I. General Information and Terminology
A. Each year in the United States there are approximately 2,700 new bone sarcomas and 9,000 new soft-tissue sarcomas. Most of these sarcomas are high-grade malignancies with a high propensity to metastasize to the lungs.
B. Benign bone conditions
1. Developmental processes
2. Reactive processes (osteomyelitis, stress fractures)
3. Benign tumors (giant cell tumor, chondroblastoma)
C. Malignant bone conditions
1. Malignancies that arise from mesenchymal derivatives are called sarcomas.
2. Primary bone sarcomas include osteosarcoma and chondrosarcoma.
3. Bone malignancies that are not sarcomas include metastatic bone disease, multiple myeloma, and lymphoma.
D. Soft-tissue masses
1. Most common soft-tissue tumors
a. Benign: lipoma
b. Malignant: malignant fibrous histiocytoma, liposarcoma
2. Nonneoplastic reactive conditions include hematomas and heterotopic ossification.
II. Bone Tumors
A. Classification/staging systems
1. Lichtenstein system—Modified by Dahlin to group conditions together based on the type of proliferating cell and whether the lesion is benign or malignant (
*Frank J. Frassica, MD, is a consultant or employee for SLACK Inc.
2. Bone tumors can be classified according to whether the process involves intramedullary bone or surface bone.
a. Common intramedullary tumors
b. Common surface tumors
ii. Periosteal chondroma
iii. Parosteal osteosarcoma
3. Bone sarcomas also can be characterized as being primary or secondary.
a. Common primary bone sarcomas
ii. Ewing sarcoma
b. Common secondary sarcomas
i. Chondrosarcoma arising in an osteochondroma
ii. Malignant fibrous histiocytoma arising in a bone infarct
4. Bone tumor grade
Grade 1 (G1): low grade (well differentiated)
i. Parosteal osteosarcoma
ii. Low-grade intramedullary osteosarcoma (rare)
iv. Intramedullary chondrosarcoma
[Table 1. Dahlin Modification of Lichtenstein Classification System]
Grade 2 (G2): intermediate grade (moderately differentiated)
i. Periosteal osteosarcoma
ii. Grade 2 chondrosarcoma of bone
Grades 3 (G3) and 4 (G4): high grade (poorly differentiated or undifferentiated)
ii. Ewing sarcoma
iii. Malignant fibrous histiocytoma
5. Enneking system—Enneking and associates developed a staging system for benign and malignant musculoskeletal tumors.
a. Benign lesions—Classified into stages 1, 2, and 3 (
b. Malignant bone tumors—Classified into stages I, II, and III (
[Table 2. Enneking Classification of Benign Bone Tumors]
[Table 3. Enneking Classification of Malignant Bone Tumors]
6. American Joint Commission for Cancer (AJCC) classification system
a. Based on the tumor grade, size, and presence or absence of discontinuous tumor or regional/systemic metastases (
b. In this system, the order of importance of prognostic factors is:
i. Presence of metastasis (stage IV)
ii. Discontinuous tumor (stage III)
iii. Grade (I—low, II—high)
(a) T1 ≤ 8 cm
(b) T2 > 8 cm
B. Patient presentation of malignant bone tumors
1. Pain—Patients with high-grade malignant bone tumors present with bone pain.
[Table 4. AJCC Classification System for Bone Tumors]
a. The pain begins as intermittent and progresses to constant pain that does not respond to nonsteroidal anti-inflammatory drugs or weak narcotic medications.
b. A common presentation is severe pain that occurs at rest and with activity.
c. Night pain is often present.
2. Mass—Patients present with a hard, fixed, soft-tissue mass adjacent to the bone lesion that is often tender on deep palpation.
3. Range of motion—The range of motion of the affected joint is often diminished, and muscle atrophy is common.
a. Fractures occur in 5% to 10% of patients with malignant bone tumors.
b. A history of antecedent pain is common.
c. These fractures generally occur with minor trauma or following activities of daily living.
1. Imaging strategy
a. Primary lesion—Radiographs and MRI (occasionally thin cut CT if osteoid osteoma suspected).
b. Pulmonary staging
i. Chest radiograph is used for initial screening.
ii. CT is used as a baseline to detect pulmonary metastases not seen on chest radiographs and to use for future comparison.
2. Plain radiographs—AP/lateral views of the lesion.
a. Inspect cortices for bone destruction.
b. Assess if lesion is mineralized.
i. Rings/stipples suggest cartilage lesion.
ii. Cloud, ivory-like suggests bone formation.
c. Check for evidence of periosteal reaction.
