|
J.Orthopaedics 2005;2(4)e4
Introduction
Pigmented villonodular
synovitis is an uncommon disease characterized by hyperplastic
synovium, large effusions and bone erosions. The disease was
first described by Jaffe et al. as a distinct entity in 1941.1
Pigmented villonodular synovitis (PVNS) is a locally aggressive
benign tumor that arises from the synovial tissue. Another
variant, giant cell tumor of tendon sheath is a similar synovial
tumor that occurs in tendon sheaths. In the original description
of the disease, the term "pigmented villonodular synovitis" was
applied to a lesion that occurred in the synovial membrane of
joints and tendon sheaths and was characterized by fibrous
stroma, hemosiderin deposition, histiocytic infiltrate and giant
cells.1 Subsequently, two forms of the disease were identified:
a localized subtype characterized by a pedunculated lesion and a
subtype with diffuse joint involvement.2
Etiology
The exact cause of PVNS
remains controversial 2-6. It doesn't seem to run in families.
It doesn't seem to be caused by certain jobs or activities. Some
people with PVNS remember that they hurt their joints at some
time. Several theories are based on the histological appearance
and cellular components of the lesion. The theories regarding
cause include:
(1) Localized lipid
metabolic derangement
(2) Repeated nontraumatic
inflammation
(3) A benign neoplastic
process
(4) A response to blood or
blood products within the joint.
The most widely held theory
is that the disease is an inflammatory reaction of the
synovium.1, 2 However, some evidence exists that it is a benign
neoplastic process.5
Epidemiology
The incidence of pigmented
villonodular synovitis is 1.8 cases per 1 million people per
year, with no environmental, genetic, ethnic or occupational
predilection.7 Most studies show equal prevalence in males and
females, although some investigations report a slightly greater
predilection in males.7 The localized form of the disease
usually has a female predominance. PVNS is rare in children and
affects mostly young adults. It has the highest prevalence
during the third and fourth decades, however, it has been found
in patients as young as 11 years and as old as 70 years.8
Clinical features
PVNS is considered locally
aggressive because it may invade the adjacent bones, although
this usually does not happen, except when the affected joint is
the hip. It usually does not spread beyond the affected area.
The vast majority of patients with pigmented villonodular
synovitis have monoarticular complaints of pain and swelling.
Polyarticular involvement is rare. In both the localized and
diffuse subtypes, the knee is the most commonly affected joint
(about 80 percent of patients) 3. The hip joint is the second
most common location, followed by the small joints of the hand,
foot, temporomandibular joint, ankle or elbow. The presentations
of the disease in the knee and hip are somewhat different. The
localized form in hand occurs most commonly in the fingers, in
particular, the volar aspect of the first 3 fingers, and is the
most common soft tissue tumor of the hand.
Clinical features depend on
the size and location of the tumor. Symptoms may include
-
Swelling of a joint
(usually painless)
-
Joint effusion (fluid,
usually bloody), in the joint
-
Pain (sometimes).
Sometimes limping or
difficulty in using legs, arms, hands or feet
Patient may have a
"popping" sensation while moving the joint. The symptoms usually
start slowly and may come and go over time. Patients with hip
involvement occasionally report episodes of extreme pain, which
may represent hemorrhage into the joint space. During these
exacerbations, patients may be able to relieve the pain by
positioning their hip in a flexed and externally rotated
position. This positional relief of pain is typical of a joint
effusion or inflammatory process of the synovium, in that the
repositioning minimizes pressure within the joint.
Physical examination
reveals one or more palpable nodules or diffuse joint swelling.
Swelling may feel warm and be somewhat tender to palpation. Up
to 96 percent of patients with knee involvement have distention
of the suprapatellar pouch and a large effusion.4 As many as 40
percent of patients have a diffuse palpable synovial mass.4
Patients also have a slightly decreased ability to flex and
extend the joint. Up to 90 percent of patients complain of mild
to moderate tenderness, mainly over the medial patellofemoral
area.4 In addition, arthrocentesis yields blood-tinged synovial
fluid in 44 to 69 percent of patients.4, 7
Differential Diagnosis
Pigmented villonodular
synovitis remains a diagnostic challenge. On average, the
disease is not correctly identified until 4.4 years after
presentation9. The difficulty stems from the insidious onset
and nonspecific presentation of the disease, as well as its
subtle radiographic findings. Pigmented villonodular synovitis
should be considered in the differential diagnosis of patients
from 20 to 45 years of age who have monoarticular symptoms
(Table 1). Diffuse pigmented villonodular synovitis of the knee
can also mimic extensor mechanism malalignment (patellofemoral
syndrome), ligament instability and meniscal lesion.4
TABLE 1
Differential Diagnosis
Osteoarthritis
Inflammatory arthritis
Rheumatoid arthritis
Psoriatic arthritis
Systemic lupus
erythematosus
Septic arthritis
Synovial chondromatosis
Pigmented villonodular
synovitis
Benign or malignant bone
tumor
Avascular necrosis (hip
only)
Imaging
X-rays: The radiological
appearance of PVNS depends on the location. A nodule in the hand
may have soft tissue swelling and bone erosion on plain x-ray.
