AAOS Comprehensive Orthopaedic Review

Section 4 - Orthopaedic Oncology and Systemic Disease

Chapter 39. Malignant Bone Tumors

I. Bone Tumors

A. Osteosarcoma—Classic intramedullary osteosarcoma is a malignant bone-forming tumor.

 

1. Demographics

 

a. Male to female ratio = 1.5:1

 

b. Most common malignant bone tumor in children (1,000 to 1,500 new cases/year in United States)

 

c. Bimodal age distribution

 

i. Most common in second decade of life

 

ii. Late peak in sixth decade of life

 

2. Genetics/etiology

 

a. Associated with retinoblastoma gene (RB1), which is a tumor-suppressor gene

 

b. Increased incidence in patients with p53 mutations, Paget disease, prior radiation, Rothmund-Thomson syndrome, and retinoblastoma

 

c. MDM2HER2/neu, c-myc, and c-fos are oncogenes overexpressed in osteosarcoma.

 

3. Clinical presentation

 

a. Commonly presents with intermittent pain progressing to constant (rest, night) pain unrelieved by medications

 

b. Swelling, decreased range of motion, limp, and weakness depending on location

 

c. Often present after injury or sporting activity (coincident with age group, no causality known to trauma)

 

d. Most commonly noted in metaphysis of distal femur, proximal tibia, proximal humerus, and pelvis

 

e. 10% of patients present with a pathologic fracture.

 

4. Imaging

 

a. Classically, osteosarcomas have a mixed appearance with bone destruction and bone formation (

Figures 1 and

2).

 

b. In skeletally immature patients, most do not extend past the epiphyseal plate.

 

c. Most have cortical destruction and soft-tissue mass with adjacent Codman triangle (normal reactive bone near tumor)

 

d. Classic osteosarcomas originate in medullary canal.

 

e. Radiographic differential diagnosis includes osteomyelitis and Ewing sarcoma.

 

f. Technetium Tc 99m bone scan can identify skip lesions.

 

g. MRI delineates extent of marrow involvement, proximity of soft-tissue mass to adjacent neurovascular structures, and skip lesions (Figures 1, C and 2, C).

 

5. Pathology

 

a. The gross appearance varies from a soft, fleshy mass to a firm, fibrous or sclerotic lesion (Figure 1, D).

 

b. The low-power histologic appearance is frankly sarcomatous stroma forming tumor osteoid that permeates existing trabeculae (Figure 1, E).

 

c. On high power, the osteoblastic cells are malignant and form the neoplastic new bone (Figure 1, F).

 

d. Osteosarcoma is defined by the presence of malignant osteoid.

 

e. Extensive pleomorphism and numerous mitotic figures are present.

 

f. Areas of necrosis, cartilage, or giant cells may be present within the lesion.

 

g. The histologic differential diagnosis includes fibrous dysplasia.

 

6. Treatment/outcome

 

a. The standard treatment of osteosarcoma is neoadjuvant chemotherapy followed by surgical resection (limb-sparing or amputation), followed by additional adjuvant chemotherapy.

 

b. The most common chemotherapy agents include

 

[Figure 1. Osteosarcoma of the left distal femur in a 15-year-old boy. AP (A) and lateral (B) radiographs demonstrate extensive bone formation and an ossified soft-tissue mass after several cycles of chemotherapy. C, Axial MRI reveals an extensive circumferential soft-tissue mass abutting the neurovascular bundle posteriorly. D, Gross specimen after distal femoral resection showing a clear proximal margin and tumor extending into the epiphysis. E, Low-power histology shows the classic osteoid formed by malignant stromal cells. Note the lacelike pattern. F, High power reveals the pleomorphic cells producing the new bone.]

   adriamycin (doxorubicin), cis-platinum, methotrexate, and ifosfamide (

Table 1).

 

c. Radiation plays no role in the standard treatment of osteosarcoma.

 

d. Limb-sparing surgery can be performed in 90% of cases.

 

e. Patients who present with a pathologic fracture can be treated with limb-salvage surgery but have a higher risk of local recurrence if the fracture is widely displaced.

 

f. Local recurrence after surgical resection is approximately 5%; these patients have a dismal prognosis.

 

g. Good histologic response and wide surgical margins are associated with a low risk of local recurrence.

 

h. Reconstructive options depend on patient age and tumor location but include metal prostheses, osteoarticular/intercalary allografts, allograft-prosthetic composites, expandable prostheses, or vascularized fibular autografts.

 

i. Tumor stage is the most important prognostic indicator.

 

j. The percentage of necrosis within the tumor after neoadjuvant chemotherapy is related to overall survival (>90% necrosis is associated with significantly increased survival).

 

k. Elevated lactate dehydrogenase (LDH) and alkaline phosphatase have been reported to be poor prognostic factors.

 

l. Survival

 

i. The 5-year survival of patients with localized

 

[Figure 2. Osteosarcoma of the right proximal tibia in an 8-year-old boy. A, AP radiograph demonstrates collapse of the medial cortex with a minimally displaced fracture. There is both bone destruction and formation. B, A technetium Tc 99m bone scan reveals avid uptake in the area of the tumor. C, Axial MRI reveals a small medial soft-tissue mass.]

   osteosarcoma in an extremity is 65% to 70%.

 

ii. The 5-year survival of patients with localized pelvic osteosarcoma is 25%.

 

iii. The 5-year survival of patients who present with metastatic disease is 20%.

 

m. The most common site of metastasis is the lungs, followed by the bones.

 

i. Aggressive treatment of late (>1 year) pulmonary metastasis with thoracotomy allows ~30% 5-year survival.

 

ii. Patients with bone metastasis usually die of the disease.

 

n. Skip lesions occur in 10% of patients; prognosis is similar to those with lung metastasis.

 

B. Osteosarcoma subtypes

 

1. Parosteal osteosarcoma—Low-grade surface osteosarcoma composed of dense bone.

 

a.

Demographics

i. Female to male ratio = 2:1

 

ii. Accounts for 5% of all osteosarcomas

 

iii. Most patients are 20 to 45 years of age.

b.

Clinical presentation

i. Classic presentation is swelling of long duration (often years).

 

ii. Pain, limited joint range of motion, limp are variable

 

iii. The most common location is the posterior aspect of the distal femur (75%), followed by the proximal tibia and the proximal humerus.

 

[Table 1. Chemotherapy Drugs Used in the Treatment of Osteosarcoma]

c.

Imaging

i. Dense, lobulated lesion on the surface of the bone (

Figure 3, A)

 

ii. May have underlying cortical thickening

 

iii. Attachment to the cortex may be broad.

 

iv. Occasional minor intramedullary involvement

 

v. The tumor is most dense in the center and least ossified peripherally.

 

[Figure 3. Parosteal osteosarcoma of the distal femur. A, Lateral radiograph of the knee reveals a densely ossified surface lesion on the posterior distal femur that is consistent with a parosteal osteosarcoma.B, CT scan demonstrates the relationship between the tumor and the femoral cortex. C, Gross specimen confirms that it is truly a surface osteosarcoma. D, Low-power histology reveals a bland appearance with regular, ordered, dense trabeculae and interspersed fibrous stroma. E, Higher power reveals minimal cellular atypia.]

