Bone & Soft Tissue Pathology
Case 2 -
Low-Grade Central Osteosarcoma
University of Chicago
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A 52-year-old woman presented with a right lower arm mass that had been slowly growing for 4 years.
She gave a history of having a lesion in the same area 25 years ago, for which she had surgery. No
previous records were available and the patient was unaware of the diagnosis at the time of the previous
On exam the lower arm was markedly distorted by a mass that on radiograph proved to be a poorly
marginated fusiform expansion of the distal ulna. Central mineralization and ground glass appearance was
present, accompanied by periosteal reaction and mineralization. A biopsy was performed.
Case 2 - Slide 1
Case 2 - Figure 1 - Clinical appearance of right lower arm prior to surgery
Case 2 - Figure 2 - Radiograph of right arm prior to surgery. Note expanded metaphysis/diaphysis and periosteal reaction in the distal ulna.
Case 2 - Figure 3 - Low power of biopsy from lesion. Note well formed spicules of bone and intervening fibrous matrix.
Case 2 - Figure 4 - Intermediate power of biopsy. Note focal osteoblastic and osteoclastic activity and relative paucicellularity of the stroma.
Case 2 - Figure 5 - High power of biopsy. Note the mixed lamellar and woven bone comprising the trabeculae
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 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.
Histologic Differential Diagnosis:
- 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
Desmoplastic fibroma of bone
- Bone production, but areas of the tumor may have this appearance
Low grade Central Osteosarcoma
Low-grade central osteosarcoma accounts for approximately 1 to 2% of all
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
As with all bone tumors, diagnosis is heavily dependent on radiologic features, but particularly when
evaluating a biopsy such as this case. Ideally the consultation of a musculoskeletal radiologist or
experienced orthopaedic oncologist should be sought. 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.
Histologically, 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. 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
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.
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. 
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