Image Quiz

Hip Pain in a Seventeen-Year-Old Girl (continued)

Answer: Pigmented villonodular synovitis.

Fig. 1	Fig. 1 Anteroposterior pelvic radiograph made at initial consultation reveals the presence of subchondral radiolucencies (A) and slight sclerosis of the sourcil of the acetabulum (B). The presence of early arthritic changes is evidenced by mild narrowing of the joint space. For larger view, click on image
Fig. 2-A	Fig. 2-B	Fig. 2-C
Figs. 2-A, 2-B, and 2-C T2-weighted (Fig. 2-A) and T1-weighted (Figs. 2-B and 2-C) magnetic resonance imaging scans show a heterogeneous intra-articular process with predominant signal characteristics of edema, thickening of the synovium (multiple disorganized layers of synovium) (A), and subchondral cysts in the head and acetabulum (B).
Fig. 3	Fig. 3 Histologic specimen showing a large number of mononuclear cells (A), deposition of hemosiderin within macrophages (B), multinucleated giant cells (C), and dense fibrosis (D) (hematoxylin and eosin stain, 400×). For larger view, click on image

Discussion and Treatment

This patient presented with a classic example of pigmented villonodular synovitis of the hip. Pigmented villonodular synovitis can be considered as a benign tumor of the synovium in joints, bursae, and tendon sheaths. Despite its benign histologic characteristics, the disease may exhibit an aggressive behavior with invasion of the adjacent bone and cartilage if not treated in a timely manner. The World Health Organization is discussing a possible change in terminology for this condition to better reflect its biologic behavior.

Clinically, the symptoms and signs in this patient were consistent with a variety of entities, including femoral acetabular impingement, stress fracture, and transient synovitis, among others. Although the patient had a positive impingement test, a diagnosis of femoral acetabular impingement was unlikely because the femoral head-neck offset appeared to be normal, there was no evidence of either pincer or cam-type impingement on the plain radiographs (Fig. 1), and there was no evidence of acetabular retroversion, which is also associated with femoral acetabular impingement². In addition, there was no evidence of a labral tear on the magnetic resonance image (although that examination was performed without the benefit of contrast), nor was there any evidence of so-called herniation pits or cysts in the femoral neck³. Stress fracture, which was not evident on the plain radiographs or on the magnetic resonance images, was also ruled out as a possible causative entity. Transient synovitis is not associated with cysts or joint-space narrowing and thus was also ruled out.

Although the radiographic presentation resembled inflammatory arthropathy, the lesion appeared dark on both the T1-weighted and T2-weighted magnetic resonance images, thus ruling out not only inflammatory arthropathy but also synovial hemangioma.

Septic arthritis, which usually presents as an acute condition that worsens rapidly, was also ruled out, as our patient had had symptoms for more than three years. In addition, the findings on radiographic and magnetic resonance imaging and the results of histologic examination ruled out infection as a possibility and pointed to pigmented villonodular synovitis as the most likely condition.

In some patients with pigmented villonodular synovitis, intranuclear inclusions may be seen histologically, which can result in an erroneous diagnosis of sarcoma or melanoma. The hallmark of pigmented villonodular synovitis is villonodular hyperplasia, dense fibrosis, and deposition of hemosiderin within the macrophages, all of which were very clearly seen in this patient. Histologic analysis confirmed that the lesion was benign^4,5.

Pigmented villonodular synovitis mostly affects patients in the third or fourth decade of life, but it can also be seen in younger or older individuals^5,6. Its prevalence has been reported to be as low as 1 to 1.8 cases per million in the population of the United States⁶. There is no gender or racial preponderance⁷.

The origin of the disease is mostly unknown. Genetic predisposition^8,9, chronic inflammation¹⁰, and vascular trauma have been implicated. In addition, trisomy genetic abnormalities, especially trisomy 7^9,11 and trisomy 5⁹, have been strongly linked with pigmented villonodular synovitis⁸. The disease may have an aggressive course with the potential for malignant transformation in patients with these genetic abnormalities⁹. In addition, other genetic abnormalities, such as defects in the short arm of chromosome 1 (the locus for coagulation factors III and V) have also been detected in patients with pigmented villonodular synovitis¹². Other reported findings associated with pigmented villonodular synovitis include alteration in the regulatory pathways (e.g., the p53 pathway and the retinoblastoma pathway) of cell division¹³.

There are two main variants of pigmented villonodular synovitis at presentation: a diffuse type that is mostly villous in character, and a localized type that is predominantly nodular in appearance. The diagnosis is not usually made clinically, since the symptoms often mimic more common diseases of the hip. In one study, the diagnosis of pigmented villonodular synovitis was delayed by an average of 4.4 years¹⁴.

