| Patient Education |
|
Click here for patient education.
|
|
You are in: eMedicine Specialties >
Orthopedic Surgery > NEOPLASMS
Low-Grade Central Osteosarcoma
Article Last Updated: Dec 11, 2007
AUTHOR AND EDITOR INFORMATION
Section 1 of 12  
Author: Barnaby Dedmond, MD, Staff Physician, Department of Orthopedic Surgery, Palmetto Richland Memorial Hospital and University of South Carolina
Barnaby Dedmond is a member of the following medical societies: Alpha Omega Alpha, American Academy of Orthopaedic Surgeons, and Orthopaedic Trauma Association
Coauthor(s):
John Eady, MD, Chief, Orthopaedic Surgery, Dorn VA Hospital, Columbia, SC 29209
Editors: Timothy A Damron, MD, David G Murray Endowed Professor, Department of Orthopedic Surgery, Professor, Orthopedic Oncology and Adult Reconstruction, Vice Chair, Department of Orthopedics, State University of New York Upstate Medical University at Syracuse; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Dinesh Patel, MD, FACS, Associate Clinical Professor of Orthopedic Surgery, Harvard Medical School; Chief of Arthroscopic Surgery, Department of Orthopedic Surgery, Massachusetts General Hospital; Harris Gellman, MD, Consulting Surgeon, Broward Hand Center, Voluntary Clinical Professor of Orthopedic Surgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami School of Medicine
Author and Editor Disclosure
Synonyms and related keywords:
well-differentiated intramedullary osteosarcoma, low-grade intraosseous osteosarcoma, central osteosarcoma of low-grade malignancy, low-grade endosteal osteosarcoma
Osteosarcoma of bone is a high-grade tumor with a long-term survival rate of 60-85%. Several variants of osteosarcoma exist. High-grade variants include telangiectatic osteosarcoma, small-cell osteosarcoma, high-grade surface osteosarcoma, and secondary osteosarcoma. Other variants, such as low-grade central osteosarcoma, parosteal osteosarcoma, and periosteal osteosarcoma, are less aggressive entities with a lower rate of metastasis and a long-term survival rate approaching 90%. Low-grade central osteosarcoma is a rare variant of osteosarcoma that is often mistaken for fibrous dysplasia.1 (See also the eMedicine articles Osteosarcoma, Variants and Parosteal Osteosarcoma.) Initial diagnosis of osteosarcoma is often difficult. Frequently, it is diagnosed only after a recurrence of disease in an area of bone where a diagnosis of fibrous dysplasia had previously been made. Osteosarcoma has also been mistaken for other benign and malignant bone conditions, including nonossifying fibroma, well-differentiated fibrosarcoma, aneurysmal bone cyst, osteoblastoma, and desmoplastic fibroma.2 Its rarity likely contributes to these inaccurate diagnoses.
To the author's knowledge, the largest series in the literature to date is that of Kurt and colleagues, which was published in 1990 and included 80 cases.3 Low-grade central osteosarcoma has a better prognosis than that of high-grade osteosarcoma. (See also the eMedicine articles Fibrous Cortical Defect and Nonossifying Fibroma, Fibrosarcoma, Aneurysmal Bone Cyst[Orthopedic Surgery], Aneurysmal Bone Cyst [Radiology], Osteoblastoma [Orthopedic Surgery], and Osteoblastoma [Radiology].)
Problem
Low-grade central osteosarcoma is a rare variant of osteosarcoma that originates within the medullary cavity of bone. At histologic examination, it appears as a Broders grade 1 or grade 2 lesion. The Broders grading system was designed to determine the grade of malignancy of a given tumor on the basis of histologic features. These characteristics include the following:
- Degree of cellularity
- Cellular pleomorphism or anaplasia
- Mitotic activity
- Necrosis
- Expansive or infiltrative growth
Frequency
The above-mentioned study by Kurt and coauthors revealed low-grade central osteosarcoma accounts for 1.2-1.9% of all cases of osteosarcoma.3 Internationally, low-grade central osteosarcoma accounts for 0.7% of all cases of osteosarcoma, as reported by the Instituto de Rizzoli at the University of Bologna, Italy.
