Miller- Ortho Onc Bone Flashcards
Review Bone Tumor Presentation
The patient with a bone tumor may present with pain, a mass, or a fracture, or the mass lesion be incidentally found.
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Pain may occur from a mechanical disruption of bone, a pathologic fracture, or compression by an expanding tumor.
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Pain may occur with weight bearing and may progress to constant pain at rest that is not relieved by pain medications.
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High-grade tumors typically manifest with a short interval of pain (1–3 months).
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With low-grade tumors there may be a longer interval of mild to moderate pain (> 3 months).
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Osteoid osteoma has a characteristic night pain or diurnal pain pattern relieved with aspirin or NSAIDS.
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Bone sarcomas
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Malignant neoplasms of connective tissue (mesenchymal) origin
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Exhibit rapid growth in a centripetal manner and invade adjacent normal tissues
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Each year in the United States, about 2800 new bone sarcomas are diagnosed.
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High-grade, malignant bone tumors tend to destroy the overlying cortex and spread into the soft tissues.
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Low-grade tumors are generally contained within the cortex or the surrounding periosteal rim.
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Bone sarcomas metastasize primarily via the hematogenous route; the lungs are the most common site.
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Osteosarcoma and Ewing sarcoma may also metastasize to other bone sites either at initial manifestation or later in disease.
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Benign bone tumors
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These may be small with a limited growth potential or large and destructive.
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Tumor simulators and reactive conditions
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These processes occur in bone but are not true neoplasms (e.g., osteomyelitis, aneurysmal bone cyst, bone island).
Review Osteoid Osteoma
Self-limiting benign bone lesion
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Presentation
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Young patient (<30 years of age)
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Pain at night, or diurnal pattern that increases with time
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Pain is classically relieved by salicylates and other NSAIDs.
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Pain may be referred to an adjacent joint, and when the lesion is intracapsular, it may simulate arthritis.
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Common locations include the diaphyseal bone, proximal femur, tibia, and spine.
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May produce painful nonstructural scoliosis, growth disturbances, and flexion contractures
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Scoliosis caused by an osteoid osteoma results in a curve with the lesion on the concave side. This is thought to result from marked paravertebral muscle spasm.
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Imaging
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Radiographs usually show intensely reactive bone and a radiolucent nidus (Fig. 9.9 in Table 9.20). Because of the intense reactive sclerosis, it may be possible to detect the nidus only with CT or MRI.
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The nidus is less than 1 cm in diameter, although the area of reactive bone sclerosis may be greater.
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CT is superior to MRI in detecting and characterizing osteoid osteomas because CT provides better contrast between the lucent nidus and the reactive bone.
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Histology
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There is a distinct demarcation between the nidus and the reactive bone—nidus shows mineralized woven bone with nonmalignant rimming osteoblasts and appears similar to osteoblastoma.
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Trabecular organization is haphazard.
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The greatest degree of mineralization is in the center of the lesion.
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Treatment
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Patients can be treated with three different methods: NSAIDs, CT-guided radiofrequency ablation, and surgical removal.
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In about 50% of patients treated with NSAIDs, the lesions burn out over time (several years), with no further medical or surgical treatment necessary.
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CT-guided radiofrequency ablation (RFA) is the standard of care.
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A radiofrequency probe is placed into the lesion, and the nidus is heated to 80°C.
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A lesion close to a critical structure (i.e., neurovascular bundle or the spinal cord) is a contraindication to RFA; in this situation, surgery is preferred.
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Differential diagnosis: Osteoblastoma, stress fracture
Review osteoblastoma
Bone-producing tumor that is greater than 2 cm; its growth is not self-limiting.
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Presentation
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Pain
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Common locations include the spine, proximal humerus, proximal femur, and acetabulum.
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Imaging
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Bone destruction with or without the characteristic reactive bone formation in osteoid osteoma.
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Area of bone destruction occasionally has a motheaten or permeative appearance simulating a malignancy.
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Size is greater than 2 cm (Fig. 9.10A in Table 9.20).
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Histology: Mineralized woven bone with nonmalignant rimming osteoblasts that appears similar to osteoblastoma (Fig. 9.10B).
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Treatment: Intralesional resection with curettage
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Differential diagnosis: Osteoid osteoma and osteoblastoma are easily confused; a comparison is shown in
What is the difference between osteoid osteoma and osteoblastoma?
Review osteosarcoma
General
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Spindle cell neoplasm that produces osteoid
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There are many types of osteosarcoma.
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Lesions include high-grade intramedullary osteosarcoma (ordinary or classic osteosarcoma), parosteal osteosarcoma, periosteal osteosarcoma, telangiectatic osteosarcoma, osteosarcoma occurring with Paget disease, and osteosarcoma after irradiation.
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Presentation: pain or a pathologic fracture
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Imaging: Variable according to type
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Treatment
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Multiagent chemotherapy has dramatically improved long-term survival and the potential for limb salvage.
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Agents typically used are:
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Doxorubicin (cardiac toxicity)
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Cisplatin (neurotoxicity)
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Methotrexate (for cases of myelosuppression, leucovorin also administered)
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Chemotherapy both kills the micrometastases that are present in 80%–90% of the patients at presentation and sterilizes the reactive zone around the tumor.
