AAOS Basic Science MCQs (Set 4): Bone Physiology, Biomechanics, & Biomaterials

The radiograph shows an eccentric, cortically based lytic lesion in the proximal fibula. The CT and MRI scans confirm that it is well circumscribed and cortically based with significant surrounding edema. The radiographic differential diagnosis would be a Brodie's abscess or osteoid osteoma. An osteoblastoma would have to be greater than 2 cm in size. A chondroblastoma may also have significant edema around it, but it is an epiphyseal-based lesion, not cortically based. The well-circumscribed nature of the lesion is not consistent with osteosarcoma. The pathology shows a very cellular and vascular stroma with plump, but not atypical osteoblast cells making a matrix of immature woven bone. There are no abundant inflammatory cells or dead bone suggestive of osteomyelitis or a Brodie's abscess. Therefore, the clinical and histologic picture is most consistent with an osteoid osteoma. Percutaneous radiofrequency ablation, usually with CT guidance, has become the preferred method for treating most cases of osteoid osteoma. Rosenthal DI: Radiofrequency treatment. Orthop Clin North Am 2006;37:475-484.

This is a nonossifying fibroma of the proximal tibia. The lesion is eccentric, cortically based, with sclerotic margins and no evidence of a soft-tissue mass. Nonossifying fibromas are benign lesions that need no biopsy or surgical treatment when classic findings appear on radiographs. A follow-up radiograph should be performed 2 to 3 months after the initial presentation to ensure that the lesion is not progressive. Surgery is reserved for large lesions with risk of pathologic fracture or for cases where a displaced pathologic fracture has occurred and internal fixation is needed for fracture treatment. Nondisplaced pathologic fractures through nonossifying fibromas are best treated by allowing the fracture to heal and observation of the lesion. Vaccaro AR (ed): Orthopaedic Knowledge Update 8. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2005, pp 197-215.

Melorheostosis is a rare disorder characterized by the classic radiographic appearance of flowing hyperostosis in a long bone. The hyperostosis may be on the periosteal or endosteal surface of the bone and frequently gives the appearance of wax falling down the side of a candle. The radiographs are diagnostic; therefore, no further work-up is indicated. Menendez LR (ed): Orthopaedic Knowledge Update: Musculoskeletal Tumors. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2002, pp 87-102.

The findings are consistent with an osteoblastoma. The radiographs show a bone-forming lesion of the distal humerus. The lesion has an osseous component extending out of the native cortex with a thin sclerotic border. The T2-weighted MRI scan shows the lesion extending anteriorly beyond the native cortex. No fluid-fluid levels are seen. Histology shows large osteoblasts producing osteoid and woven bone. The tissue between the spicules of bone and osteoid contains thin fibrous tissue and capillaries. Osteoid osteoma is a smaller lesion usually with sclerotic reactive bone around a small nidus. The histology differentiates osteoblastoma from osteosarcoma because no malignant cells are seen. There is no cartilage production or chondroblasts in the histologic specimen, eliminating chondroblastoma. Giant cell tumors of bone typically occur in a epiphyseal metaphyseal location, most commonly after skeletal maturity, and contain numerus giant cells. Menendez LR (ed): Orthopaedic Knowledge Update: Musculoskeletal Tumors. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2002, pp 87-102.

The most common site of metastases from a soft-tissue sarcoma is the lungs and occurs in 40% to 60% of patients. The second most common site of metastases in soft-tissue sarcomas is the lymph nodes. Nodal metastases are seen with regularity in synovial sarcoma, epithelioid sarcoma, and rhabdosarcoma. The liver, brain, bone, and muscle are occasional sites of spread, but the occurrence is very rare. Simon SR (ed): Orthopaedic Basic Science. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1994, pp 219-276.

The radiograph shows a purely radiolucent lesion without matrix mineralization in the epiphysis of the distal radius. The lesion is "hot" on bone scan, and the MRI scan reveals cortical destruction with a soft-tissue mass. These findings are most consistent with giant cell tumor. The distal radius is a common location for giant cell tumors. The other options would be very uncommon in this location in a 45-year-old patient. The photomicrograph demonstrates multinucleated giant cells in a sea of mononuclear cells. The nuclei of the giant cells and the nuclei of the mononuclear stromal cells are identical. This feature helps distinguish giant cell tumor from other lesions that might contain giant cells. Cheng CY, Shih HN, Hsu KY, et al: Treatment of giant cell tumor of the distal radius. Clin Orthop Relat Res 2001;383:221-228.