In patients with pigmented villonodular synovitis of the knee,
plain radiographs often appear normal. However, radiographic
findings in diffuse disease (Fig1) can include a periarticular
soft tissue density (in up to 80 percent of patients), expansion
of the suprapatellar pouch and local osseous changes mainly
confined to the patellofemoral articulation10. The changes at
the patellofemoral joint result from abnormal patellar tracking
because of the synovial mass lifting and stretching the extensor
mechanism, thereby allowing shear forces to act on the articular
cartilage. Osteopenia is occasionally found, and degenerative
changes may be detected in 30 to 40 percent of patients.10 In
general, bone and joint changes are less common in the knee than
in the hip, because of the ability of the knee capsule to expand
to accommodate the hyperplastic synovium. Bone erosion or cysts
will be present in tighter joints like the hip, elbow, ankle or
wrist. Calcifications are not a usual feature of PVNS. Rarely, a
focus of dystrophic calcification may be seen in an area of PVNS.
In pigmented villonodular synovitis of the hip, radiographs
show bony erosions in the head and neck of the femur and
acetabulum in 95 percent of patients.3 These erosions are found
early in the course of hip disease and appear as cyst like
structures on anteroposterior radiographs. An average of three
to four erosions, ranging from a few millimeters to 5 cm in
diameter, is typically seen3. A thin sclerotic rim may also be
present and is due to the slow growth of the process. In the
late stages of the disease, the articular joint space decreases,
most often superolaterally, in 70 to 75 percent of patients3.
Plain radiographs cannot confidently exclude effusion as a cause
for symptoms, nor can it help determine the extent of disease.
Arthrography: Radiographic
contrast may be injected into the joint following joint
aspiration. With contrast filling of the joint, findings
demonstrate multiple irregular nodular-filling defects of
variable sizes, which produce the typical cobblestone appearance
of the synovium seen on arthrography.
Bone scan: Technetium-99m etidronate bone scanning may show diffuse mild uptake when bone
erosions are present. However, the study may reveal no findings
when the disease is confined to the synovium. Thus, a normal
bone scan does not exclude the diagnosis of pigmented
villonodular synovitis.
Computed tomography: CT
scan is able to pick up the hemosiderin and demonstrates the
extent of the synovial involvement as well as bone erosion and
cysts. CT imaging is useful for
needle biopsy guidance when a histological diagnosis is required.
CT is hobbled by its inability to completely show the extent of
disease and other pathology around or within the joint.
Magnetic resonance imaging: MRI is highly sensitive and specific for the diagnosis of
pigmented villonodular synovitis. Characteristic MRI findings
(Fig3) include joint effusion, lifting of the joint capsule, low
signal intensity on both T1- and T2-weighted images (because of
hemosiderin deposition), hyperplastic synovium (that appears as
a lobulated synovial mass), bony erosions and preservation of
bone density.9, 11, 12 Hyperplastic and
hypervascular synovium enhances following intravascular
administration of gadolinium chelates. MRI findings are not
pathognomonic for PVNS, and similar findings may be seen in
rheumatoid arthritis, hemophilic arthropathy, amyloid
arthropathy, synovial osteochondromatosis, and degenerative
joint disease. Differentiating calcifications from hemosiderin-laden
foci in the setting of PVNS may be difficult, and plain films
should be used in this setting to confirm or deny the presence
of calcifications.
A combination of plain
films and MRI should be used in preoperative evaluation of a
patient with PVNS. This combination yields an accurate diagnosis
and maps out the extent of disease for the surgeon prior to
treatment.
Pathology
Gross pathologic features include
thickened synovium, with a combination of villous and nodular
proliferation depending on the site of involvement. Two types of
villi are present in the diffuse form of PVNS, including coarse
villi with a "shag carpet" appearance and fine or fernlike villi.