In a symptomatic superficial joint such as the knee, joint aspiration may be diagnostic^5,6; however, joint aspiration may yield normal results in many patients. The results of most peripheral-blood tests will also be normal. Plain radiographs that are made in the early stages of disease may demonstrate a periarticular mass⁵, with no other changes. With progression of the disease, other radiographic abnormalities, such as subchondral cysts, joint narrowing, and osseous erosion, may appear.

Although ultrasonography is a useful imaging modality for the detection of synovial pathology, it cannot adequately depict the joint effusion, cyst formation, and villous thickening of the synovium typically seen with pigmented villonodular synovitis¹⁵. Magnetic resonance imaging is the imaging modality of choice to establish a diagnosis of pigmented villonodular synovitis. The magnetic resonance image, especially the T2-weighted image, is very useful for detection of hemosiderin deposition inside the nodules^5,6,16-18. Pigmented villonodular synovitis appears dark on both T1-weighted and T2-weighted images. A bone scan may also be useful but is nonspecific, and thus histological confirmation of the disease is almost always needed^19,20.

In patients with long-standing pigmented villonodular synovitis, recurrent intra-articular bleeding stimulates mononuclear cells and fibroblast proliferation, setting up a recurring inflammatory cycle¹⁰. With continuation of the disease process, adjacent tissues (such as bone and cartilage) may become involved, resulting in periarticular bone erosions and cartilage-narrowing. Tissue destruction is believed to be due to expression of matrix metalloproteinase^21,22. Matrix metalloproteinases are activated by cytokines, such as tumor necrosis factor-alpha (TNF-α), and interleukins, such as interleukin-1 and interleukin-6²¹. The high expression of the latter factors results in activation of the multinucleated cells and osteoclasts with resultant subchondral resorption and cyst formation²³.

The proliferative process is usually monoarticular²⁴, and it affects the knee in 66% to 80% of patients with pigmented villonodular synovitis. Any part of the knee joint can be involved, with involvement resulting in abnormalities such as popliteal cysts²⁵ or lesions of the posterior cruciate ligament²⁶, popliteal tendon²⁷, or patellar fat pad²⁸. "Contamination" of arthroscopy portals, with spread of the disease to subcutaneous tissue, has also been reported²⁹. In most series, the hip joint is reported as the second most commonly involved joint^30,31. Pigmented villonodular synovitis has also been reported to involve the ankle, the shoulder³², the elbow, the wrist (intra and extra-articular), the foot, the spine (especially the cervical spine³³), the temporomandibular joint³⁴, the retroperitoneal tissues³⁵, the femoral triangle, and the gluteal region.

Surgical intervention remains the main treatment strategy. The affected joint may be débrided arthroscopically, if possible^36-38. Because of the extent and the type of joint involvement, open surgical resection of the lesion may be necessary. Our patient had long-standing disease and extensive involvement that necessitated surgical dislocation of the hip and débridement of the joint. The femoral head and the acetabular cartilage as well as the entire synovial membrane were found to be involved.

Adjuvant treatment in the form of irradiation therapy may be needed to reduce recurrence³⁹. Irradiation therapy may be delivered as an external radiation beam or through the inoculation of radioisotopes such as yttrium-90 (⁹⁰Y)⁵. The effectiveness of radiation therapy is not currently known. Cryosurgery directed toward the synovium, while avoiding the articular cartilage, has also been reported as curative in some patients⁴⁰. Immunotherapy involving administration of TNF-α blockers for treatment of refractory pigmented villonodular synovitis has also been reported⁴.

The recurrence rate of pigmented villonodular synovitis is dependent on the type of treatment and has been reported as varying from 10%¹³ to 14%³⁸ to 45%²⁹ to 70%¹³. The wide range of recurrence rates reported in the cited publications may be due to differences in the thoroughness and method of follow-up. Clearly identified predisposing factors for recurrence of pigmented villonodular synovitis have not been identified^7,13. Malignant transformation of pigmented villonodular synovitis is exceedingly rare but has been reported^13,41. Some authors have reported pulmonary metastases with pigmented villonodular synovitis¹³. It is likely, however, that pigmented villonodular synovitis may have been a misdiagnosis in cases in which malignant transformation and metastasis have occurred.

Conclusion

Pigmented villonodular synovitis of the hip is rare, and the diagnosis of this condition can be challenging. A high index of suspicion for this condition, together with the performance of appropriate imaging studies, will result in the proper diagnosis for the majority of patients. Although pigmented villonodular synovitis has a specific appearance on magnetic resonance images, histologic examination remains critical to the confirmation of the diagnosis. Surgical resection with or without adjuvant treatment is the main treatment strategy for this condition. Recurrence following surgical treatment is not rare.

*The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

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