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 epiphyseal lesions
Blue Cell tumors
LERNM
Review ABC vs UBC
Difference between Fibrous dysplasia, osteofibrous dysplasia and Adamantinoma
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
