Introduction
This article focuses on high-grade intramedullary osteosarcoma (also referred to as simply osteosarcoma), including its classic osteoblastic form and its fibroblastic and chondroblastic forms. Osteosarcoma is the most common malignant bone tumor.1,2 This disease is thought to arise from primitive mesenchymal bone-forming cells, and its histologic hallmark is the production of malignant osteoid. Other cell populations may also be present, as these types of cells may also arise from pluripotential mesenchymal cells, but any area of malignant bone in the lesion establishes the diagnosis as osteosarcoma.
The mainstay of therapy is surgical removal of the malignant lesion. Most often, limb-sparing (limb-preserving) procedures can be used to treat patients with this disease and, thus, preserve function. Chemotherapy is also required to treat micrometastatic disease, which is present but often not detectable in most patients (about 80%) at the time of diagnosis.
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Related eMedicine topic:
Osteosarcoma, Variants
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History of the Procedure
Osteosarcoma is an ancient disease that is still incompletely understood. The term "sarcoma" was introduced by the English surgeon John Abernathy in 1804 and was derived from Greek roots meaning "fleshy excrescence."3 In 1805, the French surgeon Alexis Boyer (personal surgeon to Napoleon) first used the term "osteosarcoma."3,4 Boyer realized that osteosarcoma is a distinct entity from other bone lesions, such as osteochondromas (exostoses).
Evidence of further organized thought and purposeful investigation regarding this disease was found by the mid 1800s. Peltier recorded that in 1847, the Baron Guillaume Dupuytren demonstrated his intimate knowledge of the gross pathologic appearance of osteosarcoma when he wrote the following3 :
"Osteosarcoma, which is a true cancerous degeneration of bone, manifests itself in the form of a white or reddish mass, lardaceous and firm at an early stage of the disease; but presenting at a later period, points of softening, cerebriform matter, extravasating blood, and white or straw colored fluid of a viscid consistence in its interior."3
Under the auspices of the American College of Surgeons, Ernest Amory Codman (along with James Ewing and Joseph Bloodgood) created the Registry of Bone Sarcoma in 1921.5 This was a significant step forward in studying these rare and ominous tumors, as individual surgeons had only limited experience to guide them.
Another major institution that began to take shape in the early 1900s was the Rizzoli Institute in Bologna, Italy. This institute, whose bone tumor roots were nurtured by Vittorio Putti (1880-1940), prospered under the later guidance of persons such as Scaglietti and Campanacci.6 Major contributions from this institution have included innovative treatment for unicameral bone cysts (Scaglietti) and intense study of osteofibrous dysplasia (Campanacci tumor).
By the mid 1900s, great strides were being made in the United States in the field of bone pathology by Henry L. Jaffe (1896-1979) and his colleague Louis Lichtenstein (1906-1977). Each of these men published textbooks devoted to bone pathology. Jaffe is also often credited with bringing order to the chaos that was orthopedic pathology. Together, Jaffe and Lichtenstein established virtually all of the key histologic criteria that are used to diagnose most of the commonly encountered bone tumors.
A different Dr Jaffe (Norman Jaffe), along with other researchers, helped expand the use of a variety of effective chemotherapeutic agents in the 1970s and early 1980s.7 Not the least of these agents were Adriamycin and methotrexate. These medications (and others that followed) dramatically improved the treatment of patients with osteosarcoma through their ability to treat the micrometastatic disease that was thought to be present in approximately 80% of patients.8 These drugs were found to be useful both preoperatively and postoperatively in patients with osteosarcoma, a discovery made at the Sloan-Kettering Memorial Cancer Center somewhat serendipitously while custom-made prostheses were being fabricated for patients awaiting surgery.9 Such preoperative use of chemotherapy came to be referred to as neoadjuvant chemotherapy.
An orthopedic surgeon from Gainesville, Florida, William F. Enneking, MD, introduced his surgical staging system for musculoskeletal sarcomas.10,11 This staging system helped organize the orthopedic surgical approach to both biopsy and definitive tumor resection for osteosarcoma, as well as for other musculoskeletal sarcomas. Dr. Enneking's influence extended far beyond his staging system because of his intense commitment to educating others regarding musculoskeletal tumors. He has educated numerous orthopedic oncology fellows, published numerous research articles, and continued to conduct a yearly continuing medical education course focusing on benign and malignant tumors.