 

vi.

Radiographic differential diagnosis includes myositis ossificans and osteochondroma.

 

vii.

MRI or CT scans are helpful in defining the lesional extent before surgery (Figure 3, B).

 

viii.

Dedifferentiated parosteal osteosarcoma has ill-defined areas on the surface of the lesion and hypervascularity on angiographic studies.

 

d.

Pathology

i. Regular, ordered osseous trabeculae (Figure 3, D and E)

 

ii. Bland, fibrous stroma with occasional slightly atypical cells (grade 1)

 

iii. Dedifferentiated parosteal osteosarcoma contains a high-grade sarcoma juxtaposed to the underlying low-grade lesion.

e.

Treatment/outcome

i. Wide surgical resection is the treatment of choice (

Figure 4).

 

ii. High risk of local recurrence with inadequate resection

 

iii. Often the knee joint can be maintained after resection of the lesion and posterior cortex of the femur.

 

iv. Survival is 95% if wide resection is achieved.

 

v. Dedifferentiated variants occur in 25% of patients and are more common after multiple recurrences; survival is 50%.

 

[Figure 4. Radiograph of the proximal femur of a 43-year-old man who was assumed to have metastatic disease; an intramedullary rod was placed in the right femur. Note the osteoblastic appearance of the proximal femur. A later biopsy after continued pain revealed an osteosarcoma. The patient required a hindquarter amputation. This case highlights the importance of a preoperative biopsy.]

2. Periosteal osteosarcoma—Rare, intermediate-grade surface osteosarcoma.

 

a. Demographics

 

i. Occurs in patients 15 to 25 years of age

 

ii. Extremely rare

 

b. Clinical presentation

 

i. Pain is the most common presenting symptom.

 

ii. Most commonly occurs in the femoral or tibial diaphysis

 

c. Imaging

 

i. Lesion has a sunburst periosteal elevation in the diaphysis of long bones (

Figure 5, A).

 

ii. The underlying cortex may be saucerized.

 

iii. No involvement of the medullary canal

 

d. Pathology

 

i. Gross appearance is lobular and cartilaginous (Figure 5, B)

 

ii. Histology reveals extensive areas of chondroblastic matrix, but the tumor produces osteoid (Figure 5, C).

 

iii. Without any osteoid production, the lesion would be a chondrosarcoma.

 

iv. Cellular appearance is grade 2 to 3.

 

[Figure 5. Periosteal osteosarcoma. A, Radiograph demonstrates a lesion in the proximal femur. B, Gross pathology. C, The histology reveals a lobular cartilaginous lesion with moderate cellularity. From this appearance, a malignant cartilage lesion would be suspected. One area reveals osteoid production confirming the diagnosis of periosteal osteosarcoma, which is typically chondroblastic in appearance.]

e. Treatment/outcome

 

i. Some controversy exists whether to use chemotherapy,

 

[

Figure 6. Telangiectatic osteosarcoma. A, AP radiograph of a 14-year-old girl with an osteolytic lesion in the medial aspect of the left proximal tibia. The differential diagnosis includes telangiectatic osteosarcoma or ABC. B, Coronal MRI reveals a lesion of high intensity on T2-weighted imaging, but no fluid levels are seen. C, Low-power histology reveals large blood-filled spaces with intervening fibrous septa. D, The high-power view is required to determine that this is a telangiectatic osteosarcoma with pleomorphic osteoblasts producing osteoid. E, Postoperative radiograph after wide resection of the proximal tibia and reconstruction with a modular proximal tibial endoprosthesis.]

   but the current standard is neoadjuvant chemotherapy followed by wide surgical resection followed by additional chemotherapy.

 

ii. Metastasis develops in 25% of patients.

 

3. High-grade surface osteosarcoma

 

a. Definition—rare, high-grade variant of osteosarcoma that occurs on the bone surface

 

b. Demographics, genetics, etiology, clinical presentation, and pathology are the same as for classic osteosarcoma (see I.A.).

 

c. Radiographic appearance

 

i. Similar to the appearance of a classic osteosarcoma except that it occurs solely on the cortical surface

 

ii. No intramedullary involvement

 

4. Telangiectatic osteosarcoma—Rare histologic variant of osteosarcoma containing large, blood-filled spaces.

 

a. Demographics, genetics/etiology, clinical presentation

 

i. Similar to classic osteosarcoma

 

ii. Rare (only 4% of all osteosarcomas)

 

iii. 25% present with pathologic fracture.

 

b. Imaging

 

i. Purely lytic lesion that occasionally obliterates entire cortex

 

ii. Differential diagnosis primarily includes aneurysmal bone cyst (ABC) (Figure 6).

 

iii. Osteosarcoma has more intense uptake than ABC on bone scan.

 

iv. MRI may show fluid-fluid levels and extensive surrounding edema.

 

c. Pathology

 

i. Grossly, the tumor is described as a "bag of blood."

 

ii. Histology shows large blood-filled spaces (Figure 6, C).

 

iii. Intervening septa contain areas of high-grade sarcoma with atypical mitoses (Figure 6, D).

 

iv. May produce only minimal osteoid

 

v. Occasionally contains benign giant cells

 

vi. Differential diagnosis: primarily ABC

 

d. Treatment/outcome—Same as classic osteosarcoma (see I.A.6).



II. Fibrous/Histiocytic Tumors

A. Malignant fibrous histiocytoma—Malignant fibrous histiocytoma (MFH) is a primary malignant bone tumor similar to osteosarcoma but with histiocytic differentiation and no osteoid (

Figures 7 and

8).

 

1. Demographics

 

a. Occurs in patients 20 to 80 years of age (most are >40 years)

 

b. Slight male predominance

 

2. Genetics/etiology—25% of cases occur as secondary lesions in the setting of a bone infarct, Paget disease, or prior radiation.

 

3. Clinical presentation

 

a. Pain is the primary symptom, followed by swelling, limp, decreased range of motion, and pathologic fracture.

 

b. MFH of bone most commonly occurs in the metaphyses of long bones, primarily the distal femur, proximal tibia, and proximal humerus.

 

4. Imaging

 

a. Lytic, destructive lesion with variable periosteal reaction (Figures 7, A and B, and 8)

 

b. No bone production

 

c. Often has cortical destruction with a soft-tissue mass

 

d. Appearance is often nonspecific, and the differential diagnosis includes any malignant bone tumor or metastasis.

 

5. Pathology

 

a. MFH of bone is the same entity as "undifferentiated pleomorphic sarcoma."

 

b. Storiform appearance with marked pleomorphism and mitotic figures (Figure 7, D)

 

c. Fibrous fascicles radiate from focal hypocellular areas.

 

d. Multinucleated tumor cells with histiocytic nuclei (grooved)

 

e. Areas of chronic inflammatory cells

 

f. Variable collagen production

 

6. Treatment/outcome

 

a. Treat MFH of bone similarly to osteosarcoma with neoadjuvant chemotherapy, wide surgical resection, and postoperative chemotherapy.