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Preoperative chemotherapy is delivered for 8–12 weeks, followed by resection of the tumor.
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Other features
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Rate of long-term survival is approximately 60%–70%.
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Osteosarcoma metastasizes most commonly to the lung and next most commonly to bone.
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Prognostic factors that adversely affect survival include (1) expression of P-glycoprotein, high serum levels of alkaline phosphatase and LDH, vascular invasion, and no alteration of DNA ploidy after chemotherapy, (2) the absence of anti–heat-shock protein 90 antibodies after chemotherapy, and (3) a poor response to chemotherapy as shown by the presence of histologic tumor necrosis (<90%).
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Osteosarcoma is associated with an abnormality in the tumor suppressor genes Rb (retinoblastoma) and p53 (Li-Fraumeni syndrome).
Review intramedullary osteosarcoma
Also called “classic” osteosarcoma, this neoplasm is the most common type of osteosarcoma and usually occurs about the knee in children and young adults, but its incidence has a second peak in late adulthood.
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Presentation: Pain, in the proximal humerus, proximal femur, and pelvis
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Imaging
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Radiographs demonstrate a lesion in which there is bone destruction and bone formation (Fig. 9.11 in Table 9.21). On occasion, the lesion is purely sclerotic or lytic.
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MRI and CT are useful for defining the anatomy of the lesion with regard to intramedullary extension, involvement of neurovascular structures, and muscle invasion.
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Histology: Diagnosis depends on two histologic criteria: (1) the tumor cells produce osteoid and (2) the stromal cells are malignant.
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Treatment: Neoadjuvant chemotherapy (i.e., before surgery), followed by wide-margin surgical resection and adjuvant chemotherapy (i.e., after surgery)
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Other features: More than 90% of intramedullary osteosarcomas are high-grade and penetrate the cortex early to form soft tissue masses (stage IIB lesions).
Review Parosteal osteosarcoma
Parosteal osteosarcoma (low-grade surface)
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Presentation
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Painless mass that occurs on the surface of the metaphysis of long bones
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Most common sites are the posterior aspects of the distal femur, proximal tibia, and proximal humerus.
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Imaging: Characteristic radiographic appearance: a heavily ossified, lobulated mass “stuck on bone,” with no intramedullary extension (see Fig. 9.11)
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Histology: Regularly arranged osseous trabeculae; between the nearly normal trabeculae are slightly atypical spindle cells.
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Treatment
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Resection with a wide margin is curative.
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Low-grade lesion: Chemotherapy not required
Review Periosteal osteosarcoma
Rare surface form of osteosarcoma that occurs most often in the diaphysis of long bones (typically the femur or tibia)
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Presentation: Pain
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Imaging: Radiographic appearance is fairly constant: a sunburst-type lesion rests on a saucerized cortical depression (Fig. 9.12 in Table 9.21).
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Histology: The lesion is predominantly chondroblastic, and the grade of the lesion is intermediate.
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Other features
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The prognosis for periosteal osteosarcoma is intermediate between those of very low-grade parosteal osteosarcoma (Fig. 9.13 in Table 9.21) and high-grade intramedullary osteosarcoma.
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Preoperative chemotherapy, resection, and maintenance chemotherapy constitute the preferred treatment.
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The risk of pulmonary metastasis is 10%–15%.
Table review comparing osteosarcomas
Review MFH
“stem cell sarcoma”
Presentation
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Pain and swelling.
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Most common locations include the distal femur, proximal tibia, proximal femur, ilium, and proximal humerus.
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Imaging: This lesion is destructive, with either purely lytic bone destruction or a mixed pattern of bone destruction and formation (Fig. 9.14).
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Histology: Malignant fibrous hystiocytoma (MFH) is a primary bone osteosarcoma with a mesenchymal origin and cellular pattern, but no osteoid is produced or seen on histologic examination. The histologic findings determine the diagnosis (i.e., undifferentiated pleomorphic sarcoma [UPS], fibrosarcoma).
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Treatment: Same as for osteogenic sarcoma: chemotherapy and surgery.
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Other: UPS, MFH, fibrosarcoma, leiomyosarcoma
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Presentation and localization are similar to those of osteosarcoma.
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Lytic bone destruction is often in a permeative pattern
Review table of chondrogenic lesions
Review Enchondromas
Enchondroma
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Benign cartilage in the medullary cavity in the metaphysis of long bones, especially the proximal femur, humerus, and distal femur.
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Presentation: Asymptomatic and found incidentally
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Imaging: Radiographically there may be a prominent stippled or mottled calcified appearance (see Fig. 9.17).
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Histology: Composed of binuclear cells that lie in lacunar spaces; the lesion is hypocellular, and the cells have a bland appearance (no pleomorphism, anaplasia, or hyperchromasia).
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Treatment
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When lesions are not causing pain, serial radiographs are obtained to ensure that the lesions are inactive (not growing). Radiographs are obtained every 3–6 months for 1–2 years and then annually as necessary.
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For most enchondromas, no treatment other than observation is required. When surgical treatment is necessary, enchondromas are treated with intralesional resection by curettage.
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Differential diagnosis
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Enchondroma can be distinguished from low-grade chondrosarcoma on serial plain radiographs.
