Tenosynovial giant cell tumor | |
---|---|
Other names | Localized: Localized pigmented villonodular synovitis (L-PVNS), Giant cell tumor of the tendon sheath (GCT-TS), Nodular tenosynovitis, Localized nodular tenosynovitis, and L-TGCT Diffuse: Pigmented villonodular synovitis (PVNS), Conventional PVNS, and D-TGCT |
Micrograph of diffuse TGCT, also known as pigmented villonodular synovitis. H&E stain. | |
Specialty | Rheumatology |
Symptoms | Swelling, pain, sensitivity, and/or limited range of motion |
Complications | Spreading of tumors to surrounding tissues |
Types | Diffuse and localized |
Diagnostic method | MRI, biopsy, surgery |
Treatment | Surgery, CSF1R inhibitors |
Tenosynovial giant cell tumor (TGCT) is a group of rare, typically non-malignant tumors of the joints. TGCT tumors often develop from the lining of joints (also known as synovial tissue). [1] [2] [2]: 100 [3] [3]: 245
Common symptoms of TGCT include swelling, pain, stiffness and reduced mobility in the affected joint or limb. [2]: 102 This group of tumors can be divided into different subsets according to their site, growth pattern, and prognosis. [4] [4]: 361 Localized TGCT is sometimes referred to as "giant cell tumor of the tendon sheath"; [2]: 100 diffuse TGCT is also called "pigmented villonodular synovitis" (PVNS). [2]: 102
TGCT tumors grow due to genetic overexpression of colony stimulating factor 1. This causes colony-stimulating factor-1 receptor (CSF1R) cells to accumulate in the joint tissue. [5] [6]
TGCT can be diagnosed by magnetic resonance imaging ( MRI), by biopsy, or during surgery. [7] [8] The disorder is difficult to identify and is often not diagnosed for years due to nonspecific symptoms or a general paucity of symptoms. [9] TGCT cases are often misdiagnosed as osteoarthritis, [10] localized trauma, [11] sports injuries, [12] [13] xanthomas, [14] or other conditions. [15] One study of 122 diffuse TGCT patients found that the average delay in diagnosis was 2.9 years. [16]
Surgery has been the most common form of treatment for both localized [2]: 101 [4]: 361 and diffuse TGCT. [2]: 103 [4]: 361 [17]: 1 After surgery, patients may receive physical therapy in order to help rehabilitate affected joints. [12] [18] However, recurrence of TGCT after surgery is common, [10] with a higher rate of recurrence for diffuse TGCT than for localized TGCT. [4]: 361 In cases of recurrent or resistant disease, multiple surgeries, total joint arthroplasties, or amputation may be required. [17]: 1
A multidisciplinary approach, supplementing surgery with radiotherapy or other treatments, can also improve outcomes in cases of recurrent TGCT. [19] In the late 2010s, treatment with CSF1R inhibitors emerged as an option [20] that may help improve functionality for patients with recurrent TGCT or TGCT that is not easily managed by surgery. [4]: 361
A study conducted in the Netherlands estimated that the worldwide incidence of TGCT is 43 cases per million person-years. The majority – 39 cases per million person-years – were estimated to be localized TGCT; the remaining 4 cases per million person-years were estimated to be diffuse TGCT. [21] TGCT can occur in patients of any age, but people with localized TGCT are typically between 30 and 50 years old, [2]: 100–101 while diffuse TGCT tends to affect people under the age of 40. [2]: 102–103
Classification for TGCT encompasses two subtypes that can be divided according to site – within a joint (intra-articular) or outside of the joint (extra-articular) – and growth pattern (localized or diffuse) of the tumor(s). [2]: 100 [4]: 361 Localized and diffuse subsets of TGCT differ in their prognosis, clinical presentation, and biological behavior, but share a similar manner of disease development. [2]: 100
Localized TGCT is sometimes referred to as localized pigmented villonodular synovitis (L-PVNS), giant cell tumor of the tendon sheath (GCT-TS), nodular tenosynovitis, localized nodular tenosynovitis, and L-TGCT. [1]: 1 [2]: 100
The localized form of TGCT is more common. [2]: 100 [3]: 245 Localized TGCT tumors are typically 0.5 cm-4 cm), [2]: 101 develop over years, [2]: 100 are benign and non-destructive to the surrounding tissue, and may reoccur in the affected area. [2]: 101 The most common symptom is painless swelling. [2]: 101 Localized TGCT most often occurs in fingers, but can also occur in other joints. [2] [21]
Diffuse TGCT is sometimes referred to as pigmented villonodular synovitis (PVNS), conventional PVNS, and D-TGCT. [1]: 1 [4]: 361 [17]: 1 [2]: 102