 

[Figure 7. Malignant fibrous histiocytoma. AP (A) and lateral (B) radiographs in a 43-year-old man with a destructive lesion in the intertrochanteric region of the right femur. A needle biopsy revealed MFH of bone. He sustained a pathologic fracture during preoperative chemotherapy. C, Gross specimen after proximal femoral resection and reconstruction with a modular endoprosthesis. D, The histology reveals a storiform pattern with marked pleomorphism and a few multinucleated cells.]

[Figure 8. AP radiograph of the right hip and pelvis of a 54-year-old woman with a destructive lesion in the ilium. It is poorly defined, and cortical disruption is seen along the medial wall. A biopsy was consistent with MFH of bone.]

b. As with osteosarcoma, reconstructive options depend on patient age and tumor location but include metal prostheses, osteoarticular/intercalary allografts, allograft-prosthetic composites, expandable prostheses, or vascularized fibular autografts.

 

c. Survival is slightly worse than osteosarcoma, with metastasis primarily to the lung and bones.

 

d. Secondary MFH in a preexisting lesion has a worse prognosis.

 

B. Fibrosarcoma of bone—Rare malignant bone tumor characterized by spindle cells.

 

1. Demographics—Presents in patients from 20 to 70 years of age (most >40 years).

 

2. Clinical presentation

 

a. Pain is the predominant symptom.

 

b. Variable swelling, limp, decreased range of motion

 

c. Occurs most commonly in the femur

 

d. 25% present secondary to preexisting lesions such as Paget disease, prior radiation, or an infarct.

 

[

Figure 9. High-power histologic view of a fibrosarcoma of bone reveals moderately atypical spindle cells arranged in a herringbone pattern along with collagen fibers.]

3. Imaging

 

a. Purely lytic lesion that occurs primarily in the metaphysis

 

b. Focal periosteal reaction

 

c. Poorly defined margins

 

d. May have a soft-tissue mass best defined with MRI

 

e. Appearance is often nonspecific; the differential diagnosis includes any malignant bone tumor or metastasis.

 

4. Pathology

 

a. Histology is spindle cells arranged in a herringbone pattern—fascicles at right angles (Figure 9).

 

b. Can occur in low- to high-grade variants

 

c. Differential diagnosis includes desmoplastic fibroma.

 

d. The number of mitotic figures correlates with the grade of the lesion.

 

5. Treatment/outcome

 

a. The standard treatment of high-grade fibrosarcoma is similar to that for osteosarcoma: neoadjuvant chemotherapy, wide surgical resection, and postoperative chemotherapy.

 

b. Overall survival is correlated with grade of the tumor (30% for high grade, 80% for low grade).

 

c. Overall survival is slightly worse than for osteosarcoma.



III. Cartilage Tumors

A. Chondrosarcoma—Classic intramedullary chondrosarcoma is a malignant cartilage-producing bone tumor that arises de novo or secondary to other lesions.

 

1. Demographics

 

a. Occurs in adult patients (40 to 75 years)

 

b. Slight male predominance

 

c. Central and surface lesions occur with equal frequency.

 

d. Incidence

 

i. Grade 1 = 60%

 

ii. Grade 2 = 25%

 

iii. Grade 3 = 5%

 

iv. Dedifferentiated = 10%

 

2. Genetics/etiology—correlation between high expression of telomerase RT and metastasis

 

3. Clinical presentation

 

a. Pain of prolonged duration (pain can differentiate low-grade chondrosarcoma from benign enchondroma)

 

b. Slow-growing firm mass

 

c. Bowel/bladder symptoms may develop with large pelvic lesions.

 

d. Most common locations include pelvis, proximal femur, scapula

 

e. Location is important for diagnosis (scapula = malignant, hand = benign).

 

f. Wide range of aggressiveness, depending on grade

 

g. Secondary chondrosarcomas occur in the setting of a solitary osteochondroma (<1%), multiple hereditary osteochondromas (1% to 10%), Ollier disease (25% to 40%), or Maffucci disease (100%).

 

4. Imaging

 

a. Radiographic appearance varies by grade of tumor.

 

b. Low-grade intramedullary lesions are similar to enchondromas but they have cortical thickening/expansion, extensive endosteal erosion, and occasional soft-tissue extension (

Figure 10).

 

[Figure 10. Low-grade chondrosarcoma. A, AP radiograph of the left proximal femur in a 65-year-old woman with constant thigh pain shows thickened cortices and proximal intramedullary calcification within the lesion. These findings are consistent with a low-grade chondrosarcoma. B, Coronal MRI reveals the intramedullary extent of the lesion. There is no soft-tissue mass. C, Low-power histology reveals the interface between the bone and a relatively hypocellular cartilage lesion. D, Higher power reveals a grade 1 chondrosarcoma with a bland cellular appearance, extensive basophilic cytoplasm, and no mitotic figures.]

[

Figure 11. High-grade chondrosarcoma. A, AP radiograph of the left anterior pelvis in a 42-year-old woman reveals a destructive lesion of the inferior pubic ramus with a soft-tissue mass. B, CT scan defines the mass. There is evidence of intralesional calcium within the mass. This radiographic appearance is consistent with a chondrosarcoma. C, The histology reveals a hypercellular lesion with atypical cells and permeation of the trabecular spaces consistent with a high-grade lesion.]

[

Figure 12. Grade 2 chondrosarcoma. A, AP radiograph of the left foot in a 68-year-old man with a destructive lesion in the metatarsal. B, Axial MRI reveals an extensive soft-tissue mass and the tissue diagnosis was a grade 2 chondrosarcoma. He required a below-knee amputation.]

c. Low-grade lesions have rings, arcs, and stipples and are usually mineralized.

 

d. Low-grade chondrosarcoma is usually >8 cm in the long bones.

 

e. Low-grade pelvic chondrosarcoma can grow to large size (>10 cm) with extensive soft-tissue extension toward surrounding viscera.

 

f. Intermediate- or high-grade chondrosarcoma is less well defined, involves frank cortical destruction, and often has an associated soft-tissue mass (Figures 11 through

13).

 

g. Dedifferentiated chondrosarcoma is a high-grade sarcoma juxtaposed to a benign or low-grade malignant cartilage lesion, noted radiographically by a calcified intramedullary lesion with an adjacent destructive lytic lesion (

Figure 14).

 

h. Secondary chondrosarcomas appear with ill-defined edges or thickened cartilage caps (>2cm) next to an enchondroma or osteochondroma, respectively (

Figure 15).

 

i. Bone scan shows increased uptake in all variants and grades of chondrosarcoma.

 

j. CT or MRI scans are helpful in defining cortical destruction and marrow involvement, respectively.

 

5. Pathology

 

a. Low-grade tumors are grossly lobular, whereas higher grade tumors may be myxoid.

 

b. Needle biopsy is not helpful in determining the grade of a cartilage tumor.

 

c. Low-grade chondrosarcomas have a bland histologic appearance, but permeation and entrapment of the existing trabeculae are present (Figure 10, C and D).

 

d. Mitotic figures are rare.

 

e. Higher grade chondrosarcomas have a hypercellular pattern with binucleate forms and occasional myxoid change (Figure 11, C).