The radiographs show a very ill-defined, aggressive, moth-eaten bony destruction involving the distal left femoral diaphysis just above the metaphyseal junction. The differential diagnosis includes Ewing's sarcoma, osteosarcoma, lymphoma of bone, eosinophilic granuloma, osteomyelitis, and others. MRI would further define the lesion, and soft-tissue and intramedullary extension. There is aggressive periosteal reaction in the posteromedial aspect of the adjacent lesion with some multilayered components in the distal interface of the periosteum. The lateral radiograph shows cortical penetration and irregular periosteal reaction of the posterior margin, suggesting some posterior soft-tissue extension at this site as well. Gebhardt MC, Ready JE, Mankin HJ: Tumors about the knee in children. Clin Orthop Relat Res 1990;255:86-110.

Metastatic lesions to bone are usually located in the axial and proximal appendicular skeleton. Metastases below the elbow and knee are rare, but when they do occur they are most commonly from lung carcinoma. Hayden RJ, Sullivan LG, Jebson PJ: The hand in metastatic disease and acral manifestations of paraneoplastic syndromes. Hand Clin 2004;20:335-343.

Radiation-associated sarcomas typically occur at least 5 years following radiation therapy, in the radiation therapy field, and with different histology than the original disease. The radiograph shows a lytic destructive lesion of the medial clavicle. The radiographic differential could include any of the above etiologies. The CT and MRI scans show this same reaction with extension into the adjacent soft tissue and periosteal reaction. These findings eliminate a degenerative process or radiation-induced osteonecrosis but do not distinguish between a neoplastic and infectious process. A PET scan showed marked uptake in the distal clavicle, which is more consistent with a malignant neoplastic process than a reactive process, like that of an infection. These findings, combined with the cellular atypia and bone formation on the biopsy specimen, confirm the diagnosis of radiation-associated sarcoma. In this older patient, radiation-associated sarcoma appears in an unusual location secondary to her previous radiation treatment in that region, which can occur 3 to 50 years after previous radiation therapy. Shaheen M, Deheshi BM, Riad S, et al: Prognosis of radiation-induced bone sarcoma is similar to primary osteosarcoma. Clin Orthop Relat Res 2006;450:76-81.

Solitary bone lesions require biopsy, for there is the possibility that the lesion may represent a primary bone sarcoma, which will necessitate a different treatment plan. This is especially true in patients with remote histories of cancer. The most likely cause of a lytic bone lesion in a patient older than age 40 years is a metastatic lesion. Rougraff BT, Kneisl JS, Simon MA: Skeletal metastases of unknown origin: A prospective study of a diagnostic strategy. J Bone Joint Surg Am 1993;75:1276-1281.

Bisphosphonates are stable analogues of pyrophosphate that have a strong affinity for bone hydroxyapatite; these agents inhibit bone resorption by reducing the recruitment and activity of osteoclasts and increasing apoptosis. Bone formed while patients are receiving bisphosphonate treatment is histologically normal. Bisphosphonates have been shown to be effective in decreasing pathologic fractures, bone pain, and the need for radiation therapy in patients with multiple myeloma and metastatic carcinoma to bone. The most effective method of administration is via monthly intravenous infusion. Osteonecrosis of the mandible is sometimes a complication of this treatment. Gass M, Dawson-Hughes B: Preventing osteoporosis-related fractures: An overview. Am J Med 2006;119:S3-S11.

Ewing's sarcoma is the second most common primary tumor of bone in children. Depending on the site and extent of disease, chemotherapy, radiation therapy, and surgery are all treatment options. In this patient with extensive pelvic and metastatic disease, chemotherapy and radiation therapy offer the best oncologic control while preserving functional outcome. Gibbs CP Jr, Weber K, Scarborough MT: Malignant bone tumors. Instr Course Lect 2002;51:413-428. Thacker MM, Temple HT, Scully SP: Current treatment for Ewing's sarcoma. Expert Rev Anticancer Ther 2005;5:319-331.

Glomus tumors are rare vascular lesions typically occurring about the nail of the distal phalanx of the hand. The diagnostic "triad" of glomus tumors consists of local pain, sensitivity to cold, and paroxysmal pain. They tend to present with pain as the most typical symptom and this can be exacerbated by changes in temperature that is felt to cause a vascular response within the lesion. The biopsy specimen confirms a glomus tumor showing the typical vascular spaces surrounded by glomus epithelioid glomus cells. Zook EG, Brown RE: The perionychium, in Green DP, Hotchkiss RN, Pederson WC (eds): Green's Operative Hand Surgery, ed 4. Philadelphia, PA, Churchill Livingstone, 1999, vol 2, pp 1353-1380.

