BACKGROUND

 

 

An understanding of the basic biology and pathology of bone and soft tissue tumors is essential for appropriate planning of their treatment.

 

This chapter reviews the unique biologic behavior of soft tissue and bone sarcomas, which provides the basis for their staging and resection and the use of appropriate adjuvant treatment modalities.

 

A detailed description of the clinical, radiographic, and pathologic characteristics for the most common sarcomas is presented.

 

EPIDEMIOLOGY

 

Soft tissue and bone sarcomas are a rare and heterogeneous group of tumors. These neoplasms represent less than 0.2% of all adult and 15% of pediatric malignancies.

 

As of 2013, the annual incidence in the United States, which remains relatively constant, is approximately

11,400 soft tissue sarcomas (STS) and 3010 new bone sarcomas.1 About 4390 deaths from STS and 1440 deaths from bone cancers are expected in 2013.

 

In adults, over 40% of primary bone cancers are chondrosarcomas.

 

This is followed by osteosarcomas (OSs) (28%), chordomas (10%), Ewing tumors (8%), and malignant fibrous histiocytoma (MFH)/fibrosarcomas (4%). The remainder of cases are several rare types of bone cancers.

 

In children and teenagers (those younger than 20 years), OS (56%) and Ewing tumors (34%) are much more common than chondrosarcoma (6%).

 

In the United States, the 5-year survival rates for all bone sarcomas is about 70%. OS and Ewing sarcoma were comparable among 15 to 29 years old, about 60% for the most recent era. The U.S. bone cancer mortality was highest for males and females 15 to 19 years of age.

 

The 5-year survival rates for localized STS is 83% in 2013. This drops to 16% for systemic disease.2

 

RISK FACTORS

 

Risk factors for soft tissue and bone sarcomas include previous radiation therapy, exposure to chemicals (eg, vinyl chloride, arsenic); immunodeficiency; prior injury (scars, burns); chronic tissue irritation (foreign body implants, lymphedema, chronic infection); neurofibromatosis; Paget disease; bone infarcts; and genetic cancer syndromes (eg, hereditary retinoblastoma, Li-Fraumeni syndrome, Gardner syndrome, Rothmund-Thomson syndrome, Werner syndrome, Bloom syndrome), Maffucci syndrome, Ollier disease, multiple osteochondromatosis, and hereditary multiple exostoses. In most patients, however, no specific etiology can be identified.

 

PATHOPHYSIOLOGY AND BIOLOGIC BEHAVIOR

 

Sarcomas originate primarily from elements of the mesodermal embryonic layer.

 

STS are classified according to the adult tissue that they resemble.

 

 

Bone sarcomas usually are classified according to the type of matrix production: Osteoid-producing sarcomas are classified as OSs, and chondroid-producing sarcomas are classified as chondrosarcomas.

 

Tumors arising in bone and soft tissues have characteristic patterns of biologic behavior because of their common mesenchymal origin and anatomic environment. Those unique patterns form the basis of the staging system and current treatment strategies.

 

 

Histologically, sarcomas are graded as low, intermediate, or high grade. The grade is based on tumor morphology, extent of pleomorphism, atypia, mitosis, matrix production, and necrosis, with the two main factors being mitotic count and spontaneous tumor necrosis.

 

Tumor grade represents the tumor's biologic aggressiveness and correlates with the likelihood of metastases. Low-grade lesions rarely metastasize. High-grade lesions metastasize in over 20% of patients.

 

Sarcomas form a solid mass that grows centrifugally, with the periphery of the lesion being the least mature.

 

 

In contradistinction to the true capsule that surrounds benign lesions, which is composed of compressed normal cells, sarcomas usually are enclosed by a reactive zone or pseudocapsule. This pseudocapsule consists of compressed tumor cells and a fibrovascular zone of reactive tissue with a variable inflammatory component that interacts with the surrounding normal tissues.

 

The thickness of the reactive zone varies according to the histogenic type and grade of malignancy. High-grade sarcomas have a poorly defined reactive zone that may be locally invaded by the tumor (FIG 1A).

 

Tumor foci within the reactive zone are called satellite lesions.

 

High grade, and occasionally low grade, may break through the pseudocapsule to form metastases, termed skip metastases, within the same anatomic compartment in which the lesion is located. By definition, these are locoregional micrometastases that have not passed through the circulation (FIG 1B).

 

 

This phenomenon may be responsible for local recurrences that develop in spite of apparently negative margins after a resection.

 

Although low-grade sarcomas regularly interdigitate into the reactive zone, they rarely form tumor skip nodules beyond that area (FIG 1C,D).

 

 

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FIG 1 • A. Gross specimen. A pseudocapsule of a high-grade STS (arrowheads) composed of compressed tumor cells and a fibrovascular zone of reactive inflammatory response. B. Pathology specimen. Multiple satellite nodules (arrows) associated with a high-grade MFH. Note the normal intervening tissue. C. Biologic behavior of bone and STS. Unique features are formation of reactive zone, intracompartmental growth, and, rarely, the presence of skip metastases. Skip nodules are tumor foci not in continuity with the main tumor mass that form outside the pseudocapsule. “Satellite” nodules, by contrast, form within the pseudocapsule. D. Gross specimen. Skip metastases (arrows) from an OS of the distal femur. This finding is documented preoperatively in less than 5% of patients. E. Sagittal section of a high-grade OS of the distal femur. The growth plate, although not invaded by the tumor in this case, is not considered an anatomic barrier to tumor extension, probably because of the numerous vascular channels that pass through the growth plate to the epiphysis.

However, the articular cartilage is an anatomic barrier to tumor extension and very rarely is directly violated by a tumor. F. Coronal section of a high-grade OS of the distal femur. Although gross involvement of the epiphysis and medial cortical breakthrough and soft tissue extension are evident, the articular cartilage is intact. This phenomenon allows intra-articular resection of high-grade sarcomas of the distal femur in most cases. Thick fascial planes are barriers to tumor extension. G. Axial MRI, showing a high-grade

leiomyosarcoma of the vastus lateralis and vastus intermedius muscles. The tumor does not penetrate, looking in a clockwise direction, the lateral intermuscular septum, the adductor compartment, and the aponeuroses of the sartorius and rectus femoris muscles. (Courtesy of Martin M. Malawer.)

 

 

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Sarcomas respect anatomic borders. Local anatomy influences tumor growth by setting natural barriers to extension. In general, sarcomas take the path of least resistance and initially grow within the anatomic compartment in which they arose. It is only at a later stage that the walls of the compartment are violated

(either the cortex of a bone or aponeurosis of a muscle), at which time, the tumor breaks into a surrounding compartment.

 

 

Typical anatomic barriers are articular cartilage, cortical bone, and fascial borders. The growth plate is not considered an anatomic barrier because it has numerous vascular channels that run through it to the epiphysis (FIG 1E-G).

 

Sarcomas are defined as intracompartmental if they are encased within an anatomic compartment.

 

Extracompartmental tumors are those that grow out through the compartment barrier or tumors that have arisen in extracompartmental spaces (space tumors), that is, popliteal fossa, groin, sartorial canal, axilla, and antecubital fossa (FIG 2A,B).

 

Most bone sarcomas are bicompartmental at the time of presentation; they destroy the overlying cortex and extend directly into the adjacent soft tissues through the Haversian system and Volkmann canals of the cortical bone.

 

 

 

 

FIG 2 • Extracompartmental extension. Ewing sarcoma of the distal two-thirds of the femur (A) and OS of the proximal tibia (B). Note the extraosseous component of the tumor. Most high-grade bone sarcomas are

bicompartmental at the time of presentation (ie, they involve the bone of origin as well as the adjacent soft tissues). Tumors at that extent are staged as IIB. C. Plain radiograph of the proximal femur revealed direct invasion through the cortical bone with a pathologic fracture of the lesser trochanter (arrowheads). D. Axial MRI, showing metastatic bladder carcinoma to the posterior thigh. E. In surgery, exploration of the sciatic nerve revealed direct tumor involvement with extension under the epineural sheath. (Courtesy of Martin M. Malawer.)

 

 

Carcinomas, which typically present in the extremities as metastatic disease, directly invade the surrounding tissues, irrespective of compartmental borders (FIG 2C-E).

 

Joint involvement in sarcoma is uncommon because direct tumor extension through the articular cartilage is rare. Mechanisms of joint involvement in sarcoma are as follows:

 

 

 

Pathologic fracture with seeding of the joint cavity Pericapsular extension

 

Structures that pass through the joint (eg, the cruciate ligaments) may act as a conduit for tumor growth (FIG 3).

 

 

Transcapsular skip nodules: demonstrated in 1% of all OSs Direct articular extension

Metastatic Bone and Soft Tissue Sarcoma

 

Unlike carcinomas, bone and STS disseminate almost exclusively through the blood. Hematogenous spread of extremity sarcomas is commonly manifested by pulmonary involvement and less commonly by bony involvement. Abdominal and pelvic STS, on the other hand, typically metastasize to the liver and lungs.

 

Low-grade STS have a low (under 15%) rate of subsequent metastasis, whereas high-grade lesions have a significantly higher (over 20%) rate of metastasis.

 

 

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FIG 3 • A. The five major mechanisms of joint involvement by a bone sarcoma. The most common mechanisms are pathologic fracture and pericapsular extension. B. Pericapsular extension of an OS of the proximal humerus (arrowheads). C. Extension of an OS of the distal femur to the knee joint along the cruciate ligaments (arrow points to tumor); the articular cartilage is intact. Knee joint extension of a high-grade sarcoma of the distal femur is a rare event, necessitating extra-articular resection (ie, en bloc resection of the distal femur, knee joint, and a component of the proximal tibia). (Courtesy of Martin M. Malawer.)