3. Technetium Tc 99m bone scan
a. Technetium Tc 99m forms chemical adducts to sites of new bone formation.
b. Detects multiple sites of bone involvement
c. Very sensitive but not specific
d. High false-negative rate in multiple myeloma
4. Magnetic resonance imaging
a. Sensitive and specific for detecting bone marrow involvement
b. Defines anatomic features (T1-weighted sequences)
5. Computed tomography
a. Determines the mineral distribution in normal and abnormal bone
b. Helpful in evaluating pelvic and spine lesions
III. Soft-Tissue Tumors
1. Soft-tissue tumors are classified histologically, according to the predominant cell type.
2. This system encompasses benign and malignant neoplasms and reactive conditions.
3. There are hundreds of different soft-tissue tumors; some of the most significant are listed in
B. Staging—The most common system is the AJCC system (
Table 6). The order of importance of prognostic factors is:
1. Presence of metastasis (stage IV)
a. Low—stage I
b. High—stage II
3. Size (>5 cm)
4. Location (superficial or deep)
[Table 5. Histologic Classification of Soft-Tissue Tumors]
1. Biopsy is a key step in the evaluation and treatment of patients with bone or soft-tissue lesions.
[Table 6. AJCC Staging System for Soft-Tissue Sarcomas]
2. Significant problems can occur when a biopsy is not done correctly.
a. Altered treatment
b. Major errors in diagnosis
c. Complications (infection, nerve, injury, etc)
d. Nonrepresentative tissue
e. Adverse outcome (local recurrence etc)
f. Unnecessary amputation
B. Major types of biopsy
1. Needle biopsy—Most common method of establishing a diagnosis, but requires an experienced cytopathologist and surgical pathologist.
a. Fine needle aspiration (FNA)—Needle aspiration of cells from the tumor.
b. Core needle biopsy—A larger bore needle is placed into the tumor and a core of tissue is extracted.
2. Open incisional biopsy—Surgical procedure to obtain tissue.
a. The entire biopsy tract should be designed to be excised at the time of the definitive resection if the tumor is malignant.
i. The incision should be small and usually is oriented longitudinally.
ii. Occasionally, a nonlongitudinal incision is used
(a) A transverse incision is used for the clavicle.
(b) An oblique incision is used for the scapular body.
b. Soft-tissue flaps are not elevated; the biopsy is performed directly onto the tumor mass.
c. A frozen section analysis is often performed to ensure that diagnostic tissue has been obtained.
3. Excisional biopsy
a. Indicated only when the surgeon is sure that the lesion is benign or when the tumor can be removed with a wide margin (eg, if the radiographic appearance suggests a superficial, small soft-tissue malignancy)
b. Two low-grade malignancies for which an excisional biopsy is sometimes performed are parosteal osteosarcoma and low-grade chondrosarcoma.
Table 7. Tumor Suppressor Genes]
V. Molecular Markers/Genetic Considerations
A. Tumor suppressor genes—Tumor suppressor genes and associated conditions are listed in Table 7.
B. Chromosomal alterations
1. Chromosomal alterations in malignant tumors are generally translocations (
2. Alterations often produce unique gene products that may affect prognosis.
[Table 8. Chromosomal Alterations]
Top Testing Facts
1. The most common site of metastases from bone and soft-tissue sarcomas is the pulmonary system.
2. The most common low-grade bone sarcomas are chondrosarcoma, parosteal osteosarcoma, adamantinoma, and chordoma.
3. The most common high-grade sarcomas are osteosarcoma, Ewing sarcoma, and malignant fibrous histiocytoma.
4. The order of importance of prognostic factors in bone tumor staging is presence of metastases, discontinuous tumor, grade, and size.
5. A high rate of false-negative results occur with technetium Tc 99m bone scanning in multiple myeloma.
6. The order of importance of prognostic factors in soft-tissue tumor staging is presence of metastases, grade, size, and depth.
7. The retinoblastoma gene is the tumor suppressor gene associated with osteosarcoma.
8. EXT1/EXT2 are the tumor suppressor genes associated with multiple exostoses.
9. Ewing sarcoma and primitive neuroectodermal tumor (PNET) have a characteristic chromosomal translocation t(11;22).
10. Synovial sarcoma has a characteristic chromosomal translocation t(X;18).
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