Pigmented villonodular synovitis: Four pediatric cases and brief review of literature.

Pigmented villonodular synovitis (PVNS) is a rare benign disorder of a joint which affects its synovium, tendon sheaths and bursas. While most cases of PVNS are adult patients aged between 20-50 years, few afflicted children have also been reported. Clinical signs of PVNS are insidious and non-specific. Pain, swelling and stiffness are the major symptoms. Magnetic Resonance Imaging (MRI) is the best radiological method for diagnosis of PVNS, as the initial X-ray is normal in early phase of disease in most cases. Therefore, diagnosis is often delayed or confused with mechanical disorders, haemophilic arthropathy, tuberculosis, juvenile idiopathic arthritis (JIA), and other disorders. Four paediatric PVNS cases are being reported in this case series with the aim to highlight that PVNS should be considered in the differential diagnoses of chronic monoarthritis. Two of our cases were initially misdiagnosed as JIA and the remaining two as Familial Mediterranean fever (FMF). They did not respond to conventional anti-inflammatory treatment and eventually only benefited from surgery. These four cases emphasize that the radiologist and clinician should collaborate carefully while managing any child with monoarthritis to ensure that the diagnosis of PVNS is not missed.

Introduction

Pigmented villonodular synovitis (PVNS) is a rare benign disorder of a joint, which affects its synovium, tendon sheaths and bursas. The predicted incidence of PVNS is nearly 1.8 patients in one million people, although the real prevalence is unknown.[1] While most cases with PVNS are adult patients aged between 20-50 years, there are also small number of afflicted children reported.[234] The youngest case in literature is that of an 8-month-old child.[5]

The aetiology of PVNS is not known clearly; however, chronic inflammatory or neoplastic processes are responsible for the aetiopathogenesis. It may involve any joint, especially large joints such as knee, hip, ankle or shoulder. Besides, knee involvement is most frequent in paediatric age group.[234]

Clinical signs of PVNS are insidious and non-specific. Pain, swelling and stiffness are the major symptoms, and there is no specific finding in initial conventional radiography. Therefore, diagnosis is often delayed or confused with mechanical disorders, haemophilic arthropathy, tuberculosis, juvenile idiopathic arthritis (JIA), and other rheumatological and malignant disorders.

Four paediatric PVNS cases are reported in this case series in order to reiterate that this condition should be considered in the differential diagnoses of chronic monoarthritis.

Case Presentations

Case-1

A 14-year-old male had swelling and pain on his left knee for one year. He had been evaluated by another paediatric rheumatologist 4 months earlier and diagnosed as having monoarticular JIA. He had been started on methotrexate (MTX) 15 mg/m2/week subcutaneously (sc). Magnetic resonance imaging (MRI) of his left knee had been reported as having effusion in suprapatellar bursa. Despite this treatment, there was no improvement and he was referred to our department. Slit lamp examination did not show any uveitis. His serum C-reactive protein (CRP) was normal (2.3 mg/L); and ANA and tuberculin skin test were negative. His chest X-ray was normal. MRI of left knee was repeated and evaluated by a paediatric radiologist. Joint effusion and a lesion compatible with PVNS were observed in left suprapatellar recess [Figure 1]. Arthroscopic synoviectomy was performed and the lesion was characterized by marked fresh and old hemosiderin deposition in the synovial membrane and joint collagenous capsule, and the histopathological features were compatible with PVNS. However, we did not have the facility to do immunohistochemical study. The child is in complete remission after surgical treatment.