 

Metastases from sarcomas to regional lymph nodes are uncommon; the condition is observed in only 13% of patients with STS and 7% of those with bone sarcomas at initial presentation. The prognosis is somewhat better than to that of distant metastasis (FIG 4).

 

 

Most patients with high-grade primary bone sarcomas, unlike STS, have distant micrometastases at presentation; an estimated 80% of patients with OS have micrometastatic lung disease at the time of diagnosis. For this reason, in most cases, cure of a high-grade primary bone sarcoma can be achieved only with systemic chemotherapy and surgery.

 

 

 

 

FIG 4 • Metastatic sarcomas. Lateral plain radiograph of the lumbar spine, showing metastatic high-grade OS to the body of L3 vertebra (arrow). (Courtesy of Martin M. Malawer.)

 

 

As mentioned, high-grade STS have a lower metastatic potential. Because of that difference in metastatic capability, the role of chemotherapy in the treatment of STS and its impact on survival are still matters of some controversy.

PROGNOSTIC FACTORS

 

Prognostic factors for bone sarcomas include grade, size, extension of tumor beyond the bone cortex, regional and metastatic disease, and response of the tumor to chemotherapy (necrosis rate).

 

Prognostic factors for STS include grade, tumor size, depth, age, margin status, location (proximal vs. distal), histologic subtypes, and metastatic disease.

 

Staging

 

Staging is the process of classifying a tumor, especially a malignant tumor, with respect to its degree of differentiation, as well its local and distant extent, to plan the treatment and estimate the prognosis. Staging of a musculoskeletal tumor is based on the findings of the physical examination and the results of imaging studies. Biopsy and histopathologic evaluation are essential components of staging but should always be the final ste An important variable in any staging system for musculoskeletal tumors, unlike a staging system for carcinomas, is the grade of the tumor.

 

The system most commonly used for the staging of STS is the one developed by the American Joint

Committee on Cancer (Table 1).3 It is based primarily on the Memorial Sloan Kettering staging system and does not apply to rhabdomyosarcoma. Critics of this system point out that it is based largely on single-institution studies that were not subjected to multi-institutional tests of validity. The Musculoskeletal Tumor

 

Society adopted staging systems that originally were described by Enneking et al4,5,6 for malignant soft tissue and bone tumors (Table 2), and the American Joint Committee

 

Table 1 System of the American Joint Committee on Cancer for the Staging of Soft Tissue Sarcomas

TX

Primary tumor cannot be assessed

T0

No evidence of primary tumor

T1

Tumor ≤5 cm in greatest dimension

(Size should be regarded as a continuous variable, and the measurement should be provided)

T1a

Superficial tumora

T1b

Deep tumora

T2

Tumor >5 cm in greatest dimensiona

T2a

Primary Tumor (T)

 

on Cancer developed, with a few changes, a staging system for malignant bone tumors (Tables 3 and 4).

5

 

6

 

 

 

Superficial tumora

T2b Deep tumor

 

 

Regional Lymph Nodes (N)

 

 

 

 

NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis

N1b Regional lymph node metastasis

 

 

Distant Metastasis (M)

 

 

M0 No distant metastasis

 

 

M1 Distant metastasis

 

 

Anatomic Stage/Prognostic Groups

 

 

 

Stage IA

T1a N0 M0 G1, GX

 

 

T1b N0 M0 G1, GX

 

 

 

Stage IB

T2a N0 M0 G1, GX

 

 

T2b N0 M0 G1, GX

 

 

 

Stage IIA

T1a N0 M0 G2, G3

 

 

T1b N0 M0 G2, G3

 

 

 

Stage IIB

T2a N0 M0 G2

 

 

T2b N0 M0 G2

 

 

 

Stage III T2a, T2b N0 M0 G3

 

 

Any T N1 M0 Any G

 

 

 

Stage IV

Any T Any N M1 Any G

 

 

 

aSuperficial tumor is located exclusively above the superficial fascia without invasion of the fascia; deep tumor is located either exclusively beneath the superficial fascia, superficial to the fascia with

 

 

invasion of or through the fascia, or both superficial yet beneath the fascia.

 

bPresence of positive nodes (N1) in M0 tumors is considered stage III.

Reprinted with permission from American Joint Committee on Cancer. Soft tissue sarcoma. In: Edge SB, Byrd DR, Compton CC, et al, eds. AJCC Cancer Staging Manual, ed 7. New York: Springer, 2010:291-298.

 

 

Stage

Grade

Sitea

Metastasis

 

IA	Low grade	T1—intracompartmental	M0 (none)
IB	Low grade	T2—extracompartmental	M0 (none)
IIA	High grade	T1—intracompartmental	M0 (none)
IIB	High grade	T2—extracompartmental	M0 (none)
III	Metastatic	T1—intracompartmental	M1 (regional or distant)
III	Metastatic	T2—extracompartmental	M1 (regional or distant)

 

Stage

Tumor Grade

Tumor Size

 

IA	Low	<8 cm
IB	Low	>8 cm
IIA	High	<8 cm
IIB	High	>8 cm

Table 2 System of Enneking et al for Staging of Bone Sarcomas

aIntracompartmental, bone tumors are confined within the cortex of the bone; extracompartmental,

bone tumors extend beyond the bone cortex.

From Enneking WF. A system of staging musculoskeletal neoplasms. Clin Orthop Relat Res 1986;

(204):9-24.

 

 

Table 3 System of the American Joint Committee on Cancer for the Staging of Bone Sarcomas

 

III

Any tumor grade, skip metastasesa

IV

Any tumor grade, any tumor size, distant metastases

aSkip metastases: discontinuous tumors in the primary bone site.

Reprinted with permission from American Joint Committee on Cancer. Bone. In: Edge SB, Byrd DR,

Compton CC, et al, eds. AJCC Cancer Staging Manual, ed 7. New York: Springer, 2010:281-290.

 

 

Enneking's classical staging system is based on three factors: histologic grade (G), site (T), and the presence or absence of metastases (M). The anatomic site (T) may be either intracompartmental (A) or extracompartmental (B). This information is obtained preoperatively on the basis of the data gained from the various imaging modalities. A tumor is classified as intracompartmental if it is bounded by natural barriers to extension, such as bone, fascia, synovial tissue, periosteum, or cartilage. An extracompartmental tumor may be either a tumor that has violated the borders of the compartment from which it originated, or a tumor that has originated and remained in the extracompartmental space. A tumor is assigned to stage III (M1) if a metastasis is present at a distant site or in a regional lymph node.

Table 4 Enneking's System for the Staging of Benign Bone Tumors

Stage Definition

Biologic Behavior

Soft Tissue

Tumor

Bone Tumor

1

Latent

Remains static or heals spontaneously

Lipoma

Nonossifying

fibroma

2

Active

Progressive growth, limited by natural

barriers

Angiolipoma

Aneurysmal

bone cyst

3

Aggressive Progressive growth, invasive, not

limited by natural barriers

Aggressive

fibromatosis

Giant cell

tumor

 

 

Enneking's classification system is based on clinical data from an era in which chemotherapy was not given preoperatively and compartmental resections were much more common. Therefore, there was a clear correlation between the extent of the tumor at presentation, its relation to the boundaries of the compartment in which it is located, and the extent of surgery. A close correlation also was found between surgical stage of bone sarcoma and patient survival (FIG 5). Since that time, the use of neoadjuvant chemotherapy has been shown to decrease tumor size and facilitate limb-sparing surgery as well as reduce the local recurrence rate. As a result, compartmental resections have become rare. Nonetheless, Enneking's classification is based on the biologic behavior of soft tissue and bone sarcomas, and its underlying concept is as relevant today as it was in the early 1980s (see Tables 1,2,3 and 4).

 

Typical Example

From Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res 1980;153:106-120.

 

 

 

 

 

FIG 5 • Survival by Enneking's surgical stage of 219 patients with primary bone sarcoma. (Courtesy of Martin M. Malawer.)

 

 

Approximate survival rates by stage for extremity STS are 90% for stage I, 70% for stage II, and 50% for stage III.

 

Staging Benign Bone Tumors

 

Enneking also described a staging system for benign bone tumors, which remains the one that is most commonly used (see Table 4). That system is based on the biologic behavior of these tumors as suggested by their clinical manifestation and radiologic findings. Benign bone tumors grow in a centrifugal fashion, as do their malignant counterparts, and a rim of reactive bone typically is formed as a response of the host bone to the tumor. The extent of that reactive rim reflects the rate at which the tumor is growing: It usually is thick and well-defined around slowly growing tumors and barely detectable around fast-growing, aggressive tumors.

 

Latent benign bone tumors are classified as stage 1. Such tumors usually are asymptomatic and commonly are discovered as an incidental radiographic finding. Their natural history is

 

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of slow growth, and in most cases, they heal spontaneously. These lesions never become malignant and

usually heal following simple curettage. Examples include fibrous cortical defects and nonossifying fibromas (NOF) (FIG 6A).

 

 

 

FIG 6 • A. NOF of the distal femur (arrow). As in most cases of NOF, the lesion was asymptomatic, and the plain radiographs were ordered because of a trauma to the knee. Aneurysmal bone cyst of the distal tibia as seen by plain radiographs: anteroposterior (AP) (B) and lateral (C) views. Plain radiographs of benign GCT of the proximal tibia: AP (D) and lateral (E) views. The tumor had been neglected for 18 months and necessitated proximal tibia resection and reconstruction with endoprosthesis. (Courtesy of Martin M. Malawer.)

 

 

Active benign bone tumors are classified as stage 2 lesions. These tumors grow progressively but do not violate natural barriers. Associated symptoms may occur. Curettage and burr drilling are curative in most cases (FIG 6B-E).

 

Aggressive benign bone tumors (stage 3) may cause destruction of surrounding bone and usually break through the cortex into the surrounding soft tissues. Local control can be achieved only by curettage and meticulous burr drilling with a local adjuvant such as liquid nitrogen, argon beam laser, or phenol. Wide resection of the lesion with a margin of normal tissue (FIG 6D,E) is another option.