Problem
Osteosarcoma is a deadly form of musculoskeletal cancer that most commonly causes patients to die from pulmonary metastatic disease.3,6,12,13,14 Image 1 illustrates the chest radiograph of a patient who died from pulmonary metastatic disease. Most osteosarcomas arise as solitary lesions within the fastest growing areas of the long bones of children. The top 3 affected areas are the distal femur, the proximal tibia, and the proximal humerus, but virtually any bone can be affected. Images 2-6 illustrate the clinical and radiologic findings of a patient who presented with osteosarcoma of the proximal humerus.
Not all osteosarcomas arise in a solitary fashion, as multiple sites may become apparent within a period of about 6 months (synchronous osteosarcoma), or multiple sites may be noted over a period longer than 6 months (metachronous osteosarcoma).12 Such multifocal osteosarcoma is decidedly rare, but when it occurs, it tends to be in patients younger than 10 years.12
Frequency
In the United States, the incidence of osteosarcoma is 400 cases per year (4.8 per million population <20 y).15 The overall 5-year survival rate for patients diagnosed between 1974 and 1994 was 63% (59% for males, 70% for females).
The incidence is slightly higher in blacks than in whites. Data from the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Pediatric Monograph 1975-1995 are as follows15 :
- Blacks – 5.2 cases per million per year (persons <20 y)
- Whites – 4.6 cases per million per year
The incidence of osteosarcoma is slightly higher in males than in females. In males, it is 5.2 per million per year. In females, the incidence is 4.5 per million per year.
Osteosarcoma is very rare in young children (0.5 cases per million per year in children <5 y). However, the incidence increases steadily with age, increasing more dramatically in adolescence, corresponding with the adolescent growth spurt.
- Age 5-9 years – 2.6 (black) or 2.1 (white) cases per million per year
- Age 10-14 years – 8.3 (black) or 7 (white) cases per million per year
- Age 15-19 years – 8.9 (black) or 8.2 (white) cases per million per year
Etiology
The exact cause of osteosarcoma is unknown. However, a number of risk factors are apparent, as follows3,6,12,13,14,16,17,18,19,20,21 :
- Rapid bone growth: Rapid bone growth appears to predispose persons to osteosarcoma, as suggested by the increased incidence during the adolescent growth spurt, the high incidence among large-breed dogs (eg, Great Dane, St. Bernard, German shepherd), and osteosarcoma's typical location in the metaphyseal area adjacent to the growth plate (physis) of long bones.
- Environmental factors: The only known environmental risk factor is exposure to radiation. Radiation-induced osteosarcoma is a form of secondary osteosarcoma and is not discussed further in this article.
- Genetic predisposition: Bone dysplasias, including Paget disease, fibrous dysplasia, enchondromatosis, and hereditary multiple exostoses and retinoblastoma (germ-line form) are risk factors. The combination of constitutional mutation of the RB gene (germline retinoblastoma) and radiation therapy is associated with a particularly high risk of developing osteosarcoma, Li-Fraumeni syndrome (germline p53 mutation), and Rothmund-Thomson syndrome (autosomal recessive association of congenital bone defects, hair and skin dysplasias, hypogonadism, and cataracts).
Related eMedicine topics:
Enchondroma and Enchondromatosis
Fibrous Dysplasia
Li-Fraumeni Syndrome
Paget Disease
Retinoblastoma
Rothmund-Thomson Syndrome
Pathophysiology
Osteosarcoma is a bone tumor and can occur in any bone, usually in the extremities of long bones near metaphyseal growth plates. The most common sites are the femur (42%, 75% of which are in the distal femur), tibia (19%, 80% of which are in the proximal tibia), and humerus (10%, 90% of which are in the proximal humerus). Other significant locations are the skull and jaw (8%) and pelvis (8%).
A number of variants of osteosarcoma exist, including conventional types (osteoblastic, chondroblastic, and fibroblastic), telangiectatic, multifocal, parosteal, and periosteal. This article only addresses conventional osteosarcoma.