 

f. Dedifferentiated chondrosarcomas reveal a high-grade sarcoma (MFH, fibrosarcoma, osteosarcoma) adjacent to a low-grade or benign cartilage tumor (Figure 14, D).

 

[Figure 13. CT scan of the scapula reveals a large soft-tissue mass with tissue consistent with a grade 3 chondrosarcoma. There are intralesional calcifications. The scapula is a common location for this tumor.]

6. Treatment/outcome

 

a. Grade 1 chondrosarcomas in the extremities can be treated with careful intralesional curettage or wide resection.

 

b. All pelvic chondrosarcomas should be resected with an adequate margin (may require amputation).

 

c. Local recurrence rate at 10 years is ~20%.

 

d. Recurrent lesions have a 10% chance of increasing in grade.

 

e. Grade 2, 3, or dedifferentiated chondrosarcomas require wide surgical resection regardless of location.

 

f. No current role for chemotherapy or radiation except in dedifferentiated chondrosarcoma (receive chemotherapy depending on patient age/condition)

 

[Figure 14. Dedifferentiated chondrosarcoma. A, AP radiograph of the femur in a 73-year-old man reveals a lesion similar to an enchondroma within the medullary canal but there is an ill-defined lucency distal to the lesion. B, Coronal MRI reveals the intramedullary extent of the lesion, which is much different from an enchondroma and raises the concern for a dedifferentiated chondrosarcoma. C, Axial MRI demonstrates a circumferential soft-tissue mass consistent with a high-grade lesion. D, A high-power histologic view shows low-grade cartilage juxtaposed to a high-grade sarcomatous lesion. This is a dedifferentiated chondrosarcoma.]

[Figure 15. Chondrosarcoma. A, AP radiograph in a 35-year-old woman with multiple hereditary osteochondromas who has new onset of hip pain that has become constant. Note the proximal femoral osteochondroma with an ill-defined area proximal to the lesion. B, Coronal MRI reveals the osteochondroma to have the same appearance as the adjacent pelvic marrow, but the proximal aspect is composed of soft tissue consistent with malignant degeneration. C, Gross appearance of the lesion after resection of the proximal femur. The histology revealed a grade 1 chondrosarcoma.]

[

Figure 16. The low-power view of a clear cell chondrosarcoma reveals a cellular lesion with minimal matrix. The cartilage cells have clear cytoplasm, and there are additional benign giant cells within the lesion.]

g. Metastasis to the lungs is treated with thoracotomy.

 

h. Slow progression of disease requires long-term follow-up (~20 years).

 

i. Overall survival depends on the grade of the tumor.

 

i. Grade 1 = 90%

 

ii. Grade 2 = 60% to 70%

 

iii. Grade 3 = 30% to 50%

 

iv. Dedifferentiated = 10%

 

B. Chondrosarcoma subtypes

 

1. Clear cell chondrosarcoma—Rare malignant cartilage tumor with immature cartilaginous histiogenesis.

 

a. Demographics, genetics/etiology, and clinical presentation are the same as for classic chondrosarcoma (see III.A.1-3).

 

b. Radiographic appearance

 

i. Clear cell chrondrosarcoma occurs in the epiphysis of long bones, most commonly in the proximal femur or proximal humerus.

 

ii. Lytic, round, expansile well-defined lesion

 

iii. No periosteal reaction

 

iv. Mineralization may be evident within the lesion.

 

v. Most often confused with a benign chondroblastoma

 

c. Pathology

 

i. Intermediate- to high-grade lesion formed of immature cartilage cells (Figure 16)

 

ii. Lobular growth pattern

 

iii. Benign giant cells throughout the tumor

 

[

Figure 17. Chondrosarcoma. A, A composite lateral and AP radiograph of the distal femur in a 28-year-old woman reveals a poorly defined lytic lesion with destruction of the anterior cortex. B, Low-power histology reveals a biphasic appearance to the lesion with cartilage as well as small round cells consistent with a mesenchymal chondrosarcoma. C, Higher power of the junction between the low-grade cartilage and the sheets of small cells.]

iv. Extensive clear cytoplasm with minimal matrix

 

d. Treatment/outcome

 

i. Wide surgical resection required for cure

 

ii. Chemotherapy and radiation not effective

 

iii. Metastasis to bones and lungs

 

iv. Good prognosis—5-year survival is 80%

 

2. Mesenchymal chondrosarcoma—Rare primary bone tumor composed of a biphasic pattern of cartilage and small round cell components (Figure 17).

 

a. Demographics—Occurs in younger individuals (10 to 40 years of age) than classic chondrosarcoma.

 

b. Clinical presentation

 

i. Most common in the flat bones (ilium, ribs, skull), but can occur in the long bones

 

ii. 30% of cases involve only soft tissue.

 

iii. May involve multiple skeletal sites at presentation

 

iv. Pain and swelling of long duration are the most common symptoms.

 

c. Radiographic appearance

 

i. Lytic destructive lesions with stippled calcification within the lesion (Figure 17, A)

 

ii. Expansion of bone with cortical thickening and poor margination

 

iii. Nonspecific appearance can be included in a differential of any malignant or metastatic lesion.

 

d. Pathology—Biphasic histologic pattern of low-grade islands of cartilage alternating with sheets of small anaplastic round cells (Figure 17, B and C).

 

e. Treatment/outcome

 

i. Treatment: chemotherapy and wide surgical resection

 

ii. Survival: 30% to 60% at 5 years

 

iii. Few series in the literature



IV. Round Cell Lesions

A. Ewing sarcoma/primitive neuroectodermal tumor (PNET)—Malignant bone tumor composed of small round blue cells.

 

1. Demographics

 

a. Male to female ratio = 3:2

 

b. Uncommon in African Americans and Chinese

 

c. Second most common primary bone tumor in children (80% are younger than 20 years)

 

2. Genetics/etiology

 

a. Cell of origin unknown

 

b. Hypothesized to be of neuroectodermal differentiation. PNET is thought to be the differentiated neural tumor, whereas Ewing sarcoma is the undifferentiated variant.

 

c. Classic 11:22 chromosomal translocation (EWS/FLI1 is the fusion gene)

 

3. Clinical presentation

 

a. Pain is the most common symptom.

 

b. Swelling, limp, and decreased range of motion are variable.

 

c. Frequent fever, occasional erythema (mistaken for infection)

 

[

Figure 18. Ewing sarcoma/PNET. A, AP and B, lateral radiographs of the left tibia/fibula in an 11-year-old boy reveal a lesion in the fibular diaphysis. After needle biopsy, it was diagnosed as a Ewing sarcoma. The initial periosteal reaction ossified slightly after two cycles of neoadjuvant chemotherapy. C, Axial MRI reveals an extensive soft-tissue mass at diagnosis consistent with a small round cell lesion. D, Low-power histology reveals a small round blue cell lesion with large sheets of necrosis. E, Higher power reveals the monotonous small cells with prominent nuclei and scant cytoplasm.]

d. Elevated erythrocyte sedimentation rate (ESR), LDH, white blood cell count

 

e. The most common locations are the pelvis, diaphysis of long bones, and scapula.