EVALUATION OF THE PATIENT WITH A MUSCULOSKELETAL LESION

Presenting Symptoms

 

Bone sarcomas typically present with pain that starts out as intermittent and progresses to a constant pain. Night pain often is a component. Pain typically is deep-seated and dull and may resemble that of a toothache. Patients with high-grade tumors present with a history of several months of pain. Patients with low-grade tumors, by contrast, present with a history of mild pain, typically lasting more than half a year. Local soft tissue swelling is common.

 

STS can arise anywhere in the body, but the lower extremities are the most common site. The incidence is as follows:

 

 

Lower extremities: 46%

 

Trunk: 19%

 

Upper extremities: 13%

 

 

 

Retroperitoneum: 12% Head and neck: 9% Other locations: 1%

 

The presenting symptoms and signs of STS are nonspecific. These lesions commonly present as a painless, slow-growing mass, but in 20% of patients, they present as a painful, rapidly growing mass.

 

Physical Examination

 

Patients with suspected musculoskeletal tumors should be examined thoroughly. The affected site is inspected for soft tissue mass or swelling, overlying skin changes, lymphadenopathy, neurologic deficit, and vascular deficiency.

 

Imaging and Other Staging Studies

Plain Radiography

 

Plain radiographs remain key in imaging bone tumors. Based on medical history, physical examination, and plain

 

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radiographs, bone tumors can be diagnosed accurately in over 80% of cases.

 

Because of the fine trabecular detail revealed by plain radiographs, bone lesions of the extremities can be

detected at an earlier stage; lesions of the spine and pelvis, however, are not diagnosed until a large volume of bone has been destroyed.

 

Plain radiographs can show the location of the tumor in the bone, cortical destruction and thickening, periosteal response to the tumor (eg, Codman triangle, sunburst), type of matrix produced by the tumor (osteoid, chondroid, fibrous), and soft tissue calcifications.

 

Computed Tomography

 

Computed tomography (CT) is the imaging modality of choice to evaluate the extent of bone destruction. CT should be performed on a helical scanner that enables improved two-dimensional images and three-dimensional (3-D) reconstruction capability. The field of view should be small enough to allow adequate

resolution, particularly of the lesion and the adjacent neurovascular bundle and muscle groups. A slice thickness of 1 mm or less through the tumor enables accurate 3-D reconstructions. Intravenous contrast dye should be employed to demonstrate the anatomic relation between the tumor and arterial vessels and to enhance soft tissue tumors, unless there is a clear contraindication for its use.

 

 

 

 

FIG 7 • A. 3-D CT angiogram. This is a new technique for evaluating the relation between bone tumors and the adjacent arteries. This radiograph demonstrates the relationship of the popliteal artery and trifurcation to a posterior tibial OS. Note the relation of the vessels to the tumor. B. CT scan showing lung metastases. C,D. Primary lymphoma of the distal femur. Plain radiographs suggest cortical integrity. This is confirmed by axial CT (E) and T2-weighted MRI (F), which demonstrates the intraosseous extent of the tumor. (continued)

 

 

 

FIG 7 • (continued) G. MRI of a large thigh, high-grade (stage IIB) STS. The thigh is the most common site for extremity STS. MRI evaluation is the most useful study in determining the extent of STS. H. Bone scan of a proximal humeral (right) OS. I. Limb-sparing surgery for a proximal humeral OS. The defect was reconstructed by a modular segmental prosthesis. J. Extensive GCT of the proximal tibia. Angiography performed prior to a proximal tibia resection documented an absent peroneal artery. A successful effort was made to preserve the anterior tibial artery during the resection; otherwise, the leg would have been dependent on a single vessel. K. Angiogram of a distal femoral (diaphyseal) OS following induction chemotherapy. Note that the tumor is avascular. The decrease of tumor vascularity is an extremely reliable finding in predicting tumor necrosis. L. Gross specimen of a diaphyseal OS following resection and induction chemotherapy. There was 100% tumor necrosis. M. Axillary venogram showing venous occlusion. Venography is especially useful in evaluating tumors of the pelvis and shoulder girdle. (C-F,J: Courtesy of Martin M. Malawer.)

 

 

A 3-D CT reconstruction with intravenous contrast accurately demonstrates blood vessels that are likely to be distorted or, less commonly, incorporated directly into the tumor mass. This information helps the surgeon plan the anatomic approach and gauge the likelihood that a major blood vessel has to be resected en bloc with the

tumor (FIG 7A).

 

Chest CT is the modality of choice when evaluating the patient for metastatic lung disease for both preoperative staging and postoperative follow-up (FIG 7B).

 

 

 

 

Magnetic Resonance Imaging

 

Magnetic resonance imaging (MRI) has been proven to be superior to CT in the evaluation of the intramedullary and extraosseous soft tissue extent of bone tumors (FIG 7C-F) and STS.

9 10

 

Anatomic location and relation of the tumor can be defined accurately because the signal intensity of a tumor is assessed by comparing it with that of the adjacent soft tissues, specifically skeletal muscle and subcutaneous fat. MRI also make it possible to view a lesion in all three planes (ie, axial, sagittal, and coronal).

 

Contrast-enhanced MRI is useful in evaluating the relation between a tumor and the adjacent blood vessels and in characterizing cystic lesions. The anatomic relation between the tumor and peripheral nerves may be assessed. The presence of orthopaedic hardware or surgical clips is not a contraindication to the performance of MRI; however, if a lesion is immediately adjacent to the location of the hardware, the local field may be distorted.

 

MRI can accurately diagnose a variety of soft tissue tumors, including lipomas, liposarcomas, synovial cysts, pigmented villonodular synovitis, hemangiomas, and fibromatoses. Hematomas often have a characteristic appearance on MRI; however, high-grade sarcomas that have undergone significant intratumoral hemorrhage may resemble hematomas (FIG 7G). For this reason, the diagnosis of a simple hematoma should be made cautiously, and, once it is made, close clinical monitoring must be made until the condition has been resolved. The general guidelines regarding narrowing of the field and recommended number of slices per tumor are similar to those for CT.

 

MRI allows accurate evaluation of the medullary extent of bone tumors to determine the level of bone resection with safe but narrow margins.

 

Bone Scan

 

Bone scan currently is used to determine the presence of metastatic and polyostotic bone disease and the involvement of a bone by an adjacent STS. This modality is more sensitive than plain radiographs for identifying bone lesions (FIG 7H,I).

 

The appearance of a bone lesion in the flow and pool phases of a three-phase bone scan reflects its biologic activity and may be helpful in differentiating between benign and malignant lesions. This feature is known as tumor blush. Malignant tumors show uptake in the late flow phase. Response to chemotherapy can be evaluated by comparing the tumor blush before and after neoadjuvant chemotherapy.

 

Other Studies

 

Angiography

 

 

Angiography is useful in demonstrating arterial displacement and occlusion, which are common in tumors that have a large extraosseous component. It also can detect vascular anomalies (FIG 7J) and establish patency of collateral vessels. Proximal femur resection, for example, often necessitates ligation of the profundus femoral artery (PFA). A patent superficial femoral artery (SFA) must be documented by

angiography prior to surgery; otherwise, the extremity will suffer severe ischemia following ligation of the PFA. CT angiography is an emerging modality that will likely replace angiography in preoperative tumor evaluation.

 

Preoperative embolization may be useful in preparing for resection of metastatic vascular carcinomas if an intralesional procedure is anticipated. Metastatic hypernephroma is an extreme example of a vascular lesion that may bleed extensively and cause exsanguination without prior embolization.

 

Serial angiographs may demonstrate reduced tumor vascularity as a result of chemotherapy treatment. Such a reduction has been shown to indicate a good response to preoperative chemotherapy (FIG 7K-L).

 

Venography

 

 

Contrast venography demonstrates partial occlusion or complete obliteration of major veins as a result of direct tumor invasion or indirect compression by the tumor mass. Venography is used for direct assessment of deep vein thrombosis.

 

Venography also can indirectly assess tumor invasion into major nerves that lie in close proximity. Axillary tumors often are found to have invaded the brachial plexus when venography shows axillary vein occlusion (FIG 7M).

 

Positron emission tomography (PET) CT

 

 

PET is a functional diagnostic imaging technique that provides very different information from that obtainable with other imaging modalities.

 

The most widely used radiotracer is F-18 fluoro-2-deoxy-D-glucose (FDG), which is an analog of glucose. The FDG uptake in cells is directly proportional to glucose metabolism, which is increased many times in malignant cells. FDG-PET now is the standard of care in initial staging, monitoring the response to therapy, and management of various cancers (eg, breast cancer, lung cancer, lymphoma).

 

The introduction of combined PET-CT scanners, which provide not only functional but also structural information leading to a detection of subcentimeter lesions, has made this technique useful in the early detection of the disease process and in decreasing false-positive lesions. The FDG uptake is measured in standardized uptake value units, quantifying uptake and thereby differentiating malignant disease from other possible causes such as inflammatory or infectious processes.

 

FIG 8 summarizes the use of the various imaging modalities in the staging process of a primary bone sarcoma.

 

Biopsy

 

The concept and practice of biopsy of musculoskeletal tumors are discussed in Chapter 2.

 

Laboratory Studies

 

Laboratory studies often are nonspecific. For patients younger than 40 years of age, they include a complete blood count with differential, peripheral blood smear, and erythrocyte sedimentation rate. Patients older than 40 years also need blood calcium and phosphate levels, serum and urine electrophoresis, and urinalysis.

 

Serum alkaline phosphatase levels in primary OSs correlate with disease prognosis; therefore, pretreatment levels should be recorded.