Diffuse TGCT occurs less frequently and is locally aggressive (in some cases, tumors may infiltrate surrounding soft tissue). [3]: 245 [1]: 1 [2]: 102 [17] [17]: 1 It most commonly affects people under 40 years old, though the age of occurrence varies. [2]: 102 Diffuse TGCT may occur inside a joint (intra-articular) or outside of a joint (extra-articular). Intra-articular tumors typically occur in the knee (approximately 75% of cases) and hip (approximately 15% of cases). [2]: 102 Extra-articular tumors are usually found in the knee, thigh, and foot. [2]: 101 Symptoms include swelling, pain, sensitivity, and/or limited range of motion. [2]: 102 The rate of reoccurrence is estimated to be 18-46% for intra-articular tumors and 33-50% for extra-articular tumors. [2]: 103 [17]: 1
Diffuse TGCT is locally aggressive and can spread to surrounding tissues, causing bone erosion and tissue damage. If not treated early, it can spread to areas outside the joint, extra-articular, and potentially cause permanent loss of range as well as intense pain. [22] [18]
The CSF1 translocations result in overexpression of CSF1. In cases of TGCT and PVNS carrying this translocation, it is present in a minority of the intratumoral cells, leading to CSF1 expression only in these cells, whereas the majority of cells express CSF1R but not CSF1, suggesting a tumor-landscaping effect with aberrant CSF1 expression in the neoplastic cells, leading to the abnormal accumulation of nonneoplastic cells that form a tumorous mass.
As the CSF1 translocation is postulated to play an important role in the biology of PVNS/TGCT, the consistent presence of CSF1 expression in translocation-negative cases implies that other mechanisms can lead to CSF1 up-regulation.
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The tumor-permissive and immunosuppressive characteristics of tumor-associated macrophages (TAM) have fueled interest in therapeutically targeting these cells. In this context, the colony-stimulating factor 1 (CSF1)/colony-stimulating factor 1 receptor (CSF1R) axis has gained the most attention, and various approaches targeting either the ligands or the receptor are currently in clinical development.
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: CS1 maint: unflagged free DOI (
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Category:Dermal and subcutaneous growths Category:Ailments of unknown cause Category:Musculoskeletal disorders Category:Rare diseases
Tenosynovial giant cell tumor | |
---|---|
Other names | Localized: Localized pigmented villonodular synovitis (L-PVNS), Giant cell tumor of the tendon sheath (GCT-TS), Nodular tenosynovitis, Localized nodular tenosynovitis, and L-TGCT Diffuse: Pigmented villonodular synovitis (PVNS), Conventional PVNS, and D-TGCT |
Micrograph of diffuse TGCT, also known as pigmented villonodular synovitis. H&E stain. | |
Specialty | Rheumatology |
Symptoms | Swelling, pain, sensitivity, and/or limited range of motion |
Complications | Spreading of tumors to surrounding tissues |
Types | Diffuse and localized |
Diagnostic method | MRI, biopsy, surgery |
Treatment | Surgery, CSF1R inhibitors |
Tenosynovial giant cell tumor (TGCT) is a group of rare, typically non-malignant tumors of the joints. TGCT tumors often develop from the lining of joints (also known as synovial tissue). [1] [2] [2]: 100 [3] [3]: 245
Common symptoms of TGCT include swelling, pain, stiffness and reduced mobility in the affected joint or limb. [2]: 102 This group of tumors can be divided into different subsets according to their site, growth pattern, and prognosis. [4] [4]: 361 Localized TGCT is sometimes referred to as "giant cell tumor of the tendon sheath"; [2]: 100 diffuse TGCT is also called "pigmented villonodular synovitis" (PVNS). [2]: 102
TGCT tumors grow due to genetic overexpression of colony stimulating factor 1. This causes colony-stimulating factor-1 receptor (CSF1R) cells to accumulate in the joint tissue. [5] [6]
TGCT can be diagnosed by magnetic resonance imaging ( MRI), by biopsy, or during surgery. [7] [8] The disorder is difficult to identify and is often not diagnosed for years due to nonspecific symptoms or a general paucity of symptoms. [9] TGCT cases are often misdiagnosed as osteoarthritis, [10] localized trauma, [11] sports injuries, [12] [13] xanthomas, [14] or other conditions. [15] One study of 122 diffuse TGCT patients found that the average delay in diagnosis was 2.9 years. [16]
Surgery has been the most common form of treatment for both localized [2]: 101 [4]: 361 and diffuse TGCT. [2]: 103 [4]: 361 [17]: 1 After surgery, patients may receive physical therapy in order to help rehabilitate affected joints. [12] [18] However, recurrence of TGCT after surgery is common, [10] with a higher rate of recurrence for diffuse TGCT than for localized TGCT. [4]: 361 In cases of recurrent or resistant disease, multiple surgeries, total joint arthroplasties, or amputation may be required. [17]: 1