Presentation
Symptoms may be present for weeks or months (occasionally longer) before patients are diagnosed. The most common presenting symptom of osteosarcoma is pain, particularly pain with activity. Patients may be concerned that their child has a sprain, arthritis, or growing pains. Often, there is a history of trauma, but the precise role of trauma in the development of osteosarcoma is unclear.
Pathologic fractures are not particularly common. The exception is the telangiectatic type of osteosarcoma, which is more commonly associated with pathologic fractures. The pain in an extremity may result in a limp. There may or may not be a history of swelling, depending on the size of the lesion and its location. Systemic symptoms, such as fever and night sweats, are rare. Tumor spread to the lungs only rarely results in respiratory symptoms and usually indicates extensive lung involvement. Metastases to other sites are extremely rare, and, therefore, other symptoms are unusual.
Physical examination findings are usually limited to the site of the primary tumor, as follows:
- Mass: A palpable mass may or may not be present. The mass may be tender and warm, although these signs are indistinguishable from osteomyelitis. Increased skin vascularity over the mass may be discernible. Pulsations or a bruit may be detectable.
- Decreased range of motion: Involvement of a joint should be obvious on physical examination.
- Lymphadenopathy: Involvement of local or regional lymph nodes is unusual.
- Respiratory findings: Auscultation is usually uninformative unless the disease is extensive.
Related eMedicine topics:
Osteomyelitis, Acute Pyogenic
Osteomyelitis, Chronic
Indications
The 2 main procedures performed by orthopedic surgeons in patients with osteosarcoma are biopsy and wide resection. Neither of these procedures should be undertaken unless complete tumor staging has been completed preoperatively. Such staging would typically include (but not be limited to) the following:
- Plain radiography of the involved bone, including the joint above and the joint below the affected region
- Total body bone scanning
- Magnetic resonance imaging (MRI) of the primary tumor area to include the entire bone of origin
- Computed tomography (CT) scanning of the lungs
The biopsy of malignant bone lesions is not an insignificant procedure. An improperly performed biopsy can result in the amputation of an otherwise salvageable extremity. It has also been shown repeatedly that oncologic outcomes are optimized when the biopsy is performed by the same surgeon who will be responsible for the definitive tumor resection (if one is needed).22,23 Incisional biopsies or core needle biopsies (Craig needle biopsy) are the most common types of biopsies performed by orthopedic surgeons.24 Open lines of communication between the orthopedic surgeon and the pathologist are vital to help ensure that adequate tissue is obtained for diagnostic purposes (see Images 10-11).
Wide resection is the goal for patients in whom primary tumor resection is contemplated. Simply defined, a wide resection means that the entire malignant tumor has been surgically excised, and no microscopic evidence of tumor cells at the resection margins remains (ie, negative margins). Over the years, many authors have suggested variable and arbitrary amounts of the normal tissue cuff to remove along with the primary tumor to increase the likelihood of negative margins.
No universally accepted definition exists of the appropriate thickness of the normal cuff. In a technical sense, a wide margin still exists even if the distance between the normal tissue and tumor is 1 cell thick. From an oncologic standpoint, the width achieved is less important (limb-sparing surgery vs amputation) than the achievement of a negative margin. In other words, a limb-sparing surgery without wide margins could do the patient less of a service than an amputation with wide margins. This would apply in most cases in which maximal preservation of life is considered the primary goal.
Relevant Anatomy
See Surgical therapy.
Contraindications
Because osteosarcoma is a deadly form of cancer, no absolute contraindications to treatment exist. Relative contraindications would include situations in which the patient is so frail that the risks of general anesthesia outweigh any potential benefits of surgery. Another relative contraindication would be a situation in which the patient has extensive, overwhelming metastatic disease, and the benefits of comfort and/or hospice care outweigh the potential benefits of surgical intervention.
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References
Marulanda GA, Henderson ER, Johnson DA, Letson GD, Cheong D. Orthopedic surgery options for the treatment of primary osteosarcoma. Cancer Control. Jan 2008;15(1):13-20. [Medline]. [Full Text].
Vander Griend RA. Osteosarcoma and its variants. Orthop Clin North Am. Jul 1996;27(3):575-81. [Medline].
Peltier LF. Tumors of bone and soft tissues. Orthopedics: A History and Iconography. San Francisco, Calif: Norman Publishing; 1993:264-91.