 

 

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FIG 8 • Schematic of preoperative imaging studies for bony sarcomas. Bone scans, CT, MRI, and angiography are routinely required. (Courtesy of Martin M. Malawer.)

 

Formulating an Initial Assessment

 

Age of the patient

 

 

In younger patients (10 to 25 years), the common malignant bone tumors are OS, Ewing sarcoma, and leukemia. The common benign bone tumors are enchondroma, fibrous dysplasia, and eosinophilic granuloma.

 

In the older age groups (40 to 80 years), the common malignant bone tumors are metastatic bone disease, myeloma, and lymphoma.

 

Anatomic location of the tumor within the bone. Certain lesions have a predilection for occurring at particular locations:

 

 

Adamantinoma: in the tibia

 

Chondroblastoma: in the epiphysis of long bones

 

Giant cell tumor (GCT): in the metaphysis and extending through the epiphysis to lie just below the cartilage, typically around the knee

 

 

 

OS: in the metaphysis of the distal femur or proximal tibia Parosteal OS: in the distal femur (posterior cortex) Chondrosarcoma: in the pelvis

 

Chordoma: in the sacrum

 

Synovial sarcoma: in the foot and ankle

 

Enchondroma and metastatic lung carcinoma: in the fingers

 

The effect of the lesion on the bone

 

 

High-grade lesions spread rapidly, causing early cortical bone destruction and expansion. The typical lytic appearance is permeative or moth-eaten.

 

Low-grade tumors spread at a slower pace but may still destroy cortical bone and produce a soft tissue mass.

 

The response of the bone to the lesion

 

 

High-grade lesions spread rapidly and give the bone little ability to contain the process. Cortical destruction, periosteal elevation (eg, Codman triangle, onion skin appearance), and soft tissue spread (sunburst appearance) often are seen.

 

Matrix production

 

 

Osteoid mineralization often is cloudlike and is typical of bone-forming tumors.

 

 

Cartilage calcification often appears stippled and is characteristic of cartilage-forming tumors. Fibrous-forming tumors have a typical “ground-glass” appearance.

SURGICAL MANAGEMENT

Classification of Surgical Procedures

 

Four basic types of excisions are used, each of which is based on the relation between the dissection plane and the tumor and its pseudocapsule: intralesional, marginal, wide, and radical excisions (FIG 9).

 

 

An intralesional excision is performed within the tumor mass and results in removal of only a portion of the tumor; the pseudocapsule and macroscopic tumors are left behind.

 

In a marginal excision, the dissection plane passes through the pseudocapsule of the tumor. Such a resection may leave microscopic disease.

 

Wide (en bloc) excision entails removal of the tumor, its pseudocapsule, and a cuff of normal tissue surrounding the tumor in all directions. This is the desired resection margin for sarcoma; however, the adequate thickness of the normal tissue cuff is a matter of some controversy. For both soft tissue and bone sarcomas, it generally is believed to be between 0.5 and 2 cm.

 

Radical excision involves removal of the tumor and the entire anatomic compartment within which it arises. Although traditionally mentioned as the fourth excision type, it does not define the component of the tumor that is left behind. In other words, a radical excision can achieve a marginal or a wide margin, depending on how close the tumor is to the border of the compartment. However, radical excision excludes the possibility of skip metastases.

 

 

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FIG 9 • A. Multiple excision types for STS. B. Various excision types for bone sarcoma. (Courtesy of Martin M. Malawer.)

 

 

In general, benign bone tumors are adequately treated by either an intralesional procedure (eg, curettage and burr drilling, cryosurgery) or by marginal excision. Primary bone sarcomas are treated with wide excision.

Metastatic tumors are treated according to the general intent of the surgery. When a palliative surgery is performed, metastatic lesions are treated by an intralesional procedure. If a curative procedure is performed, as in the case of solitary breast metastasis, for example, the lesion is treated as if it was a primary bone sarcoma (ie, wide excision).

 

Successful limb-sparing surgery consists of three phases:

 

 

Resection of tumor. Resection follows the principles of oncologic surgery strictly. Avoiding local recurrence is the criterion of success and the main determinant of the amount of bone and soft tissue to be removed.

 

Skeletal reconstruction. The average skeletal defect following adequate bone tumor resection measures 15 to 20 cm. Techniques of reconstruction (eg, prosthetic replacement [FIG 10], arthrodesis, allograft, or combination) vary and are independent of the resection, although the degree of resection may favor one technique over the other.

 

Soft tissue and muscle transfers. Muscle transfers are performed to cover and close the resection site and to restore lost motor power. Adequate skin and muscle coverage is mandatory to decrease postoperative morbidity.

Guidelines for Surgical Resection

 

The major neurovascular bundle must be free of tumor.

 

 

Wide resection of the affected bone with a normal muscle cuff in all directions should be achieved. All previous biopsy sites and all potentially contaminated tissues should be removed en bloc.

 

Bone should be resected 2 to 3 cm beyond abnormal uptake as determined by bone scan or MRI scan which indicates the level of marrow change by the tumor. (This is a safe margin to avoid intraosseous tumor extension.)

 

The adjacent joint and joint capsule should be resected.

 

Adequate motor reconstruction must be accomplished by regional muscle transfers.

 

 

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

 

MALIGNANT BONE TUMORS

 

Primary malignancies of bone arise from mesenchymal cells (sarcoma) and bone marrow cells (myeloma and lymphoma). Bone also is a common site of metastasis from a variety of carcinomas. OS and Ewing sarcoma, the most common malignant mesenchymal bone tumors, usually occur during childhood and adolescence.

Other mesenchymal tumors (eg, MFH, fibrosarcoma, chondrosarcoma), while occasionally seen in childhood, are more common in adults. Multiple myeloma and metastatic carcinoma typically increase in frequency with increasing patient age and usually are seen in patients older than 40 years of age. This section describes the clinical, radiographic, and pathologic characteristics and treatment of the primary bone sarcomas.

 

OS provides the model on which treatment of all other sarcomas is based. The effectiveness of multiagent chemotherapy regimens has been proven with the increase in overall survival rates from the bleak statistic of 15% to 20% with surgery alone in the 1970s to 55% to 80% today. In parallel with improved survival, dramatic advances in reconstructive surgery have made it possible for limb salvage to supplant amputation as the standard method of treatment.

 

Osteosarcoma

 

OS is the most common primary bone sarcoma. OS is a high-grade malignant spindle cell tumor arising within a bone. Its distinguishing characteristic is the production of “tumor” osteoid, or immature bone, directly from a malignant spindle cell stroma. OS typically occurs during childhood and adolescence. In patients older than the age of 40 years, it usually is associated with a preexistent disease such as Paget disease, irradiated bones, multiple hereditary exostosis, or polyostotic fibrous dysplasia.

 

The incidence of OS peaks to 8 per million per year between the ages of 10 and 20 years. Survival of OS patients has

 

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improved greatly over the past 30 years. The 5-year survival rate is 60%, except in patients older than the age of 45 years, where it is 40%.

 

 

 

FIG 10 • A. Various modular prostheses for limbsparing surgeries. B-D. Arthrodesis for a proximal tibial OS. B. Plain radiograph. C. Intraoperative photograph. D. Radiograph of a patient with 30 years follow-up following arthrodesis. (A: Courtesy of Stryker Orthopaedics, Inc., Mahwah, NJ.)

 

 

The most common bone sites are the knee joint (50%) and the proximal humerus (25%). Between 80% and 90% of OSs occur in the long tubular bones; the axial skeleton rarely is affected (FIG 11).

 

Pain, accompanied by a tender soft tissue swelling, is the most common complaint on presentation, with a firm, soft tissue mass fixed to the underlying bone found on physical examination. Systemic symptoms are rare. The incidence of pathologic fractures is less than 1%.

 

Radiographic Characteristics

 

Typical radiographic findings include increased intramedullary sclerosis due to tumor bone or calcified cartilage, an area of radiolucency due to nonossified tumor, a pattern of permeative destruction with poorly defined borders, cortical destruction, periosteal elevation, and extraosseous extension with soft tissue ossification. This combination of characteristics is not seen with any other lesion.

 

Three broad categories are based on radiographic evaluation (FIG 12A-C): sclerotic OS (32%), osteolytic OS (22%), and mixed (46%). Although there is no statistically significant difference among overall survival rates of these types, it is important to recognize the patterns. The sclerotic and mixed types offer few diagnostic problems. Errors of diagnosis most often occur with pure osteolytic tumors. The differential diagnosis of osteolytic OS includes GCT, aneurysmal bone cyst, fibrosarcoma, and MFH.

 

 

 

FIG 11 • Skeletal locales of osteogenic sarcoma.

 

 

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FIG 12 • The three radiographic matrix types of OS: osteolytic (A; arrowheads indicate tumor), mixed (B), and sclerosing (C). There is no prognostic difference in survival based on the radiographic type of matrix formation.

D. Classical high-grade OS reveals a population of pleomorphic spindle cells intimately associated with a mesh of immature lacy osteoid. The amount of osteoid can be minimal, or it may be a predominant element forming wide intersecting trabeculae lined by the malignant osteoblasts. Giant cells also can be present. E. Pathologic specimen. High-grade OS of the proximal humerus with cortical breakthrough and tumor extension into the soft tissues. F. CT scan demonstrating a large pelvic OS. (A-E: Courtesy of Martin M. Malawer.)

 

 

15

Microscopic Characteristics

 

The diagnosis of OS is based on the following findings:

 

 

Identification of a malignant stroma that produces unequivocal osteoid matrix. The stroma consists of a haphazard arrangement of highly atypical cells.

 

Pleomorphic cells that contain hyperchromatic, irregular nuclei. Mitotic figures, often atypical, usually are

easy to identify. Between these cells is a delicate, lacelike eosinophilic matrix, assumed to be malignant osteoid (FIG 12D).

