AAOS & ABOS Basic Science MCQs (Set 1): Biomechanics, Bone Physiology & Cartilage Biology for OITE

The imaging studies show a permeative lesion of the left hemipelvis with a large soft-tissue mass. The photomicrograph demonstrates a small blue cell tumor with pseudorosettes. The most likely diagnosis is primitive neuroectodermal tumor (Ewing's sarcoma family of tumors). MIC-2 is a highly sensitive and specific marker for this family of tumors. Cytokeratin is an epithelial marker. Vimentin is a mesenchymal marker. Thus, Ewing's sarcomas are cytokeratin negative and vimentin positive. Before discovery of the MIC-2 antigen, PAS and reticulin stains were commonly used to help differentiate Ewing's sarcoma from lymphoma. In contrast to lymphoma, Ewing's sarcomas are typically PAS positive and reticulin negative. Halliday BE, Slagel DD, Elsheikh TE, et al: Diagnostic utility of MIC-2 immunocytochemical staining in the differential diagnosis of small blue cell tumors. Diagn Cytopathol 1998;19:410-416.

Localized PVNS is a variant of the disease process where the synovial proliferation occurs in one area and usually presents as a discrete mass. It has been effectively treated with complete excision. This may be performed arthroscopically or with arthrotomy. Complete synovectomy and radiation therapy are unnecessary to eradicate the localized form of PVNS. Tyler WK, Vidal AF, Williams RJ, et al: Pigmented villonodular synovitis. J Am Acad Orthop Surg 2006;14:376-385.

The radiographs show a well-defined, irregular, eccentric lesion in the distal tibia metaphysis with a thin sclerotic margin. The radiographs are diagnostic of nonossifying fibroma, a common entity in this age group and in this location. No further work-up is indicated. The patient was asymptomatic prior to the injury and the lesion is small and thus not worrisome for an impending pathologic fracture; therefore, no treatment is indicated beyond observation. The natural history of these lesions is to gradually ossify as the patient reaches skeletal maturity. Menendez LR (ed): Orthopaedic Knowledge Update: Musculoskeletal Tumors. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2002, pp 69-75.

Women older than age 50 years should receive daily supplementation with calcium and vitamin D to help preserve bone density. Bone mineral density testing is recommended for women age 65 years or older and postmenopausal women with at least one risk factor for osteoporotic fractures: prior fragility fracture, low estrogen levels, premature menopause, long-term secondary amenorrhea, glucocorticoid therapy, maternal history of hip fracture, or low body mass index. Hormone therapy is not approved for the treatment of osteoporosis. Gass M, Dawson-Hughes B: Preventing osteoporosis-related fractures: An overview. Am J Med 2006;119:S3-S11.

The radiographs show a benign-appearing, well-defined lytic lesion with a thin rim of surrounding reactive bone. The photomicrograph shows spindle cells with a myxoid cartilaginous matrix. These findings are diagnostic of chondromyxoid fibroma. This is a rare, benign tumor that usually causes pain and can be locally aggressive. Lersundi A, Mankin HJ, Mourikis A, et al: Chondromyxoid fibroma: A rarely encountered and puzzling tumor. Clin Orthop Relat Res 2005;439:171-175.

Malignant fibrous histiocytoma (MFH) is the most common soft-tissue sarcoma. MFH typically presents as a large mass, deep to the fascia with heterogeneous signal on MRI. The MRI scans show a heterogeneous lesion in the posterior thigh. There is significant high signal uptake on the T2-weighted image. The histology shows malignant histiocytic cells with marked atypia and pleomorphism. Histology of a hematoma would show only old hemorrhage and some granulation tissue. Lipoma and liposarcoma are both seen as a fat-containing lesion on histology. No significant fat tissue is seen in this histologic specimen. Histology of myositis ossificans would show bone formation. Simon SR (ed): Orthopaedic Basic Science. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1994, pp 219-276.