Rutkow IM. The nineteenth century. Surgery: An Illustrated History. St Louis, Mo: Mosby-Year Book; 1993:321-504.
Mallon WJ. The registry of bone sarcoma. Ernest Amory Codman: The End Result of a Life in Medicine. Philadelphia, Pa: WB Saunders Co; 2000:107-21.
Campanacci M. Preface. Bone and Soft Tissue Tumors: Clinical Features, Imaging, Pathology and Treatment. 2nd ed. New York, NY: Springer-Verlag; 1999.
Link MP, Goorin AM, Miser AW, et al. The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med. Jun 19 1986;314(25):1600-6. [Medline].
Jaffe N. Historical perspective of the treatment of osteosarcoma: an interview with Dr Norman Jaffe. Interview by Margaret Pearson. J Pediatr Oncol Nurs. Apr 1998;15(2):90-4. [Medline].
Rosen G, Murphy ML, Huvos AG, Gutierrez M, Marcove RC. Chemotherapy, en bloc resection, and prosthetic bone replacement in the treatment of osteogenic sarcoma. Cancer. Jan 1976;37(1):1-11. [Medline].
Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res. Nov-Dec 1980;153:106-20. [Medline].
Enneking WF, Spanier SS, Goodman MA. Current concepts review. The surgical staging of musculoskeletal sarcoma. J Bone Joint Surg Am. Sep 1980;62(6):1027-30. [Medline]. [Full Text].
Weis LD. Common malignant bone tumors: osteosarcoma. In: Simon MA, Springfield D, eds. Surgery for Bone and Soft-Tissue Tumors. Philadelphia, Pa: Lippincott-Raven; 1998:265-74.
Link MP, Eilber F. Osteosarcoma. In: Pizzo PA, Poplack DG, eds. Principles and Practice of Pediatric Oncology. 3rd ed. Philadelphia, Pa: Lippincott-Raven; 1997:889-920.
Arceci RJ, Weinstein HJ. Neoplasia. In: Avery GB, Fletcher MA, MacDonald MG, eds. Neonatology: Pathophysiology and Management of the Newborn. 4th ed. Philadelphia, Pa: JB Lippincott; 1994:1211-28.
Ries LAG, Smith MA, Gurney JG, et al. Cancer incidence and survival among children and adolescents: United States SEER program 1975-1995. Bethesda, Md: National Cancer Institute; 1999. NIH Pub No 99–4649. Available at http://seer.cancer.gov/publications/childhood/. Accessed March 21, 2008.
Clark JC, Dass CR, Choong PF. A review of clinical and molecular prognostic factors in osteosarcoma. J Cancer Res Clin Oncol. Mar 2008;134(3):281-97. [Medline].
Pochanugool L, Subhadharaphandou T, Dhanachai M, et al. Prognostic factors among 130 patients with osteosarcoma. Clin Orthop Relat Res. Dec 1997;345:206-14. [Medline].
Tsuchiya H, Tomita K. Prognosis of osteosarcoma treated by limb-salvage surgery: the ten-year intergroup study in Japan. Jpn J Clin Oncol. Oct 1992;22(5):347-53. [Medline].
Taylor WF, Ivins JC, Unni KK, et al. Prognostic variables in osteosarcoma: a multi-institutional study. J Natl Cancer Inst. Jan 4 1989;81(1):21-30. [Medline].
Hudson M, Jaffe MR, Jaffe N, et al. Pediatric osteosarcoma: therapeutic strategies, results, and prognostic factors derived from a 10-year experience. J Clin Oncol. Dec 1990;8(12):1988-97. [Medline].
Meyer WH, Schell MJ, Kumar AP, et al. Thoracotomy for pulmonary metastatic osteosarcoma. An analysis of prognostic indicators of survival. Cancer. Jan 15 1987;59(2):374-9. [Medline].
Mankin HJ, Lange TA, Spanier SS. The hazards of biopsy in patients with malignant primary bone and soft-tissue tumors. J Bone Joint Surg Am. Oct 1982;64(8):1121-7. [Medline]. [Full Text].
Mankin HJ, Mankin CJ, Simon MA. The hazards of the biopsy, revisited. Members of the Musculoskeletal Tumor Society. J Bone Joint Surg Am. May 1996;78(5):656-63. [Medline].