 

The predominance of one tissue type in many OSs has led to a histologic subclassification of this neoplasm.

 

The term osteoblastic osteosarcoma is used for those tumors in which the production of malignant osteoid prevails. Calcification of the matrix is variable.

 

Some tumors reveal a predominance of malignant cartilage production; hence, they are referred to as chondroblastic osteosarcoma. Even though the malignant cartilaginous elements may be overwhelming, the presence of a malignant osteoid matrix warrants the diagnosis of OS.

 

Yet another variant is characterized by large areas of proliferating fibroblasts, arranged in intersecting fascicles. Such areas are indistinguishable from fibrosarcoma, and thorough sampling may be necessary to identify the malignant osteoid component.

 

As the neoplasm permeates the cortex, the periosteum may be elevated. This stimulates reactive bone formation and accounts for a distinctive radiologic feature called Codman triangle. Longitudinal sectioning of the involved bone often reveals wide extension within the marrow cavity. Rarely, skip areas within the medullary canal can be demonstrated. There may be necrotic and hemorrhagic foci. At the time of diagnosis, most tumors already have caused substantial cortical destruction. Continued tumor growth results in involvement of the adjacent soft tissues (FIG 12E).

 

Natural History and Chemotherapy

 

Prior to the development of adjuvant chemotherapy, effective treatment was limited to radical margin amputation. Metastasis to the lungs and other bones generally occurred within 24 months. Overall survival

rates 2 years after surgery ranged from 5% to 20%.10 No significant correlation between overall survival and histologic subtypes, tumor size, patient age, or degree of malignancy was seen. The most significant clinical variable was anatomic site: pelvic and axial lesions had a lower survival rate compared with extremity tumors, and tibial lesions had a better survival rate than femoral lesions (FIG 12F).

 

The dismal outcome associated with OS has been altered dramatically by adjuvant chemotherapy and also by aggressive thoracotomy for pulmonary disease. No difference in local recurrence or overall survival was seen between patients undergoing amputation and those undergoing limbsparing surgery.

 

Overall Treatment Strategy

 

The patient with a primary tumor of the extremity without evidence of metastases requires surgery to control the primary tumor and chemotherapy to control micrometastatic disease. From 80% to 90% of all patients with OS fall into this category.

 

Chemotherapy protocols typically have included various combinations and dosage schedules of high-dose methotrexate (HDMTX), doxorubicin hydrochloride (Adriamycin), and cisplatin. Ifosfamide, which is as effective as Adriamycin in single-agent studies, recently has supplanted methotrexate in many ongoing protocols.

Multiagent chemotherapy using various dosing schedules is now considered standard treatment for OS. Success with adjuvant chemotherapy led to investigation of treatment in the neoadjuvant (preoperative) setting. When used in that setting, tumor response results in shrinkage of the soft tissue components, facilitating surgical excision and subsequent limb salvage. Tumor response is measured by tumor necrosis rate on microscopic pathology and is a significant prognostic factor.

 

Limb salvage surgery is a safe surgical procedure for approximately 85% to 90% of patients. This technique may be used for all spindle cell sarcomas, regardless of histogenesis. The majority of OSs can be treated

safely by a limb-sparing resection combined with effective adjuvant treatments. The successful management of localized OS and other sarcomas requires careful coordination and timing of staging studies, biopsy, surgery, and preoperative and postoperative chemotherapy, radiation therapy, or both. The site of the lesion is evaluated as previously described. Preoperative studies allow the surgeon to understand the local anatomy and the volume of tissue to be resected and reconstructed.

 

Surgery alone results in a cure rate of 15% to 20% at best. The choice between amputation and limb-sparing resection must be made by an experienced orthopaedic oncologist, taking into account tumor location, size, or extramedullary extent; the presence or absence of distant metastatic disease; and patient factors such as age, skeletal development, and lifestyle preference that might dictate the suitability of limb salvage or amputation. Routine amputations are no longer performed; all patients should be evaluated for limb-sparing options.

Intensive, multiagent chemotherapeutic regimens have provided the best results to date. Patients who are judged unsuitable for limb-sparing options may be candidates for presurgical chemotherapy; those with a good response may then become suitable candidates for limb-sparing operations. The management of these patients mandates close cooperation between chemotherapist and surgeon.

 

Variants of Osteosarcoma

 

There are 11 recognizable variants of the classic OS. OS arising in the jaw bones is the most common of these. Parosteal and periosteal OS are the most common variants of the classic OS occurring in the extremities. In contrast to classic OS, which arises within a bone (intramedullary), parosteal and periosteal OS arise on the surface (juxtacortical) of the bone.

 

Parosteal OS

 

 

Parosteal OS is the most common of the unusual variants, representing about 4% of all OSs.

 

Parosteal OS is a distinct variant of OS. Its prevalence is estimated to be 4%. It arises from the cortical bone and generally occurs in an older age group and has a better overall prognosis than OS. As in OS, the distal femur is the most common location; characteristically, the tumor attaches to its posterior aspect (FIG 13A-C). The proximal humerus and the proximal tibia are the next most common sites.

 

 

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FIG 13 • A. Gross specimen of a resection of a distal femoral OS. The average bony defect is 15 to 20 cm. Note how the biopsy site is removed en bloc with the tumor. The proximal tibia routinely is removed en bloc. The length of bone resected is determined by preoperative CT and MRI evaluation. B. CT scan of a typical parosteal OS. C. Gross specimen of a distal femoral parosteal OS. There is minimal intraosseous extension. D,E. Plain radiographs of the distal femur, AP (D) and lateral (E) views, show a dense, irregular, sclerotic lesion, attached to the posterior femoral cortex. The posterior aspect of the distal femur is a classic location for parosteal OSs and that diagnosis should be considered for any sclerotic lesion in that location.

F. The relation of the parosteal OS to the medullary canal is better viewed on this CT scan, which shows no tumor extension to the canal. In contrast to osteochondromas, the medullary canal of the bone is not contiguous with that of the tumor. G. Gross pathologic specimen. H. Specimen shown illuminated with tetracycline fluorescence, which demonstrates minimal medullary tumor extension through the posterior cortex. I. Parosteal OS. There are parallel or intersecting osseous trabeculae (arrows) that may be either lamellar or woven-type bone matrix. The intervening fibrocollagenous tissue is composed of bland, widely-spaced fibroblastic cells. (D-I: Courtesy of Martin M. Malawer.)

 

 

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Parosteal OSs usually present as a mass, occasionally associated with pain. The natural history is slow growth and late metastasis. The long-term survival rate is 75% to 85%. The tumor arises from the cortical surface and presents as a protuberant multinodular mass. The surface of the lesion may be covered in part by a cartilaginous cap resembling an osteochondroma; other areas may infiltrate into the adjacent soft tissues. The tumor usually encircles, partially or completely, the shaft of the underlying bone. In contrast to osteochondromas, the medullary canal of the bone is not contiguous with that of the neoplasm.

 

Radiologically, parosteal OS presents as a large, dense, tabulated mass that is broadly attached to the underlying bone without involvement of the medullary canal (FIG 13D,E). If present long enough, the tumor may encircle the entire bone. The periphery of the lesion typically is less mature than the base. Despite careful evaluation, intramedullary extension is difficult to determine from plain radiographs. It is more accurately detected with CT scan.

 

Diagnosis of parosteal OS, more than that of other bone tumors, must be based on the clinical, radiologic, and pathologic findings (FIG 13F-H). Most parosteal OSs are low grade; they do not require neoadjuvant and adjuvant chemotherapy and are best treated with wide excision. This tumor commonly is mislabeled by inexperienced clinicians and pathologists as osteochondroma, myositis ossificans, or conventional OS. In the classic low-grade lesion, irregularly formed osteoid trabeculae, usually of woven bone, are surrounded by a spindle cell stroma containing widely spaced, bland-appearing fibroblastic spindle cells (FIG 13I).

There may be foci of atypical chondroid differentiation. With the higher grades, the likelihood of intramedullary involvement is increased. This, in turn, correlates well with the presence of distant metastases.

 

Chondrosarcomas (Central and Peripheral)

Clinical Characteristics and Physical Examination

 

Half of all chondrosarcomas occur in persons older than the age of 40 years. The most common sites are the pelvis, femur, and shoulder girdle. The clinical presentation varies. Peripheral chondrosarcomas may become quite large without causing pain, and local symptoms develop only because of mechanical irritation. Pelvic chondrosarcomas often are large and present with referred pain to the back or thigh, sciatica secondary to sacral plexus irritation, urinary symptoms from bladder neck involvement, unilateral edema due to iliac vein obstruction, or as a painless abdominal mass. Conversely, central chondrosarcomas present with dull pain. A mass is rarely present. Pain, which indicates active growth, is an ominous sign of a central cartilage lesion.

This cannot be overemphasized. An adult with a plain radiograph suggestive of a “benign” cartilage tumor but who is experiencing pain most likely has a chondrosarcoma (FIG 14A).

 

Radiographic Findings

 

 

Central chondrosarcomas have two distinct radiologic patterns.4 One is a small, well-defined lytic lesion with a narrow zone of transition and surrounding sclerosis with faint calcification. This is the most common malignant bone tumor that may appear radiographically benign (FIG 14B,C).

 

The second type has no sclerotic border and is difficult to localize. The key sign of malignancy is endosteal scalloping. This type is difficult to diagnose on plain radiographs and may go undetected for a long period of time.

 

Peripheral chondrosarcoma is easily recognized as a large mass of characteristic calcification protruding from a bone. Correlation of the clinical, radiographic, and histologic data is essential for accurate diagnosis and evaluation of the aggressiveness of cartilage tumor. In general, proximal or axial location, skeletal maturity,

and pain point toward malignancy, even though the cartilage may appear benign.

