Secondary Aneurysmal Bone Cyst in Fibrous Dysplasia of the Proximal Femur

By Maurizio Montalti, MD; Marco Alberghini, MD; Pietro Ruggieri, MD

Abstract
Fibrous dysplasia of bone is a congenital skeletal disorder characterized by proliferation of spindle cells inside an intramedullary collagenous stroma and by formation of metaplastic bone. An aneurysmal bone cyst is a lesion of unknown etiology. Macroscopically it appears like a blood-filled cavity that expands the affected bone. Histologically, fibrous septa are bordered by macrophages, giant cells, inflammatory cells, and areas of bone production. Hemorrhagic areas can rise into fibrous dysplasia. The lesion appears as an aggressive and destructive process that is difficult to diagnose properly. A 29-year-old woman presented with a 2-year history of left inguinal and lumbar pain. She reported increased pain after physical activity. Magnetic resonance imaging of the left femur (without intravenous gadolinium) showed a mass extending 14 cm along the femoral metaphysis. This lesion involved cortical bone that was broken in the posteromedial site. Computed tomography confirmed the osteostructural lytic alteration that blows up the proximal femur metaphysis. A trochar biopsy allowed the diagnosis of aneurysmal bone cyst on fibrous dysplasia, excluding malignancy. The lesion was treated with curettage and local adjuvants and filled with bone grafts. Internal fixation with a sliding screw plate was also performed. Radiographs at 1 year postoperatively showed good consolidation of the grafts and absence of local recurrence. The patient achieved active and passive mobilization of the left hip with no pain.
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Fibrous dysplasia of bone is a congenital skeletal disorder characterized by proliferation of spindle cells inside an intramedullary collagenous stroma and by formation of metaplastic bone. Fibrous dysplasia can be asymptomatic or cause pain, swelling, deformity, and pathologic fracture.1-4 This benign lesion is able to degenerate into a high-grade sarcoma (osteosarcoma, fibrosarcoma, chondrosarcoma, or malignant fibrous histiocytoma) with an incidence ranging from 0.5% in monostotic disease to 4% in McCuneAlbright syndrome.5 Hemorrhagic areas can rise into fibrous dysplasia; some authors describe them as secondary aneurysmal bone cysts.6,7 At imaging the lesion appears as an aggressive and destructive process that is difficult to diagnose properly. Approximately 30 cases were found in the literature of aneurysmal bone cysts associated with fibrous dysplasia.6-8

in the literature of aneurysmal bone cysts associated with fibrous dysplasia.6-8 An aneurysmal bone cyst is a lesion of unknown etiology.7 Macroscopically, it appears as a blood-filled cavity that expands the affected bone. Histologically, fibrous septa are bordered by macrophages, giant cells, inflammatory cells, and areas of bone production.7,8 This lesion is slightly more common in women and usually occurs in the first or second decades of life. It has a predilection for metaphyses of the long bones; the proximal tibia and distal femur are the most common sites. Aneurysmal bone cysts can also be a secondary vascular phenomenon developing in a preexisting lesion.7 This article describes a case of a 29-year-old woman with a secondary aneurysmal bone cyst in fibrous dysplasia of the proximal femur. She was treated with curettage, bone grafts, and internal fixation.

Case Report
A 29-year-old woman presented with a 2-year history of left inguinal and lumbar pain. She reported increased pain after physical activity. At admission, she was unable to ambulate. On physical examination, antalgic restriction of the left hip mobilization, negative Lasgues sign, and absence of neurovascular peripheral deficits were observed. A single, small caf-au-lait spot with irregular borders (Coasts of Maine)4 measuring approximately 3 cm was present on the patients back. Radiographs showed a lytic area in the proximal femoral metadiaphysis with cortical involvement and bony expansion. The lesion was active according to Ennekings staging system (Figure 1).9 Magnetic resonance imaging (MRI) of the left femur (without intravenous gadolinium) showed a mass extending 14 cm along the femoral metaphysis. This lesion involved cortical bone that was broken in the posteromedial site. In the intramedullary canal, some areas of inhomogeneous signal (probably hemorrhagic phenomena) were evident. On MRI, there was no appearance of perilesional soft tissue edema (Figure 2).

