Synovial proliferative diseases and miscellaneous
arthropathies/arthritides
Synovial proliferative diseases
Synovial Osteochondromatosis
a rare benign, synovial proliferative disease, characterized by cartilaginous metaplasia of the
intimal layer of the synovial membrane of joints, tendons and bursas, which can subsequently
mineralize and even ossify. Most often affecting middle-aged men but has been reported in
children and teenagers. The knee is most commonly affected and involvement is typically
monoarticular. Patients generally have pain and swelling in the early stages, but multiple loose
bodies can result in locking of the knee (cartilage nodules break free into the articular space,
resulting in loose bodies). In later stages of the disease, knee ROM may be decreased. Knee
stiffness may be caused by thickened metaplastic synovium and may portend a poor prognosis if
severe.
Imaging: Rx may be diagnostic if the chondroid bodies are calcified resembling popcorn,
but Rx can be non-diagnostic in 30%. MRI: nodules of cartilage in the synovium which are dark
on T1 and bright on T2 due to water content in the hyaline cartilage. Loose bodies can be seen.
Dx: secondary osteochondromatosis in association with OA: presents at an older age
and is characterized by loose bodies that are less numerous and with greater variation in size.
Treatment of symptomatic synovial osteochondromatosis involves arthroscopic removal
of symptomatic loose bodies. In the first and second phases of disease, active synovium should
be excised. Recurrence is treated by repeated arthroscopic debridement.
Complications: never metastasizes but may undergo malignant transformation into a
chondrosarcoma.
Pigmented villonodular synovitis
or tenosynovial giant cell tumor (TGCT), is a rare benign proliferative process of periarticular
tissue, involving the synovial tissue particularly of large joints. Due to the presence of a
characteristic translocation, TGCT is considered to be a clonal neoplastic lesion. It usually
presents as an indolent, progressive monoarticular arthritis or tenosynovitis, affecting mostly
the knee or the hand. Patients may have a history of recurrent atraumatic knee hemarthrosis
with no underlying bleeding disorder. TGCT is characterized by hypervascular proliferative
synovium containing multinucleated giant cells, macrophages and hemosiderin. The
multinucleated cells express features of osteoclasts.
Cause: a translocation in CSF1 gene (fused to the collagen VI gene) leads to
overexpression of colony stimulating factor-1 (CSF-1), with subsequent recruitment of CSF1R-
expressing macrophages that constitute the tumor mass.
Clinical: 4 forms:
1) Tenosynovial giant cell tumor (often at hand) typically presents as an
enlarging mass adherent to a tendon, usually in adult women. Its appearance is like that of a
ganglion and it never becomes malignant. Tendon and adjacent bone can be damaged if the
disease remains untreated.
2) The diffuse form (knee) presents as slowly progressive, painful swelling of a
single joint. The knee is the joint most commonly affected, with the hip and ankle being the next
most often involved. Rarely, it can occur in other appendicular joints or in the spine. This form of
, PVNS damages joints with a tight capsule, such as the hip or facets. It often generates the
characteristic radiographic appearance of scalloped erosions, usually with a sclerotic margin at
the site of synovial insertion or reflection, which is believed to result from pressure on or direct
invasion of bone by the synovial mass. Aspiration of brown or hemorrhagic synovial fluid in the
absence of recent trauma is characteristic and may often be the first indication of the disease.
3) Localized PVNS is the least frequently occurring form, it involves a discrete
section of the synovium and projects as a pedunculated nodule into the synovial cavity, often of
the knee, where it can cause signs and symptoms of a loose body. Patients with the localized
form of PVNS typically experience mild pain and locking of the affected joint.
4) Multifocal form with 2-5 lesions along a single tendon (of the hand) is a very
rare entity (case reports).
MRI: the mainstay for imaging of PVNS and has predominantly low signal on T1/T2 and
high signal on T1 + IVC, with a characteristic image because of the large deposits of hemosiderin.
Dx: hemophilia, hemosiderosis from recurrent hemarthroses and hemochromatosis can
also produce iron-pigmented tissue. For localized PVNS, dx from synovial osteochondromatosis
(which has ↓T1, ↑T2 *water content of the cartilage]).