 

Grading and Prognosis

 

Chondrosarcomas are graded 1, 2, and 3; most are either grade 1 or grade 2. The metastatic rate of moderate grade versus high grade is 15% to 40% versus 75%.3 Grade 3 lesions have the same metastatic potential as OSs.9

 

In general, peripheral chondrosarcomas are a lower grade than central lesions. Ten-year survival rates among those with peripheral lesions are 77% and 32% among those with central lesions.

 

Secondary chondrosarcomas arising from osteochondromas (FIG 14D,E) also have a low malignant potential; 85% are grade 1. The multiple forms of benign osteochondromas or enchondromas have a higher rate of malignant transformation than the corresponding solitary lesions. The pelvis, shoulder girdle, and ribs are the most common sites of malignant transformation of osteochondromas. The risk of malignant transformation is approximately 20% to 25%.

 

Microscopic Characteristics

 

The histologic spectrum of chondrosarcomas varies tremendously.

High-grade examples are easy to identify, whereas certain low-grade tumors are exceedingly difficult to distinguish from chondromas. Correlation between the histologic features (FIG 14F) and both the clinical setting and the radiographic changes is, therefore, of utmost importance in avoiding serious diagnostic error. The grade of malignant cartilaginous tumors correlates with clinical behavior. Grade 1 tumors are characterized by an increased number of chondrocytes set in a matrix that is chondroid to focally myxoid.

 

Areas of increased cellularity with more marked variation in cell size, significant nuclear atypia, and frequent pleomorphic forms define a grade 2 lesion. Binuclear forms are more common in this grou

 

Grade 3 chondrosarcomas, which are relatively uncommon, show even greater cellularity, often with spindle cell areas, and reveal prominent mitotic activity. Chondrocytes may contain large, bizarre nuclei. Areas of myxoid change are common.

 

Treatment

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

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FIG 14 • A. Pelvic CT scan of a patient with multiple hereditary exostosis. Note the large chondrosarcoma in the left hip and a normal-appearing osteochondroma in the right hi The pelvis, shoulder girdle, and ribs are the most common sites of malignant transformation of osteochondromas. The risk of malignant transformation is approximately 20% to 25%. B-D. Secondary low-grade chondrosarcomas, arising from osteochondromas of the proximal humerus (B), proximal femur (C), and proximal tibia (D; arrowheads point to the region of the cartilage cap that has undergone malignant transformation). E,F. Secondary chondrosarcoma arising from the left proximal femur in a patient with multiple hereditary enchondromatosis.

E. Plain radiograph shows a large, benign-appearing enchondroma arising from the right proximal femur and a large, poorly demarcated cartilage tumor, arising from the left. F. CT shows a marked difference between the two lesions. The destructive neoplastic tissue has completely replaced the enchondroma on the left, and it is almost fungating through the skin. The patient underwent modified hemipelvectomy and remains disease-free after more than 10 years of follow-u (B-F: Courtesy of Martin M. Malawer.)

 

Variants of Chondrosarcoma

 

There are three less-common variants of classic chondrosarcoma. Each is briefly described in the following text (FIG 15).

 

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

 

Mesenchymal chondrosarcoma is a rare, aggressive variant of chondrosarcoma characterized by a biphasic histologic pattern, that is, small, compact cells intermixed with islands of cartilaginous matrix. This tumor has a predilection for

 

 

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flat bones; long tubular bones rarely are affected. It tends to occur in the younger age group and has a high-metastatic potential. The 10-year survival rate is 28%. This type responds favorably to radiation therapy.

 

 

 

 

FIG 15 • A,B. Plain radiographs of the proximal tibia: AP and lateral views show a central chondrosarcoma

(arrows). Macrosections of central chondrosarcomas of the proximal tibia (C) and proximal femur (D). E. Plain radiograph of the femoral shaft shows a central chondrosarcoma, presenting as a well-defined lytic lesion with a sharp transition zone, calcifications, and endosteal scalloping. Immunohistochemical stains, differentiation among these tumors has become simpler. F. Cross-section of an intramedullary chondrosarcoma discloses its lobular architecture and translucent, hyaline-like matrix. Note the characteristic endosteal erosions (arrows).

G. Low-grade chondrosarcoma maintains a lobular architecture. There is slightly increased cellularity, occasional binucleate cells, and nuclear atypia. These cells typically are found in lacunae. The tumor tends to permeate between the normal osseous trabeculae. H. The juxtaposition of high-grade spindle sarcoma with lobules of low-grade chondrosarcoma is the hallmark of dedifferentiated chondrosarcoma. The spindle cell component usually reveals features of MFH, OS, or it may be unclassifiable. This neoplasm pursues an aggressive clinical course with very low long-term survival. (Courtesy of Martin M. Malawer.)

 

 

Dedifferentiated chondrosarcoma. About 10% of chondrosarcomas may dedifferentiate into either a

fibrosarcoma or an OS.3,9 They occur in older individuals and often are fatal. Surgical treatment is similar to that described for other high-grade sarcomas. Adjuvant therapy is warranted.

 

Ewing Sarcoma

 

Ewing sarcoma is the second most common bone sarcoma of childhood; it is approximately one-half as common as OS. The lesion is characterized by poorly differentiated, small, round cells with marked homogeneity. The exact cell of origin is unknown. These mesenchymal cells are rich in glycogen and typically manifest a unique reciprocal chromosomal translocation, t(11;22)(q24;q12) that results in a chimeric protein, EWS/FLI-1. This translocation occurs in approximately 90% of these tumors. The clinical and biologic behavior is significantly different from that of spindle cell sarcomas. Within the past two decades, the prognosis of patients with Ewing sarcomas has been improved dramatically thanks to a combination of adjuvant chemotherapy, improved radiation therapy techniques, and the select use of limited surgical resection.

 

Clinical Characteristics and Physical Examination

 

Ewing sarcomas tend to occur in young children, although rarely in those younger than 5 years. The flat and axial bones are involved in 50% to 60% of cases. When a long (tubular) bone is involved, it most often is the proximal or diaphyseal area that is affected (FIG 16). In contrast, OSs occur in adolescence (average age, 15 years), most often around the knees, and involve the metaphysis of long bones.

 

 

 

FIG 16 • A. CT scan of a Ewing sarcoma of the scapula demonstrating a large soft tissue component. Ewing sarcomas often have a large soft tissue component, especially when a flat bone is involved. B. Gross photograph of a Ewing sarcoma of the scapula following resection. Note the large soft tissue extension both anterior and posterior to the glenoid. C. Ewing sarcoma belongs to the ever-expanding category of small, round, blue cell tumors. It is composed of round cells with scanty cytoplasm and round to oval nuclei. The nuclear chromatin tends to be fine and homogeneous. Differentiation from the other members of the round cell family may require the use of immunohistochemistry, electron microscopy, and cytogenetic and oncogene markers. (Courtesy of Martin M. Malawer.)

 

 

Another unique finding with Ewing sarcomas is systemic signs, that is, fever, anorexia, weight loss,

leukocytosis, and anemia.3 All may be a presenting sign of the disease and are seen in 20% to 30% of patients; this is in contrast to the distinct absence of systemic signs with OS until late in the disease process. The most common complaint is pain or a mass. Localized tenderness often is present with associated erythema and induration. These findings, in combination with systemic signs of fever and leukocytosis, closely mimic those of osteomyelitis.

 

Radiographic Findings

 

Ewing sarcoma is a highly destructive radiolucent lesion without evidence of bone formation. The typical pattern consists of a permeative or moth-eaten destruction associated with periosteal elevation. Multilaminated periosteal elevation (onion skin appearance) or a sunburst appearance is characteristic. When Ewing sarcoma occurs in flat bones, however, these findings usually are absent. Tumors of flat bones appear as a destructive lesion with a large soft tissue component. The ribs and pelvis are involved most often. Pathologic fractures occur secondary to extensive bony destruction and the absence of tumor matrix.

 

The differential diagnosis is osteomyelitis, osteolytic OS, metastatic neuroblastoma, and eosinophilic granuloma.

 

Natural History

 

Ewing sarcoma is highly lethal and disseminates rapidly. Historically, fewer than 10% to 15% of patients

remained disease free at 2 years.3

 

Many patients present with metastatic disease. The most common sites for metastases are other bones and the lungs.

 

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Ewing sarcoma once was thought to be a multicentric disease because of the high incidence of multiple bone involvement. Unlike other bone sarcomas, Ewing sarcoma is associated with visceral, lymphatic, and meningeal involvement, and all of these areas must be investigated.

 

Radiographic Evaluation and Staging

 

No general staging system for Ewing sarcoma exists. The musculoskeletal staging system does not apply to the round cell sarcomas of the bone.

 

Because these lesions have a propensity to spread to other bones, bone marrow, the lymphatic system, and the viscera, evaluation is more extensive than that for spindle cell sarcomas. It must include a careful clinical examination of regional and distal lymph nodes and radiographic evaluation for visceral involvement. Liver-spleen scans and bone marrow aspirates are required in addition to CT of the lungs and the primary site.

Angiography is required only if a primary resection is planned.

 

Microscopic Characteristics

 

Because accurate pathologic interpretation often is difficult, and bone heating is subject to several potential problems, the following guidelines have been established for the biopsy of suspected round cell tumors:

 

 

 

Adequate material must be obtained for histologic evaluation and electron microscopy. Routine cultures should be made to aid in the differentiation from osteomyelitis.

 

Biopsy of the bony component is not necessary. The soft tissue component usually provides adequate material. Bone biopsy should be through a small hole on the compressive side of the bone. Pathologic fracture through an irradiated bone often does not heal.

 

Large nests and sheets of relatively uniform round cells are typical. The sheets often are compartmentalized by intersecting collagenous trabeculae. The cells contain round nuclei with a distinct nuclear envelope.

