Low-Grade Central Osteosarcoma 

Updated: Apr 19, 2018
Author: Barnaby Dedmond, MD; Chief Editor: Harris Gellman, MD 

Overview

Background

Osteosarcoma of bone is a high-grade tumor with a long-term survival rate of 60-85%. Several variants of osteosarcoma exist.[1, 2] High-grade variants include telangiectatic osteosarcoma, small-cell osteosarcoma, high-grade surface osteosarcoma, and secondary osteosarcoma. Other variants (eg, 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 originates within the medullary cavity of bone and is often mistaken for fibrous dysplasia.[3]  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.[4]  These characteristics include the following:

  • Degree of cellularity
  • Cellular pleomorphism or anaplasia
  • Mitotic activity
  • Necrosis
  • Expansive or infiltrative growth

Initial diagnosis of osteosarcoma is often difficult.[5, 6] 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.[7] 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.[8, 9] 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 et al, which was published in 1990 and included 80 cases.[10] Low-grade central osteosarcoma has a better prognosis than high-grade osteosarcoma does. (See also Aneurysmal Bone Cyst Imaging and Osteoblastoma Imaging.)

Anatomy

Low-grade central osteosarcoma may occur in long bones (82.25%),[11] flat bones (13.75%), or the hands and feet (4%).

Sites in specific long bones are as follows:

  • 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%

Sites in specific flat bones are as follows:

  • Ribs - 3.75%
  • Mandible - 2.5%
  • Maxilla, clavicle, occipital bone, scapula, vertebra, and ilium - 1.25% each

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.

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,[12] inoculation with Moloney sarcoma virus,[13] injection of bone-seeking radionucleotides,[14] and inhalation of aerosolized plutonium 238 dioxide.[15] Many of these induced tumors are well-differentiated osteosarcomas, including low-grade central osteosarcomas.

Epidemiology

In the study by Kurt et al, low-grade central osteosarcoma accounted for 1.2-1.9% of all cases of osteosarcoma.[10]  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.

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, though 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.

Prognosis

Recurrences rates for of low-grade central osteosarcoma are as follows:

  • Recurrence rate after wide excision - Less than 5%
  • Recurrence rate after intralesional curettage or marginal excision - 80-100%

Survival rates for patients with the disease are as follows:

  • 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.

 

Presentation

History and Physical Examination

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.

 

Workup

Laboratory Studies

No laboratory studies have been shown to be helpful for diagnosing low-grade central osteosarcoma, with the exception of histologic examination.

Imaging Studies

Standard radiography

Standard radiography may be helpful. Radiographs show a large amount of variation among low-grade osteosarcomas (see the image below).

Standard radiographs of a low-grade central osteos Standard radiographs of a low-grade central osteosarcoma of the distal femur.

Characteristic features include the following:

  • 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.[16]

At least two of the following three radiographic signs were present in all eight cases presented by Ellis et al[17] :

  • Cortical discontinuity (the radiographic sign that was considered to be the most useful feature for distinguishing low-grade central osteosarcoma from benign entities)
  • Poorly marginated soft-tissue extension
  • Cloudlike tumor matrix pattern

Accordingly, these signs are thought to be suggestive of malignancy.

Standard anteroposterior and lateral chest radiographs are used to assess pulmonary metastases.

Computed tomography

Computed tomography (CT) is useful for evaluating the degree of cortical destruction. On CT, 85% of low-grade central osteosarcomas show cortical destruction (compared with 55% on plain radiography). CT scans show the trabecular pattern of the lesion and its relation to adjacent healthy bone more clearly than do other images. CT of the chest is also used to evaluate pulmonary metastases.

Magnetic resonance imaging

Compared with other techniques, magnetic resonance imaging (MRI) enables better assessment of potential soft-tissue and marrow extension (see the images below).

Magnetic resonance image (MRI) of low-grade centra Magnetic resonance image (MRI) of low-grade central osteosarcoma of the distal femur.
Magnetic resonance image (MRI) of low-grade centra Magnetic resonance image (MRI) of low-grade central osteosarcoma of the distal femur.
Magnetic resonance image (MRI) of low-grade centra Magnetic resonance image (MRI) of low-grade central osteosarcoma of the distal femur.

Bone scanning

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 the image below).

Bone scan of a low-grade central osteosarcoma of t Bone scan of a low-grade central osteosarcoma of the distal femur.

Angiography

Angiography is usually not necessary. Angiographic findings are normal until soft-tissue extension (which typically occurs late) is present.

Biopsy

Biopsy of the lesion may be necessary to obtain tissue for histologic diagnosis.

Core needle biopsy (CNB) 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 the images below):

  • Spindle cell tumor
  • Irregular bone production - Chinese-characters pattern of fibrous dysplasia (14%); desmoid pattern with scanty osteoid production and many collagen fibers (33%); parosteal sarcoma pattern with heavy, irregular osteoid seams (40%)
  • Low cellularity - Small foci of cartilage differentiation (18%); small clusters of benign-appearing giant cells (36%)
  • Few mitotic figures - In 82% of low-grade central osteosarcomas, one or two mitotic figures are present per 10 high-power fields; in 18% of low-grade central osteosarcomas, three or four 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. [18, 19, 20, 21, 22] ; differentiation of these two 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 Juxtacortical Tumors)
Photomicrograph of a low-grade central osteosarcom Photomicrograph of a low-grade central osteosarcoma (original magnification, X40). Courtesy of Dr Ronald Burns, Palmetto Richland Department of Pathology.
Photomicrograph of a low-grade central osteosarcom Photomicrograph of a low-grade central osteosarcoma (original magnification, X100). Courtesy of Dr Ronald Burns, Palmetto Richland Department of Pathology.
Photomicrograph of a low-grade central osteosarcom Photomicrograph of a low-grade central osteosarcoma (original magnification, X400). Courtesy of Dr Ronald Burns, Palmetto Richland Department of Pathology.

Detection of GNAS mutations in primary bone tumors has been useful in clinical practice for diagnosing fibrous dysplasia; however, a study by Salinas-Souza et al found that GNAS mutations are highly specific for fibrous dysplasia and rarely, if ever, occur in low-grade osteosarcomas.[22]

Staging

Two staging systems are used to stage sarcomas of bone: the American Joint Committee on Cancer (AJCC) staging protocol and the Musculoskeletal Tumor Society (MSTS) staging system.[23]

The AJCC 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 AJCC 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, and those with distant metastasis are classified as stage IVB.

 

Treatment

Approach Considerations

Because of its potential for metastasis and local, infiltrative destruction, the presence of a low-grade central osteosarcoma is an indication for treatment. The only contraindication for the treatment of osteosarcoma is the presence of widespread metastases. Palliative treatment may then be indicated.

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.

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.[24]

Surgical Therapy

Wide excision, which may include amputation, is the treatment of choice for low-grade central osteosarcoma.[25, 9, 26] 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.

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.[27, 28] 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 two or more major compartments.

Intraoperatively, 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.[16]

Postoperative Care

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.

Complications

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

Long-Term Monitoring

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.