Treatment: complete surgical removal of the pathologic synovium, but recurrences can
occur, especially if excision has been incomplete. Radiosynovectomy, radiotherapy, or IA
injection of radioactive colloid can be used as local adjuvant treatment after synovectomy.
Because PVNS expresses high levels of CSF1 (which recruits cells such as
macrophages and osteoclasts that express the CSF1 receptor), oral tyrosine kinases inhibitors
targeting CSF-1R signaling: vimseltinib and pexidartinib (black box warning for potentially fatal
hepatotoxicity) or older tyrosine kinases inhibitors alternatives imatinib (Glivec), nilotinib.
Vimseltinib: approved as an alternative to surgery, for patients with symptomatic TGCT for
whom resection would cause worsening functional limitation or severe morbidity.
Synovial sarcoma
highly malignant and generally occurs in the lower extremities (70%) of young people, with peak
age 15-30yrs. The tumor usually arises in the periarticular tissues of the knee or ankle. Only 10%
arise directly within the joint itself. Clinical: slowly growing, often minimally symptomatic mass
adjacent to the joint. Pain only in 50%. Soft-tissue calcification on Rx in 30-50%. The majority are
caused by a translocation that fuses genes on X chromosome, resulting in activation of the
transcription factor Sox2 which promotes self-renewal of stem cells without inhibition.
Treatment: aggressive combination of radical surgery, radiation therapy and chemotherapy.
Complications: progressive disease is usually due to extensive pulmonary metastasis. Other
common sites of metastasis include regional lymph nodes, bones, liver, skin and brain.
Arthropathies
Charcot (Neuropathic arthropathy)
Relatively painless, progressive, destructive arthropathy caused by a neurologic deficit. The
features include fragmentation of bone, progressive destruction and disorganization. Patients
don’t perceive minor injuries and keep walking. Despite sensory neuropathy, pain is often
present. Unilateral mono-, oli-, but also polyarthropathy.
arthropathies/arthritides
Synovial proliferative diseases
Synovial Osteochondromatosis
a rare benign, synovial proliferative disease, characterized by cartilaginous metaplasia of the
intimal layer of the synovial membrane of joints, tendons and bursas, which can subsequently
mineralize and even ossify. Most often affecting middle-aged men but has been reported in
children and teenagers. The knee is most commonly affected and involvement is typically
monoarticular. Patients generally have pain and swelling in the early stages, but multiple loose
bodies can result in locking of the knee (cartilage nodules break free into the articular space,
resulting in loose bodies). In later stages of the disease, knee ROM may be decreased. Knee
stiffness may be caused by thickened metaplastic synovium and may portend a poor prognosis if
severe.
Imaging: Rx may be diagnostic if the chondroid bodies are calcified resembling popcorn,
but Rx can be non-diagnostic in 30%. MRI: nodules of cartilage in the synovium which are dark
on T1 and bright on T2 due to water content in the hyaline cartilage. Loose bodies can be seen.
Dx: secondary osteochondromatosis in association with OA: presents at an older age
and is characterized by loose bodies that are less numerous and with greater variation in size.
Treatment of symptomatic synovial osteochondromatosis involves arthroscopic removal
of symptomatic loose bodies. In the first and second phases of disease, active synovium should
be excised. Recurrence is treated by repeated arthroscopic debridement.
Complications: never metastasizes but may undergo malignant transformation into a
chondrosarcoma.
Pigmented villonodular synovitis
or tenosynovial giant cell tumor (TGCT), is a rare benign proliferative process of periarticular
tissue, involving the synovial tissue particularly of large joints. Due to the presence of a
characteristic translocation, TGCT is considered to be a clonal neoplastic lesion. It usually
presents as an indolent, progressive monoarticular arthritis or tenosynovitis, affecting mostly
the knee or the hand. Patients may have a history of recurrent atraumatic knee hemarthrosis
with no underlying bleeding disorder. TGCT is characterized by hypervascular proliferative
synovium containing multinucleated giant cells, macrophages and hemosiderin. The
multinucleated cells express features of osteoclasts.