The imaging studies and histology are most consistent with Ewing's sarcoma. Tuberculosis can show small round blue cells on histology (lymphocytes associated with chronic infection) but would more typically involve the knee joint and periarticular bone. Osteosarcoma and MFH do not have small round blue cells histologically. Sissons HA, Murray RO, Kemp HBS: Orthopaedic Diagnosis. Berlin, Springer-Verlag, 1984, pp 254-256.

The radiograph demonstrates thickened trabeculae and thickened cortices in the left proximal femur compared to the right, and the bone scan shows increased uptake in this area. The MRI scans show thickened trabeculae with normal marrow signal. These findings are diagnostic of Paget's disease. Medical treatment, including bisphosphonates and calcitonin, is indicated for painful bone lesions. Hadjipavlou AG, Gaitanis IN, Kontakis GM: Paget's disease of the bone and its management. J Bone Joint Surg Br 2002;84:160-169.

The diagnosis is myositis ossificans resulting from an injury. The initial radiograph reveals a small amount of mineralization in the soft tissues overlying the left hip. The MRI scan shows signal abnormality of the entire gluteus minimus muscle with a mineralized mass in the center. The current radiograph shows a lesion within the abductor musculature with mature ossification peripherally. The imaging studies are diagnostic and the patient is asymptomatic; therefore, the management of choice is observation with no further evaluation or treatment indicated. Miller AE, Davis BA, Beckley OA: Bilateral and recurrent myositis ossificans in an athlete: A case report and review of treatment options. Arch Phys Med Rehabil 2006;87:286-290.

Any large (greater than 5 cm), deep, heterogeneous mass in the extremities should be considered a sarcoma until proven otherwise. Sarcomas are rare, and without a high index of suspicion, the lesions may be misdiagnosed or there may be a delay in diagnosis. Needle biopsies can obtain sufficient tissue for diagnosis and are associated with less morbidity than open biopsy. Marginal resections or excisional biopsies should be reserved for a few select benign lesions and locations. Damron TA, Beauchamp CP, Rougraff BT, et al: Soft-tissue lumps and bumps. Instr Course Lect 2004;53:625-637.

Dedifferentiated parosteal osteosarcoma designates high-grade transformation of conventional low-grade parosteal osteosarcoma. Unlike conventional parosteal osteosarcoma, where wide surgical excision alone is considered adequate treatment, patients with dedifferentiated osteosarcoma are treated with neoadjuvant chemotherapy and wide local resection. Recognition of dedifferentiated areas with angiography can localize the area that should be biopsied and thus render an accurate diagnosis. Percutaneous biopsy of hypervascular areas should prompt the administration of chemotherapy and wide local excision to optimize patient outcome. Sheth DS, Yasko AW, Raymond AK, et al: Conventional and dedifferentiated parosteal osteosarcoma: Diagnosis, treatment, and outcome. Cancer 1996;78:2136-2145.

The patient has a plexiform neurofibroma and multiple café-au-lait spots, all characteristic of von Recklinghausen's neurofibromatosis. This disease has been linked to a defect of the gene NF1 on chromosome 17. EWS is one of the genes associated with the 11;22 translocation found in Ewing's sarcoma and several other sarcomas. EXT1 is the most common gene affecting patients with multiple hereditary exostosis. P53 and Rb are tumor suppressor genes whose inactivation has been associated with tumors in conditions such as Li-Fraumeni and retinoblastoma, respectively. Theos A, Korf BR, American College of Physicians, et al: Pathophysiology of neurofibromatosis Type 1. Ann Intern Med 2006;144:842-849.

The histologic appearance of the soft-tissue lesion reveals compact nests of cells with a clear cytoplasm surrounded by a delicate border of fibrocollagenous tissue. There can be scattered multinucleated giant cells. This is consistent with a clear cell sarcoma, also called malignant melanoma of soft parts. This tumor is usually positive for S-100 and HMB45 (a melanoma-associated antigen). These tumors are frequently found around the foot and ankle. Similar to epithelioid sarcoma, it is usually intimately bound to tendons or tendon sheaths. Often the tumors are present for many years. The classic histologic appearance of this lesion differentiates it from the other choices. Enzinger FM, Weiss SW: Soft Tissue Tumors, ed 3. St Louis, MO, Mosby, 1995, p 913.

