previous classification systems and other tumors (carcinomas). A tumor is considered intracompartmental if it is limited by natural boundaries, such as fascia, bone, periosteum, or synovial tissue. A tumor is considered extracompartmental if it penetrates beyond its natural boundaries. It was postulated that the anatomic site (T) was the greatest factor in prognosis because it represented a composite of anatomic site, rate of growth, and delay in diagnosis. The primary extent of disease is initially limited by the natural boundaries of the anatomic compartment in which the lesion is located. Lesions that develop in poorly compartmentalized anatomic sites (such as the groin, popliteal fossa, or perivascular space) are, by the nature of that site, usually associated with a worse prognosis.
The histologic grading system proposed for sarcomas by the Enneking system was simplified to a two-grade system, of high-grade versus low-grade histology. There was no allowance for intermediate-grade histology because there was no intermediate surgical treatment. This system required the pathologist to classify all sarcomas as either high-grade or low-grade lesions, in contradiction to most classic sarcoma grading systems, which typically describe histology as high, low, or intermediate grade. Grading still remains a topic of controversy, especially for soft tissue sarcomas, which do occur as intermediate-grade lesions in certain cases. Tumor grading should not be based on the histologic type alone. The theory that some histologic diagnoses always represent high-grade lesions and a worse prognosis, regardless of their histologic grade, is not generally accepted.
In the original Enneking staging system, the prognosis for a patient with regional lymph node involvement was believed to be as poor as that for a patient with pulmonary metastasis. Therefore lymph node metastasis and pulmonary metastasis were represented by stage III disease. Malignant bone tumors rarely metastasize to lymph nodes. The same holds true for soft tissue sarcomas with a few exceptions: epithelioid sarcoma, clear cell sarcoma, synovial sarcoma, and rhabdomyosarcoma.
Simplicity is both the strength and weakness of the Enneking staging system. By emphasizing high-grade versus low-grade histology and by limiting the number of tumor stages (to IA, IB, IIA, IIB, and III), this system is simple enough to be used by a wide group of specialists and allows a variety of treatments. Thus an IA lesion is malignant, low grade, and intracompartmental. A IIA lesion is high grade and intracompartmental, and IIB is high grade and extracompartmental. Critics of the Enneking system cite the major weaknesses as being the overly simplistic nature of a two-grade system, the fact that subcutaneous sarcomas are difficult to define, and the lack of statistical validation of the system.
In the AJCC system, malignant tumors are denoted as stage I, II, III, or IV (see Table 22-1 ), depending on the histologic grade (G), primary tumor extent (T), regional nodes (N), and the presence of metastases (M). Grade IV lesions are metastatic, regardless of the grade or anatomic site of the lesion. The system is somewhat different for soft tissue (see Table 22-2 ).
The anatomic or surgical site classification (T) defines the primary lesion in relation to its position in the anatomic compartment of origin. Tumors are described as encapsulated (T0), intracompartmental (T1), or extracompartmental (T2). This designation is based on the Enneking compartmental theory, in which an anatomic compartment is described as a space or potential space defined by natural boundaries. Tumors contained within an anatomic compartment can violate the boundaries of the compartment with growth—usually a sign of an aggressive benign or malignant tumor. Active benign tumors are typically well encapsulated (T0) and intracompartmental, whereas aggressive benign lesions may be poorly encapsulated but remain intracompartmental (T1). Low-grade malignant lesions are typically intracompartmental (T1), whereas extracompartmental lesions (T2) usually represent high-grade malignancies. Extracompartmental tumors can extend from one compartment into another or from one compartment into a surrounding extrafascial plane, or they can arise within a poorly compartmentalized, extracompartmental space. Poorly compartmentalized anatomic spaces include perivascular areas, such as the subsartorial space of the common femoral artery; the popliteal fossa; the antecubital fossa; or the midhand, midfoot, axilla, or groin.
The stage of the lesion and the surgical margin achieved by a procedure are associated with a certain local recurrence rate as described in the work of Enneking (see the “ Surgical Margin ” section and Table 22-5 ). These recurrence rates are based on an extensive retrospective review of the literature and reflect the risk of local recurrence after surgical resection without the use of adjuvant treatment. A benign aggressive (stage 3) lesion treated with a wide margin has a recurrence rate of 10% or less. High-grade malignant tumors (IIB), such as a typical osteosarcoma, require a wide surgical margin that includes a surrounding cuff of normal tissue to prevent a local recurrence.