 

f. Staging workup includes a bone marrow biopsy in addition to the standard studies (CT chest, radiograph/MRI of primary lesion, bone scan).

 

4. Imaging

 

a. Purely lytic bone destruction

 

b. Periosteal reaction in multiple layers (the classic reaction, called "onion skin") or sunburst pattern (Figure 18, A and B).

 

c. Poorly marginated and permeative

 

d. Extensive soft-tissue mass often present despite more subtle bone destruction (

Figures 19 and

20)

 

e. MRI necessary to identify soft-tissue extension and marrow involvement (Figure 18, C)

 

f. Radiographic differential diagnosis includes osteomyelitis, osteosarcoma, eosinophilic granuloma, osteoid osteoma, lymphoma.

 

5. Pathology

 

a. Gross appearance may be a liquid consistency, mimicking pus.

 

b. Small round blue cells with round/oval nuclei (Figure 18, D and E)

 

c. Indistinct cell outlines

 

d. Prominent nuclei and minimal cytoplasm

 

[Figure 19. Ewing sarcoma of the pelvis. A, AP radiograph reveals an indistinct abnormality in the right supra-acetabular region. B, Technetium Tc 99m bone scan reveals avid uptake in this area. C, Axial MRI of the acetabular region reveals an elevated periosteum. A biopsy was consistent with Ewing sarcoma.]

[Figure 20. Ewing sarcoma in a 14-year-old boy. AP (A) and lateral (B) radiographs of the femur reveal a diaphyseal lesion with a sunburst pattern of periosteal reaction. C, Axial MRI reveals an extensive soft-tissue mass. A biopsy revealed Ewing sarcoma.]

e. Reactive osseous or fibroblastic tissue may be present.

 

f. Can be broad sheets of necrosis and widely separated fibrous strands

 

g. Differential diagnosis includes lymphoma, osteomyelitis, neuroblastoma, rhabdomyosarcoma, eosinophilic granuloma, leukemia.

 

h. Immunohistochemical stains helpful—-CD99 positive (013 antibody)

 

i. 11:22 chromosomal translocation produces EWS/FLI1, which can be identified by polymerase chain reaction and differentiates Ewing sarcoma from other round cell lesions.

 

j. Additional features seen only in PNET include a more lobular pattern and arrangement of the cells in poorly formed rosettes around an eosinophilic material (

Figure 21).

 

6. Treatment/outcome

 

a. Standard treatment of Ewing sarcoma is neoadjuvant chemotherapy.

 

b. Most common chemotherapy drugs include vincristine, adriamycin (doxorubicin), ifosfamide, etoposide, cytoxan, and actinomycin D.

 

[Figure 21. High-power histology of a PNET lesion. Note that the cells are arranged in a rosette pattern around a central eosinophilic substance.]

c. Local control of the primary tumor can be achieved by either wide surgical resection or external beam radiation.

 

d. Most isolated extremity lesions are treated with surgical resection rather than radiation because of potential side effects of radiation and better local control with surgery.

 

e. Radiation is often used for the primary lesion when patients present with metastatic disease.

 

f. Local control is controversial for pelvic Ewing sarcoma: surgery or radiation or both.

 

g. Complications of radiation in skeletally immature patients include joint contractures, fibrosis, growth arrest, fracture, and secondary malignancy (usually 10 to 20 years later).

 

h. Response to chemotherapy (percent necrosis) is used as a prognostic indicator for overall survival.

 

i. Patients with isolated extremity Ewing sarcoma have a 5-year survival of 65% to 70%.

 

j. Patients who present with metastatic disease have a poor prognosis (5-year survival <20%).

 

k. Metastases occur primarily in the lungs but also in the bone and bone marrow.

 

l. Adverse prognostic factors include nonpulmonary metastasis, <90% necrosis, large tumor volume, pelvic lesions.

 

m. PNET is thought to have a slightly worse prognosis than Ewing sarcoma.



V. Notochordal and Miscellaneous

A. Chordoma—Slow-growing malignant bone tumor arising from notochordal rests and occurring in the spinal axis.

 

1. Demographics

 

a. Male to female ratio = 3:1 (most apparent in sacral lesions)

 

b. Occurs in adult patients (older than 40 years)

 

c. Lesions at base of skull present earlier than sacral lesions

 

2. Genetics/etiology—Chordoma is thought to develop from residual notochordal cells that eventually undergo neoplastic change.

 

3. Clinical presentation

 

a. Insidious onset of low back or sacral pain

 

b. Frequently misdiagnosed as osteoarthritis, nerve impingement, disk herniation

 

c. Infrequent distal motor/sensory loss because most lesions occur below S1

 

d. Bowel/bladder symptoms are common.

 

e. 50% can be identified on a careful rectal examination. (Do not perform a transrectal biopsy.)

 

f. 50% occur in the sacrococcygeal region, 35% in the spheno-occipital region, and 15% in the mobile spine.

 

4. Imaging

 

a. Chordomas occur in the midline, consistent with prior notochord location.

 

b. Subtle findings on plain radiographs because of overlying bowel gas

 

c. Cross-sectional imaging with CT or MRI required (

Figure 22, A through C)

 

d. CT reveals areas of calcification within the lesion.

 

e. MRI (low intensity on T1-weighted images, high intensity on T2-weighted images) defines the extent of the frequent anterior soft-tissue mass and the bony involvement (usually involves multiple sacral levels).

 

f. Radiographic differential diagnosis includes chondrosarcoma, multiple myeloma, metastatic disease, giant cell tumor, and lymphoma (

Table 2).

 

5. Pathology

 

a. Grossly, chordoma appears lobulated and jelly-like,

 

[Figure 22. Chordoma. A, CT scan of the sacrum in a 66-year-old man reveals a destructive lesion with an anterior soft-tissue mass containing calcifications. B, Axial MRI further defines the soft-tissue extension anteriorly and toward the left pelvic sidewall. C, Sagittal T1-weighted MRI shows the lesion at S3 and below. The anterior extension abuts the rectum. D, Low-power histology of this lesion reveals a tumor lobule surrounded by fibrous tissue. E, Higher power reveals the physaliferous cells of a chordoma with a bubbly appearance to the cytoplasm.]

   with tumor tracking along the nerve roots.

 

b. The signature cell is the physaliferous cell, which contains intracellular vacuoles and appears bubbly (cytoplasmic mucous droplets) (Figure 22, D and E).

 

c. Lobules of the tumor are separated by fibrous septa.

 

d. Physaliferous cells are keratin-positive, which differentiates this tumor from chondrosarcoma.

 

e. Weakly S100-positive

 

f. Differential diagnosis includes chondrosarcoma and metastatic carcinoma.

 

6. Treatment/outcome

 

a.

The main treatment is wide surgical resection.

b.

Local recurrence is common (50%) and is directly related to the surgical margin achieved.

 

[Table 2. Tumors Occurring in the Vertebrae]

[

Figure 23. Adamantinoma. A, AP radiograph of the tibia in a 38-year-old woman reveals multiple diaphyseal lucent lesions separated by sclerotic bone. They have a bubbly appearance consistent with adamantinoma. B, A gross specimen from a different patient reveals lesions in both the tibia and fibula that expand the bone. C, The histologic appearance is nests of epithelial cells in a fibrous stroma.]

c.