Nucleoli are uncommon, and mitotic activity is minimal. Occasional rosette-like structures may be found, although neuroectodermal origin has never been confirmed. In the vicinity of necrotic tumor, small pyknotic cells may be observed. Vessels in these necrotic regions often are encircled by viable tumor cells. The cells often contain cytoplasmic glycogen. This neoplasm belongs to the category of small, blue round cell tumors, a designation that also includes neuroblastoma, lymphoma, metastatic OS, and, occasionally, osteomyelitis and histiocytosis. When confronted with this differential diagnosis, the pathologist may turn to electron microscopy or immunohistochemistry for additional information.

 

Combined Multimodality Treatment

 

Ewing sarcomas generally are considered radiosensitive. Radiation therapy to the primary site has been the traditional mode of local control. Within the past decade, surgical resection of selected lesions has become increasingly popular. Although detailed management is beyond the scope of this chapter, the following sections summarize some common aspects of the multimodality approach.

 

Chemotherapy

 

Doxorubicin, actinomycin D, cyclophosphamide, and vincristine are the most effective agents. A variety of

different combinations and schedules are used. All patients require intensive chemotherapy to prevent dissemination. Overall survival in patients with lesions of the extremities now ranges between 40% and 75%.

 

Radiation Therapy

 

Radiation must be administered to the entire bone at risk. The usual dose is 4500 to 6000 cGy, delivered over 6 to 8 weeks. To reduce the morbidity of radiation, it is recommended that between 4000 and 5000 cGy be delivered to the whole bone, with an additional 1000 to 1500 cGy given to the tumor site.

 

Surgical Treatment

 

The role of surgery in the treatment of Ewing sarcoma currently is changing. The Intergroup Ewing's Study recommends surgical removal of “expendable” bones such as the ribs, clavicle, and scapula. In general, surgery is reserved for tumors located in high-risk areas, for example, the ribs, ilium, and proximal femur. Risk is defined as an increased incidence of local recurrence and metastases. In general, surgery is considered an adjunct to the other treatment modalities.

 

Interest recently has increased in primary resection of Ewing sarcoma following induction (neoadjuvant) chemotherapy, similar to the treatment of OS. When this resection is performed, radiation therapy is not given if the surgical margins are negative (ie, wide resection). The goal of this approach is to increase local control as well as minimize the complications and functional losses that are associated with high-dose radiation therapy given to a young patient.

 

Giant Cell Tumor of Bone

 

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

 

Clinical Characteristics and Physical Examination

 

GCTs occur slightly more often in females than in males. Eighty percent of GCTs in the long bones occur after skeletal maturity; 75% of these develop around the knee joint. A joint effusion or pathologic fracture, uncommon with other sarcomas, is common with GCTs. GCTs occasionally occur in the distal radius, the

vertebrae (2% to 5%), and the sacrum (10%).3

 

Natural History and Potential Malignancy

 

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

known GCTs become malignant following local recurrence.3 This rate decreases to less than 10% if patients who have undergone radiation therapy are excluded. Approximately 40% of

 

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malignant GCTs become malignant at the first recurrence. The remainder typically become malignant by the second or third recurrence; thus, each recurrence increases the risk of malignant transformation. A recurrence after 5 years is extremely suspicious for a malignancy. Primary malignant GCT generally has a better prognosis than does secondary malignant transformation of typical GCT, especially if the transformation occurs after radiation therapy. Local recurrence of a GCT is determined by the adequacy of surgical removal rather than by histologic grade.

 

Radiographic and Clinical Evaluation

 

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

 

Microscopic Characteristics

 

Two basic cell types constitute the typical GCT.

 

 

The stroma is characterized by polygonal to somewhat spindled cells containing central round nuclei.

 

Benign, multinucleated giant cells are scattered diffusely throughout the stroma. Small foci of osteoid matrix, produced by the benign stroma cells, can be observed; however, chondroid matrix never occurs.

 

Treatment

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

Cryosurgery has been used with more success for GCTs than for any other type of bone tumor. Cryosurgery is effective in eradicating the tumor while preserving joint motion and avoiding the need for resection or amputation. Liquid nitrogen is a very effective physical adjuvant and is recommended following curettage resection. Curettage alone is not recommended because of the associated high rate of local recurrence.

 

 

 

COMMON SOFT TISSUE SARCOMAS

Treatment

The treatment of high-grade STS has undergone fundamental changes within the past decade. Treatment of these patients requires a multimodality approach, and successful management requires cooperation among the surgeon, medical oncologist, and radiation oncologist. The appropriate role of each modality is continuously changing, but general descriptions are provided in the following sections.

Chemotherapy

The impact of chemotherapy for high-grade STS on survival remains controversial. Combination chemotherapy has been shown to be more effective than single-agent therapy in preventing pulmonary dissemination from high-grade sarcomas. The most effective drugs in use today are doxorubicin hydrochloride (Adriamycin) and ifosfamide. Dacarbazine, methotrexate, and cisplatin also have activity against these tumors and are included in many current protocols. The various combinations traditionally are given in an adjuvant (postoperative) setting and are presumed effective against clinically undetectable micrometastases.

Neoadjuvant (preoperative) chemotherapy is being evaluated in several institutions. Early results have indicated that significant reduction in tumor size can occur, thereby facilitating attempts at limb salvage. In patients with tumors deemed unresectable who are therefore destined for limb amputation, the tumors

may shrink drastically in response to preoperative chemotherapy, thereby making them candidates for wide resection and limb-sparing surgery.

Radiation Therapy

 

Radiation typically is administered in a dose of 5000 to 6500 cGy over many fractions. This modality is effective in an adjuvant setting in decreasing local recurrence following nonablative resection. The degree to which the initial surgical volume should be decreased in these circumstances is controversial, although the rate of local recurrence following a wide excision and postoperative radiation therapy is 5% to 10%.

 

Radiation therapy includes irradiating all the tissues at risk, shrinking fields, preserving a strip of unirradiated skin, and using filters and radiosensitizers. Local morbidity has been greatly decreased within the past decade. Preoperative radiation is effective in reducing tumor volume but is associated with increased morbidity resulting from significant wound-healing complications and, therefore, is not recommended as often as postoperative radiation.

Surgery

 

Removal of the tumor is necessary to achieve local control, by either a nonablative resection (limb salvage) or an amputation. The procedure chosen depends on results of the preoperative staging studies. A prospective randomized National Cancer Institute (NCI) trial established that a multimodality approach employing limb salvage surgery combined with adjuvant radiation and chemotherapy offered local control and survival rates comparable to those of amputation plus chemotherapy while simultaneously preserving a functional extremity.

 

The use of adjuvant therapy (chemotherapy or radiation) permits limb-sparing procedures for most

extremity STS. Enneking et al5,6 have shown that a radical resection for an STS has a local recurrence rate of about 5% with surgery alone. Wide excision (without adjuvant radiation or chemotherapy) has a 50% rate of local failure. Results from the NCI showed that the rate of local recurrence decreased to 5% following local excision (either a marginal or wide excision) when combined with postoperative radiation therapy and chemotherapy. Others have reported similar good results from preoperative radiation, with or without preoperative

 

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chemotherapy. Contraindications to limb-sparing surgery are similar to those for the bony sarcomas. In general, nerve or major vascular involvement is a contraindication.

 

Studies of referred patients show that approximately half of all patients with STS treated with attempted excisional biopsy by the referring surgeon will have microscopic or gross tumor remaining. As a result, referred patients undergo routine re-resection of the surgical site to ensure adequate local control prior to institution of adjuvant treatment.

 

GENERAL SURGICAL TECHNIQUE AND CONSIDERATIONS

 

All tissue at risk should be removed with a wide, en bloc excision that includes the tumor, a cuff of normal muscle, and all potentially contaminated tissues. It is not necessary to remove the entire muscle grou The biopsy site should be removed with 3 cm of normal skin and subcutaneous tissue en bloc with the tumor.

 

The tumor or pseudocapsule should never be visualized during the procedure (FIG 17). Contamination of the wound with tumor greatly increases the risk of local recurrence.

 

Distant flaps should not be developed at the time of resection. This may contaminate a noninvolved area.

 

The margin surrounding the surgical wound should be marked with metallic staples to help the radiotherapist determine the high-risk area if radiation treatment is needed later.

 

Reconstruction of the defect should include local muscle transfers to protect exposed neurovascular bundles and bone cortex.

 

All dead space should be closed, and there should be adequate drainage to prevent hematoma.

 

Perioperative antibiotics should be given. These procedures have a low but significant rate of postoperative infection. The risk of infection following preoperative adjuvant therapy is particularly high.

 

Undifferentiated Pleomorphic Sarcoma

 

Undifferentiated pleomorphic sarcoma (UPS) is the most common STS in adults. UPSs are a heterogeneous collection of poorly differentiated sarcomas, many of which can be specifically classified with the application of DNA and protein analysis. It most commonly affects the lower extremity and has a predilection for originating in deep-seated skeletal muscles.

 

 

 

 

FIG 17 • Gross specimen of a STS arising within the anterior compartment of the leg treated by an amputation. Note the relation to the adjacent bone and related vessels of the popliteal (arrows) trifurcation. The reactive zone and pseudocapsule are shown.

 

 

The tumor usually presents as a multinodular mass with wellcircumscribed or ill-defined infiltrative borders. The size and location at the time of diagnosis often correlate with the ease of clinical detection: Superficial variants, presenting as dermal or subcutaneous masses, may be only a few centimeters in diameter, whereas those arising in the retroperitoneum often attain a diameter of 15 cm or more. Color and consistency vary considerably and reflect, in part, the cellular composition. Red-brown areas of hemorrhage and necrosis are not uncommon. The myxoid variant of UPS contains a predominance of grayish white, soft, mucoid tumor lobules, created by the high content of myxoid ground substance.