After careful anatomic staging of the tumor, the appropriate surgical procedure can be predicted by considering the grade of the lesion and the extent of involvement at the primary site (the stage). The difficulty of that resection will also become apparent from this evaluation. A patient’s prognosis and the risk of local recurrence can similarly be assessed by considering the grade of the tumor and the surgical margin achieved at the time of the surgical procedure. This articulation , or correlation of the tumor stage and the surgical margin, allows an assessment of the risk of local recurrence as a result of the procedure and margin achieved.
Thorough initial evaluation and staging, before treatment, remain the crucial ingredients for a successful outcome. A universally accepted staging classification system is important for directing patient care and for the adequate assessment of clinical results regarding disease-free status. Unfortunately, widespread intraobserver and interobserver disagreement continue to limit the clinical utility of musculoskeletal staging systems.
The staging evaluation involves an assessment by various radiographic studies to determine the precise anatomic extent of the primary disease, as well as whether regional or distant metastases have occurred. Typical staging studies include plain radiographs, along with technetium bone scan, computed tomography (CT), MRI, and other studies that better define a lesion’s location. A total body bone scan is the best study to assess the extent of the primary bone lesion and the possibility of bony metastatic disease. CT scans are excellent for visualizing cortical geography and bone involvement at the primary site on a two-dimensional plane. CT scanning of the lung is routinely performed to assess possible pulmonary metastasis, and it is a more sensitive method than plain radiographs.
MRI is indicated for evaluating soft tissue disease, intramedullary bony disease, and spinal or pelvic lesions. However, MRI does image the peripheral inflammatory reactive zone with a bright signal that might or might not contain a tumor. Similarly, the radiologist can overread soft tissue margins when interpreting malignancies, such as osteosarcoma and Ewing sarcoma because of the inability to distinguish inflammation from tumor on MRI.
Imaging is especially important for tumors in the shoulder area because of the increased complexity of proximal humeral and shoulder girdle tumors.
Although MRI is clearly the optimal imaging modality for demonstrating anatomic detail and the extent of tumor involvement in both bone and soft tissue malignancies, positron emission tomography (PET), using fluorodeoxyglucose, is the preferred dynamic modality for assessing a tumor’s degree of malignancy and response to chemotherapy ( Fig. 22-2A to C ). PET scans have the benefit of being quantifiable; that is, the technique can be validated to yield a specific numerical value, typically referred to as the standard uptake value (SUV), which gives an indication of the tumor’s degree of malignancy and activity. This assessment is valuable for the initial grading of tumors, evaluating the response to treatment, assessing heterogeneity, and assessing local recurrences. Although PET scans for sarcoma applications are relatively early in their development, there is no doubt that they are valuable for assessing tumor grade, response to treatment, and the possibility of recurrence.
Molecular Biology
The staging systems described thus far 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 ( Table 22-3 ). 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 might allow the clinician to tailor therapy based on the anticipated outcome of the disease.
| 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
Although the histologic classification of tumors has limitations in predicting the prognosis and directing treatment, it does serve a purpose in identifying tumor subtypes and their general tendencies. The most common lesions of bone, cartilage, and soft tissue are described with their general histologic, radiographic, and clinical characteristics. Clinical features, such as patient age, type of radiographic abnormality, and type of tissue involvement can, in many cases, lead to a significant and limited differential diagnosis.
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. Osteoid osteoma typically displays the classic symptom of night pain, which is relieved by salicylates. Radiographically, it is characterized by a large area of reactive bone surrounding a small, subcentimeter radiolucent nidus. On technetium bone scan, osteoid osteoma has impressive increased activity, and the central nidus can be visualized as a distinct cortical hole on CT scanning or tomography. Plain x-ray tomography can also be an effective diagnostic tool for localizing many osteoid osteomas. The differential diagnosis consists of osteoblastoma, osteomyelitis (Brodie abscess), intraosseous ganglion, stress fracture, and bone island. Histologically, this lucent nidus is a well-demarcated, small area of immature and very active osteoblastic tissue. Preoperative localization is an extremely important strategy to prevent intraoperative difficulty in locating these lesions and thus in minimizing local recurrences.