Etiology
The exact etiology of low-grade central osteosarcoma is unknown. Osteosarcomas have been experimentally induced in animals by a variety of means, including irradiation, inoculation with Moloney sarcoma virus, injection of bone-seeking radionucleotides, and inhalation of aerosolized plutonium 238 dioxide. Many of these induced tumors are well-differentiated osteosarcomas, including low-grade central osteosarcomas.
Pathophysiology
Low-grade central osteosarcomas typically develop de novo in the long bones of patients aged 20-30 years. Patients typically seek treatment when symptoms, which usually involve pain only at the site of the tumor, persist. The tumor grows locally within the bone of origin. Approximately 25-55% of these tumors invade the surrounding, adjacent soft tissue. If the tumor is not adequately resected early in its course, pulmonary metastasis may develop as a late complication.
Clinical
The mean patient age at presentation is 28.3 years. Patients with low-grade central osteosarcoma are approximately 1 decade older than patients with traditional osteosarcoma, although cases have been reported in patients aged 9-83 years. The male-to-female ratio is 1:1; this is unlike traditional osteosarcoma, which has a male-to-female ratio of 1.4:1. Pain is the most common symptom of low-grade central osteosarcoma; this is sometimes associated with local swelling. Typically, the duration of symptoms is long, with a mean of 1.8 years. About 5% of cases are found incidentally on radiographs obtained during an examination for reasons other than the evaluation of low-grade central osteosarcoma. Pathologic fractures are rare.
Because of its potential for metastasis and local, infiltrative destruction, the presence of a low-grade central osteosarcoma is an indication for treatment.
Low-grade central osteosarcoma may occur in the following locations:
- Long bones - 82.25%4
- Distal femur - 41%
- Proximal tibia - 12.5%
- Distal tibia - 8.75%
- Fibula - 5%
- Radius - 5%
- Proximal femur - 3.75%
- Midshaft femur - 2.5%
- Humerus - 2.5%
- Ulna - 1.25%
- Flat bones - 13.75%
- Ribs - 3.75%
- Mandible - 2.5%
- Maxilla, clavicle, occipital bone, scapula, vertebra, and ilium - 1.25% each
- Hands and feet - 4%
The only contraindication to the treatment of osteosarcoma is the presence of widespread metastases. Palliative treatment may then be indicated.
Lab Studies
- No laboratory studies have been shown to be helpful for the physician in diagnosing low-grade central osteosarcoma, with the exception of histologic examination.
Imaging Studies
- Standard radiography may be helpful.
- Radiographs show a large amount of radiographic variation among low-grade osteosarcomas (see Image 1).
- Location within the bone - Metaphyseal, 67%; at the junction of the diaphysis and the metaphysis, 17%; diaphyseal, 16%
- Degree of margination - Poor, 50-68%; intermediate, 11-20%; sharp, 22-30%
- Other features seen on standard radiographs include the following:
- Cortical destruction - 55-70%
- Expansive lesion - 40-51%
- Soft-tissue extension - 40-55%
- Periosteal new bone formation - 22-50%
- Crossing of previously fused physes - 60% (In one study, 0 of 11 cases crossed radiographically open physes.)
- Radiographic findings may be suggestive of malignancy.
- Enneking reported that the main radiologic feature that distinguishes low-grade central osteosarcoma from fibrous dysplasia is increased radiopacity.5
- At least 2 of 3 of the following radiographic signs were present in 8 of 8 cases presented by Ellis and colleagues; thus, these signs are thought to be suggestive of malignancy: (1) cortical discontinuity (the radiographic sign that was considered to be the most useful feature for distinguishing low-grade central osteosarcoma from benign entities), (2) poorly marginated soft-tissue extension, and (3) a cloudlike tumor matrix pattern.
- Standard anteroposterior and lateral chest radiographs are used to assess pulmonary metastases.