Elastofibroma is a rare, benign soft-tissue pseudotumor characteristically located in the subscapular region. Most patients are between 50 and 70 years of age and have pain, decreased shoulder range of motion, or a mass. The lesion usually is best visualized with the arm elevated forward and adducted to displace the scapula laterally and allow the mass to protrude from the chest wall. They are frequently bilateral. Grossly, the mass is ill-defined, oblong or spherical, firm, and ranges in size from 5 cm to 10 cm. These masses appear infiltrative and frequently are mistaken for a sarcomatous lesion. Histologically, the mass is composed of a mixture of intertwining eosinophilic collagen and elastic fibers, and scattered fibroblasts, mucoid material, and fat. Vastamaki M: Elastofibroma scapulae. Clin Orthop Relat Res 2001;392:404-408. Nielsen T, Sneppen O, Mykre-Jensen O, et al: Subscapular elastofribroma: A reactive pseudotumor. J Shoulder Elbow Surg 1996;5:209-213.

The biopsy specimen is a low-power view of a soft-tissue sarcoma with a biphasic pattern of epithelial cells and fibrous spindle cells that are typical of a synovial sarcoma. A deep, painless soft-tissue mass greater than 5 cm in size is suspicious for a sarcoma. The imaging in this patient is indeterminate and the patient requires a biopsy for an accurate diagnosis. The biopsy reveals a tumor with a biphasic appearance consistent with a synovial sarcoma. These tumors are slow growing, occur primarily in the lower extremities, and are found in a younger demographic population compared to malignant fibrous histiocytoma and liposarcoma. They can occur in a biphasic pattern with clumps of epithelial cells and fibrous spindle cells or in a monophasic pattern. Synovial sarcomas stain positively for keratin. Keratin is positive in nearly all biphasic types and in many tumors of the monophasic fibrous type. Sixty percent of these tumors are found in the lower extremity. The area around the knee is the most common location, followed by the ankle and foot. Epithelioid and clear cell sarcomas are found associated with tendon sheaths of the hand and feet and are generally smaller in size. Epithelioid sarcoma may resemble granulomatous inflammation histologically; clear cell sarcoma is composed of nests of clear cells with occasional multinucleated giant cells. Pigmented villonodular synovitis is found within the synovium and is characterized by a villous histologic appearance with hemosiderin-laden macrophages. Malignant fibrous histiocytoma has a storiform histologic pattern with an abundance of pleomorphic cells. Enzinger FM, Weiss SW: Soft Tissue Tumors, ed 3. St Louis, MO, Mosby, 1995, p 757.

Schwannomas (neurilemomas) occur at all ages but are most frequently seen in persons between the ages of 20 and 50 years. MRI features of schwannomas are fairly nonspecific, but when they are associated with a large named nerve, the identification of a mass in continuity with that nerve is highly suggestive of a schwannoma. Most have a fairly homogeneous appearance with a high water content and often fusiform shape. Classically, the histology shows alternating Antoni A (dense spindle cell region) areas and Antoni B (loose myxoid tissue) areas. They also demonstrate uniform intense immunostaining with S-100 protein. Damron TA, Sim FH: Soft-tissue tumors about the knee. J Am Acad Orthop Surg 1997;5:141-152.

Distant bone metastasis is associated with an extremely poor prognosis for patients with osteosarcoma (5-year survival rate of less than 10%). Most osteosarcomas are high grade and extracompartmental, and approximately half are greater than 8 cm at presentation. The 5-year survival rate for these patients is approximately 70%. Patients with a solitary pulmonary metastasis have a prognosis worse than patients without detectable metastases but not as bad as those with bone metastases. Bielack SS, Kempf-Bielack B, Delling G, et al: Prognostic factors in high-grade osteosarcoma of the extremities or trunk: An analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 2002;20:776-790. Heck RK, Stacy GS, Flaherty MJ, et al: A comparison study of staging systems for bone sarcomas. Clin Orthop Relat Res 2003;415:64-71.

The radiograph reveals an aggressive purely lytic lesion of the distal femoral metaphysis. There is no apparent matrix mineralization or periosteal reaction. The photomicrographs show a malignant spindle cell neoplasm in a storiform pattern. Based on these findings, the diagnosis is malignant fibrous histiocytoma of bone. At most institutions, patients with this tumor are treated similar to patients with osteosarcoma with multi-agent chemotherapy and surgery with wide margins (resection or amputation). Menendez LR (ed): Orthopaedic Knowledge Update: Musculoskeletal Tumors. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2002, pp 203-209.