Treatment of an osteoid osteoma may be nonoperative or operative. These tumors will spontaneously involute over time and often can be successfully managed with nonsteroidal antiinflammatory drugs. In reality, however, involution can take many years and few patients are willing (or able) to tolerate such long-term use of nonsteroidal antiinflammatory drugs. CT-guided percutaneous radiofrequency ablation has been popularized as a successful, minimally invasive method of treating osteoid osteomas. Curettage with bone grafting remains the gold standard and recurrence is rare with proper removal of the tumor; however, surgical localization can prove challenging in many anatomic locations.
Osteoblastoma
Some clinicians regard osteoblastoma as a larger version of osteoid osteoma (i.e., giant osteoid osteoma), and it is typified by a large lucent area (>2 cm in diameter) of osteoblastic tissue surrounded by a thin, sclerotic reactive rim of bone. Radiographically, osteoblastoma is generally seen as a lucent lesion that has expanded the overlying cortex into a thin rim. The most common locations include the spine, femur, and tibia. As with osteoid osteoma, osteoblastoma may be difficult to localize radiographically and requires careful preoperative imaging to prevent recurrence. Osteoblastoma, unlike osteoid osteoma, also occurs in an aggressive (stage 3) form that is less well defined radiographically, has a high recurrence rate, and can have a histologic appearance that is difficult to distinguish from low-grade osteosarcoma. Technetium bone scanning and CT scans are good imaging techniques for examining both of these lesions.
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. The pseudomalignant form is typically seen as a symptomatic enlarging soft tissue mass that develops in the second decade of life, and it occurs in the shoulder in 15% of cases.
The typical radiographic appearance is an osseous density in soft tissue that demonstrates peripheral radiographic maturity or margination of the mass, separated from adjacent cortical bone by a narrow zone of uninvolved soft tissue. This characteristic histologic margination or zonation phenomenon (peripheral maturity) is a reflection of the more active (immature) osteoblastic tissue being located centrally in the lesion; this is in contrast to osteosarcoma, which demonstrates the most active histologic area peripherally. Isotope scans of myositis ossificans demonstrate high uptake peripherally that can continue for 8 to 12 weeks or until spontaneous maturation occurs. Before excision, a mature lamellar pattern should be seen radiographically; surgery before that time is associated with a high recurrence rate.
In some patients myositis ossificans may be confused with osteosarcoma or a soft tissue sarcoma, but 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). 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.
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 (largely representing secondary tumors).
Classic osteosarcoma is a high-grade, aggressive tumor that develops in metaphyseal bone, typically as a stage IIB lesion and usually with an extraosseous soft tissue component present at initial evaluation. The typical patient experiences intrinsic bone pain at night that is typically unrelated to activity ( Box 22-1 ). 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 or osteoblastic pattern, with penetration of the adjacent cortex ( Fig. 22-3A ). Differential diagnosis includes aneurysmal bone cyst, Ewing sarcoma, osteoblastoma, giant cell tumor, and metastatic disease. Osteosarcomas usually have increased activity on bone scan ( Fig. 22-3B ), and a hemorrhagic soft tissue mass is seen on CT scan ( Fig. 22-3C ) and MRI ( Fig. 22-3D ). 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 intraarterial chemotherapy ( Fig. 22-3E ). 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 basic histologic criterion for the diagnosis of osteosarcoma includes a malignant spindle cell stroma that directly produces neoplastic osteoid. The overall survival rate at 5 years for patients with osteosarcoma is approximately 70% with appropriate chemotherapy and surgery. Prognostic factors for survival include age, the stage at presentation, and the degree of histologic necrosis at resection (following neoadjuvant chemotherapy).
Benign Cartilaginous Lesions
Osteochondroma
The incidence of cartilaginous tumors in the shoulder is second only to those occurring about the pelvis. Solitary osteochondroma is the most common benign tumor of the shoulder; approximately one fourth of all osteochondromas occur in the proximal part of the humerus. Osteochondromas actually represent a developmental abnormality arising from the peripheral growth plate and are typically active, benign (stage 2) lesions during skeletal growth. The plain radiograph is usually diagnostic in demonstrating a smooth excrescence of metaphyseal cancellous bone that is confluent and continuous with normal metaphyseal bone ( Fig. 22-4 ).