Figure 1

Left suprapatellar effusion and nodular synovial thickening that may be compatible with PVNS on T-1 weighed MR images

Case-2

A 1-year-old female had swelling on her right knee for 3 months after a minor trauma. On physical examination, she had effusion of the right knee, which was confirmed by joint ultrasonography. She did not have uveitis and serum ANA and tuberculin skin test were negative. Her serum CRP (1.8 mg/L) and chest X-ray were normal. Oligoarticular JIA was suspected. Ibuprofen 30 mg/kg per day was initiated and intraarticular triamcinolone hexacethonide injection was given. The synovial fluid culture was negative. However, she did not respond and MTX 15 mg/m2/week sc was initiated. Despite intensive therapy, there was no change in the articular findings after three months. An MRI under general anaesthesia showed focal lesions with high signal in T2-weighted images in suprapatellar and intraarticular areas, which were compatible with the diagnosis of PVNS [Figure 2a]. Open approach total synoviectomy was performed. Histopathological examination of synovium revealed multinuclear giant cells and extensive areas with hemosiderin deposits (on haematoxylin eosin staining). Although there was no immunohistochemically assessment, lesions were diagnosed as PVNS by histopathological features [Figure 2b]. She is in complete remission after surgical treatment.

Figure 2

(a) Hyperintense, scattered and focal lesions in right suprapatellar bursa (blooming artefact) suggestive of PVNS seen in T2 weighed MR images; (b) Intraoperative image showing pigmented deposits in the right knee taken during open approach synoviectomy

Case-3

An eleven-year-old female was referred to our department with recurrent swelling and pain in her right knee. These events lasted for 2-3 days and resolved spontaneously. They were accompanied by abdominal pain and vomiting. Familial Mediterranean Fever (FMF) was suspected, for she had signs of peritonitis with knee arthritis, and elevated acute phase reactants. Also, A744S/R202Q compound heterozygote mutations were detected in the MEFV analysis. Her tuberculin skin test and QuantiFERON tests were negative. Her chest X-ray was normal. Colchicine was started 1 mg/kg/per day. Abdominal pain attacks resolved with colchicine, but articular symptoms persisted. MRI of the right knee detected focal hyper-intense lesions in T2-weighted images compatible with PVNS [Figure 3]. Total synoviectomy was performed. Histopathological evaluation of synovium showed mononuclear histiocyte-like cells with rare multinucleated giant cells and hemosiderin-laden macrophages. Post-operative the girl remained symptom-free.

Figure 3

Hyperintense lesion with lobulated contour, which is filling suprapatellar and infrapatellar areas and intercondylar region in T2-weighed MR image of right knee

Case-4

After minor trauma two years ago, a 5-year-old female had developed pain and swelling of her right knee. A diagnosis of chronic arthritis had been made supported by MRI and ultrasonographic findings in another hospital. Brucella agglutination test, tuberculin skin test and ANA were also negative, and there was no uveitis seen on slit lamp examination. Chest X-ray was normal. A positive family history of FMF and elevated acute phase reactants with joint symptoms led to FMF being suspected by them. But R202Q heterozygous MEFV mutation study ruled had it out. She was then referred to our department as her joint complaints had not responded to colchicine. Second MRI done in our hospital demonstrated high signalled lesions in right suprapatellar bursa compatible with hemosiderin deposits and lateral patellar dislocation of the right knee [Figure 4]. These radiological findings were compatible with PVNS and arthroscopic synoviectomy has been planned.

Figure 4

Suprapatellar hyper-intense lesion compatible with hemosiderin deposits (white arrow) and lateral dislocated right patella (red arrow) on T2-weighed MR image of right knee

Discussion

PVNS is a rare disorder of joint that may be confused with other causes of chronic arthritis. There are two forms of PVNS diffuse and local, which have similar histological features, but they differ in terms of severity and prognosis. Diffuse PVNS (DPVNS) generally involves the entire synovial tissues, tends to be poorly localized, and swelling and pain symptoms are more prominent than in localized PVNS (LPVNS). Consequently, it has a poor prognosis, as compared to the localized form, due to it being more destructive, having a lower response to treatment and a higher recurrence after surgical excision.