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On radiographs of low-grade chondrosarcomas, cortical bone changes (large erosions [>50%] of the cortex, cortical thickening, and destruction) or lysis of the previously mineralized cartilage is visible.
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Other features
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Enchondromas are also common in the hand, where they usually occur in the diaphysis and metaphysis.
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Lesions in the hand may be hypercellular and display worrisome histologic features, and pathologic fractures in the hand are common.
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Ollier disease/Maffucci syndrome
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When there are many lesions, the involved bones are dysplastic, and the lesions tend toward unilaterality, the diagnosis is multiple enchondromatosis, or Ollier disease.
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Inheritance pattern is sporadic.
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If soft tissue angiomas are also present, the diagnosis is Maffucci syndrome.
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Patients with multiple enchondromatosis are at increased risk of malignancy (in Ollier disease, 30%; in Maffucci syndrome, 100%).
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Patients with Maffucci syndrome also have a markedly increased risk of visceral malignancies, such as astrocytomas and gastrointestinal malignancies.
Review osteochondromas
Osteochondroma
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Benign surface lesions probably arise secondary to aberrant cartilage (from the perichondrial ring) on the surface of bone.
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Presentation
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Painless mass discovered incidentally.
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Occurs about the knee, proximal femur, and proximal humerus.
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Imaging
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Characteristic appearance: A surface lesion in which the cortex of the lesion and the underlying cortex are confluent with the medullary canal ( see Fig. 9.18).
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Osteochondroma may have a narrow stalk (pedunculated) or a broad base (sessile).
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The lesion typically occurs at the site of a tendon insertion, and the affected bone is abnormally wide.
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Underlying cortex is covered by a thin cap of cartilage (usually only 2–3 mm thick; in a growing child, the cap thickness may exceed 1–2 cm).
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Histology: Chondrocytes are arranged in linear clusters, in appearance resembling the normal physis.
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Treatment
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When asymptomatic, these lesions are treated with observation only.
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Surgery is considered when a patient experiences pain secondary to muscle irritation, mechanical trauma (contusions), or an inflamed bursa over the lesion.
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Differential diagnosis: Parosteal osteosarcoma, heterotopic ossification
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Other features
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Malignant transformation (<1% of cases) to a “secondary chondrosarcoma”
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Pain in the absence of mechanical factors warns of malignant change.
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Destruction of the subchondral bone, mineralization of a soft tissue mass, and an inhomogeneous appearance are radiographic changes of malignant transformation.
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A low-grade chondrosarcoma is usually present, although a dedifferentiated chondrosarcoma may occur in rare cases.
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The prognosis is excellent; these low-grade tumors rarely metastasize.
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Multiple hereditary exostoses
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The osteochondromas in MHE are often sessile and large. This is an autosomal dominant condition with mutations in the EXT1 and EXT2 gene loci. In approximately 10% of patients with multiple exostoses, a secondary chondrosarcoma develops. The EXT1 mutation is associated with a greater burden of disease and higher risk of malignancy.
Review Chondroblastoma
Centered in the epiphysis in young patients, usually with open physes; it may also occur in an apophysis
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Presentation
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Pain referable to the involved joint
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The most common locations are the distal femur, proximal tibia, and proximal humerus.
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Imaging
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Shows a central region of bone destruction that is usually sharply demarcated from the normal medullary cavity by a thin rim of sclerotic bone (Fig. 9.19 in Table 9.23).
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Mineralization may or may not occur within the lesion.
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Histology
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The basic proliferating cells are thought to be chondroblasts.
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Scattered multinucleated giant cells are found throughout the lesion.
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Zones of chondroid are present.
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Mitotic figures may be found.
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Treatment: Intralesional resection with curettage and reconstruction
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Differential diagnosis: Brodie’s abscess and giant cell tumor of bone (Fig. 9.20 in Table 9.23).
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Other features: Less than 5% metastasize to the lungs.
review chondromxyoid fibroma
Chondromyxoid fibroma
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Rare, benign cartilage tumor that contains variable amounts of chondroid, fibromatoid, and myxoid elements
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Presentation
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Focal pain
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Pathognomonic location is the tibia; may also be found in the pelvis and distal femur.
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Imaging: A lytic, destructive lesion that is eccentric and sharply demarcated from the adjacent normal bone
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Histology: This lesion grows in lobules, and there is often a concentration of cells at the periphery of the lobules.