Osteochondromas can appear as pedunculated, stalk-like lesions or as flat, sessile lesions. These tumors are typically diagnosed in the skeletally immature individual. Treatment of a solitary osteochondroma involves excision through the base of the lesion. In the sessile form care should be taken to excise the cartilaginous cap to prevent a recurrence. The most common complication of excision is iatrogenic injury to the adjacent growth plate or neurovascular structures at the time of excision. Adequate surgical exposure should be emphasized, especially for proximal humeral lesions, which are usually large and adjacent to the major neurovascular bundle.
Concern regarding a possible secondary chondrosarcoma can arise in adult patients with pain, an enlarging soft tissue mass, a thickened cartilaginous cap (>1 to 2 cm), or intraosseous bony erosions. Dedifferentiation is rare and associated with a poor prognosis. The risk of a secondary chondrosarcoma arising out of an osteochondroma is approximately 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, or Codman tumor, is an unusual benign cartilaginous tumor that occurs in the skeletally immature in the proximal humeral epiphysis (in 25% of cases) as a round or oval lesion containing fine calcifications surrounded by a reactive bony margin. Histologically it consists of aneurysmal tissue, chicken-wire calcifications, and immature paving-stone chondroblasts. Chondroblastoma occurs as an active, benign stage 2 lesion, although it also has a more aggressive stage 3 form. In very rare cases metastasis to the lungs has been demonstrated.
Treatment usually involves extensive intralesional curettage, which results in a large subchondral defect of the humeral head that requires bone graft to prevent subchondral and cartilaginous collapse. An adjuvant agent, such as hydrogen peroxide or cryotherapy, can help reduce local recurrence rates. The radiographic appearance of this epiphyseal lesion is usually typical ( Fig. 22-5A and B ). The differential diagnosis is dependent on age and includes other benign bone tumors in children and giant cell tumor, chondrosarcoma, or metastatic adenocarcinoma in adults.
Periosteal Chondroma
Periosteal chondroma is another benign cartilaginous lesion of the proximal end of the humerus that is usually located just proximal to the deltoid insertion of the lateral humeral shaft. It typically manifests as a minimally symptomatic or asymptomatic mass that is radiographically evident as a sessile lesion with a distinct, well-defined margin of reactive cortex underlying the radiolucent cartilaginous mass. Marginal excision results in a cortical defect of the humerus that might or might not require bone grafting. There may be recurrence following simple curettage. The differential diagnosis includes periosteal osteosarcoma, which does not have the well-defined underlying sclerotic cortex. Periosteal osteosarcoma is a more aggressive intracortical lesion that can extend into the medullary canal in a small percentage of cases.
Enchondroma
Enchondroma is a benign, central cartilaginous lesion that is most commonly found in the small tubular bones of the hand but which also occurs in the proximal end of the humerus in 10% to 15% of cases. Enchondromas are usually solitary, but multiple, typically unilateral lesions with extensive deformity that can be seen in Ollier disease (enchondromatosis) ( Fig. 22-6 ) or Maffucci syndrome (enchondromatosis with multiple hemangiomas of skin or viscera, or both).
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. 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 a sharp increase in tumor size.
It is common for enchondromas of the proximal humerus to be encountered incidentally during a work-up for shoulder pain. Unexplained shoulder pain in the presence of an enchondroma can provide a diagnostic dilemma. As enchondromas are rarely symptomatic, every effort should be made to rule out other sources of pain prior to treating the enchondroma. When an enchondroma occurs adjacent to a joint that is symptomatic for degenerative reasons, clinical assessment of bone pain related to the enchondroma may be difficult. This scenario is not uncommon, and it makes the initial evaluation of intraosseous cartilage tumors difficult. The typical radiographic appearance of a benign enchondroma is that of a central lucent lesion with a well-defined bony margin and intrinsic calcifications. Figure 22-7 shows such a lesion in a 45-year-old woman with rotator cuff symptoms and a calcified benign cartilage lesion.
Malignant Cartilaginous Lesions
Chondrosarcoma
Low-grade chondrosarcomas may be difficult to distinguish from enchondromas. Clinical and radiographic clues include pain, large size, increasing size, and full-thickness cortical penetration, particularly with periosteal reaction and/or a soft tissue mass ( Fig. 22-8A and B ). Technetium bone scans are typically moderately hot for both enchondroma and low-grade chondrosarcoma and are not helpful in distinguishing one from the other. The histologic differentiation between enchondroma and low-grade chondrosarcoma is difficult and requires radiographic correlation.