Craig FS. Vertebral-body biopsy. J Bone Joint Surg Am. Jan 1956;38-A(1):93-102. [Medline]. [Full Text].
Kim MS, Lee SY, Cho WH, et al. Initial tumor size predicts histologic response and survival in localized osteosarcoma patients. 1: J Surg Oncol. Feb 12 2008;97(5):456-61. [Medline].
Winkelmann WW. Rotationplasty. Orthop Clin North Am. Jul 1996;27(3):503-23. [Medline].
Antunes M, Bernardo J, Salete M, et al. Excision of pulmonary metastases of osteogenic sarcoma of the limbs. Eur J Cardiothorac Surg. May 1999;15(5):592-6. [Medline].
Aparicio J, Segura A, Montalar J, et al. Long-term results after combined modality treatment for non-metastatic osteosarcoma. Med Oncol. Dec 1999;16(4):255-60. [Medline].
Bacci G, Briccoli A, Mercuri M, et al. Osteosarcoma of the extremities with synchronous lung metastases: long-term results in 44 patients treated with neoadjuvant chemotherapy. J Chemother. Feb 1998;10(1):69-76. [Medline].
Bacci G, Ferrari S, Longhi A, et al. Pattern of relapse in patients with osteosarcoma of the extremities treated with neoadjuvant chemotherapy. Eur J Cancer. Jan 2001;37(1):32-8. [Medline].
Boriani S, Biagini R, De Iure F, et al. En bloc resections of bone tumors of the thoracolumbar spine. A preliminary report on 29 patients. Spine. Aug 15 1996;21(16):1927-31. [Medline].
Boriani S, Weinstein JN, Biagini R. Primary bone tumors of the spine. Terminology and surgical staging. Spine. May 1 1997;22(9):1036-44. [Medline].
Davis AM, Devlin M, Griffin AM, Wunder JS, Bell RS. Functional outcome in amputation versus limb sparing of patients with lower extremity sarcoma: a matched case-control study. Arch Phys Med Rehabil. Jun 1999;80(6):615-8. [Medline].
Delepine N, Delepine G, Cornille H, et al. Dose escalation with pharmacokinetics monitoring in methotrexate chemotherapy of osteosarcoma. Anticancer Res. Mar-Apr 1995;15(2):489-94. [Medline].
Eilber F, Giuliano A, Eckardt J, et al. Adjuvant chemotherapy for osteosarcoma: a randomized prospective trial. J Clin Oncol. Jan 1987;5(1):21-6. [Medline].
Ferrari S, Bacci G, Picci P, et al. Long-term follow-up and post-relapse survival in patients with non-metastatic osteosarcoma of the extremity treated with neoadjuvant chemotherapy. Ann Oncol. Aug 1997;8(8):765-71. [Medline].
Gebhardt MC. What's new in musculoskeletal tumor surgery. J Bone Joint Surg Am. Apr 2001;83-A(4):629-34. [Medline]. [Full Text].
Gherlinzoni F, Picci P, Bacci G, Campanacci D. Limb sparing versus amputation in osteosarcoma. Correlation between local control, surgical margins and tumor necrosis: Istituto Rizzoli experience. Ann Oncol. Apr 1992;3(suppl 2):S23-7. [Medline].
Goorin A, Strother D, Poplack D, et al. Safety and efficacy of l-leucovorin rescue following high-dose methotrexate for osteosarcoma. Med Pediatr Oncol. Jun 1995;24(6):362-7. [Medline].
Goorin AM, Shuster JJ, Baker A, et al. Changing pattern of pulmonary metastases with adjuvant chemotherapy in patients with osteosarcoma: results from the multiinstitutional osteosarcoma study. J Clin Oncol. Apr 1991;9(4):600-5. [Medline].
Gralla RJ, Osoba D, Kris MG, et al. Recommendations for the use of antiemetics: evidence-based, clinical practice guidelines. American Society of Clinical Oncology. J Clin Oncol. Sep 1999;17(9):2971-94. [Medline]. [Full Text].
