AAOS Basic Science MCQs (Set 1): Bone Physiology, Biomechanics & Pharmacology | Ortho Board Review

The ground glass appearance on the radiograph, the hot bone scan, and histologic findings of bony spicules without osteoblastic rimming in a background of bland fibrous tissue all suggest fibrous dysplasia. Stress-related pain is common with activity because of the dysplastic bone. Parosteal osteosarcomas are surface lesions. Simple cysts, aneurysmal bone cysts, and eosinophilic granuloma are all possible radiographically; however, the histology is most consistent with fibrous dysplasia. Harris WH, Dudley HR Jr, Barry RS: The natural history of fibrous dysplasia: An orthopaedic, pathological and roentgenographic study. J Bone Joint Surg Am 1962;44:207.

The most likely diagnosis is osteosarcoma. The imaging studies show an aggressive primary tumor of bone, and the histology slide shows a typical chondroblastic osteosarcoma, with osteoid deposited along the surface of bone trabeculae. Ewing's sarcoma histologically consists of small round blue cells. Osteochondroma and periosteal chondroma can occur near the knee but have different radiographic and histologic patterns. Chondrosarcoma rarely occurs in children. Simon M, Springfield D, et al: Osteogenic sarcoma: Surgery for Bone and Soft Tissue Tumors. Philadelphia, PA, Lippincott Raven, 1998, p 267.

The radiographs show a bone-producing lesion in the femoral diaphysis. The radiographic appearance of small round cell tumors is more permeative with an elevated periosteum and no matrix production. The appearance of this lesion is most consistent with osteosarcoma. Patients who carry the Rb gene are predisposed to osteosarcoma. However, Ewing's sarcoma, primitive neuroectodermal tumor, and osteomyelitis can all occur in this location. Unni KK: Dahlin's Bone Tumors: General Aspects and Data on 11,087 Cases, ed 5. Philadelphia, PA, Lippincott-Raven, 1996, pp 143-160.

Ewing's sarcoma has an 11;22 translocation that creates the EWS/FLI1 fusion gene, and synovial sarcoma has an X;18 translocation that creates the STT/SSX fusion gene. The other tumors do not have consistent translocations. Sandberg AA: Cytogenetics and molecular genetics of bone and soft-tissue tumors. Am J Med Genet 2002;115:189-193.

The classic MRI appearance of a soft-tissue sarcoma is a well-defined heterogeneous mass deep to the fascia. MRI has greatly enhanced our ability to identify and characterize soft-tissue masses. In many patients, MRI is diagnostic and may obviate the need for biopsy. In other patients, it may indicate with high probability that the mass is malignant and consideration for referral can be made. A common misconception is that sarcomas are infiltrative; therefore, physicians mistakenly exclude the diagnosis of a sarcoma based on a well-defined mass seen on MRI. However, sarcomas grow centrifugally with balloon-like expansion compressing surrounding normal tissue; as such, they appear well defined. Many benign soft-tissue masses such as lipomas are similarly well defined. However, MRI is especially useful in identifying fat. Lipomas appear to be homogeneous masses with fat signal characteristics on all sequences. Ill-defined soft-tissue masses include infection, trauma, and desmoid tumors. Heterogeneity is not unique to malignant tumors but is a characteristic of soft-tissue sarcomas. Bancroft LW, Peterson JJ, Kransdorf MJ, Nomikos GC, Murphey MD: Soft tissue tumors of the lower extremities. Radiol Clin North Am 2002;40:991-1011. Berquist TH, Ehman RL, King BF, et al: Value of MR imaging in differentiating benign from malignant soft-tissue masses: Study of 95 lesions. Am J Roentgenol 1990;155:1251-1255.

Although factors such as a high-grade tumor and large size are associated with decreased survival, the presence of metastases carries the worst prognosis. Good results are very rare when metastases are present. Soft-tissue sarcomas, as a whole, respond poorly to chemotherapy, leading to a poor prognosis when metastases are present. Collin C, Goobold J, Hadju SI, Brennan MF: Localized extremity soft tissue sarcoma: An analysis of factors affecting survival. J Clin Oncol 1987;5:601-612.