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Treatment: Intralesional curettage
Review orthobullets
Chondromyxoid fibroma
A rare and benign chondrogenic lesion characterized by variable amounts of chondroid, fibromatoid and myxoid elements
Epidemiology demographics
more common in males
most common in second and third decades of life
may affect patients up to 75 years old
location long bones (ie. tibia, distal femur)
often affects metaphyseal (proximal tibia) regions
pelvis
feet or hands
Pathophysiology
may arise from physeal remnants
Genetics mutations
a genetic rearrangement may affect chromosome 6 (postion q13)
Prognosisnatural historyrecurrence in CMF is not uncommon
may occur in 20-30% of cases
negative prognostic variables
children
tumor is more lobulated with abundant myxoid material
metastasis
has not been reported
Presentation
History
long standing pain (months to years)
may be incidentally identified
Symptoms
pain and mild swelling
Imaging
Radiographs findingslytic, eccentric metaphyseal lesion
sharply demarcated from adjacent bone
scalloped and sclerotic rim
calcifications are rare
cortical expansion may be seen
lesion size may range from two to ten centimeters
MRI findings
low signal on T1-weighted images
high signal on T2-weighted images
Bone scan findings
increased signal uptake will be seen
Studies
Histologyfindingslow-power biphasic appearancehypercellular area with lobules of fibromyxoid tissue spindle-shaped cells or stellate-shaped cells
the cells contain hyperchromatic nuclei
multinucleated giant cells and fibrovascular tissue are located between lobules
hypocellular area with chondroid material
high power
myxoid stroma with stellate cells
regions of pleiomorphic cells with bizarre nuclei may be seen
Diagnostic criteria
histopathologic examination is mandatory for confirmation of the diagnosis
Differential
Radiographic
aneurysmal bone cyst (ABC)
chondroblastoma
non-ossifying fibroma
Histologic
chondroblastoma
enchondroma
chondrosarcoma
Treatment
Operative intralesional curretage and bone grafting (or PMMA) indications
mainstay of treatment
Complications
Recurrence
occurs in 25% of cases
Review Cartilage tumors
Review MFH
Presentation
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Pain and swelling.
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Most common locations include the distal femur, proximal tibia, proximal femur, ilium, and proximal humerus.
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Imaging: This lesion is destructive, with either purely lytic bone destruction or a mixed pattern of bone destruction and formation (Fig. 9.14).
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Histology: Malignant fibrous hystiocytoma (MFH) is a primary bone osteosarcoma with a mesenchymal origin and cellular pattern, but no osteoid is produced or seen on histologic examination. The histologic findings determine the diagnosis (i.e., undifferentiated pleomorphic sarcoma [UPS], fibrosarcoma).
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Treatment: Same as for osteogenic sarcoma: chemotherapy and surgery.
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Other: UPS, MFH, fibrosarcoma, leiomyosarcoma
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Presentation and localization are similar to those of osteosarcoma.
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Lytic bone destruction is often in a permeative pattern (Fig. 9.15).
review epiphyseal lesions
Review nonossifying fibroma
Nonossifying fibroma (also known as metaphyseal fibrous defect, nonosteogenic fibroma, and xanthoma)
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Presentation
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Asymptomatic, incidentally found lesion in a young patient
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Most common locations are the distal femur, distal tibia, and proximal tibia.
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Imaging
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Characteristic radiographic appearance: A lucent lesion that is metaphyseal, eccentric, and surrounded by a sclerotic rim (Fig. 9.21)
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The overlying cortex may be slightly expanded and thinned.
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Histology: Cellular, fibroblastic connective tissue background, with the cells arranged in whorled bundles
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Treatment
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Asymptomatic lesions: Observation if the radiographic appearance is characteristic and there is no risk of pathologic fracture. Lesions resolve spontaneously and are not true neoplasms.
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Symptomatic lesions: Curettage and fixation are performed.
Review Chordoma
Chordoma is a malignant neoplasm in which the cell of origin is derived from primitive notochordal tissue.
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Presentation
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Patients present with an insidious onset of pain. Lesions in the sacrum may manifest as pain in the pelvis, low back, or hip or with primarily gastrointestinal symptoms (obstipation, constipation, loss of rectal tone). When vertebral bodies are involved, neurologic symptoms may vary widely because of nerve compression.
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Occurs predominantly at the ends of the vertebral column clivus of the skull or sacrum (sacrococcygeal)
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About 10% of chordomas occur in the vertebral bodies (cervical, thoracic, and lumbar regions).
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Imaging
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Radiographs often do not reveal the true extent of sacrococcygeal chordomas.
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MRI shows midline bone destruction and a soft tissue mass (Fig. 9.22).
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Other MRI findings
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Low signal on T1-weighted images
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Very bright signal on T2-weighted images
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Sacrum is often expanded, and the soft tissue mass may exhibit irregular mineralization.
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Histology
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The tumor grows in distinct lobules.
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Chordoma cells sometimes have a vacuolated appearance and are called physaliferouscells.
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Treatment
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Wide-margin surgical resection
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Radiation therapy may be added if a wide margin is not achieved.
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Other features: Chordomas metastasize late in the course of disease, and local extension can be fatal.
Blue Cell tumors
LERNM
Review lymphomas
Presentation
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Pain in patients of all ages.
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The most common locations include the distal femur, proximal tibia, pelvis, proximal femur, vertebra, and shoulder girdle.
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Imaging
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Images often show a lesion that involves a large portion of the bone (Fig. 9.23).
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Bone destruction is common and often has a mottled appearance.
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A large soft tissue mass out of proportion to the amount of bone destruction is characteristic of lymphoma of bone.
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Histology
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A mixed cellular infiltrate is usually present. Most lymphomas of bone are diffuse, large B-cell lymphomas.
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IHC: CD45 and leukocyte common antigen (LCA) positive.
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Treatment
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Multiagent chemotherapy ( [CHOP]) is curative.
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Surgery is used only to stabilize fractures.
Review Myeloma
Plasma cell dyscrasias represent a wide range of conditions from monoclonal gammopathy of undetermined significance (MGUS; Kyle disease) to multiple myeloma.