Figure 1: AP radiograph of the left hip show ing a lytic area (active lesion) involving the proxim al fem ur in the intertrochanteric area. The lesion expands the affected bone and causes erosion of the cortex. Figure 2: Sagittal T1-w eighted spin echo MRI of the left proxim al fem ur (w ithout intravenous gadolinium ) show ing an interm ediate-to-low signal intensity (A). Sagittal T2-w eighted MRI of the left proxim al fem ur show ing a high signal intensity (B). The areas of inhom ogeneous signal could correspond to hem orrhagic phenom ena.

Computed tomography (CT) scan confirmed the osteostructural lytic alteration that blows up the proximal femur metaphysis. The femoral cortex was thinned on >1 side. Cystic components with fluidfluid levels were not identified since contrast medium was not given. A double component of the lesion was evident on CT scan, and consequently fibrous dysplasia associated with malignant lesion or secondary aneurysmal bone cyst was considered as differential diagnoses. The patient underwent CT-guided biopsy that was not diagnostic. In this first histological diagnosis, the presence of blood and active osteoblasts did not rule out a malignant lesion such as osteosarcoma. A second trochar biopsy allowed the diagnosis of aneurysmal bone cyst on fibrous dysplasia, excluding malignancy (Figure 3). The lesion was treated with curettage and local adjuvants and filled with bone grafts (bone chips and 2 cortical segmental fibulas). Internal fixation with a sliding screw plate was also performed. Other sites of fibrous dysplasia were not identified, nor were deformities or hormonal alterations that could appear in polyostotic fibrous dysplasia associated with McCune-Albright syndrome. Weight bearing was not allowed for 1 month, then was progressively allowed, reaching full weight bearing at 3 months. During this time, thromboembolic prophylaxis with fondaparinux sodium was given. Radiographs at 1 year postoperatively showed good consolidation of the grafts and absence of local recurrence (Figure 4). The patient also achieved active and passive mobilization of the left hip with no pain at 1 year.

Figure 3: Histological exam ination show s the double com ponent of fibrous dysplasia and aneurysm al bone cyst (A). Bone trabeculae appear dipped in the fibrous strom a and are not bordered by active osteoblasts. Hem orrhagic areas are present, w ith the typical features of an aneurysm al bone cyst (B). Figure 4: AP radiograph of the left hip 1 year after curettage, bone grafting, and internal fixation.

Discussion
Fibrous dysplasia was first described by Jaffe and Lichtenstein4 in 1942 as a characteristic kind of skeletal lesion developing in the interior of affected bones.. It is usually diagnosed before age 30 and represents nearly 1% of primary bone tumors.10 The lesion is asymptomatic in a majority of patients. Radiographic features are variable and include expansion of bone, perilesional sclerosis, and a ground-glass appearance due to new bone formation. Fibrous dysplasia appears in monostotic and polyostotic forms; the latter is rare and generally larger. Moreover, this disease can be associated with multiple melanotic irregular border spots that represent abnormal skin pigmentation (cafe-au-lait spots with jagged and irregular borders like the coast of Maine)4 and with various endocrinopathies in McCune-Albright syndrome (hyperthyroidism, acromegaly, and hypophosphatemia).11,12 Campanacci1 reported 347 cases of fibrous dysplasia, and in his series the three most frequently involved sites were the proximal femur, tibial diaphysis, and ribs. A typical deformity is the shepherds crook deformity of the proximal femur due to a coxa vara resulting from multiple repeated fractures of the medial cortex. The femoral neck is the most frequent site for both monostotic and polyostotic disease. In polyostotic disease, ribs are also a frequent site. Spinal localization, not rare in monostotic disease, is frequent in polyostotic disease, as are skullfacial localizations.13 Imaging of fibrous dysplasia often shows calcifications due to frequent cartilaginous tissue areas, as confirmed by histologic examination. McCune-Albright syndrome, described in 193611 and 1937,12 includes polyostotic fibrous dysplasia, cafe-au-lait skin areas, and various endocrinopathies. In 1957, Mazabraud and Girard14 described the association of fibrous dysplasia with multiple benign intramuscular myxomas. An aneurysmal bone cyst is the result of a pathophysiologic change rather than a unique entity. It may be the consequence of trauma or a tumor-induced vascular process. In approximately one-third of cases, the preexisting lesion can be clearly identified.7,8,10 On imaging it can be misdiagnosed as a malignant tumor, as it shows radiologic and pathologic aggressiveness. The first histologic diagnosis of our case showed the presence of immature bone production and blood elements; therefore, it was not possible to exclude an osteosarcoma. This was probably due to the reparative processes of the broken cortex showing active osteoblasts. The literature describes a malignant lesion outbreak on a previous fibrous dysplasia.5-8,10-15 Radiographic features of a secondary aneurysmal bone cyst usually show a subperiosteal lesion with an undefined osteolysis and thinning or expansion of the cortex. Computed tomography scan and MRI may show fluidfluid levels with persistent contrast enhancement inside the cyst. On MRI, the lesion and internal septa may show a well-defined border of decreased signal intensity due to fibrous tissue. Bone scans usually show increased uptake with a cold central area. According to Ennekings staging system,9 our case was staged 29: an active lesion that creates a cortical-bone sclerotic reaction in some areas but can also lead to a partial cortical-bone permeation without frankly involving soft tissues. Treatment of aneurysmal bone cysts usually consists of curettage and filling the resulting defect with cancellous bone grafts. Most recently, materials such as demineralized bone matrix have been used to fill lesions.9,16 To decrease the risk of local recurrence, local adjuvants such as phenol, liquid nitrogen, or polymethylmethacrylate are used.17,18 In rare cases, aneurysmal bone cysts can be treated with bone resection or, more frequently, with selective arterial embolization.19 Our patient was treated with curettage of the lesion with a high-speed burr. Phenol was subsequently applied 3 times, alternated with alcohol and saline solutions lavages. The residual cavity was filled with cancellous bone and cortical grafts, and internal fixation was performed.

