Parosteal Osteosarcoma

Parosteal osteosarcoma, also known previously as juxtacortical osteosarcoma, is a rare variant of osteosarcoma, accounting for 7-10% of all osteosarcoma cases. Unlike the more aggressive high-grade forms, parosteal osteosarcoma is primarily low-grade and tends to grow slowly on the periosteal surface of cortical bone, where it appears as if “stuck on.” As such, this tumor is distinct from periosteal osteosarcoma, which is the other form of osteosarcoma that can originate on the surface of the bone and is discussed on the chapter on Osteosarcoma. The posterior surface of the distal femur is the most common site, although it can develop on the surface of any bone. Due to its low-grade nature, chemotherapy is generally not indicated. Instead, treatment involves only surgical resection with negative margins. Reflecting its lower grade, parosteal osteosarcoma carries a much better prognosis than conventional high-grade osteosarcoma. A small number of parosteal osteosarcomas will ultimately be found to contain some areas of high-grade dedifferentiation, usually upon careful pathologic examination of the resected specimen. In these cases, chemotherapy is usually administered in the adjuvant setting.

Epidemiology

Parosteal osteosarcoma accounts for approximately 5% of all osteosarcomas but is the most common subtype of surface-based osteosarcomas, making up about 65% of these cases. This variant shows a slight female predominance and typically arises in patients between 20 and 40 years of age. Compared to conventional osteosarcomas, parosteal osteosarcoma has relatively low rates of local recurrence and distant metastasis consistent with its low-grade histology. However, incomplete excisions with positive margins increase the risk of local recurrence. While metastasis is uncommon in the low-grade form, it occurs at a significantly higher rate in dedifferentiated cases.

Clinical Features

Most commonly, this tumor will slowly develop on the surface of the posterior distal femur, although it can develop juxtacortically on any bone. Long standing lesions can eventually invade through the underlying cortex which is a good relative but not absolute barrier to tumor penetration. Patients present with worsening pain, swelling and frequently decreased range of motion in the adjacent joint. The duration of symptoms before diagnosis can range from 3 to 48 months, with an average of about 12 months.

Radiologic Features

On radiographs, parosteal osteosarcoma typically appears as a large, well-defined, sclerotic mass projecting from the cortex and may contain some lytic areas (Figure 1). Radiographically, it can be challenging to determine the grade and nature of a surface-based tumor: a low-grade parosteal osteosarcoma can resemble a periosteal chondroma or even a high-grade surface osteosarcoma. Additionally, distinguishing a central lesion with a large sclerotic soft-tissue component from a truly surface-based lesion can be difficult.

Figure 1: Lateral x-ray of the distal femur demonstrating a dense, sclerotic mass sitting on the posterior cortex.

Unlike osteochondromas, parosteal osteosarcomas lack corticomedullary continuity. Magnetic resonance imaging (MRI) is useful for detecting tumor growth into the medullary space, particularly when cortical thickening and marrow replacement are visible on T1-weighted sequences (Figure 2).

A minority of these tumors may demonstrate the so-called “string sign”: a thin radiolucent cleavage plane separating the densely ossified surface mass from the underlying cortex. On plain radiographs or CT, this presents as a narrow dark line between the tumor and native bone. This lucency represents a thin layer of periosteum or fibrous tissue, indicating partial preservation of the cortex during early tumor growth.

Figure 2: Sagittal STIR (left) and axial T1 (right) MRI scans of distal femur parosteal osteosarcoma.

Pathology

Grossly, these tumors exhibit a well-defined mass that adheres to the underlying bone. There may be cartilaginous, fibrous, and sclerotic bony areas.

Histologic examination of a parosteal osteosarcoma will demonstrate islands of dense neoplastic bone with a background comprised of low-grade, fairly benign appearing spindle cells (Figure 3). The cells are well-differentiated and have a low percentage of atypia, and the neoplastic bone that they create matures at different rates. In the absence of radiographic correlation, the histologic appearance of parosteal osteosarcoma can be confused with benign fibro-osseous lesions, and communication of the clinical and radiographic findings is critical to arriving at the appropriate histopathologic diagnosis.

Figure 3: H&E stained slide of parosteal osteosarcoma: Irregular, parallel trabeculae of woven bone interspersed with a low-grade atypical spindle cell proliferation. (Image courtesy of Dr. Gord Zhu.)

In approximately 15% of cases, parosteal osteosarcomas may undergo dedifferentiation, transforming into a high-grade malignant tumor, usually high-grade osteosarcoma. The cortex offers less resistance to high-grade tumors than to low-grade forms, enabling easier intramedullary spread. Even in grade I cases, up to 20% of patients may show some degree of intramedullary involvement. The cortex is frequently affected, and it can be challenging to discern the boundary between tumor bone and normal cortex, even histologically.

Genetic studies of parosteal osteosarcomas have demonstrated amplification of sequences from the long arm of chromosome 12 (MDM2 and CDK4), as well as the development of ring chromosomes.

Differential Diagnosis

The differential diagnosis for surface-based bone lesions is broad, encompassing both benign and malignant entities. Periosteal chondroma, which is a surface-based cartilaginous tumor, also rests atop an intact cortex into which it tends to scallop but may closely mimic parosteal osteosarcoma on imaging studies requiring a biopsy for clarification. The chondroma will lack histologic presence of the low-grade fibrous, spindle cell stroma characteristic of parosteal osteosarcoma. Osteochondroma and exostosis can be distinguished from parosteal osteosarcoma through cross-sectional imaging, as they exhibit corticomedullary continuity with the parent bone.

Additional potential causes of cortical hypertrophy and juxtacortical ossification include conditions such as tumoral calcinosis, melorheostosis, myositis ossificans and benign parosteal osteochondromatous proliferation (also known by its initials, “BPOP”, or the eponym “Nora’s Lesion”). Florid reactive periostitis, related to trauma, inflammation, or hemorrhage, is another consideration. Each of these conditions has distinct lesion-defining locations, histopathologic characteristics, and genetic aberrations, aiding in their differentiation from parosteal osteosarcoma.

Accurate diagnosis is crucial, especially in distinguishing low-grade parosteal osteosarcoma from high-grade surface osteosarcoma, and conventional intramedullary osteosarcoma with a large soft-tissue component. Radiologically, these distinctions can occasionally be challenging, and all grades of osteogenic sarcoma should be considered in the differential diagnosis of a cortically based osseous lesion until histopathologic analysis is available. This delineation is essential, as the treatment plan, including the potential need for systemic therapy, depends on an accurate diagnosis.

Disease Course: Treatment and Prognosis

Parosteal osteosarcoma is typically treated with wide margin surgical resection alone. At diagnosis, comprehensive staging is essential to evaluate for metastases, which are most likely to develop in the lungs, particularly when the primary tumor has dedifferentiated.

The goal of surgical treatment is resection with clear, negative margins. Thorough removal of any tumor extension into the underlying cortex and medullary space is critical to minimize the risk of local recurrence. In some cases, a hemi-cortical resection may be feasible, allowing for preservation of the bone involved.

Compared to high-grade osteosarcoma, parosteal osteosarcoma has a much more favorable prognosis. Local recurrences generally result from incomplete initial excision, while distant metastases are more often associated with dedifferentiation of the tumor to a higher-grade form.

Key Exam Points

Parosteal osteosarcoma commonly presents as a sclerotic mass with a “stuck on” appearance of the posterior aspect of the distal femur.
Histologically, it appears as low-grade spindle cell stroma, making islands of neoplastic woven bone.
Treatment of this malignancy is via wide margin resection without chemotherapy or radiation.