A mucous cyst is thought to be a ganglion arising from the DIP joint in patients with osteoarthritis. They are frequently associated with nail deformities. Treatment involves removal of the cyst with debridement of DIP joint osteophytes. Fritz GR, Stern PJ, Dickey M: Complications following mucous cyst excision. J Hand Surg Br 1997;22:222-225.

Chondroblastomas are benign cartilage lesions frequently seen in adolescents or young adults. They are found in the epiphyseal or apophyseal regions of bones. The radiograph shows a radiolucent lesion with mineralization and a well-marginated rim of reactive bone. The lesion is composed of sheets of immature chondroblasts (polygonal cells with a clear, bluish cytoplasm and a small round central nucleus). In some regions, classic "chicken-wire" matrix calcifications and a "cobblestone" pattern of cell arrangement may be seen. Treatment consists of curettage and bone grafting. Campanacci M: Bone and Soft Tissue Tumors, ed 2. New York, NY, Springer-Verlag, 1999, pp 247-264.

Certain histologic subtypes of soft-tissue sarcoma have been noted to arise preferentially in the hand and the foot, such as epithelioid sarcoma, clear cell sarcoma, and synovial sarcoma. Synovial sarcoma is the most common foot sarcoma. Frequently there is a delay in diagnosis because the lesions are rare. The lesions tend to occur in younger adults, typically between the ages of 15 and 40 years. Patients with hand and foot sarcomas have been described as having improved overall survival, but this is likely a result of the smaller size of tumors arising in these locations. In this patient, the tumor has grown to a substantial size and involves many of the bones of the midfoot. Limb salvage may be a possibility when incorporated into a multidisciplinary treatment program, but this will entail months of adjuvant treatment and significant morbidity. Amputation and early prosthetic fitting still have a role in management of some soft-tissue sarcomas, most frequently in the foot. Ferguson PC: Surgical considerations for management of distal extremity soft tissue sarcomas. Curr Opin Oncol 2005;17:366-369.

Langerhans cell histiocytosis or eosinophilic granuloma is a nonneoplastic lesion that is part of a spectrum of clinical diseases featuring histiocytes. Most occur during the first two decades of life within any bone. Radiographs show a radiolucent lesion, frequently diaphyseal in location. A periosteal response is occasionally seen and can resemble more aggressive lesions such as osteomyelitis or Ewing's sarcoma. Histology demonstrates CD1a positive histiocytes with large oval-shaped nuclei with indentation, and a variable presence of eosinophils. Plasschaert F, Craig C, Bell R, et al: Eosinophilic granuloma: A different behaviour in children than in adults. J Bone Joint Surg Br 2002;84:870-872.

Synovial sarcomas have a number of features that differentiate them from other soft-tissue sarcomas. They often have small areas of calcifications within the lesion. They occur in a younger patient population than most soft-tissue sarcomas. A subset of patients with synovial sarcoma tend to be chemosensitive. They often contain the SYT-SSX translocation. Although they can occur intra-articular, this is rare, despite their name. Campanacci M: Bone and Soft Tissue Tumors, ed 2. New York, NY, Springer-Verlag, 1999, pp 1109-1126.

Patients with a mutation of the retinoblastoma gene (RB) have an increased likelihood for the development of osteosarcoma. The EWS-FLI1 gene is the fusion product of a chromosomal translocation of 11:22. EGF-R and IGF-R are growth factor receptors, but mutations in these genes have not been correlated with osteosarcoma. VEGF is a proangiogenic molecule that is involved in tumor formation in multiple sites but not the development of osteosarcoma. Scholz RB, Kabisch H, Delling G, et al: Homozygous deletion within the retinoblastoma gene in a native osteosarcoma specimen of a patient cured of a retinoblastoma of both eyes. Pediatr Hematol Oncol 1990;7:265-273.

Osteoid osteoma is a round or oval, well-circumscribed lesion with a radiolucent nidus. A small area of calcification may be present within the center of the nidus. The radiolucent nidus is surrounded by a thick rim of sclerotic bone. These diagnostic features are frequently better seen on CT. An increase in cyclooxygenase activity has been demonstrated within osteoid osteomas, which may explain why aspirin and other nonsteroidal anti-inflammatory drugs classically relieve the pain associated with these lesions. Kneisl JS, Simon MA: Medical management compared with operative treatment for osteoid-osteoma. J Bone Joint Surg Am 1992;74:179-185.