Histopathological features of PVNS are characterized by synovial cell proliferation with hemosiderin deposits. Lipid laden macrophages, multinucleated giant cells, fibroblast and stromal cell proliferation can be also detected. Although many predisposing factors are believed to be responsible for PVNS, such as, prior trauma with subsequent bleeding, abnormal metabolic activity and benign neoplastic processes, the most accepted mechanism is probably chronic inflammation. Oehler et al. have reported that histopathological examination of synovial tissue in all their patients having PVNS revealed features of chronic inflammation. They also have postulated that iron in PVNS lesions stimulate synoviocytes and fibroblasts to develop macrophage-like characteristics.[6] Furthermore, Yoshida et al have studied the histologic and cellular characteristics of mononuclear cells and multinuclear giant cells, that predominantly constitute PVNS, and reported that PVNS has a hyperplastic property consisting of the CD68-positive monocytic cell lineage with differentiation of osteoclastic giant cells from monocyte and probably controlled against proliferation by wild-type p53, p21, and p16.[7] Histopathologically, all three of our patients had inflammatory synovial cells along with hemosiderin deposition, however; we could not perform immunohistochemical evaluation.

The age range of reported pediatric PVNS cases is wide and both genders are equally affected. In a study by Willimon et al., their age range was reported as 3-19 years, and in other case series by Neubauer et al. and Baroni et al. the same value was 7-15 (mean 10.8 years) and 2-15 (mean 9.8 years) years, respectively.[234] In our series, there was a wide age range of 1-14 years, and three out of four cases were females. The most common symptoms of PVNS are pain and swelling in the affected joint; and localized tenderness, palpable soft tissue mass and stiffness can be observed. Willimon et al. have reported that 82% had swelling and 77% had pain in their 25 paediatric PVNS cases.[4] Mechanical complications such as meniscal injury and patellar dislocation is rarer in paediatric cases than in adults. In our four cases, all had joint swelling; three of them had pain, and one of them had a dislocated patella.

PVNS is usually monoarticular, and it usually involves the knee in paediatric cases.[234] Most of the children with polyarticular involvement have been reported to have other congenital problems, such as skin lesions, pulmonary stenosis, mental retardation, Noonan syndrome and fetal hydantoin syndrome suggesting a possible genetic basis for this disease.[234] All of our four cases had monoarticular knee joint involvement, and had no extra articular findings.

PVNS usually develops insidiously, and its diagnosis is often delayed.[234] In Baroni's and Neubauer's case series, average diagnostic delay period were 33 months and >1 year, respectively.[23] It is usually confused with JIA, haemophilic arthropaties and other malignant/infectious disorders in childhood. The average diagnostic delay time in our cases was 13.5 months and they were initially wrongly diagnosed as JIA or FMF. Subacute bacterial infections (e.g. due to brucellosis) and tuberculosis must be kept in mind in the differential diagnosis of monoarthritis. All of our patients had negative tuberculin skin test and normal chest X-ray.

MRI is the best radiological method for diagnosing PVNS. It should be remembered that routine X-ray is normal in early period of the disease in most cases. MRI reveals hyperplastic synovium with low signal and fibrous components of lesion on T1-weighed MR images. Moreover, hemosiderin deposits are seen as scattered and irregular high signal intensity lesions on T2-weighed images, which is named as “blooming artefact”.[8] Biopsy of the synovium and histopathological evaluation is the gold standard in PVNS diagnosis. In all our cases, the diagnosis of PVNS was made by a careful MRI evaluation, by an expert paediatric radiologist. In three of our cases the diagnosis was confirmed with biopsy.

The aim of treatment is to remove all abnormal tissue surgically. Open or arthroscopic subtotal synoviectomy is the most valuable treatment modality.[9] Open approach synoviectomy have been preferred by some surgeons for low recurrence rates and decreased risk of portal contamination.[10] However, arthroscopic approach has also been shown to be equally effective with its added advantage of being less invasive. Radiotherapy and isotopic synoviorthesis have been used in adults for relapse cases or as adjuvant modality, but the use of radiotherapy in children is controversial, due to the possibility of post-irradiation sarcoma and damage to the epiphysis.

To conclude, PVNS should be kept in mind as a differential diagnosis in a child presenting with monoarticular arthritis. A thorough radiological review of the MRI of the joint can help suspect PVNS early.

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Conflicts of interest

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