Cause: a translocation in CSF1 gene (fused to the collagen VI gene) leads to
overexpression of colony stimulating factor-1 (CSF-1), with subsequent recruitment of CSF1R-
expressing macrophages that constitute the tumor mass.
Clinical: 4 forms:
1) Tenosynovial giant cell tumor (often at hand) typically presents as an
enlarging mass adherent to a tendon, usually in adult women. Its appearance is like that of a
ganglion and it never becomes malignant. Tendon and adjacent bone can be damaged if the
disease remains untreated.
2) The diffuse form (knee) presents as slowly progressive, painful swelling of a
single joint. The knee is the joint most commonly affected, with the hip and ankle being the next
most often involved. Rarely, it can occur in other appendicular joints or in the spine. This form of
, PVNS damages joints with a tight capsule, such as the hip or facets. It often generates the
characteristic radiographic appearance of scalloped erosions, usually with a sclerotic margin at
the site of synovial insertion or reflection, which is believed to result from pressure on or direct
invasion of bone by the synovial mass. Aspiration of brown or hemorrhagic synovial fluid in the
absence of recent trauma is characteristic and may often be the first indication of the disease.
3) Localized PVNS is the least frequently occurring form, it involves a discrete
section of the synovium and projects as a pedunculated nodule into the synovial cavity, often of
the knee, where it can cause signs and symptoms of a loose body. Patients with the localized
form of PVNS typically experience mild pain and locking of the affected joint.
4) Multifocal form with 2-5 lesions along a single tendon (of the hand) is a very
rare entity (case reports).
MRI: the mainstay for imaging of PVNS and has predominantly low signal on T1/T2 and
high signal on T1 + IVC, with a characteristic image because of the large deposits of hemosiderin.
Dx: hemophilia, hemosiderosis from recurrent hemarthroses and hemochromatosis can
also produce iron-pigmented tissue. For localized PVNS, dx from synovial osteochondromatosis
(which has ↓T1, ↑T2 *water content of the cartilage]).
Treatment: complete surgical removal of the pathologic synovium, but recurrences can
occur, especially if excision has been incomplete. Radiosynovectomy, radiotherapy, or IA
injection of radioactive colloid can be used as local adjuvant treatment after synovectomy.
Because PVNS expresses high levels of CSF1 (which recruits cells such as
macrophages and osteoclasts that express the CSF1 receptor), oral tyrosine kinases inhibitors
targeting CSF-1R signaling: vimseltinib and pexidartinib (black box warning for potentially fatal
hepatotoxicity) or older tyrosine kinases inhibitors alternatives imatinib (Glivec), nilotinib.
Vimseltinib: approved as an alternative to surgery, for patients with symptomatic TGCT for
whom resection would cause worsening functional limitation or severe morbidity.
Synovial sarcoma
highly malignant and generally occurs in the lower extremities (70%) of young people, with peak
age 15-30yrs. The tumor usually arises in the periarticular tissues of the knee or ankle. Only 10%
arise directly within the joint itself. Clinical: slowly growing, often minimally symptomatic mass
adjacent to the joint. Pain only in 50%. Soft-tissue calcification on Rx in 30-50%. The majority are
caused by a translocation that fuses genes on X chromosome, resulting in activation of the
transcription factor Sox2 which promotes self-renewal of stem cells without inhibition.
Treatment: aggressive combination of radical surgery, radiation therapy and chemotherapy.
Complications: progressive disease is usually due to extensive pulmonary metastasis. Other
common sites of metastasis include regional lymph nodes, bones, liver, skin and brain.
Arthropathies
Charcot (Neuropathic arthropathy)
Relatively painless, progressive, destructive arthropathy caused by a neurologic deficit. The
features include fragmentation of bone, progressive destruction and disorganization. Patients
don’t perceive minor injuries and keep walking. Despite sensory neuropathy, pain is often
present. Unilateral mono-, oli-, but also polyarthropathy.