The images show an epiphyseal lesion. The MRI scan shows extensive bone edema surrounding the lesion, consistent with chondroblastoma. Histology shows polygonal chondroblasts in a cobblestone-like pattern and areas of calcification consistent with chondroblastoma. Although some giant cells are seen, the age of the patient and the polygonal chondroblasts differentiate this lesion from giant cell tumor. Clear cell chondrosarcoma is an epiphyseal lesion that occurs in an older population, and the cells have clear cytoplasm. This lesion is not producing bone on imaging or histologic specimen, eliminating osteosarcoma. Tuberculous septic arthritis can be an epiphyseal lesion, but granulomas would be seen on histology. Menendez LR (ed): Orthopaedic Knowledge Update: Musculoskeletal Tumors. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2002, pp 103-111.

The findings are consistent with Ewing's sarcoma. The radiographs reveal a lytic lesion in the diaphysis of the right fibula. There is elevation of the periosteum and evidence of a surrounding soft-tissue mass. The biopsy specimen shows diffuse small round blue cells surrounding the lamellar bone. It is the second most common malignant bone tumor in children. The most common treatment regimen consists of chemotherapy followed by surgical resection and/or radiation therapy. Surgical resection is employed when the lesion can be removed with wide margins and causes less morbidity than radiation therapy. McCarthy EF, Frassica FJ: Pathology of Bone and Joint Disorders with Clinical and Radiographic Correlation. Philadelphia, PA, WB Saunders, 1998, p 258.

Although the classic radiographic appearance of fibrous dysplasia is one of a central metaphyseal lesion with ground glass matrix, it is not unusual to see either a more radiodense-appearing lesion or a more peripheral location. The histologic finding of spicules of woven bone without osteoblastic rimming in a bland fibrous background is diagnostic of fibrous dysplasia. The imaging studies could be consistent with low-grade osteosarcoma, osteoblastoma, or osteomyelitis, but all have a very different histologic picture. Observation is indicated in the absence of symptoms, impending fracture, or deformity. Fibrous dysplasia most commonly occurs in the proximal femur. Huvos AG: Bone Tumors: Diagnosis, Treatment, and Prognosis. Philadelphia, PA, WB Saunders, 1991, pp 30-43.

The biopsy specimen shows a wavy collagenous matrix with elongated cells; this is most consistent with neurofibroma. The patient has a mass in the region of the sciatic nerve. Imaging characteristics, homogeneous and very low signal on T1-weighted and very high signal on the T2-weighted sequences, are consistent with a myxoid-type lesion. These include myxoma, myxoid sarcomas, and nerve sheath tumors. Campanacci M: Bone and Soft Tissue Tumors, ed 2. New York, NY, Springer-Verlag, 1999, pp 1135-1136

The use of bisphosphonates has been recently associated with the development of osteonecrosis of the jaw. Length of exposure seems to be the most important risk factor for this complication. The type of bisphosphonate may play a role and previous dental procedures may be a precipitating factor. Bisphosphonates are a class of therapeutic agents originally designed to treat loss of bone density (ie, alendronate). The primary mechanism of action of these drugs is inhibition of osteoclastic activity, and it has been shown that these drugs are useful in diseases with propensities toward osseous metastases. In particular, they are effective in diseases in which there is clear upregulation of osteoclastic or osteolytic activity, such as breast cancer and multiple myeloma, and have developed into a mainstay of treatment for individuals with these diseases. Although shown to reduce skeletal events, there has been no improvement in patient survival. Bamias A, Kastritis E, Bamia C, et al: Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: Incidence and risk factors. J Clin Oncol 2005;23:8580-8587. Thakkar SG, Isada C, Smith J, et al: Jaw complications associated with bisphosphonate use in patients with plasma cell dyscrasias. Med Oncol 2006;23:51-56.