- Computed tomography (CT) scanning is useful for evaluating the degree of cortical destruction.
- On CT scans, 85% of low-grade central osteosarcomas show cortical destruction (compared with 55% on plain radiographs).
- CT scans show the trabecular pattern of the lesion and its relationship to adjacent healthy bone more clearly than do other images.
- CT scanning of the chest is also used to evaluate pulmonary metastases.
- Compared with other techniques, magnetic resonance imaging (MRI) enables better assessment of potential soft-tissue and marrow extension (see Images 2-4).
- Bone scanning reveals intense radioisotope uptake by the lesion, demonstrates the approximate local extent of the lesion, and may depict distant metastatic lesions to bone (see Image 5).
- Angiography is usually not necessary. Angiographic findings are normal until soft-tissue extension (which typically occurs late) is present.
Diagnostic Procedures
- Biopsy of the lesion may be necessary to obtain tissue for histologic diagnosis.
- Core-needle biopsy may be performed to obtain tissue when sufficient soft-tissue extension is present. In most cases, a Craig needle or an equivalent biopsy needle is necessary to enter the bone to obtain tissue for diagnosis.
- Formal open biopsy also may be performed. The authors recommend sealing the site of biopsy with bone cement to prevent local extension of the tumor. However, because of the risk of tumoral dissemination into the venous circulation and lungs, this technique is controversial.
Histologic Findings
General histologic characteristics of low-grade central osteosarcomas include the following (see Images 6-8):
- Spindle cell tumor
- Irregular bone production
- Specific patterns and the percentage of low-grade central osteosarcomas displaying them:
- A parosteal sarcoma pattern with heavy, irregular osteoid seams - 40%
- A desmoid pattern with scanty osteoid production and many collagen fibers - 33%
- A Chinese-characters pattern of fibrous dysplasia - 14%
- Low cellularity
- Cellularity characteristics and the percentage of low-grade central osteosarcomas displaying them:
- Small clusters of benign-appearing giant cells - 36%.
- Small foci of cartilage differentiation - 18%.
- Few mitotic figures
- In 82% of low-grade central osteosarcomas, 1-2 mitotic figures are present per 10 high-power fields.
- In 18% of low-grade central osteosarcomas, 3-4 mitotic figures are present per 10 high-power fields.
- Minimal cytologic atypia
- Other
- Low-grade central osteosarcomas are often indistinguishable from parosteal osteosarcoma at histologic analysis.6
- The differentiation of these 2 osteosarcomas is often based on whether a tumor is located within bone (low-grade central osteosarcoma) or has a juxtacortical presence (parosteal osteosarcoma). (See also the eMedicine article Juxtacortical Tumors.)
Staging
Two staging systems are used to stage sarcomas of bone: the American Joint Committee on Cancer staging protocol and the Musculoskeletal Tumor Society (MSTS) staging system.
- The American Joint Committee on Cancer staging system is based on tumor grade, size, and location (specifically, whether the tumor is within the cortex or extends beyond it), as well as on the presence of regional nodal or distant metastases.
- The MSTS system is based on tumor grade, site (ie, extracompartmental vs intracompartmental), and metastases.
- In both systems, low-grade central osteosarcoma is, by definition, a stage I tumor unless metastasis has occurred.
- In the MSTS system, stage IA includes intracompartmental low-grade tumors without metastases, whereas stage IB includes extracompartmental low-grade tumors. Tumors that have metastasized are classified as stage III lesions.
- In the American Joint Committee on Cancer system, stage IA includes low-grade tumors that are confined within the cortex without metastases, whereas stage IB includes low-grade tumors that have extended beyond the cortex. Tumors that have metastasized to regional lymph nodes are classified as stage IVA lesions, and those with distant metastasis are classified as stage IVB tumors.
Medical Therapy
The use of radiation therapy or chemotherapy in the treatment of low-grade central osteosarcoma is controversial because neither has been proven to be beneficial. (See also Intensified Chemotherapy Does Not Improve Osteosarcoma Survival, on Medscape.)
