Rare Dual Lesion: Extraskeletal Osteosarcoma Developing Within a Simple Lipoma

Take-Home Points

• Rare and histologically indistinguishable from osteosarcoma of bone.
• Most common presentation is an enlarging mass in the thigh or buttock.
• Secondary extraosseous osteosarcoma usually arises in the field of prior external beam radiation or brachytherapy.
• Radiographic pattern of mineralization is central amorphous or cloudlike.
• On cross sectional imaging, the soft-tissue mass is separate from the underlying bone and periosteum.

Aside from multiple myeloma, osteosarcoma is the most common primary malignancy of bone, but extraosseous osteosarcoma is rare and accounts for only 1% of soft-tissue sarcomas and only 4% of all osteosarcomas.^1-3 Benign mesenchymal tumors, such as lipomas, are common, and they are estimated to outnumber their malignant counterparts by more than a factor of 100. However, the true ratio is unknown, as many clinically benign lipomas are not biopsied.⁴ Conventional lipoma is the most common lipoma and is biologically indolent. Conventional lipoma generally does not transform biologically into a more aggressive type of neoplasm—unlike atypical lipomatous tumors, which may demonstrate this type of evolution with multiple local recurrences.

This article is the first report of a case of radiation-associated extraosseous osteosarcoma that developed within a benign conventional lipoma. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

In March 2013, a 72-year-old woman presented to a general surgeon with a right thigh mass of several weeks’ duration. The patient, who had a remote history of thyroid carcinoma, underwent thyroidectomy in 1991, excision of melanoma of the chest in 1998, and resection and adjuvant external beam radiotherapy (30 fractions) for Merkel cell carcinoma of the right proximal lateral leg (malignancy images unavailable) at an outside institution in 2003. Regional lymph node dissection at the time was negative. The patient remained disease-free the next 10 years. On presentation, magnetic resonance imaging (MRI) showed a 2.2-cm mass encircled by a tumor of lipomatous tissue within the vastus intermedius muscle, adjacent to but separate from the right distal femur (Figures 1A-1C).

Clinical examination findings suggested the sarcoma had arisen at the margins of the radiation field, but more than 10 years had passed since initial treatment, and records were unavailable for confirmation. Results of a computed tomography (CT)-guided biopsy performed at an outside institution revealed a high-grade malignancy, either an extraosseous osteosarcoma or a dedifferentiated liposarcoma. After the biopsy, the patient developed a severe medial compartment hematoma that required angiography and embolization. She was then referred to the division of orthopedic surgical oncology at our institution.

Physical examination revealed marked ecchymosis of the left groin at the access site for embolization as well as massive ecchymosis and swelling along the right distal thigh, medial knee, and medial lower leg. The neurovascular structures were intact with full motor function and sensation distally, as well as normal distal pulses. No inguinal adenopathy was identified. The proximal portion of the prior radiation tattoo was at the inferior extent of the lesion on MRI.

The patient was treated with doxorubicin and ifosfamide (2 cycles) while waiting for the hematoma to shrink. Contrast-enhanced MRI showed a 2.2-cm enhancing mass with isointense T1 signal and heterogeneously hyperintense STIR (short tau inversion recovery) signal surrounded by a circumscribed nonenhancing lipomatous tumor within the vastus intermedius muscle, adjacent to the distal femoral cortex. There was no invasion of the bone, and a fat plane between the enhancing mass and the femoral cortex was identified (Figures 2A-2E).

Fluorine 18 (¹⁸F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT (FDG-PET/CT) showed marked hypermetabolic activity within the soft-tissue mass (maximum standardized uptake value, 7.0), surrounded by metabolically nonactive fat. No hypermetabolic lung, bone, or soft-tissue metastases were seen. CT and plain radiographs showed the nonfat portion of the tumor had soft-tissue density and contained a central and peripheral curvilinear pattern of mineralization (Figures 3A-3C, 4A-4B).

The primary differential diagnosis included myositis ossificans, chondrosseous lipoma, parosteal lipoma (ossifying variant), liposarcoma with metaplastic bone, and dedifferentiated liposarcoma with osteosarcoma or chondrosarcoma component (see Discussion section).

After 3 cycles of neoadjuvant chemotherapy with doxorubicin and ifosfamide, MRI showed a marked reduction in hematoma size, to 2.4 cm × 0.7 cm × 3.2 cm (estimated volume, ~3 mL), from 10 cm × 3.4 cm × 7.3 cm (estimated volume, ~130 mL), so the decision was made to proceed with surgery, excising the hematoma and sarcoma separately. First, wide resection of the hematoma yielded a 7-cm × 4-cm resection specimen with negative margins on frozen section. Subsequently, definitive radical resection of the tumor with wide margins yielded a 13-cm × 9-cm × 4-cm specimen. The resection specimen contained an intramuscular, mobile, encapsulated 2.0-cm × 1.5-cm × 1.0-cm mass with 2 components. The first was a tan-white solid mass containing thin deposits of calcified matrix, and the second, which surrounded the first, was composed of well-circumscribed soft yellow lobulated adipose tissue (Figure 5).

Microscopic evaluation revealed that the tan-white mass consisted of a hypercellular proliferation of malignant spindle and polyhedral cells that exhibited marked pleomorphism and hyperchromasia and produced extracellular coarse lace-like neoplastic bone characteristic of a high-grade extraskeletal osteosarcoma (Figures 6A-6D).

The sarcoma was sharply demarcated from the surrounding fatty component, which consisted of lobules of mature white adipocytes with no cytologic atypia, characteristic of a lipoma. An estimated 60% of the neoplasm was the lipoma, and the other 40% was the osteosarcoma. Immunohistochemistry revealed the tumor cells from both components to be negative for desmin, myogenin, CDK4, and MDM2. P16 showed cytoplasmic staining of the malignant cells, and these results helped exclude the possibility of dedifferentiated liposarcoma. All resection margins were negative, including the deep margin of the femoral periosteum. In addition, the resected hematoma did not contain malignant cells.

After surgery, the patient’s dermatologist performed a shave biopsy of a lentiginous lesion anterior to the knee. Subsequently, the patient began having increasing knee pain and developed, on the lower extremity, small areas of erythema that were attributed to mild cellulitis. Four months after surgery, emergent contrast-enhanced MRI showed enhancement of thickened synovium of the knee joint (Figure 7).

The patient underwent arthroscopic lavage and synovial biopsy for septic arthritis after knee aspiration yielded 51,000 white blood cells with a negative bacterial culture. The biopsy yielded acute and chronic inflammatory cells compatible with infection. No malignant cells were identified, and the bacterial culture was negative.

Since the lavage, the patient remained in good condition. There was no evidence of local recurrence on contrast-enhanced MRI (Figure 8), or metastases the first year, and she remained clinically free of disease the first 22 months of follow-up.