Malignant transformation of fibrous dysplasia into sarcoma is a rare event, occurring in less than 1% of cases1,2. Malignant transformation of fibrous dysplasia can also occur as part of Mazabraud syndrome, a syndrome characterized by fibrous dysplasia and intramuscular myxomas1. However, Mazabraud syndrome is so rare that only four cases of sarcomatous degeneration have been reported in the literature1,3-5. Here we report a fifth case, which involved the development of osteosarcoma in a fibrous dysplastic lesion of the proximal part of the radius in a patient with Mazabraud syndrome.
The patient was informed that data concerning the case would be submitted for publication, and he consented.
A sixty-three-year-old man with a history of melanoma presented to our orthopaedic oncology clinic with pain in the right forearm. Fifteen years previously, the melanoma had been treated with excision, lymph-node dissection, and chemotherapy. The patient had been doing well until two months before the current presentation, when the forearm began to be painful. He described the pain as dull, aching, and moderate in severity. It bothered him mostly when he was performing heavy lifting, and he felt some relief after taking ibuprofen. He had no history of recent trauma to the area or fever, chills, night sweats, or weight loss. He had a thirty-pack-year smoking history, and his sister had died of ovarian cancer at sixteen years of age. His physical examination did not reveal any palpable masses, erythema, skin changes, or sensorimotor abnormalities, although the right forearm was slightly larger than the left.
The initial radiographs (Figs. 1-A and 1-B) showed a mixed lytic-sclerotic lesion spanning the length of the radius, with expansion of the radial head, neck, and entire diaphysis. The lesion was benign in appearance and had no obvious cortical disruption, periosteal reaction, or fracture. The initial impression was fibrous dysplasia, and magnetic resonance imaging demonstrated a 4.5 × 5-cm expansile mass replacing the radial head and neck and extending into the regional musculature. The mass demonstrated bright enhancement, as did the surrounding soft tissues and periosteum (Figs. 2-A and 2-B). A computed tomography-guided needle biopsy revealed poorly differentiated malignant cells, but no differentiation between metastatic melanoma and primary bone sarcoma could be made. An open biopsy was subsequently performed, and the final analysis of the pathologic specimen characterized the lesion as a high-grade osteoblastic osteosarcoma occurring in a background of long-standing fibrous dysplasia (Fig. 3-A).
Prior to surgery, a computed tomography scan of the chest was performed for staging purposes. No obvious metastatic lesions were detected in the lungs, but a benign-appearing lytic lesion with a sclerotic margin was detected in the right scapular neck. This was believed to be another focus of fibrous dysplasia, and a diagnosis of polyostotic fibrous dysplasia was made. The computed tomography scan also showed an incompletely visualized small fluid-density lesion in the supraspinatus muscle; the appearance of this lesion remained unchanged on a repeated computed tomography scan two months later. The patient underwent four cycles of preoperative chemotherapy with carboplatin (cisplatin caused him to have chronic renal insufficiency) and doxorubicin. The surgical plan was to resect at least 10 cm of the proximal portion of the radius and replace it with an allograft-prosthesis composite since there was no standard implant to replace this much bone at the proximal part of the radius.
At the time of surgery, the proximal part of the radius, the involved soft tissues including the supinator and anular ligament, and the biopsy track were resected. An allograft radius was soaked in Betadine (povidone-iodine) and washed with alcohol and peroxide solutions. The proximal end of the allograft was cut to the approximate size, and then cancellous bone was taken from the distal end of the allograft. The radial head was cut from the allograft and replaced with a 15-mm radial-head implant (Stryker Orthopaedics, Mahwah, New Jersey), which was cemented into place. Cement was also used to fill the allograft, except for a small recess in the distal end, which was filled with cancellous bone graft. The allograft was compressed against the native bone with a plate and bicortical self-tapping screws. Because of the unusually large diameter of the native diaphysis, the plate had to be contoured. The radial bow was not fully reestablished and the radial head dislocated anteriorly with pronation. To recreate the anular ligament, Mersilene tape was passed through a drill hole in the ulna, successfully stabilizing the radiocapitellar joint. Histologic analysis of the resected specimen confirmed the biopsy diagnosis of high-grade osteosarcoma arising in fibrous dysplasia (Fig. 3-B). The specimen had negative margins, and exhibited tumor necrosis of 75%.
Postoperatively, the patient did very well, gradually regaining hand strength and full flexion and extension at the elbow through physical therapy. He experienced some numbness and tingling over the radial aspect of the thumb and forearm initially, but these sensations decreased with time. Although he was cautioned not to attempt pronation or supination due to the risk of radial head dislocation from the lack of radial bowing, he eventually achieved nearly full pronation and 45° of supination without any symptoms of dislocation. Osseous union at the junction between the allograft and the native bone was delayed, but the hardware held the allograft in good position (Fig. 4). The patient completed three more cycles of carboplatin and doxorubicin postoperatively, after which he underwent follow-up with serial radiographs of the elbow and chest.
Nine months after surgery, he began experiencing transient pain in the ipsilateral shoulder. A radiograph showed a mixed lytic-sclerotic lesion of the right humeral neck, extending to the mid-diaphysis. There were similar smaller lesions in the glenoid and acromion. A magnetic resonance imaging scan showed additional, discontinuous soft-tissue masses in the shoulder girdle, including the lesion previously seen on the staging computed tomography scan of the chest. These findings raised the concern of metastatic disease. Soon thereafter, the patient returned without symptoms to his musculoskeletal tumor surgeon. Review of the magnetic resonance imaging scan showed multiple, well-defined intramuscular masses that appeared hypointense on T1-weighted sequences, hyperintense on T2-weighted sequences, and slightly heterogeneous (Fig. 5). These soft-tissue masses were presumed to be myxomas on the basis of their radiographic appearance. The lesions in the humerus and scapula were consistent with fibrous dysplasia. On the basis of these findings, the patient was diagnosed with polyostotic fibrous dysplasia and intramuscular myxomas: Mazabraud syndrome. He had no known endocrine abnormalities. None of the soft-tissue lesions were biopsied; therefore the diagnosis has not been completely documented. However, the radiographic evidence of myxomas was considered sufficient for the sake of management and in the best interest of the patient.
At the time of this writing (forty-seven months postoperatively), the patient has had no signs of local recurrence or metastasis. He was beginning to experience mild pain and tenderness at the radiocapitellar joint, and his most recent radiographs demonstrated some resorption of the graft proximally. The radial head and hardware remained in good position.