To achieve a satisfactory wide margin, the surgeon must be willing to sacrifice involved nerve roots, viscera, etc.

d.

Radiation can be used as an adjunct for locally recurrent disease, positive margins, or as primary treatment of inoperable tumors (protons or external beam).

e.

Radiation alone is generally not effective for local control.

f.

Chemotherapy is not effective and is currently not indicated.

g.

Chordoma metastasizes late to the lungs and occasionally bone; requires long-term follow-up (20 years).

h.

Long-term survival is 25% to 50%, due in part to local progression.

 

B. Adamantinoma—Unusual, rare, slow-growing malignant bone tumor with a predilection for the tibia (Figure 23)

 

1. Demographics

 

a. No gender predilection

 

b. Patients are generally 20 to 40 years of age.

 

c. Fewer than 300 cases in the literature

 

2. Genetics/etiology—Controversy whether adamantinoma evolves from osteofibrous dysplasia; most believe it does not.

 

3. Clinical presentation

 

a. Pain of variable duration and intensity is the major symptom.

 

b. Occasional tibial deformity or a mass

 

c. Tenderness over the subcutaneous tibial border

 

d. History of preceding trauma is common.

 

e. 90% of lesions occur in the tibial diaphysis.

 

4. Imaging

 

a. Classic radiographic appearance is multiple well-circumscribed lucent defects, usually with one dominant defect that may locally expand the bone (Figure 23, A).

 

b. Sclerotic bone between defects

 

c. "Soap bubble" appearance

 

d. Lesions may be intracortical or intramedullary, with occasional (10%) soft-tissue mass.

 

e. No periosteal reaction

 

5. Pathology

 

a. Nests of epithelial cells in a benign fibrous stroma (Figure 23, C)

 

b. Epithelial cells are columnar in appearance and keratin-positive.

 

c. Epithelial cells are bland without mitosis.

 

6. Treatment/outcome

 

a. Standard of care is wide surgical resection.

 

b. Chemotherapy and radiation are not indicated.

 

c. Local recurrence is more common when adequate margins are not achieved.

 

d. Given diaphyseal location, common reconstruction is intercalary allograft

 

e. Late metastasis to lungs, bones, lymph nodes in 15% to 20%

 

f. Requires long-term follow-up

 

g. Case series from 2000 described 87% survival at 10 years.



VI. Systemic Disease

A. Multiple myeloma—Neoplastic proliferation of plasma cells producing a monoclonal protein.

 

1. Demographics

 

a. Considered the most common primary malignant bone tumor

 

b. Affects patients >40 years of age

 

c. Twice as common in blacks as whites

 

d. Affects males more than females

 

2. Genetics/etiology

 

a. Immunoglobulins (Igs) are composed of two heavy chains and two light chains.

 

i. Heavy chains = IgG, IgA, IgM, IgD, and IgE (IgG and IgA common in myeloma)

 

ii. Light chains = κ and λ (Bence Jones proteins)

 

b. In myeloma, both heavy and light chains are produced.

 

c. Major mediators of osteoclastogenesis in myeloma include receptor activator of nuclear factor κ B ligand (RANKL), interleukin-6, and macrophage inflammatory protein-1α.

 

d. Osteoblastic bone formation is suppressed by tumor necrosis factor and Dickkopf-1 (Dkk-1).

 

3. Clinical presentation

 

a. Common symptoms include bone pain, pathologic fractures, cord compression, and recurrent infections.

 

b. Occurs throughout the skeleton but is common in bones that contain hematopoietic marrow, including the skull, spine, and long bones (

Figure 24)

 

c. Laboratory findings: normochromic, normocytic anemia, hypercalcemia, renal failure, amyloidosis, elevated ESR

 

d. Electrophoresis (99% of patients have a spike on one or both)

 

i. Serum—identifies types of proteins present.

 

ii. Urine—identifies Bence Jones proteins.

 

e. 24-hour urine collection—quantifies protein in urine.

 

[Figure 24. This 47-year-old woman presented with a pathologic fracture through a lytic lesion, and open biopsy at the time of surgery showed a plasma cell lesion consistent with multiple myeloma.]

f. β2 microglobulin—tumor marker with prognostic ability (increased β2 microglobulin = poor prognosis)

 

g. Diagnosis—One major and one minor (or three minor) diagnostic criteria must be present.

 

i. Major criteria

 

(a) Plasmacytoma—tissue diagnosis on biopsy

 

(b) >30% plasma cells in bone marrow

 

(c) Serum IgG >3.5 g/dL, IgA >2 g/dL or urine >1 g/24 hours, or Bence Jones protein

 

ii. Minor criteria

 

(a) 10% to 30% plasma cells in bone marrow

 

(b) Serum/urine protein levels lower than listed for major criteria

 

(c) Lytic bone lesions

 

(d) Lower than normal IgG levels

 

[

Figure 25. Multiple myeloma. A, AP radiograph in a 67-year-old woman with constant right shoulder pain shows a lytic lesion in the humeral head. B, A workup included a skeletal survey after a positive serum protein electrophoresis. A punched-out lytic lesion was noted in the skull, consistent with multiple myeloma. C, A high-power view of myeloma reveals numerous plasma cells with eccentric nuclei and extensive vascularity.]

[

Figure 26. Multiple myeloma. A, A lateral thoracic spine radiograph demonstrates the severe osteopenia present in multiple myeloma contributing to compression fractures. Note the prior injection of cement to stabilize a vertebral body in the lower part of the figure. B, Sagittal MRI of the thoracic spine in a patient with long-standing multiple myeloma shows multiple vertebral lesions with an area of epidural extension.]

4. Imaging

 

a. Classic appearance is multiple "punched-out" lytic lesions throughout the skeleton (Figures 25, A and Band 26, A)

 

b. No surrounding sclerosis

 

c. Skull lesions and vertebral compression fractures are common (Figures 25, B and 26, A).

 

d. Diffuse osteopenia (Figure 26, A)

 

e. Bone scan is usually negative because there is minimal osteoblastic response in myeloma.

 

f. Skeletal survey is the screening tool of choice.

 

g. MRI is not necessary for screening but is helpful in defining vertebral lesions (Figure 26, B).

 

5. Pathology

 

a. Lesion consists of sheets of plasma cells with eccentric nuclei; little intercellular material (Figure 25, C).

 

b. Nuclear chromatin arranged in a "clock face" pattern

 

c. Abundant eosinophilic cytoplasm

 

d. Rare mitotic figures

 

e. Extremely vascular, with extensive capillary system

 

f. Immunohistochemistry stains—CD38+

 

6. Treatment/outcome

 

a. Primary treatment is cytotoxic chemotherapy (often in combination with prednisone or dexamethasone).

 

b. Chemotherapy agents include melphalan, cyclophosphamide, doxorubicin, thalidomide (second line).

 

c. Bisphosphonates help to decrease number of lesions, bone pain, and serum calcium.