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Three plasma cell dyscrasias pertain to orthopaedic surgery: multiple myeloma, solitary plasmacytoma of bone, and osteosclerotic myeloma.
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Multiple myeloma
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Malignant plasma cell disorder that commonly occurs in patients between 50 and 80 years of age
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Presentation: Manifests with bone pain, usually in the spine and ribs, or as a pathologic fracture
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Fatigue is a common complaint secondary to the associated anemia.
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Symptoms may be related to complications such as renal insufficiency, hypercalcemia, and the deposition of amyloid.
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Serum creatinine values are elevated in about 50% of affected patients.
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Hypercalcemia is present in about 33% of affected patients.
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Imaging: Radiographic appearance is of punched-out, lytic lesions (see Fig. 9.13), which may show expansion and a “ballooned” appearance.
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Histology
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Sheets of plasma cells that appear monoclonal with immunostaining
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Well-differentiated plasma cells have eccentric nuclei that have peripherally clumped, chromatic “clock faces.”
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Treatment
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Systemic therapy and bisphosphonates
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Surgical stabilization with irradiation is used for pathologic fractures.
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Radiotherapy is also used for palliation of pain and treatment of neurologic symptoms.
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The prognosis is related to the stage of disease; the overall median survival time is 18–24 months.
Review solitary plasmacytoma
It is important to differentiate solitary myeloma from multiple myeloma because of the more favorable prognosis in patients with the solitary form. Diagnostic criteria include the following:
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A solitary lesion on skeletal survey
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Histologic confirmation of plasmacytoma
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Bone marrow plasmacyte count of 10% or less
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Patients with serum protein abnormalities and Bence Jones proteinuria (protein levels <1 g/24 hr) at presentation are not excluded if they meet the aforementioned criteria.
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Treatment
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External beam irradiation of the lesion (4500–5000 cGy)
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When necessary, prophylactic internal fixation
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In approximately 50%–75% of affected patients, solitary myeloma progresses to multiple myeloma.
Review Giant Cell tumor
Giant cell tumor of bone
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Presentation
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Pain and pathologic fracture
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Patients over 30 years old with closed physes
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Most common in the epiphysis and metaphysis of long bones, and about 50% of lesions occur about the knee; the vertebra, sacrum, and distal radius are involved in about 10% of cases.
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The sacrum is the most common axial location of giant cell tumors of bone.
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Imaging: A purely lytic destructive lesion in the metaphysis that extends into the epiphysis and often borders the subchondral bone (see Fig. 9.20).
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Histology
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Basic proliferating cell has a round to oval or even spindle-shaped nucleus, and the multinucleated giant cells appear to have the same nuclei as the proliferating mononuclear cells. The stromal cell directs the multinucleated giant cell.
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Stromal malignant cells produce RANKL (receptor activator for nuclear factorκB ligand).
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Multinucleated giant cells express RANK and are responsible for the osteolytic aspect of GCT.
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Treatment
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Aimed at removing the lesion, with preservation of the involved joint
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Denosumab (Prolia), a human monoclonal antibody that binds RANKL, thereby inhibiting the maturation of osteoclasts.
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Extensive intralesional resection (removal of a large cortical window over the lesion) is performed using curettage with manual and power instruments.
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Chemical cauterization may be used (phenol, peroxide).
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Area of defect is usually reconstructed with subchondral bone grafts, methylmethacrylate, or both.
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Local control with this treatment regimen has a success rate of 85%–90%.
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Other features: GCT is described as benign but is aggressive, because in rare cases (<5%) it metastasizes to the lungs.
Review Ewing Sarcoma
Presentation
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Patient age less than 30 years
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Pain and fever may be present; the presentation can be similar to that in an infection.
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Patients may exhibit elevated ESR, leukocytosis, anemia, and elevated WBC count.
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Most common locations include the pelvis, distal femur, proximal tibia, femoral diaphysis, and proximal humerus.
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Imaging
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Radiographs often show a large, destructive lesion that involves the metaphysis and diaphysis.
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The lesion may be purely lytic or may have variable amounts of reactive new bone formation (Fig. 9.24).
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The periosteum may be lifted off in multiple layers, producing a Codman triangle and an onion-skin appearance.
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The soft tissue component is distinctively large.
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Histology
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Small round blue cells with minimal cytoplasm, pseudorosettes (attempted formation of vascular channels)
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ICH: CD99 positivity.
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A classic 11:22 chromosomal translocation produces the EWS-FLI1 fusion gene.
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Bone marrow biopsy is performed for staging purposes.
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Treatment: A multimodality approach with multiagent chemotherapy, irradiation, and surgical resection
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Standard treatment includes chemotherapy.
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Standard for local tumor control is surgery.
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Radiation therapy may be used primarily for pelvic and spine disease, where resection would be morbid, or as an adjunct to surgery to maintain function while sparing critical structures.
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Differential diagnosis: When a small blue cell tumor is found in a child younger than 5 years, metastatic neuroblastoma and leukemia should be considered.
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Other features
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Survival
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The rate of long-term survival with multimodality treatment may be as high as 60%–70%.
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There is a consistent chromosomal translocation (11;22) with the formation of a fusion protein (EWS-FLI1).