Microscopic evaluation of low grade cartilage lesions is not diagnostic in a large percentage of cases. Histologic characteristics that suggest malignancy include cellularity, pleomorphism, and evidence of mitotic activity, such as double-nucleated lacunae. These findings are subtle, and the histologic evidence for low-grade chondrosarcoma versus enchondroma is often incomplete and inconclusive. This confusion has led to the use of the term “grade one-half” chondrosarcoma to describe cartilage tumors that are histologically borderline between low-grade chondrosarcoma and benign enchondroma.
Primary chondrosarcoma is more commonly seen in the middle to later decades of life, and its incidence in the shoulder is second to that in the pelvis or hip joint. It is the most common primary bone malignancy to arise in the coracoid process. These tumors typically manifest as intraosseous lesions with poorly defined margins and faint intrinsic calcifications. The differential diagnosis 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.
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 hereditary multiple osteocartilaginous exostoses.
High-grade lesions are more invasive, have a higher metastatic rate, and usually occur in long-standing lesions as a dedifferentiated chondrosarcoma.
Low-grade chondrosarcomas may be treated surgically with extended curettage utilizing adjuvant and grafting or cementation. High-grade tumors are treated with wide surgical resection. Most chondrosarcomas are considered to be relatively resistant to chemotherapy and radiation therapy, and as a result, uncontaminated surgical resections are an essential part of their treatment.
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 an aggressive synovial-histiocytic process that defies description as inflammatory or neoplastic. Treatment for the diffuse form of the disease requires aggressive complete synovectomy. Various forms of radiation therapy have been used in some centers, with acceptable early clinical results. 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. Figure 22-9A shows a simple cyst with a healing pathologic fracture in the humerus of an 8-year-old. 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. 22-9B ). 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.
The treatments of choice for symptomatic lesions consist of pressure measurement of the cyst, aspiration, and either intraosseous steroid injection or injection of 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%. Complete repair after injection is most common in more inactive cysts with lower pressure. Varying results in more recent reports have cast some doubt on the efficacy of steroid injections for simple bone cysts, especially when associated with a venogram at the time of the injection of dye into the lesion. 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.
Recurrence or persistence of the cyst after surgical curettage and bone grafting occurs in approximately 30% of cases. 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 before initiating treatment. This can abrogate the need for internal fixation.
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, giant cell tumors, 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. 22-10 ). Treatment includes curettage plus bone grafting, which is associated with a recurrence rate of 20% to 30%. 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 congenital dysplasia of bone that often surfaces as a painful lesion secondary to pathologic fracture, microfracture, or the subtle, intrinsic, diaphyseal weakness resulting from pathologic bone. The typical plain radiograph demonstrates a ground-glass density with cortical thickening. Figure 22-11A and B show 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. 22-11A ) that had persisted despite bracing. When associated with symptoms or 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 dysplastic bone. There may be a role for medical therapy, namely bisphosphonates, in alleviating pain; however, randomized clinical studies are lacking. Histologically, fibrous dysplasia demonstrates a furnace of dysplastic bone activity with similar, impressive increased activity on bone scan. Immature islands of bone are seen in a fibrous stroma without osteoblastic rimming.
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. 22-12 ). 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
Giant cell tumor (GCT) of bone is a benign, locally aggressive lesion. Although classically considered a benign tumor, in less than 3% of 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.
GCT is typically a Campanacci stage 2 active lesion (in 60% of cases) but is also found as a more aggressive stage 3 tumor in 20% of cases. Treatment of GCT includes curettage with margin extension. The local recurrence rate after curettage alone is 20% to 30% for active lesions versus 5% after extended margin curettage.
Margin extension may be achieved mechanically (through burring), or with the use of an adjuvant, such as phenol, bone cement (cementation), or liquid nitrogen (cryotherapy).
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 can suggest the diagnosis of myeloma before biopsy in a patient with a solitary lesion or unknown diagnosis. The overall prognosis is poor; however, newer treatments involving aggressive chemotherapy and plasma cell antibodies offer hope for the future. The development of new classes of bisphosphonates has had a positive effect in reducing skeletal events and bone pain.
Figure 22-13A shows the plain radiograph of a 42-year-old man in apparent good health but experiencing shoulder pain. Coronal ( Fig. 22-13B ) and transverse ( Fig. 22-13C ) 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.