The primary carcinoma most likely to metastasize distal to the elbow and knees is lung carcinoma. Renal cell carcinoma can also metastasize to distal sites. Most metastatic bone disease occurs in the vertebral bodies, pelvis, and proximal long bones. Simon MA, Bartucci EJ: The search for the primary tumor in patients with skeletal metastases of unknown origin. Cancer 1986;58:1088-1095.

The patient has a nonossifying fibroma, and the symptoms suggest that there is significant weakening of the cortex and/or microfracture; therefore, biopsy, curettage, and bone grafting is the treatment of choice. Based on the size of the lesion and the presence of symptoms, observation is likely to result in pathologic fracture. A biopsy will further weaken the bone unless combined with curettage and bone grafting. Radiation therapy is not used in the treatment of nonossifying fibroma and is rarely used in any benign condition affecting skeletally immature individuals. Steroid injection has been used in the treatment of unicameral bone cysts and in Langerhan's cell histiocytosis but not for nonossifying fibroma. Dormans, JP, Pill SG: Fractures through bone cysts: Unicameral bone cysts, aneurysmal bone cysts, fibrous cortical defects, and nonossifying fibromas. Instr Course Lect 2002;51:457-467.

Although the imaging studies are consistent with a unicameral bone cyst, aneurysmal bone cyst, or giant cell tumor, the histology shows small round blue cells that are typical of Ewing's sarcoma. Although Ewing's sarcoma frequently occurs in the diaphysis, it can occur in the metaphysis.

The imaging studies show a chondrosarcoma; therefore, surgical treatment is indicated. There is no role for intralesional treatment of an exophytic lesion, particularly in the pelvis. Even obtaining a biopsy specimen risks intrapelvic contamination, although many surgeons would still perform a biopsy prior to a resection to confirm the diagnosis. Chondrosarcoma is considered resistant to both radiation therapy and chemotherapy; therefore, radiation therapy generally is not used except for unresectable lesions. Chemotherapy would be used only for metastatic disease or in patients with high-grade chondrosarcoma. The grade would not be known until after resection, and in this patient, the histology slide showed a grade I neoplasm. Chemotherapy would not be used preoperatively because a cartilage tumor is unlikely to shrink, and in this patient, the lesion is resectable. Springfield DS, Gebhardt MS, Mcguire MH: Chondrosarcoma: A review. J Bone Joint Surg Am 1996;78:141-149.

Giant cell tumors occur near articular surfaces in young adults. The histology shows abundant giant cells with nuclei resembling the surrounding cells. Although the MRI scan shows soft-tissue involvement, curettage is still the preferred treatment. Chemotherapy is not necessary for benign lesions, and amputation is too aggressive. Cementation, phenol, and cryosurgery (liquid nitrogen) are all acceptable local adjuvants to curettage. Packing the cavity with bone graft rather than cement is also acceptable. Dahlin DC, Unni KK: Bone Tumors: General Aspects and Data on 8,542 Cases. Springfield, IL, Charles C. Thomas, 1986.

The diagnosis is squamous cell carcinoma. The radiograph shows a destructive lesion, and the histologic slides demonstrate squamous cells invading bone. The preferred treatment for squamous cell carcinoma is wide resection; however, in this location a wide margin can be achieved only with amputation. Overall survival in patients with squamous cell carcinoma secondary to chronic osteomyelitis is not significantly worse than that expected for age-matched controls. Dell PC: Hand, in Simon MA, Springfield D (eds): Surgery for Bone and Soft Tissue Tumors. Philadelphia, PA, Lippincott-Raven, 1998, pp 405-420.

The radiographs show a lytic lesion in the right proximal tibia that has a high fluid content based on the MRI findings. The radiographic appearance is consistent with either telangiectatic osteosarcoma or aneurysmal bone cyst. Low-magnification histology shows a lesion resembling an aneurysmal bone cyst, with blood lakes separated by cellular septa. However, high-magnification shows severe cytologic atypia, indicative of a telangiectatic osterosarcoma. The appropriate treatment is neoadjuvant chemotherapy followed by wide resection and reconstruction of the lesion. Unni KK: Dahlin's Bone Tumors: General Aspects and Data on 11,087 Cases, ed 5. Philadelphia, PA, Lippincott-Raven, 1996, pp 143-160.