Surgical Therapy
Wide excision, which may include amputation, is the treatment of choice for low-grade central osteosarcoma.7 The disease's recurrence rate after such treatment is negligible, while the recurrence rate following curettage or marginal excision is 80-100%. Of the tumors that recur, 15% are high-grade lesions.
Preoperative Details
Surgical planning is based on the size and location of the lesion. With low-grade central osteosarcomas located in the extremities, the primary decision is whether limb salvage is possible or if amputation is necessary. The decision is based on the tumor's proximity to major neurovascular bundles or its invasion of them, as well as on whether it will be possible to adequately perform a wide excision without sacrificing 2 or more major compartments.
Intraoperative Details
The gross appearance of a low-grade central osteosarcoma is that of dense fibrous tissue with variable amounts of bone. Enneking reported that tetracycline labeling may be useful in distinguishing the transition from healthy bone to tumor if this change is not visibly evident.5
Postoperative Details
The most important factor that affects the morbidity and mortality of low-grade central osteosarcoma is determination of whether the margins of the surgical specimen are free of tumor on histologic examination.
Follow-up
Monitoring for signs of a developing infection is vitally important. Prevention or early evacuation of hematomas is helpful in preserving locally rotated tissue flaps. Finally, attention should be turned to proper rehabilitation, which includes retraining of the patient so that functional use of an extremity can be restored after involved muscle groups have been resected.
Surgical complications vary depending on the location of the tumor and the surrounding structures. The most frequent complications include the following:
- Infection - If this complication develops at the site of a prosthesis used for limb salvage, eradication of the infection frequently requires removal of the prosthesis, and amputation is sometimes required.
- Hematoma - This may cause failure of a locally rotated tissue flap.
- Loosening of the endoprosthesis
- Distant metastases
- Local recurrence
The recurrence of low-grade central osteosarcoma and the survival rates of patients with the disease include the following:
- Recurrence rate after wide excision - Less than 5%
- Recurrence rate after intralesional curettage or marginal excision - 80-100%
- Five-year disease-free survival rate - 90%
- Ten-year disease-free survival rate - 85%
Of tumors that recur, 15% recur as high-grade osteosarcomas with prognoses similar to those associated with traditional osteosarcomas. Recurrences can be observed 6 months to 20 years after primary treatment. Pulmonary metastases are rare, but they can occur 5-10 years after successful surgical excision of the primary tumor. Metastases are more common in recurrences, especially when the lesions recur as high-grade osteosarcomas.
The most important factor in the adequate treatment of low-grade central osteosarcoma is accurate diagnosis. Because of variability in the radiographic and histologic appearance of this lesion, the participation of a team consisting of a radiologist, pathologist, and orthopedic surgeon, all specializing in musculoskeletal oncology, is important. With accurate, prompt diagnosis and adequate surgical treatment, a low-grade central osteosarcoma is a curable lesion with a favorable prognosis.
| Media file 1:
Standard radiographs of a low-grade central osteosarcoma of the distal femur. |
 |  View Full Size Image | |
Media type: X-RAY
|
| Media file 2:
Magnetic resonance image (MRI) of low-grade central osteosarcoma of the distal femur. |
 | View Full Size Image | |
Media type: MRI
|
| Media file 3:
Magnetic resonance image (MRI) of low-grade central osteosarcoma of the distal femur. |
 | View Full Size Image | |
Media type: MRI
|
| Media file 4:
Magnetic resonance image (MRI) of low-grade central osteosarcoma of the distal femur. |
 | View Full Size Image | |
Media type: MRI
|
| Media file 5:
Bone scan of a low-grade central osteosarcoma of the distal femur. |
 | View Full Size Image | |
Media type: Image
|
| Media file 6:
Photomicrograph of a low-grade central osteosarcoma (original magnification, X40). Courtesy of Dr Ronald Burns, Palmetto Richland Department of Pathology. |
 | View Full Size Image | |
Media type: Micrograph
|
| Media file 7:
Photomicrograph of a low-grade central osteosarcoma (original magnification, X100). Courtesy of Dr Ronald Burns, Palmetto Richland Department of Pathology. |
 | View Full Size Image | |
Media type: Micrograph
|
| Media file 8:
Photomicrograph of a low-grade central osteosarcoma (original magnification, X400). Courtesy of Dr Ronald Burns, Palmetto Richland Department of Pathology. |
 | View Full Size Image | |
Media type: Micrograph
|
- Franceschina MJ, Hankin RC, Irwin RB. Low-grade central osteosarcoma resembling fibrous dysplasia. A report of two cases. Am J Orthop. Jun 1997;26(6):432-40. [Medline].