This is a classic appearance for an osteosarcoma. The radiographs reveal a mixed osteolytic and osteoblastic lesion in a skeletally immature patient in the distal right femoral metaphysis. The pain pattern with progressive symptoms leading to the presence of night pain is also typical for this condition. The biopsy specimen reveals pleomorphic cells and the presence of osteoid. The current standard of care in the treatment of osteosarcoma is neoadjuvant chemotherapy followed by surgical resection or amputation followed by additional postoperative chemotherapy. Osteosarcoma is not radiosensitive. Wold LE, Adler CP, Sim FH, et al: Atlas of Orthopedic Pathology, ed 2. Philadelphia, PA, WB Saunders, 2003, p 179.

Osteofibrous dysplasia frequently presents at a very young age, usually less than 10 years. In most patients, it involves the anterior cortex of the tibial shaft and minor anterior bowing of the tibia is frequently seen. The lesion is unpredictable in nature, but local recurrence is very high in patients who undergo surgery before 15 years of age. Campanacci M, Laus M: Osteofibrous dysplasia of the tibia and fibula. J Bone Joint Surg Am 1981;63:367-375.

Epithelioid sarcoma is the most common soft-tissue sarcoma in the hand and most commonly occurs in young adults. The tumors can be superficial and may become ulcerated. Deeper lesions are often attached to tendons, tendon sheaths, or fascial structures. These are usually minimally symptomatic. The biopsy specimen reveals the typical appearance of a nodular pattern with central necrosis. They can mimic a necrotizing granulomatous process. Usually there are chronic inflammatory cells along the margin of the tumor nodules. This biopsy specimen does not have the clear cells necessary for a clear cell carcinoma or sarcoma. Nora's tumor is a bizarre parosteal osteochondromatous proliferation (BPOP) first described in 1983 by the pathologist, Nora. The lesion is defined as a reactive heterotopic ossification and is mostly found in the hands or feet of adults in the third decade of life. Enzinger FM, Weiss SW: Soft Tissue Tumors, ed 3. St Louis, MO, Mosby, 1995, p 1074.

McCune-Albright syndrome is the combination of polyostotic fibrous dysplasia, café-au-lait lesions, and endocrine dysfunction. The most common endocrine presentation is precocious development of secondary sexual characteristics. Compared with bone lesions in patients without polyostotic disease, the skeletal lesions in patients with the syndrome tend to be larger, more persistent, and associated with more complications. Bisphosphonate therapy has been shown in several studies to decrease the pain associated with the skeletal lesions of fibrous dysplasia. DiCaprio MR, Enneking WF: Fibrous dysplasia: Pathophysiology, evaluation and treatment. J Bone Joint Surg Am 2005;87:1848-1864.

Soft-tissue sarcomas most frequently metastasize to the lung, but certain histologic types have a predilection for the lymph node system as well. Rhabdomyosarcoma, clear cell sarcoma, epithelioid sarcoma, and synovial sarcoma are four of the most common types to spread in this fashion. Careful evaluation and/or sentinel lymph node biopsy plays a role in disease staging and prognosis. Riad S, Griffin AM, Liberman B, et al: Lymph node metastasis in soft-tissue sarcoma in an extremity. Clin Orthop Relat Res 2004;426:129-134.

The histology shows findings consistent with metastatic renal cell carcinoma. Renal cell carcinoma metastases are extremely vascular. Preoperative embolization helps minimize the amount of blood loss during curettage of these lesions. Chatziioannou AN, Johnson ME, Pneumaticos SG, et al: Preoperative embolization of bone metastases from renal cell carcinoma. Eur Radiol 2000;10:593-596.

The epiphyseal location on the radiograph and MRI scan and the histologic findings of polyhedral cells separated by a chondroid matrix with pericellular, lattice-like "chicken wire" calcification all suggest chondroblastoma. Although giant cell tumors of bone typically occupy an epiphyseal location, they are rare in children and when present are often metaphyseal in skeletally immature patients. Enchondromas and osteoblastomas are generally metaphyseal and, along with giant cell tumors, have very different histology than seen here. Chondromyxoid fibromas are typically metaphyseal in location. Huvos AG: Bone Tumors: Diagnosis, Treatment, and Prognosis. Philadelphia, PA, WB Saunders, 1991, pp 295-313.