Cytogenetics best demonstrates the 11;22 translocation characteristic of Ewing's sarcoma. The translocation also can be detected with polymerase chain reaction and fluorescent in situ hybridization. The Ewing antibody is used for immunostaining to check for cell membrane (surface) staining of a marker unrelated to the translocation; this could also help distinguish Ewing's sarcoma from small cell osteosarcoma. A bone scan will show increased uptake with both types of tumors. Although most Ewing's sarcoma tumors are diploid, some are polyploid as are most osteosarcomas. Flow cytometry is used to sort cells, sometimes based on antibody binding. LDH can be elevated in both Ewing's sarcoma and osteosarcoma and is a poor prognostic indicator when elevated. Lymph node metastases are uncommon in both of these tumors. Perotti D, Corletto V, Giardini R, Parafioriti A, Fossati-Bellani F, Luksch R: Retrospective analysis of ploidy in primary osseous and extraosseous Ewing family tumors in children. Tumori 1998;84:493-498. Riley RD, Burchill SA, Abrams KR, Heney D, Sutton AJ, Jones DR, et al: A systematic review of molecular and biological markers in tumours of the Ewing's sarcoma family. Eur J Cancer 2003;39:19-30.

The studies reveal significant heterotopic ossification that appears to be mature. Following resection, the most reliable way to prevent recurrence is with low-dose external-beam radiation therapy. Bisphosphonate therapy can be considered; however, when terminated, heterotopic bone may reform. Heterotopic ossification is unrelated to the patient's endocrine status and is not associated with any metabolic abnormalities. Moore K, Goss K, Anglen J: Indomethacin versus radiation therapy for prophylaxis against heterotopic ossification in acetabular fracture. J Bone Joint Surg Br 1998;80:259.

The findings are most consistent with a rupture of the anterior tibial tendon. The damaged area of tendon should be resected, followed by tendon reconstruction or tenodesis. The histology is not consistent with giant cell tumor of the tendon sheath, gout, or synovial sarcoma. Fibromatosis is characterized by a large number of spindle cells within the collagen background. Otte S, Klinger HM, Loreaz F, Haerer T: Operative treatment in case of closed rupture of the anterior tibial tendon. Arch Orthop Traum Surg 2002;122:188-190.

The most common benign bone tumors in childhood are discovered incidentally and include single bone cysts, fibrous cortical defects, nonossifying fibroma, and osteochondroma. Benign bone tumors can be classified as latent, active, or aggressive. Aggressive bone tumors usually present with pain, whereas active lesions present with pain or pathologic fracture. Only aggressive benign bone tumors are associated with a soft-tissue mass, and they are far less common than indolent bone tumors, especially in children. Aboulafia AJ, Kennon RE, Jelinek JS: Benign bone tumors of childhood. J Am Acad Orthop Surg 1999;7:377-388.

Soft-tissue sarcomas generally are treated with radiation therapy and wide surgical resection. In this patient, involvement of most of the posterior calf compartment and circumferential involvement of the posterior tibial and peroneal neurovascular bundle makes limb salvage impractical. Any attempt at wide surgical resection would leave a poorly functioning limb with questionable surgical margins. A high below-knee amputation would be the best option. Radiation therapy alone is contraindicated. Lindberg RD, Martin RG, Romsdahl MM, et al: Conservative surgery and post-operative radiotherapy in 300 adults with soft tissue sarcoma. Cancer 1981;47:2391-2397. Sim FT, Frassica FS, Frassica DA: Soft tissue tumors: Diagnosis, evaluation, and management. J Am Acad Orthop Surg 1994;2:202-211.

The incidence of malignant transformation or the formation of a secondary malignancy in pagetic bone is estimated to be less than 1%. Osteosarcoma is the most common secondary malignancy, followed by fibrosarcoma and chondrosarcoma. Ewing's sarcoma arising in pagetic bone has not been reported. Grimer RJ, Carter SR, Tillman RM, et al: Osteosarcoma of the pelvis. J Bone Joint Surg Br 1999;81:796-802.