The nodular component is seen predominantly in tendinous or
extra-articular lesions. The nodules are well demarcated and may
be sessile or pedunculated, although they lack a true capsule.
Bony invasion through the joint capsule is possible.
The diagnosis of pigmented
villonodular synovitis is confirmed by biopsy of the synovium.
On microscopy, PVNS is characterized by the presence of
hemosiderin-laden multinucleated giant cells. In addition,
lipid-laden macrophages, fibroblasts, and other large
polyhedral-shaped mononuclear cells are present, have abundant
cytoplasm, and possess oval nuclei. Hemosiderin also is found
within the surrounding tissues (fig4). The ubiquitous presence
of hemosiderin lends the tissue the characteristic pigmented
appearance. The lesions tend to be hypervascular and demonstrate
synovial hyperplasia. The location of the polyhedral cells below
the synovial membrane suggests that perhaps the cell of origin
is a fibrohistiocyte. The pathologic differential includes
hemosiderotic synovitis, rheumatoid arthritis and synovial
chondromatosis. A characteristic finding of PVNS is the invasion
of the subchondral bone with resultant cyst formation.
Treatment:
The exact treatment for
PVNS varies from patient to patient, usually depending on
-
Patient’s age, overall
health, and medical history
-
Extent of the disease and
whether it is causing pain
-
Whether the tumor has
invaded the bone
-
Patient’s tolerance for
specific medications, procedures, or therapies
-
Patient’s preference
Treatment options are:
Synovectomy: As PVNS can
continue to grow and invade the bone, the treatment of choice is
usually an operation called a synovectomy14, in which the
affected synovial tissue is surgically removed. Any associated
bony lesions should be carefully curettaged and bone grafting
should be done, if needed. Total synovectomy (open or
arthroscopic) is required for the diffuse form while local
excision may be sufficient for the nodular form. Arthroscopic
synovectomy may be indicated for nodular form or for inactive
form of diffuse disease. Open synovectomy is the treatment of
choice for patients with active form of diffuse disease. There
is a high rate of recurrence, particularly for diffuse form,
after synovectomy is performed. If it does recur it usually
causes minimal symptoms, including chronic swelling.
Radiotherapy: Radiotherapy
can be considered in patients with previous adequate resection
of disease who experience local relapse and in patients with a
large amount of disease in whom complete resection is not
possible.15It has been used in the management of recurrences
with varying success. However it is generally avoided in
children because of growth issues and the concern about
radiation associated malignancy later in life. In one
retrospective series, 15 13 of 14 patients with recurrent or
extensive diffuse disease treated with radiation therapy were
disease-free at a mean follow-up period of 69 months. Eleven
patients were characterized as having good or excellent limb
function, and three patients had fair function
Combination therapy: - In
the report by 13Blanco et al, the authors presented the results
of combined partial arthroscopic synovectomy and low-dose
radiation therapy (RT) in the treatment of diffuse PVNS of the
knee. The authors conducted a prospective study of the treatment
of 22 patients with clinical, ultrasonic, and histologically
confirmed findings of diffuse PVNS of the knee. Their protocol
included anterior (patellofemoral, medial, and lateral)
arthroscopic synovectomy and postoperative RT with a total dose
of 2,600 cGy. Combination therapy was effective in reducing
symptoms of pain and edema, and in improving overall function of
patients. Nineteen patients (86%) had good or excellent results
at an average follow-up of 33 months (range, 26 to 76 months); 3
had clinically and ultrasonographically confirmed recurrence of
disease and were treated with repeat arthroscopic synovectomy
without harmful effects from RT.
Radiation synovectomy/radiosynoviorthesis
(RS): It means radionuclide therapy of joint synovitis or
synovial processes by intra-articular injection of 90Y
silicate/citrate or 186 Re sulphide or 169 Er citrate. 90 Y
colloids are suitable for the knee joint only. 186 Re sulphur
colloid is suitable for hip, shoulder, elbow, wrist, ankle and
subtalar joints. 169 Er citrate colloid is suitable for
metacarpophalangeal, metatarsophalangeal and digital
interphalangeal joints. The reported success rate is 60-80%.
Complications specific to it are temporary increase in synovitis
and late radionecrosis.
TNF-blockade therapy:
Recently TNF-blockade with infliximab has been reported as an
effective therapy for refractory pigmented villonodular
synovitis.17
Joint reconstruction: The
bone destruction caused by PVNS may be extensive. Synovectomy
may not relieve all symptoms in patients with significant
destructive changes in the joint. In these situations,
arthrodesis or total joint replacement should be considered.