 

About 5% of UPSs undergo extensive hemorrhagic cystification termed telangiectatic transformation, leading to a clinical and radiologic misdiagnosis of hematoma. A needle biopsy can result in a benign diagnosis if only the hemorrhagic center of the tumor is sampled. For these reasons, until proven otherwise, one should assume that an underlying STS is present in any adult patient with a deep-seated hematoma that does not resolve after a few weeks, even when there is a history of trauma to that site.

 

The currently accepted broad histologic spectrum of UPS encompasses many variants that formerly were considered distinct clinicopathologic entities. These lesions, which had been named according to the predominant cell type, include fibroxanthoma, malignant fibroxanthoma, inflammatory fibrous histiocytoma, and GCT of soft parts. Immunohistochemical studies and electron microscopy can assist in the accurate diagnosis of a significant percentage of these tumors. The basic neoplastic cellular constituents of all fibrohistiocytic tumors include fibroblasts, histiocyte-like cells, and primitive mesenchymal cells (FIG 18). Both an acute and a chronic inflammatory cell component usually are present as well. The proportion of these malignant and reactive cell elements, the degree of pleomorphism of the neoplastic cells, and the predominant pattern account for the wide histologic variances.

 

The histologic pattern most commonly associated with UPS is a storiform arrangement of the tumor cells, which is characterized by fascicles of spindle cells that intersect to form a “pinwheel” or “cartwheel” pattern (see FIG 18). Atypical and bizarre giant cells, often containing abnormal mitotic figures, may be present. The histologic grade (almost always intermediate to high) is a good prognosticator of metastatic

 

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disease. In the myxoid variant, the second most common histologic type, the tumor cells are dispersed in a richly myxoid matrix. The less common giant cell type (malignant giant cell of soft parts) is characterized by abundant osteoclast-like giant cells that are diffusely distributed among the malignant fibrohistiocytic elements.

 

 

 

 

FIG 18 • MFH, a high-grade sarcoma, is characterized by pleomorphic spindle cells forming fascicular or typical storiform patterns. Bizarre tumor giant cells are interspersed. (Courtesy of Martin M. Malawer.)

 

We recently analyzed our data of 150 UPS lesions. Our 5-year survival rates were 74%, the distant recurrence rate was 28%, and the local recurrence rate was 19%. A local recurrence, large tumor size, deep tumors, close margins, and proximal location in the extremity were found to have a significant negative prognostic influence on survival.

 

Liposarcoma

 

Liposarcoma is the second most common STS in adults. It has a wide range of malignant potential that correlates well with the histologic classification of the individual tumor. The lower extremity is the most common site and accounts for over 40% of all cases. These tumors, particularly those arising in the retroperitoneum, can attain enormous size; specimens measuring 10 to 15 cm and weighing more than 5 kg are not uncommon (FIG 19A). Liposarcomas tend to be well circumscribed and multilobulated. Gross features usually correlate with the histologic composition. Well-differentiated liposarcomas contain variable proportions of relatively mature fat and fibrocollagenous tissues; vary from yellow to grayish white; and can be soft, firm, or rubbery. A tumor that is soft, is pinkish tan, and has a mucinous surface probably is a myxoid liposarcoma, the most common histologic type. The high-grade liposarcomas (ie, round cell and pleomorphic) vary from pinkish tan to brown and may disclose extensive hemorrhage and necrosis.

 

Identification of typical lipoblasts is mandatory to establish the diagnosis of liposarcoma. This diagnostic cell contains one or more round, cytoplasmic fat droplets that form sharp, scalloped indentations on the central or peripheral nucleus. Well-differentiated liposarcomas often contain a predominance of mature fat cells and only a few, widely scattered lipoblasts. Inadequate sampling can, therefore, lead to a misdiagnosis of a benign lipoma (FIG 19B). Well-differentiated liposarcomas that arise in the superficial soft tissues have been called atypical lipomas. In the sclerosing variant of a well-differentiated liposarcoma, delicate collagen fibrils that encircle fat cells and lipoblasts make up a prominent part of the matrix. Treatment with wide excision and adjuvant radiation therapy is recommended only if marginal margins were achieved. We treat high-grade liposarcomas like any other high-grade STS, with neoadjuvant chemotherapy, wide excision, and adjuvant chemotherapy. Radiation therapy is indicated if wide margins were not achieved.

 

 

 

 

FIG 19 • A. Large, low-grade liposarcoma of the posterior thigh. B. The diagnosis of a well-differentiated liposarcoma depends on the identification of characteristic lipoblasts. These cells can be mono- or multivacuolated with hyperchromatic, scalloped nuclei. This variant can closely mimic ordinary lipoma. (Courtesy of Martin M. Malawer.)

 

 

Sixty-five percent of liposarcomas arise in the extremities; the remaining 35% arise in the retroperitoneum. Negative prognostic factors for survival are retroperitoneal location, tumor size greater than 10 cm, and locally recurrent disease at initial presentation.

 

Synovial Sarcoma

 

Synovial sarcoma is the fourth most common STS. In spite of its name, this tumor rarely arises directly from a joint but, rather, arises in proximity to it, with a propensity for the distal portion of the extremities. Synovial sarcomas occur in a younger age group than do most other sarcomas: Most patients are younger than the age of 40 years. Typical findings of synovial sarcoma include a painful mass, soft tissue calcifications on radiography, and a malignant tumor of the foot. The tumor typically presents as a deep-seated, wellcircumscribed, multinodular, firm mass. Contiguity with a synovium-lined space is rare, and, occasionally, lymphatic spread occurs. Unlike most STS, synovial sarcomas may be present as a painless mass for a few years. Plain radiographs often show small calcifications within the mass. That finding should alert the physician to the diagnosis.

 

Virtually, all synovial sarcomas are high grade. These poorly differentiated neoplasms usually present as ill-defined, infiltrative lesions with a soft, somewhat gelatinous consistency. The classic histologic presentation of this tumor is a biphasic pattern, which implies the presence of coexisting but distinct cell populations, namely, spindle cells and epithelioid cells (FIG 20A). The plump spindle cells, usually the predominant component, form an interlacing fascicular pattern that is reminiscent of fibrosarcoma. Within the spindle cell portion of the tumor, areas resembling the acutely branching vascular pattern of hemangiopericytoma are common. The arrangement of epithelioid cells varies, ranging from merely solid nests to distinct, gland-like structures (FIG 20B). When they compose glandular spaces, the constituent cells range from cuboidal to tall columnar; they rarely undergo squamous metaplasia. Histochemical stains demonstrate that the

 

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glandular lamina contain epithelial-type acid mucins. The neoplasm may contain extensive areas of dense stromal hyalinization, and focal calcification is common. The presence of extensive areas of calcification, sometimes with modulation to benign osteoid, deserves recognition because this rare variant imparts a significantly more favorable prognosis than that for other forms of synovial sarcoma.

 

 

 

 

FIG 20 • A. Synovial sarcoma is characterized by a distinctive biphasic pattern that implies an admixture of spindle cell areas along with epithelioid cells forming gland-like structures. The proportions of these two components are variable. B. When only one of the elements of synovial sarcoma is present—almost invariably the spindle cell component—it is termed monophasic synovial sarcoma. (Courtesy of Martin M. Malawer.)

 

 

The existence of a monophasic spindle cell synovial sarcoma has been recognized, although distinguishing it from fibrosarcoma can be difficult. In contrast to fibrosarcoma, the spindle cell variant of synovial sarcoma may contain cytokeratins, as demonstrated with immunohistochemical studies.

 

REFERENCES

1. American Cancer Society. Bone cancer: key statistics. American Cancer Society Web Site. Available at:

   http://www.cancer.org/cancer/bonecancer/detailedguide/bone-cancer-key-statistics. Revised April 21, 2014.

   Accessed June, 2014.

    

    

2. American Cancer Society. Cancer Facts & Figures 2013. Atlanta, GA: American Cancer Society, 2013:10-

   13. Available at: http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-036845.pdf. Accessed June, 2014.

    

    

3. Dahlin DC. Bone Tumors: General Aspects and Data on 6,221 Cases, ed 3. Springfield, IL: Charles C Thomas, 1978.

    

    

4. Edeiken J. Bone tumors and tumor-like conditions. In: Edeiken J, ed. Roentgen Diagnosis and Disease of Bone. Baltimore: Williams & Wilkins, 1981:30.

    

    

5. Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res 1980;153:106-120.

    

    

6. Enneking WF, Spanier SS, Malawer MM. The effect of the anatomic setting on the results of surgical procedures for soft parts sarcoma of the thigh. Cancer 1981;47:1005-1022.

    

    

7. Malawer M, Sugarbaker PH, eds. Musculoskeletal Cancer Surgery: Treatment of Sarcomas and Allied Diseases. Dordrecht: Kluwer Academic Publishers, 2000.

    

    

8. Mankin HJ, Lange TA, Spanier SS. The hazards of biopsy in patients with malignant primary bone and soft-tissue tumors. J Bone Joint Surg Am 1982;64:1121-1127.

    

    

9. Marcove RC. Chondrosarcoma: diagnosis and treatment. Orthop Clin North Am 1977;8:811-820.

    

    

10. Marcove RC, Miké V, Hajek JV, et al. Osteogenic sarcoma under the age of twenty-one. A review of one hundred and forty-five operative cases. J Bone Joint Surg Am 1970;52:411-423.

     

     

11. Rougraff BT, Simon MA, Kneisl JS, et al. Limb salvage compared with amputation for osteosarcoma of the distal end of the femur. A long-term oncological, functional, and quality-of-life study. J Bone Joint Surg Am 1994;76:649-656.

     

     

12. Sim FH, Bowman W, Chao E. Limb salvage surgery and reconstructive techniques. In: Sim FH, ed. Diagnosis and Treatment of Bone Tumors: A Team Approach. A Mayo Clinic Monograph. Thorofare, NJ: Slack, 1983.