The current treatment regimen for Ewing's sarcoma typically involves induction chemotherapy followed by local control and further chemotherapy. Local control consists of surgery only, radiation therapy only, or a combination of the two. In bones that are easily resectable (expendable) with wide margins, surgery is usually recommended. For areas that cannot be resected (ie, large bulky pelvic tumors), radiation therapy alone is sometimes the preferred method of local control. If surgery is chosen and the margins are close, radiation therapy can be used as an adjuvant treatment. Amputation is rarely required for an isolated fibular lesion. Observation without adequate local control results in local recurrence. Nesbit ME Jr, Gehan EA, Burgert EO Jr, et al: Multimodality therapy for the treatment of primary, non-metastatic Ewing's sarcoma of the bone: A long-term follow-up of the first intergroup study. J Clin Oncol 1990;8:1664-1674.

The most common location for soft-tissue tumors to metastasize is the lungs. Depending on the grade of the sarcoma, metastases develop in as many as 50% of patients with soft-tissue sarcomas. Tumor grade is considered the most significant prognostic factor in predicting risk of metastases, with high-grade lesions at greatest risk. Staging CT of the chest should be performed once the diagnosis of a soft-tissue sarcoma is suspected or confirmed. Regular surveillance of patients treated for soft-tissue sarcomas includes follow-up CT scans at regular intervals. Intra-abdominal metastases are uncommon but may occur, particularly in patients with myxoid liposarcoma. Regional metastases are relatively uncommon and occur in approximately 5% of all patients with soft-tissue sarcoma. The incidence of regional nodal metastases is higher for synovial sarcoma and epithelioid sarcomas than other soft-tissue sarcomas. Sim FH, Frassica FJ, Frassica DA: Soft-tissue tumors: Diagnosis, evaluation, and management. J Am Acad Orthop Surg 1994;2:202-211.

The peak incidence of osteosarcoma occurs in the second decade, followed by the third decade. Up to 75% of all cases of osteosarcoma occur in patients between 10 and 25 years. It rarely occurs after age 30. Affected women tend to be younger than affect men. Osteosarcoma associated with Paget's disease or in radiation-induced osteosarcoma occurs in an older population. Simon M, Springfield D, et al: Osteogenic Sarcoma: Surgery for Bone and Soft Tissue Tumors. Philadelphia, PA, Lippincott Raven, 1998, p 266. Mirra JM: Bone Tumors: Clinical, Radiologic, and Pathologic Correlations. Philadelphia, PA, Lea and Febiger, 1989.

Multiple hereditary exostosis and enchondroma commonly present as multiple lesions in the hand. Multiple hereditary exostosis consists of cartilage capped bony exostoses arising from the metaphyseal end of rapidly growing bones. Osteosarcoma and chondrosarcoma rarely appear as multiple lesions. Fracture callus can exhibit enchondral ossification that is usually circumferential, but the radiographic findings are not consistent with fracture. Porter DE, Emerton ME, Villanueva-Lopez F, Simpson AH: Clinical and radiographic analysis of osteochondromas and growth disturbance in hereditary multiple exostoses. J Pediatr Orthop 2000;20:246-250.

The most common clinical presentation of a patient with a malignant bone tumor is pain. Malignant bone tumors rarely are diagnosed as an incidental finding or pathologic fracture. In patients who have a pathologic fracture on initial presentation, a history of increasing pain prior to the fracture is typical. While 90% of malignant bone tumors are associated with a soft-tissue mass, in many patients the soft-tissue component of the tumor is not clinically apparent. Buckwalter JA: Musculoskeletal neoplasms and disorders that resemble neoplasms, in Weinstein SL, Buckwalter JA (eds): Turek's Orthopaedics: Principles and Their Application, ed 5. Philadelphia, PA, JB Lippincott, 1994, pp 290-295.

Chondrosarcomas associated with diffuse bone lesions (enchondromas) are characteristic of Ollier's disease. When accompanied by subcutaneous masses (hemangiomas), the condition is called Maffucci's syndrome. Multiple hereditary exostosis is characterized by diffuse osteochondromas. McCune-Albright syndrome is characterized by polyostotic fibrous dysplasia with cafe-au-lait spots and precocious puberty. Neurofibromatosis can have associated bone lesions but is not associated with chondrosarcomas. Sun TC, Swee TC: Chondrosarcoma in Maffucci's syndrome. J Bone Joint Surg Am 1985;67:1214-1219. Schwartz HS, Zimmerman NB, Simon MA, et al: The malignant potential of enchondromatosis. J Bone Joint Surg Am 1987;69:269-274.