Hart RA, Boriani S, Biagini R, Currier B, Weinstein JN. A system for surgical staging and management of spine tumors. A clinical outcome study of giant cell tumors of the spine. Spine. Aug 1 1997;22(15):1773-82; discussion 1783. [Medline].
Kelley SP, Ashford RU, Rao AS, Dickson RA. Primary bone tumours of the spine: a 42-year survey from the Leeds Regional Bone Tumour Registry. Eur Spine J. Mar 2007;16(3):405-9. [Medline]. [Full Text].
Krailo M, Ertel I, Makley J, et al. A randomized study comparing high-dose methotrexate with moderate-dose methotrexate as components of adjuvant chemotherapy in childhood nonmetastatic osteosarcoma: a report from the Childrens Cancer Study Group. Med Pediatr Oncol. 1987;15(2):69-77. [Medline].
Link MP, Goorin AM, Horowitz M, et al. Adjuvant chemotherapy of high-grade osteosarcoma of the extremity. Updated results of the Multi-Institutional Osteosarcoma Study. Clin Orthop Relat Res. Sep 1991;270:8-14. [Medline].
Makley JT, Krailo M, Ertel IJ, et al. The relationship of various aspects of surgical management to outcome in childhood nonmetastatic osteosarcoma: a report from the Childrens Cancer Study Group. J Pediatr Surg. Feb 1988;23(2):146-51. [Medline].
Morgan E, Baum E, Bleyer WA, et al. Treatment of patients with metastatic osteogenic sarcoma: a report from the Children's Cancer Study Group. Cancer Treat Rep. Apr 1984;68(4):661-4. [Medline].
Pignatti G, Bacci G, Picci P, et al. Telangiectatic osteogenic sarcoma of the extremities. Results in 17 patients treated with neoadjuvant chemotherapy. Clin Orthop Relat Res. Sep 1991;270:99-106. [Medline].
Provisor AJ, Ettinger LJ, Nachman JB, et al. Treatment of nonmetastatic osteosarcoma of the extremity with preoperative and postoperative chemotherapy: a report from the Children's Cancer Group. J Clin Oncol. Jan 1997;15(1):76-84. [Medline].
Simon MA. Biopsy of musculoskeletal tumors. J Bone Joint Surg Am. Oct 1982;64(8):1253-7. [Medline]. [Full Text].
Simon MA, Biermann JS. Biopsy of bone and soft-tissue lesions. J Bone Joint Surg Am. Apr 1993;75(4):616-21. [Medline]. [Full Text].
Skrzynski MC, Biermann JS, Montag A, Simon MA. Diagnostic accuracy and charge-savings of outpatient core needle biopsy compared with open biopsy of musculoskeletal tumors. J Bone Joint Surg Am. May 1996;78(5):644-9. [Medline].
Weeden S, Grimer RJ, Cannon SR, Taminiau AH, Uscinska BM, and the European Osteosarcoma Intergroup. The effect of local recurrence on survival in resected osteosarcoma. Eur J Cancer. Jan 2001;37(1):39-46. [Medline].
Winkler K, Beron G, Kotz R, et al. Neoadjuvant chemotherapy for osteogenic sarcoma: results of a Cooperative German/Austrian study. J Clin Oncol. Jun 1984;2(6):617-24. [Medline].
Winkler K, Bieling P, Bielack S, et al. Local control and survival from the Cooperative Osteosarcoma Study Group studies of the German Society of Pediatric Oncology and the Vienna Bone Tumor Registry. Clin Orthop Relat Res. Sep 1991;270:79-86. [Medline].
Withrow SJ, Powers BE, Straw RC, Wilkins RM. Comparative aspects of osteosarcoma. Dog versus man. Clin Orthop Relat Res. Sep 1991;270:159-68. [Medline].
Further Reading
Keywords
osteogenic sarcoma, osteoblastic osteosarcoma, chondroblastic osteosarcoma, fibroblastic osteosarcoma, multifocal osteosarcoma, high-grade intramedullary osteosarcoma, typical osteosarcoma, classic osteosarcoma, conventional osteosarcoma, variant osteosarcoma, primary osteosarcoma, synchronous osteosarcoma, metachronous osteosarcoma, unicameral bone cyst, osteofibrous dysplasia, Campanacci tumor, periosteal osteosarcoma, malignant bone cancer, bone cancer