A multidisciplinary approach, supplementing surgery with radiotherapy or other treatments, can also improve outcomes in cases of recurrent TGCT. [19] In the late 2010s, treatment with CSF1R inhibitors emerged as an option [20] that may help improve functionality for patients with recurrent TGCT or TGCT that is not easily managed by surgery. [4]: 361
A study conducted in the Netherlands estimated that the worldwide incidence of TGCT is 43 cases per million person-years. The majority – 39 cases per million person-years – were estimated to be localized TGCT; the remaining 4 cases per million person-years were estimated to be diffuse TGCT. [21] TGCT can occur in patients of any age, but people with localized TGCT are typically between 30 and 50 years old, [2]: 100–101 while diffuse TGCT tends to affect people under the age of 40. [2]: 102–103
Classification for TGCT encompasses two subtypes that can be divided according to site – within a joint (intra-articular) or outside of the joint (extra-articular) – and growth pattern (localized or diffuse) of the tumor(s). [2]: 100 [4]: 361 Localized and diffuse subsets of TGCT differ in their prognosis, clinical presentation, and biological behavior, but share a similar manner of disease development. [2]: 100
Localized TGCT is sometimes referred to as localized pigmented villonodular synovitis (L-PVNS), giant cell tumor of the tendon sheath (GCT-TS), nodular tenosynovitis, localized nodular tenosynovitis, and L-TGCT. [1]: 1 [2]: 100
The localized form of TGCT is more common. [2]: 100 [3]: 245 Localized TGCT tumors are typically 0.5 cm-4 cm), [2]: 101 develop over years, [2]: 100 are benign and non-destructive to the surrounding tissue, and may reoccur in the affected area. [2]: 101 The most common symptom is painless swelling. [2]: 101 Localized TGCT most often occurs in fingers, but can also occur in other joints. [2] [21]
Diffuse TGCT is sometimes referred to as pigmented villonodular synovitis (PVNS), conventional PVNS, and D-TGCT. [1]: 1 [4]: 361 [17]: 1 [2]: 102
Diffuse TGCT occurs less frequently and is locally aggressive (in some cases, tumors may infiltrate surrounding soft tissue). [3]: 245 [1]: 1 [2]: 102 [17] [17]: 1 It most commonly affects people under 40 years old, though the age of occurrence varies. [2]: 102 Diffuse TGCT may occur inside a joint (intra-articular) or outside of a joint (extra-articular). Intra-articular tumors typically occur in the knee (approximately 75% of cases) and hip (approximately 15% of cases). [2]: 102 Extra-articular tumors are usually found in the knee, thigh, and foot. [2]: 101 Symptoms include swelling, pain, sensitivity, and/or limited range of motion. [2]: 102 The rate of reoccurrence is estimated to be 18-46% for intra-articular tumors and 33-50% for extra-articular tumors. [2]: 103 [17]: 1
Diffuse TGCT is locally aggressive and can spread to surrounding tissues, causing bone erosion and tissue damage. If not treated early, it can spread to areas outside the joint, extra-articular, and potentially cause permanent loss of range as well as intense pain. [22] [18]
The CSF1 translocations result in overexpression of CSF1. In cases of TGCT and PVNS carrying this translocation, it is present in a minority of the intratumoral cells, leading to CSF1 expression only in these cells, whereas the majority of cells express CSF1R but not CSF1, suggesting a tumor-landscaping effect with aberrant CSF1 expression in the neoplastic cells, leading to the abnormal accumulation of nonneoplastic cells that form a tumorous mass.
As the CSF1 translocation is postulated to play an important role in the biology of PVNS/TGCT, the consistent presence of CSF1 expression in translocation-negative cases implies that other mechanisms can lead to CSF1 up-regulation.
{{
cite journal}}
: CS1 maint: unflagged free DOI (
link)
{{
cite journal}}
: CS1 maint: unflagged free DOI (
link)
The tumor-permissive and immunosuppressive characteristics of tumor-associated macrophages (TAM) have fueled interest in therapeutically targeting these cells. In this context, the colony-stimulating factor 1 (CSF1)/colony-stimulating factor 1 receptor (CSF1R) axis has gained the most attention, and various approaches targeting either the ligands or the receptor are currently in clinical development.
{{
cite journal}}
: CS1 maint: unflagged free DOI (
link)
Category:Dermal and subcutaneous growths Category:Ailments of unknown cause Category:Musculoskeletal disorders Category:Rare diseases