 

d. Autologous stem cell transplant improves survival.

 

e. Radiation effective to decrease pain, avoid surgery

 

f. Surgical stabilization of pathologic fractures or impending fractures (similar principles as used in metastatic disease)

 

g. Kyphoplasty/vertebroplasty common to treat vertebral compression fractures

 

h. Survival worse with renal failure

 

i. 10-year survival is 10%.

 

j. Median survival is 3 years.

 

B. Plasmacytoma

 

1. Plasma cell tumor in a single skeletal site

 

2. Represents 5% of patients with plasma cell lesions

 

3. Negative serum/urine protein electrophoresis

 

4. Bone marrow biopsy/aspirate negative

 

5. Treated with radiation alone (4,500 to 5,000 cGy)

 

6. Progresses to myeloma in ~55% of patients

 

C. Osteosclerotic myeloma

 

1. Accounts for 3% of cases

 

2. POEMS syndrome = polyneuropathy, organomegaly, endocrinopathy, M-spike, skin changes

 

D. B-cell lymphoma—Clonal proliferation of B-cells commonly presenting as nodal disease and occasionally affecting the skeleton.

 

1. Demographics

 

a. Can occur at any age but most commonly in patients aged 35 to 55 years

 

b. Affects males more than females

 

c. Non-Hodgkin lymphoma most commonly affects the bone (B-cell much more common than T-cell variants).

 

d. 10% to 35% of patients with non-Hodgkin lymphoma have extranodal disease.

 

e. Primary lymphoma of bone can occur but is quite rare.

 

2. Genetics/etiology—Risk factors for B-cell lymphoma include immunodeficiency (human immunodeficiency virus, hepatitis) and viral/bacterial infection.

 

3. Clinical presentation

 

a. Constant pain unrelieved by rest

 

b. A large soft-tissue mass that is tender or warm is common.

 

c. Lymphoma affects bones with persistent red marrow (femur, spine, pelvis).

 

d. Neurologic symptoms from spinal lesions

 

e. 25% present with pathologic fracture.

 

f. B-symptoms = fever, weight loss, and night sweats

 

g. Primary lymphoma of bone is rare and occurs when there are no extraskeletal sites of disease (other than a single node) for 6 months after diagnosis.

 

4. Imaging appearance

 

a. Lytic, permeative lesions that can show subtle bone destruction (

Figure 27, A)

 

b. Generally involves the diaphysis in long bones

 

c. Can involve multiple sites in the skeleton

 

d. Intensely positive on bone scan

 

e. Extensive marrow involvement noted on MRI

 

f. Often large soft-tissue mass (Figure 27, B and C)

 

g. PET helpful in staging and follow-up of disease

 

h. Radiographic differential diagnosis includes metastatic disease, myeloma. and osteomyelitis.

 

5. Pathology

 

a. Difficult to diagnose on needle biopsy because the tissue is often crushed

 

b. Diffuse infiltrative rather than nodular pattern

 

c. Lesion comprised of small round blue cells (2× size of lymphocytes and can be variable) (Figure 27, D)

 

d. Immunohistochemistry stains—CD20+, CD45+

 

e. Primary lymphoma of bone; increased percentage of cleaved cells improves prognosis.

 

6. Treatment/outcome

 

a. Bone marrow biopsy and CT of the chest, abdomen, and pelvis are required as part of staging/workup.

 

b. Chemotherapy is the primary treatment. Chemotherapeutic agents include cyclophosphamide, doxorubicin, prednisone, and vincristine.

 

c. Radiation of the primary site is used in some individuals for persistent disease.

 

d. Surgical treatment is necessary only for pathologic fractures because chemotherapy alone is effective for most lesions.

 

e. 5-year survival is as high as 70% in series where chemotherapy and radiation were used for disseminated disease.

 

[Figure 27. Lymphoma. A, AP radiograph of the left pelvis in a 72-year-old woman with lateral hip pain reveals an extensive lytic lesion of the ilium causing a pathologic fracture. Coronal (B) and axial (C) MRI scans reveal the extent of the surrounding soft-tissue mass. D, A high-power histologic view reveals a small round blue cell lesion (larger than lymphocytes). A CD20 stain was positive for a B-cell lymphoma.]

f. Secondary involvement of bone in lymphoma has a worse prognosis than primary lymphoma of bone.



VII. Secondary Lesions

A. Overview

 

1. Secondary lesions can be benign (secondary ABC), but most commonly they are malignant (postradiation sarcoma, Paget sarcoma, sarcomas emanating from infarct or fibrous dysplasia, squamous carcinomas from osteomyelitis/draining sinus) (

Table 3 and

Figures 28 and

29).

 

2. These lesions develop from a preexisting tumor, process, or treatment.

 

B. Postradiation sarcoma—A postradiation sarcoma develops with a latent period after radiation has been used to treat a benign or malignant bone, soft-tissue, or visceral tumor.

 

1. Demographics

 

a. These lesions can occur at any age after radiation of a prior tumor (Ewing sarcoma, cervical/breast/prostate cancer, giant cell tumor, soft-tissue sarcoma, retinoblastoma).

 

b. More common in children exposed to radiation than in adults

 

c. Latent period is variable (4 to 40 years; median ~10 years)

 

d. Literature suggests children with Ewing sarcoma treated with radiation have a 5%-10% risk of postradiation malignancy at 20 years (7% for a postradiation sarcoma).

 

2. Genetics/etiology

 

a. Ionizing radiation causes DNA damage and creates free radicals.

 

b. Incidence dependent on dose, type, and rate of radiation treatment

 

c. May be affected by the use of chemotherapy (especially alkylating agents)

 

[Table 3. Secondary Lesions]

3. Clinical presentation

 

a. Gradual onset of intermittent, then constant, pain in a previously radiated site

 

b. Can affect any skeletal site

 

[Figure 28. Secondary sarcoma. A, AP radiograph of the right anterior pelvis in a 68-year-old man with a history of prostate cancer (note radiation seeds) shows a destructive lesion in the right pubic rami.B, Axial MRI shows the extent of the surrounding soft-tissue mass. The biopsy revealed a high-grade sarcoma that was presumably radiation-induced.]

4. Imaging appearance

 

a. Lytic, aggressive, destructive bone lesion (Figure 28, A)

 

b. Possible soft-tissue mass (Figure 28, B)

 

c. MRI used to define the extent of the lesion

 

5. Pathology

 

a. Histology shows the high-grade sarcoma (osteosarcoma, MFH, fibrosarcoma).

 

b. May be histologic evidence of prior irradiation in the surrounding tissues

 

6. Treatment/outcome

 

a. Treatment is chemotherapy and surgical resection.