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Metastatic disease involves the lungs (50%), bone (25%), and bone marrow (20%).
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Poor prognostic factors include the following:
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Spine and pelvic tumors
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Tumors greater than 100 cm3 in diameter
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A poor response to chemotherapy (<90% tumor cell necrosis)
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Elevated serum LDH (Temple)
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The p53 mutation and gene fusion products other than EWS-FLI1
Review Adamantinoma
Rare low-grade, malignant tumor of long bones that contains epithelium-like islands of cells
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Presentation
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Patient less than 30 years old with prolonged periods of pain
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The tibia is the most common site; other long bones can be but rarely are involved (fibula, femur, ulna, radius).
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Imaging: Radiographic appearance: multiple, sharply circumscribed, “soap bubble”–looking lucent defects of different sizes, with sclerotic bone interspersed between the zones and extending above and below the lucent zones (see Fig. 9.28 in Table 9.26); one of the lesions in the midshaft is the largest and is associated with cortical bone destruction.
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Histology: Cells have an epithelial quality and are arranged in a palisading or glandular pattern; the epithelial cells occur in a fibrous stroma.
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Treatment: Wide-margin surgical resection
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Other features: Tumor may metastasize either early or after multiple failed attempts at local control.
Review ABC vs UBC
Review ABC
Aneurysmal bone cyst
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Nonneoplastic reactive condition that may be aggressive in its ability to destroy normal bone and expand into the soft tissues
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Presentation: Patients are less than 30 years old and present with pain and swelling.
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Imaging
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Characteristic radiographic finding: an eccentric, lytic, expansile area of bone in the metaphysis with a thin rim of periosteal new bone surrounding the lesion. The lesion is wider than the physis of the bone it is closest to (Fig. 9.25 in Table 9.25).
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MRI usually shows the periosteal layer surrounding the lesion.
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Fluid-fluid levels visible on T2-weighted MRI are characteristic of, but not exclusive to, ABC.
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Histology
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Cavernous blood-filled spaces without an endothelial lining.
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Thin strands of bone are present in the fibrous tissue of the septa.
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Benign giant cells may be numerous.
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Treatment: Curettage and reconstruction, which may include bone grafting or fixation in the setting of a fracture.
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Differential diagnosis: Unicameral bone cyst, telangiectatic osteosarcoma
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Other features
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Local recurrence is common in children with open physes.
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ABC may arise primarily in bone or may be found in association with other tumors, such as giant cell tumor, chondroblastoma, chondromyxoid fibroma, and fibrous dysplasia.
Review Unicameral bone cysts
Presentation
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Patient less than 30 years old presents with pain, usually after a fracture caused by minor trauma (e.g., sporting event, throwing a baseball, wrestling).
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Occurs most often in the proximal humerus; other sites are the proximal femur and distal tibia.
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Imaging
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Symmetric cystic expansion with thinning of the involved cortices (Fig. 9.26in Table 9.25)
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Affected bone is often expanded; however, the bone is generally no wider than the physis.
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Often appears trabeculated
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When the cyst abuts the physeal plate, the process is called active; when normal bone intervenes, the cyst is termed latent.
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Histology: Thin, fibrous lining contains fibrous tissue, giant cells, hemosiderin pigment, and a few chronic inflammatory cells.
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Treatment
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Asymptomatic: Observation
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Symptomatic: Aspiration and injection (bone aspirate, bone graft substitute, or methylprednisolone acetate may be used)
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Unicameral bone cysts in high-stress areas (e.g., proximal femur) are often treated with curettage, grafting, and internal fixation to avoid fracture and osteonecrosis.
Review Langerhans Histocystosis
Occurs as three entities:
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LCH monostotic, also known as eosinophilic granuloma. Only a single bone or, on occasion, multiple bones involved. Most common.
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LCH polyostotic plus visceral disease, or Hand-Schüller-Christian disease
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LCH polyostotic plus visceral disease in an infant, or Letterer-Siwe disease
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The cellular abnormality is a proliferation of the Langerhans cells of the dendritic system.
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LCH monostotic
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Presentation: Pain and swelling
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Imaging
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The lesion is lytic and has well-defined margins, described as “punched out” (Fig. 9.27).
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Cortex may be destroyed, and a periosteal reaction with a soft tissue mass simulating a malignant bone tumor may be present.
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Often there are different amounts of bone destruction of the involved cortices, resulting in the appearance of a bone within a bone.
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There may be expansion of the involved bone.
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Any bone may be involved.
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Histology
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The proliferating Langerhans cell, with an indented or grooved nucleus, is the characteristic cell.
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Cytoplasm is eosinophilic.
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Nuclear membrane has a crisp border.
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Mitotic figures may be common.
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Bilobed eosinophils with bright, granular, eosinophilic cytoplasm are present in large numbers.
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Electron microscopy shows a tennis racquet–shaped Birbeck granule.
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Treatment: LCH is a self-limiting process that often resolves after biopsy and/or curettage.
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LCH polyostotic plus visceral disease: Hand-Schüller-Christian disease
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Bone lesions and visceral involvement
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Classic triad, which occurs in fewer than one fourth of patients, consists of exophthalmos, diabetes insipidus, and lytic skull lesions.
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Multifocal disease is usually treated with chemotherapy.