Figure 22-14A shows such a permeative lesion in the humeral diaphysis of a 16-year-old with a typically hot bone scan ( Fig. 22-14B ) and an associated soft tissue mass ( Fig. 22-14C ). 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 or osteoporosis circumscripta) 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, increased but purposeful trabeculation, 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, facture, 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. Zoledronic acid (approved by the FDA in 2007) is the most recent bisphosphonate to be used for treatment of this condition.
Sarcoma arising out of Paget disease is characterized by a history of progressive pain and a bony lytic lesion with a soft tissue mass ( Fig. 22-15A and B ). 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 process of Paget disease and the difficulty of assessing the extent of sarcomatous changes.
Figure 22-16A and B present early and late radiographs of Paget disease in the proximal end of the humerus. The lytic lesion, combined with a history of increasing arm pain, served notice of an early secondary osteosarcoma that showed up 3 months later with a more impressive lytic lesion in the proximal part of the humerus ( Fig. 22-16C ). Paget disease affected the full humerus, and the bone scan ( Fig. 22-16D ) was of little help in demarcating bony margins or osseous involvement by this secondary, or pagetoid, osteosarcoma. MRI and CT scans again demonstrate the soft tissue and bony extent of disease in the proximal part of the humerus ( Fig. 22-16E and 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 often appear in the anterior deltoid as a large, soft, and nontender intramuscular mass. A few lipomas are tender or firm, and a few have an equivocal history of a change in size. On MRI or CT scan, a benign lipoma usually has a uniform, fatty consistency ( Fig. 22-17 ). Clinically, a liposarcoma has a firmer, denser consistency than that of a lipoma. If a lipoma feels very dense or firm clinically, MRI should be performed for further evaluation. If MRI demonstrates areas of distinctly different density, a biopsy should precede marginal excision to exclude the possibility of a liposarcoma.
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. If they are intimately involved with a major vessel, they should also be evaluated with an arteriogram. 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. Many of these lesions recur locally because of inadequate preoperative staging, underestimation of their potential for local recurrence, and an inadequate surgical margin. Considerable confusion and contradiction is found in the literature regarding the natural history of fibromatosis. Spontaneous regression as described in some publications is unusual except in some congenital forms, and the natural history of lesions in adolescents is progressive growth and recurrence after marginal resection. These lesions rarely demonstrate pulmonary metastasis, and chemotherapy is not usually efficacious, although indications for chemotherapy do exist.
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 aggressive lesion. Preoperative and postoperative MRI studies are mandatory in these patients to fully assess the soft tissue involvement. Bone scans should also be carried out if there is any doubt about secondary bone involvement.
Soft Tissue Sarcomas
Soft tissue sarcomas occur in the upper extremity in approximately one third of all cases. Delays in diagnosis and referral to a specialist 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 ( Box 22-1 ). Adequate staging before biopsy is important for soft tissue sarcomas, just as it is for bone sarcomas ( Fig. 22-18 ). In these lesions open biopsy is often, but not always, preferred to needle biopsy for diagnosing both the histologic type and grade of the lesion.
The most common soft tissue sarcoma in adults is malignant fibrous histiocytoma (currently termed myxofibrosarcoma), which occurs most often in older adults (aged 50 to 70 years). Liposarcoma 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.
Soft tumor sarcomas arising out of a peripheral nerve (peripheral nerve sheath tumors) may occur adjacent to the brachial plexus and present surgical treatment challenges with respect to the brachial plexus, brachial vessels, and the preservation of extremity function. 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. Soft tissue sarcomas of intermediate-grade histology are problematic to treat because of their variable prognosis and response to chemotherapy. There has been some early experience with flow cytometry in identifying more active (aneuploid) tumors, and this knowledge may prove helpful in the future in subclassifying or grading intermediate-grade tumors. Synovial sarcoma, epithelioid sarcoma, and rhabdomyosarcoma are characterized as soft tissue sarcomas with a high incidence (10% to 20%) of regional lymph node metastasis and a poor prognosis, but survival is generally recognized as being closely related to an individual tumor’s histologic grade and size.
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).
The American Cancer Society estimated that in 2015 there would be 11,930 new soft tissue cancers and 2,970 new cancers involving the bone and joints in the United States annually. These were expected to cause an estimated 4,870 deaths from soft tissue cancers and 1,490 from cancers with a bone or joint origin. 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. 22-19 and 22-20 ) 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%.
