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low-grade central osteosarcoma

Monday 14 December 2009

Clinical synopsis

Low-grade central osteosarcoma accounts for approximately 1 to 2% of all osteosarcomas. A ge of occurrence ranges from the first to the ninth decade, with a peak in the second and third decades. In contrast to most bone tumors, the frequency is approximately equal in males and females, or may show a slight female predominance.

Most cases are in long bones (81%), with the distal femur and proximal tibia the most common locations. Tumors also occur in flat bones, including the rib, scapula, and bones of the face. All osteosarcoma is relatively less common in the distal upper extremity, but rare cases of low-grade central osteosarcoma in the ulna have been described.

Low-grade central osteosarcoma typically presents as a slowly growing mass, frequently of years duration. Previous biopsy with diagnosis of fibrous dysplasia or other benign lesion is not uncommon.

Radiology

Low-grade central osteosarcoma is usually medullary in origin (>85%) and metaphyseal, with purely diaphyseal lesions less common. Although slow growth and mineralization leads to an expanded cortex and ground glass appearance similar to fibrous dysplasia, the majority of cases (80%) have features suggestive of an aggressive tumor, including poor margination, cortical destruction, and soft tissue extension.

With modern CT and MRI imaging techniques, cortical destruction can be documented in all cases. In the majority of cases, the pre-operative impression will include malignancy based on the radiologic studies.

Microscopy

Histologically the lesion is fibrous with well-formed spicules comprised of both lamellar and woven bone, somewhat longer than typically seen in fibrous dysplasia. Osteoblast rimming is focally present, as is osteoclastic activity.

The lesion most frequently resembles fibrous dysplasia, although parosteal osteosarcoma-like and desmoplastic fibroma-like appearances can also be seen depending on the amount of osteoid production.

The stroma is fibrous, paucicellular, and displays minimal atypia and only very rare mitotic figures.

Where residual cortex is present the fibrous tissue appears to infiltrate into the interstices of native bone and Haversian systems.

Infiltration of the fibrous stroma into the interstices of native cortical or medullary bone and periosteal extension are diagnostic features that unfortunately are usually absent in biopsy specimens.

The majority of cases have greater than 2 mitoses per 10 hpf, but nearly 20% will have fewer. Cytologic atypia is subtle in most cases. In contrast to fibrous dysplasia, where the boney trabeculae are comprised of woven bone, those of low-grade central osteosarcoma tend to be a mixture of woven and lamellar bone. Rarely, thickened irregular plates of lamellar bone can histologically mimic Paget’s disease.

A less common chondromyxoid fibroma-like variant of osteosarcoma displays lobulated growth with myxoid areas and stellate cells. Increased mitotic figures, cellular zones with pleomorphism and direct production of osteoid by the tumor cells are atypical features indicating malignancy.

Differential Diagnosis

- fibrous dysplasia

  • Radiograph is more aggressive than fibrous dysplasia.
  • Infiltrative growth pattern not typical of fibrous dysplasia
  • Trabeculae of mixed lamellar and woven bone are not typical of fibrous dysplasia.

- osteofibrous dysplasia (ossifying fibroma)

  • wrong bone, usually tibia or fibula
  • usually cortically based
  • prominent osteoblast rimming

- parosteal osteosarcoma

  • not juxtacortical

- desmoplastic fibroma of bone

  • bone production, but areas of the tumor may have this appearance

Cytogenetics

Low-grade central osteosarcoma has a relatively stable karyotype, in contrast to high grade osteosarcoma, with relatively few changes detected on comparative genomic hybridization studies, typically +12q12-q14, +12p, and +6p21.

The 12q13-15 region contains SAS (sarcoma amplified sequence) , MDM2, and cyclin dependent kinase 2 (cdk2).

SAS amplification has been previously reported in the majority of parosteal osteosarcoma, and is also amplified in 15% of low grade central osteosarcomas.

Increased expression of MDM2 and CDK4 has also been reported in both parosteal and low-grade central osteosarcoma. By contrast, P53 mutations, common in high-grade osteosarcoma, are rare in low-grade central osteosarcoma.

Treatment and Prognosis

Treatment of low-grade central osteosarcoma is complete surgical excision; intralesional surgery is associated with essentially 100% recurrence, while radical excisions have essentially no local recurrence.

In nearly half of cases an initial biopsy will be interpreted as benign, with osteosarcoma diagnosed on subsequent material.

Recurrent lesions display dedifferentiation to a high-grade osteosarcoma in15% of cases, and rarely areas of high-grade osteosarcoma are found at primary presentation. There is a high risk of metastatic disease with dedifferentiation.

Case records

- USCAP (2006)

References

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