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Letterer-Siwe disease occurs in young children and is usually fatal.
Review Fibrous Dysplasia
Developmental abnormality of bone that is characterized by monostotic or polyostotic involvement and is the failure of the production of normal lamellar bone.
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Presentation
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Pain from a fracture or stress fracture; or an incidental finding if asymptomatic; café au lait spots with irregular borders (resembling the coast of Maine) may accompany the bone lesions.
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Any bone may be involved; the proximal femur is the most commonly affected.
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Imaging: Variable appearance that can look highly lytic or like ground glass (Fig. 9.29)
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Histology
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Well-defined rim of sclerotic bone
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Proliferation of fibroblasts (produces a dense collagenous matrix)
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Trabeculae of osteoid and bone within the fibrous stroma are present in a disorganized manner, and their appearance has been likened to “alphabet soup” and “Chinese letters.”
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Treatment
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Predicated on the presence of symptoms and the risk of fracture
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Internal fixation and bone grafting are used in areas of high stress in which nonoperative treatment would not be effective.
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Most affected patients do not need surgical treatment.
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Autogenous cancellous bone grafting is never used because the transplanted bone is quickly transformed into the woven bone of fibrous dysplasia. Cortical or cancellous allografts are usually used.
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Bisphosphonate therapy has been shown to be effective in decreasing pain and reducing bone turnover in patients with polyostotic fibrous dysplasia.
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Other features
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Genetic mutation is an activating mutation of the GSα surface protein (GNAS)
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Increased production of cAMP
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When endocrine abnormalities (especially precocious puberty) accompany multiple bone lesions and skin abnormalities, the condition is called McCune-Albright syndrome.
Review OSTEOfibrous dysplasia
Presentation: Patients present before 30 years of age, commonly with tibial disease in which bowing is very common, and affected children may experience pathologic fractures.
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Imaging: Primarily involves the tibia and is usually confined to the anterior tibial cortex (Fig. 9.30).
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Histology: Fibrous tissue stroma and a background of bone trabeculae withosteoblastic rimming.
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Treatment
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Nonoperative treatment is preferred until the child reaches maturity.
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Resection or fixation or both may be required
Difference between Fibrous dysplasia, osteofibrous dysplasia and Adamantinoma
Review Pagets Disease of Bone
Characterized by abnormal bone remodeling
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Presentation
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Patient over 50 years old presenting with pain.
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Patient may present with degenerative joint disease, fracture, or neurologic encroachment; joint degeneration is common in the hip and knee.
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Monostotic or polyostotic
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Imaging: Radiographs demonstrate coarsened trabeculae and remodeled cortices. Coarsened trabeculae give the bone a blastic appearance.
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Histology: Characteristic features are irregular, broad trabeculae; reversal or cement lines; osteoclastic activity; and fibrous vascular tissue between the trabeculae.
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Treatment
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Aimed at retarding the activity of the osteoclasts
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Agents used include diphosphonates and calcitonin (pamidronate and zoledronic acid).
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Patients undergoing arthroplasty should be treated with bisphosphonates to decrease bleeding at the time of surgery.
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Other features
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Fewer than 1% of patients with Paget disease experience malignant degeneration with the formation of sarcoma within a focus of a Paget lesion.
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Symptoms of Paget sarcoma are the abrupt onset of pain and swelling.
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Radiographs usually demonstrate cortical bone destruction and the presence of a soft tissue mass.
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Paget sarcoma is a deadly tumor with a poor prognosis (rate of long-term survival is <20%).
Review osteomyelitis
Bone infections often simulate primary tumors.
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Presentation: Patient of any age may present with fever, chills, bone pain, or a combination of these symptoms.
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Imaging
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Bone destruction and formation are the characteristic findings of chronic infections.
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Acute infections often produce cortical bone destruction and periosteal elevation.
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Serpiginous tracts and irregular areas of bone destruction are suggestive of infection rather than neoplasm.
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Histology: A mixed-cell population of inflammatory cells, plasma cells, polymorphonuclear leukocytes, eosinophils, lymphocytes, and histiocytes
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Treatment: Resection of necrotic bone and appropriate antibiotic therapy
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Other features: A chronic infection with long-standing wound drainage is occasionally complicated by squamous cell carcinoma.
treatment decisions for pathologic fracture
Overall treatment aimed at controlling pain and maintaining the independence of the patient
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Prophylactic internal fixation is performed when impending fracture is deemed likely.
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In comparison with treatment of completed pathologic fractures, prophylactic fixation results in less blood loss, shorter hospital stays, greater likelihood of discharge to home, and greater likelihood of independent ambulation.
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There are many suggested criteria for fixation. The following conditions put the patient most at risk for fracture:
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More than 50% destruction of the diaphyseal cortices
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Permeative destruction of the subtrochanteric femoral region
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More than 50%–75% destruction of the metaphysis
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Persistent pain after irradiation
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Pain on weight bearing (especially in lower extremity with every footstep)
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Treatment of pathologic fractures is almost always surgical, inasmuch as these fractures rarely have the potential to heal.
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Surgical procedures should not rely on bony healing.
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Most proximal femur fractures should be treated with an endoprosthesis, to protect the femoral shaft in patients with relatively long life expectancy.