- Choong PF, Pritchard DJ, Rock MG. Low grade central osteogenic sarcoma. A long-term followup of 20 patients. Clin Orthop Relat Res. Jan 1996;198-206. [Medline].
- Kurt AM, Unni KK, McLeod RA. Low-grade intraosseous osteosarcoma. Cancer. Mar 15 1990;65(6):1418-28. [Medline].
- Andresen KJ, Sundaram M, Unni KK, et al. Imaging features of low-grade central osteosarcoma of the long bones and pelvis. Skeletal Radiol. Jul 2004;33(7):373-9. [Medline].
- Enneking WF. Endosteal osteosarcoma. In: Musculoskeletal Tumor Surgery. vol 2. New York, NY: Churchill Livingstone; 1983:1080-90.
- Bertoni F, Bacchini P, Fabbri N, et al. Osteosarcoma. Low-grade intraosseous-type osteosarcoma, histologically resembling parosteal osteosarcoma, fibrous dysplasia, and desmoplastic fibroma. Cancer. Jan 15 1993;71(2):338-45. [Medline].
- Unni KK, Dahlin DC, McLeod RA, et al. Intraosseous well-differentiated osteosarcoma. Cancer. Sep 1977;40(3):1337-47. [Medline].
- Broders AC, Hargrave R, Meyerding HW. Pathological features of soft tissue fibrosarcoma with special reference to the grading of its malignancy. Surg Gynecol Obstet. 1939;69:267.
- Campanacci M, Bertoni F, Capanna R, et al. Central osteosarcoma of low grade malignancy. Ital J Orthop Traumatol. Apr 1981;7(1):71-8. [Medline].
- Enzinger FM, Weiss SW. General considerations. In: Soft Tissue Tumors. 3rd ed. St Louis, Mo: Mosby; 1995:6-12.
- Gossner W, Hug O, Luz A. Experimental induction of bone tumors by short-lived bone-seeking radionuclides. Recent Results Cancer Res. 1976;(54):36-49. [Medline].
- Hahn FF, Mewhinney JA, Merickel BS. Primary bone neoplasms in beagle dogs exposed by inhalation to aerosols of plutonium-238 dioxide. J Natl Cancer Inst. Oct 1981;67(4):917-27. [Medline].
- King MA, Casarett GW, Weber DA. A study of irradiated bone. III. Scintigraphic and radiographic detection of radiation-induced osteosarcomas. J Nucl Med. May 1980;21(5):426-31. [Medline]. [Full Text].
- Olson HM, Capen CC. Intratibial Moloney sarcoma virus-induced osteosarcoma in the rat: tumor incidence and pathologic evaluation. J Natl Cancer Inst. Feb 1977;58(2):433-7. [Medline].
- Park HR, Jung WW, Bacchini P, et al. Ezrin in osteosarcoma: comparison between conventional high-grade and central low-grade osteosarcoma. Pathol Res Pract. 2006;202(7):509-15. [Medline].
- Rougraff BT. Variants of osteosarcoma. Curr Opin Orthop. 1999;10:485-90.
- Simon MA. Staging systems. In: Simon MA, Springfield D. Surgery for Bone and Soft Tissue Tumors. Philadelphia, Pa: Lippincott-Raven; 1998:47-53.
Low-Grade Central Osteosarcoma excerpt Article Last Updated: Dec 11, 2007
|