residual cavity was filled with cancellous bone and cortical grafts, and internal fixation was performed. Secondary aneurysmal bone cyst appearance on a previous fibrous dysplasia involves a differential diagnosis with a secondary sarcoma. A differential diagnosis is based on complete imaging but needs histologic confirmation. A possible pathologic fracture can make the imaging diagnosis difficult and may result in a histologic differential diagnosis due to the osteogenetic activity of bone callus. The absence on CT and MRI of a clear cortical break and newly formed tissue in the surrounding soft tissue suggests the diagnosis of secondary aneurysmal bone cyst. Newly formed tissue in the surrounding soft tissue on CT and activity of the lesion on T1- and T2weighted MRI, as well as gadolinium uptake, suggests the diagnosis of a secondary malignant lesion.5-18 An aneurysmal bone cyst can appear secondary to other benign lesions, such as giant cell tumor, osteoblastoma, chondroblastoma, fibrous histiocytoma, or eosinophilic granuloma.7,8,10-12 It can also be observed in malignancies, such as osteosarcoma, fibrosarcoma, and metastatic carcinoma.7,8,10-12 Moreover, a secondary sarcoma can develop after irradiation in fibrous dysplasia; most frequently these are radio-induced osteosarcomas.5,7,19 Sarcomas in fibrous dysplasia have been also reported without prior irradiation. A Mayo Clinic series, reported by Ruggieri et al5 in 1994, included 28 cases of sarcoma in fibrous dysplasia, 15 of which without prior irradiation. Campanacci et al20 reported 6 cases of malignant degeneration of fibrous dysplasia without prior irradiation. Histology is the key to a correct diagnosis. Histologic examination shows fibrous dysplasia sites characterized by typical features of newly formed Chinese letter bone trabeculae, which appear directly embedded or dipped in the fibrous stroma. Newly formed bony trabeculae are not bordered by active osteoblasts as in osteosarcoma or osteofibrous dysplasia of the long bones.7,8,10 Sometimes cartilaginous tissue can be observed in lobules of well-differentiated hyaline cartilage. These areas have a clear demarcation in comparison to the remaining fibrous tissue. Rarely densely ossified, rounding particles called cementicles can be noticed. In secondary aneurysmal bone cysts, hemorrhagic areas are associated with the histologic features of fibrous dysplasia. These areas are characterized by dense and compact fibrous stroma surrounding hemorrhagic spaces. As in primary aneurysmal cysts, fibrous stroma is characterized by the presence of hemosiderin granules and giant cells.

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Authors
Drs Montalti and Ruggieri are from the Department of Orthopedics, University of Bologna, and Dr Alberghini is from the Anatomy and Pathological Histology Unit, Istituto Ortopedico Rizzoli, Bologna, Italy. Drs Montalti, Alberghini, and Ruggieri have no relevant financial relationships to disclose. Correspondence should be addressed to: Pietro Ruggieri, MD, Istituto Ortopedico Rizzoli, 5 Divisione, Via Pupilli #1, Bologna, Italy.