Posterior stabilized prosthesis is recommended in order to
maximize the exposure as well as the open synovectomy. If PVNS
is seen as an incidental finding, it should not affect the
decision to proceed with a preplanned reconstructive procedure.
A series of 11 patients with active diffuse pigmented
villonodular synovitis of the knee treated with synovectomy and
total knee arthroplasty showed a local control rate of
approximately 70 percent and good to excellent joint function at
a mean follow-up period of 10.8 years.16
The long-term outlook for a
patient with PVNS varies from patient to patient depending on:
-
the extent of the disease
-
the size and location of
the tumor
-
the tumor's response to
therapy
-
the age and overall health
of patient.
Generally, PVNS has a good
prognosis because it is usually not considered an aggressive
tumor.
References:
1) Jaffe HL, Lichtenstein L,
Sutro CJ. Pigmented villonodular synovitis, bursitis, and
tenosynovitis. Arch Pathol 1941;31:731-65.
2) Granowitz SP, D'Antonio J,
Mankin HL. The pathogenesis and long-term end results of
pigmented villonodular synovitis. Clin Orthop 1976;114:335-51.
3) Bravo SM, Winalski CS,
Weissman BN. Pigmented villonodular synovitis. Radiol Clin North
Am 1996;34:311-26.
4) Flandry F, Hughston JC,
McCann SB, Kurtz DM. Diagnostic features of diffuse pigmented
villonodular synovitis of the knee. Clin Orthop 1994;298:212-20.
5) Rao AS, Vigorita VJ.
Pigmented villonodular synovitis (giant-cell tumor of the tendon
sheath and synovial membrane). A review of eighty-one cases. J
Bone Joint Surg [Am] 1984;66:76-94.
6) Singh R, Grewal DS,
Chakravarti RN. Experimental production of pigmented
villonodular synovitis in the knee and ankle joints of rhesus
monkeys. J Pathol 1969;98:137-42.
7) Myers BW, Masi AT.
Pigmented villonodular synovitis and tenosynovitis: a clinical
epidemiologic study of 166 cases and literature review. Medicine
[Baltimore] 1980;59:223-38.
8) Dorwart RH, Genant HK,
Johnston WH, Morris JM. Pigmented villonodular synovitis of
synovial joints: clinical, pathologic, and radiologic features.
AJR Am J Roentgenol 1984;143:877-85.
9) Cotten A, Flipo RM,
Chastanet P, Desvigne-Noulet MC, Duquesnoy B, Delcambre B.
Pigmented villonodular synovitis of the hip: review of
radiographic features in 58 patients. Skeletal Radiol
1995;24:1-6.
10) Flandry F, McCann SB,
Hughston JC, Kurtz DM. Roentgenographic findings in pigmented
villonodular synovitis of the knee. Clin Orthop 1989;247:208-19.
11) Hughes TH, Sartoris DJ,
Schweitzer ME, Resnick DL. Pigmented villonodular synovitis: MRI
characteristics. Skeletal Radiol 1995;24:7-12.
12) Eustace S, Harrison M,
Srinivasen U, Stack J. Magnetic resonance imaging in pigmented
villonodular synovitis. Can Assoc Radiol J 1994;45:283-6.
13) Blanco CE, Leon HO,
Guthrie TB. Combined partial arthroscopic synovectomy and
radiation therapy for diffuse pigmented villonodular synovitis
of the knee. Arthroscopy 2001 May;17(5):527-31
14) DJ Ogilvie Harris et al.
Pigmented villonodular synovitis of the knee: the results of
arthroscopic synovectomy, partial synovectomy, and arthroscopic
local excision. JBJS. Vol 74-A. 1992. 119-123.
15) O'Sullivan B, Cummings B,
Catton C, Bell R, Davis A, Fornasier V, et al. Outcome following
radiation treatment for high-risk pigmented villonodular
synovitis. Int J Radiat Oncol Biol Phys 1995;32:777-86.
16) Hamlin BR, Duffy GP,
Trousdale RT, Morrey BF. Total knee arthroplasty in patients who
have pigmented villonodular synovitis. J Bone Joint Surg [Am]
1998;80:76-82
17) E-J A Kroot et al. Tumour
necrosis factor  blockade
in treatment resistant pigmented villonodular synovitis. Annals
of the Rheumatic Diseases 2005;64:497-499
|