 

b. Poor prognosis, with 25% to 50% 5-year survival (worse in sites not amenable to surgical resection)

 

c. Metastasis primarily to the lung

 

C. Paget sarcoma—Arises from a skeletal area affected by Paget disease.

 

1. Demographics

 

a. Occurs in older patients (>50 years of age)

 

b. Occurs in ~1% of patients with Paget disease

 

2. Clinical presentation

 

a. New onset of pain in an area affected by Paget disease

 

b. Possible swelling or pathologic fracture

 

c. Commonly affects pelvis, proximal femur

 

[Figure 29. Radiograph of the right lower extremity of a 64-year-old man with a diagnosis of polyostotic fibrous dysplasia. He sustained a pathologic fracture of the right proximal tibia through a lytic lesion, and an intramedullary device was placed without a preoperative biopsy. The eventual biopsy revealed a high-grade osteosarcoma developing from an area of fibrous dysplasia. The patient required an above-knee amputation.]

3. Imaging appearance

 

a. Marked bone destruction and possible soft-tissue mass in a skeletal site affected by Paget disease

 

b. Helpful to have prior documentation of the radiographic appearance

 

c. MRI helpful to define the extent of the sarcoma within the abnormal bone

 

4. Pathology—Histology shows a high-grade sarcoma (osteosarcoma, MFH, fibrosarcoma, chondrosarcoma) within an area of pagetoid bone.

 

5. Treatment/outcome

 

a. Poor prognosis, with <10% 5-year survival rate

 

b. Treat as a primary bone sarcoma with chemotherapy and surgical resection

 

c. Radiation is palliative only.

 

d. High rate of metastasis to the lung



Top Testing Facts

Osteosarcoma and Malignant Fibrous Histiocytoma

1. Osteosarcoma is the most common malignant bone tumor in children.

 

2. Osteosarcoma classically occurs in the metaphysis of long bones and presents with progressive pain.

 

3. Osteosarcoma has a radiographic appearance of bone destruction and bone formation starting in the medullary canal.

 

4. The osteoblastic stromal cells are malignant in osteosarcoma.

 

5. The 5-year survival of patients with osteosarcoma is 65% to 70%.

 

6. Parosteal and periosteal osteosarcomas occur on the surface of the bone.

 

7. Parosteal osteosarcoma is a low-grade lesion that appears fibrous histologically and is treated with wide surgical resection alone.

 

8. Periosteal osteosarcoma is an intermediate-grade lesion that appears cartilaginous and is treated with chemotherapy and surgical resection.

 

9. Telangiectatic osteosarcoma can be confused with an aneurysmal bone cyst.

 

10. Malignant fibrous histiocytoma of bone presents and is treated like osteosarcoma but no osteoid is noted histologically.

 

Chondrosarcoma

1. Chondrosarcoma occurs de novo or secondary to an enchondroma or osteochondroma.

 

2. Chondrosarcoma occurs in adults, whereas osteosarcoma and Ewing sarcoma occur primarily in children.

 

3. The pelvis is the most common location for chondrosarcoma.

 

4. Pelvic chondrosarcomas require wide resection regardless of grade.

 

5. Chemotherapy is used only in the dedifferentiated and mesenchymal chondrosarcoma variants.

 

6. Tumor grade is a major prognostic factor for chondrosarcoma.

 

7. Grade 1 chondrosarcomas rarely metastasize and have a >90% survival.

 

8. The survival for patients with dedifferentiated chondrosarcoma is the lowest of all bone sarcomas (10%).

 

9. Clear cell chondrosarcoma has a radiographic appearance similar to chondroblastoma.

 

10. Radiation is not used in the treatment of chondrosarcoma.

 

Ewing Sarcoma/PNET

1. Ewing sarcoma is one of a group of small round blue cell tumors not distinguishable based on histology alone.

 

2. Ewing sarcoma is the second most common malignant bone tumor in children.

 

3. Ewing sarcoma is found most commonly in the diaphysis of long bones as well as in the pelvis.

 

4. No matrix is produced by the tumor cells, so the radiographs are purely lytic.

 

5. There may be extensive periosteal reaction and a large soft-tissue mass.

 

6. Ewing sarcoma is CD99-positive and has the 11:22 chromosomal translocation.

 

7. Ewing sarcoma is radiation-sensitive, but surgery is used more commonly for local control unless the patient has metastatic disease.

 

8. Ewing sarcoma requires multiagent chemotherapy

 

9. Ewing sarcoma can metastasize to the lungs, bone, and bone marrow.

 

10. The 5-year survival rate of patients with isolated extremity Ewing sarcoma is 65% to 70%.

 

Chordoma and Adamantinoma

1. Chordoma occurs exclusively in the spinal axis, although many lesions should be considered in the differential of a destructive sacral lesion.

 

2. Chordoma occurs in adults and has a prolonged course; misdiagnosis is common.

 

3. Plain radiographs often do not identify sacral destruction from chordoma—cross-sectional imaging is required.

 

4. CT scan of a chordoma shows calcified areas within the tumor.

 

5. Chordoma consists of physaliferous cells on histologic examination.

 

6. Surgical cure of chordoma requires a wide resection—possibly removing nerve roots, bowel, bladder, etc.

 

7. Radiation can be used in an adjunct fashion for chordoma, but chemotherapy has no role.

 

8. Adamantinoma occurs primarily in the tibial diaphysis and has a soap bubble radiographic appearance.

 

9. Adamantinoma consists of nests of epithelial cells in a fibrous stroma and is keratin-positive.

 

10. Adamantinoma requires a wide surgical resection for cure.

 

Multiple Myeloma and Lymphoma

1. Multiple myeloma is the most common primary malignant bone tumor.

 

2. Myeloma often presents with normochromic, normocytic anemia.

 

3. Myeloma presents radiographically with multiple punched-out lytic lesions.

 

4. Myeloma is typically "cold" on bone scan.

 

5. Myeloma is composed of sheets of plasma cells.

 

6. Myeloma is treated with chemotherapy, bisphosphonates, and possibly autologous stem cell transplant.

 

7. Lymphoma affecting bone is usually non-Hodgkin B-cell subtype.

 

8. Subtle radiographic bone destruction with extensive marrow and soft-tissue involvement is typical.

 

9. Lymphoma cells are CD20+ on immunohistochemistry staining.

 

10. B-cell lymphoma is treated with chemotherapy and radiation and rarely requires surgery.

 

Secondary Lesions

1. Secondary lesions can be benign (secondary ABC or giant cell tumor) but are most commonly sarcomas.

 

2. Secondary sarcomas arise in areas of Paget disease, prior radiation, or previous lesions (bone infarcts, fibrous dysplasia).

 

3. New onset pain in the site of a previous lesion or site of radiation is suspicious for a secondary lesion.

 

4. Radiographic appearance of a secondary sarcoma is an aggressive, destructive bone tumor.

 

5. Histologic appearance is of a high-grade sarcoma (osteosarcoma, MFH, fibrosarcoma, chondrosarcoma).

 

6. Secondary sarcomas have a uniformly poor prognosis; treatment is with chemotherapy and surgery.

 

7. MFH of bone can arise in a prior infarct and has a poor prognosis.

 

8. Fewer than 1% of fibrous dysplasia lesions undergo malignant change to MFH or osteosarcoma.

 

9. Secondary squamous cell carcinoma can arise in long-standing osteomyelitis with a draining sinus tract.

 

10. Secondary chondrosarcomas can occur in prior enchondromas or osteochondromas (more commonly in patients with Ollier, Maffucci, or multiple hereditary osteochondromas).



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