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Risk factors for sudden death during insertion of a long-stem prosthesis: presence of breast cancer, hypovolemia, reduced pulmonary function
Pagets Review
Orthobullets
Introduction
A condition of abnormal bone remodeling
original osseous tissue is reconstructed through active interplay between excessive bone resorption and abnormal new bone formation
Pathophysiology
increased osteoclastic bone resorption is the primary cellular abnormality
cause is thought to be a slow virus infection (intra-nuclear nucleocapsid-like structure)
paramyxovirus
respiratory syncytial virus
Epidemiology
peak incidence in the 5th decade of life
common in Caucasians (northern European / Anglo-Saxon descent)
males = females
location
may be monostotic or polyostotic
common sites include femur > pelvis > tibia > skull > spine
Genetics inheritance
most cases are spontaneous
hereditary
familial clusters have been described with ~40% autosomal dominant transmission
genetics most important is 5q35 QTER (ubiquitine binding protein sequestosome 1) SQSTM1 (p62/Sequestosome)
tend to have severe Paget disease
also insertion mutation in TNFRSF11A for gene encoding RANK
Orthopaedic manifestations
bone pain
long bone bowing
fractures, due to brittle bone and tend to be transverse
large joint osteoarthritis
excessive bleeding during THA
malalignment during TKA
secondary sarcoma
Associated conditions
high output heart failure
Prognosis & malignancy Paget’s sarcoma
less than 1% will develop malignant Paget’s sarcoma (secondary sarcoma)
osteosarcoma > fibrosarcoma and chondrosarcoma
most common in pelvis, femur, and humerus
poor prognosis
5-year survival for metastatic Paget’s sarcoma < 10%
treatment includes chemotherapy and wide surgical resection
Classification
Phases lytic phase
intense osteoclastic resorption
mixed phase
resorption and compensatory bone formation
sclerotic phase
osteoblastic bone formation predominates
all three phases may co-exist in the same bone
Presentation
Symptoms asymptomatic
frequently asymptomatic and found incidentally
painpain may be the presenting symptom due to
stress fractures
increased vascularity and warmth
new intense pain and swelling
suspicious for Paget’s sarcoma in a patient with history of Paget’s + new intense pain and swelling
cardiac symptoms
can present with high-output cardiac failure particularly if large/multiple lesions & pre-existing diminished cardiac function
Imaging
Radiographs coarsened trabeculae which give the bone a blastic appearanceboth increased and decreased density may exist depending on phase of disease lytic phase
lucent areas with expansion and thinned, intact cortices
‘blade of grass’ or ‘flame-shaped’ lucent advancing edge
mixed phase
combination of lysis + sclerosis with coarsened trabeculae
sclerotic phase
bone enlargement with cortical thickening, sclerotic and lucent areas
remodeled cortices
loss of distinction between cortices and medullary cavity
long bone bowing
bowing of femur or tibia
fractures
hip and knee osteoarthritis
osteitis circumscripta
(cotton wool exudates) in skull
Paget’s secondary sarcoma
shows cortical bone destruction
soft tissue mass
MRI
may show lumbar spinal stenosis
Bone scan
accurately marks site of disease
intensely hot in lytic and mixed phase
less hot in sclerotic phase
CT scan
cortical thickening and coarsened trabeculae
Evaluation
Laboratory findings
elevated serum ALP
elevated urinary collagen cross-links
elevated urinary hydroxyproline (collagen breakdown marker)
increased urinary N-telopeptide, alpha-C-telopeptide, and deoxypyridinoline
normal calcium levels
Histology
Characteristic histology
woven bone and irregular broad trabeculae with disorganized cement lines in a mosaic pattern
profound bone resorption - numerous large osteoclasts with multiple nuclei per cell
virus-like inclusion bodies in osteoclasts
Paget’s osteoclasts larger, more nuclei than typical osteoclasts
fibrous vascular tissue interspersed between trabeculae
Treatment
Nonoperativeobservation and supportive therapy treatment for asymptomatic Paget’s disease
physiotherapy, NSAIDS, oral analgesics
medical therapy aimed at osteoclast inhibition bisphosphonates are 1st line treatment for symptomatic Pagetsoral
alendronate and risedronate
etidronate disodium (Didronel)
older generation medication
inhibits osteoclasts and osteoblasts
cannot be used for more than 6 months at a time
intravenouspamidronate, zoledronic acid (Zometa)
newer generation medications that only inhibit osteoclasts
disadvantageous in that they only come in IV form
calcitonin are 2nd line (after bisphosphonates)
causes osteoclasts to shrink in size and decreases their bone resorptive activity within minutes
administered subcutaneously or intramuscularly
teriparatide is contraindicated in Paget’s disease due to risk of secondary osteosarcoma
OperativeTHA / TKAindications
affected patients with degenerative joint disease
technique
treat Paget’s with pharmacologic agents prior to arthroplasty to reduce bleeding
outcomes
greater incidence of suboptimal alignment secondary to pagetoid bone
the most common complications include
malalignment with knee arthroplasty
bleeding with hip arthroplasty
metaphyseal osteotomy and plate fixation indications
fractures through pathologic bowing of long bones
impending pathologic fracture of long bone with bowing
Risk factors for heterotopic ossification
