Tenosynovial giant cell tumor

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"TGCT" redirects here. For testicular germ cell tumor, see Germ cell tumor.
Tenosynovial giant cell tumor
Other namesLocalized: 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
CSF1R inhibitors
MedicationImatinib, Pexidartinib, vimseltinib

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/nodular 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 These two distinct subtypes determined by radiographic appearance.[5] Localized TGCT is defined as a well circumscribed tumor while diffuse TGCT exhibits a locally aggressive and infiltrative behavior.[6]

Classification

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

Histopathology of localized TGCT arising in hand finger. H&E stain.

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][7]

Diffuse TGCT

Micrograph of diffuse TGCT showing pigmented hemosiderin-laden macrophages (brown/red). H&E stain.

Diffuse TGCT is sometimes referred to as pigmented villonodular synovitis (PVNS), conventional PVNS, and D-TGCT.[1]: 1 [4]: 361 [8]: 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 [8][8]: 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 [8]: 1 

Complications

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.[9][10]

Mechanism

TGCT tumors grow due to genetic overexpression of

colony-stimulating factor-1 receptor (CSF1R) cells to accumulate in the joint tissue.[11][12]

Diagnosis

TGCT can be diagnosed by magnetic resonance imaging (

xanthomas,[20] or other conditions.[21] One study of 122 diffuse TGCT patients found that the average delay in diagnosis was 2.9 years.[22]

To identify or monitor using MRI, the minimum techniques required include T1 weighted images, T2 weighted images, and a fluid sensitive sequence.[23]

Treatment

Patients affected by TGCT should be managed within expert centers or reference networks, by a dedicated, experienced sarcoma multidisciplinary treatment team, including a pathologist, radiologist, orthopaedic surgeon, pain specialist, surgical, radiation and medical oncologists.[24] Patients initially treated at cancer centers have lower recurrence rates than those initially treated by community centers.[25]

Surgery has been the most common form of treatment for both localized[2]: 101 [4]: 361  and diffuse TGCT.[2]: 103 [4]: 361 [8]: 1  After surgery, patients may receive physical therapy in order to help rehabilitate affected joints.[18][10] However, recurrence of TGCT after surgery is common,[16] 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.[8]: 1 

A multidisciplinary approach, supplementing surgery or other treatments, can also improve outcomes in cases of recurrent TGCT.[26] In the late 2010s, treatment with CSF1R inhibitors emerged as an option[27] that may help improve functionality for patients with recurrent TGCT or TGCT that is not easily managed by surgery.[4]: 361 An oral CSF-1R inhibitor pexidartinib is approved in the US and only available through a Risk Evaluation and Mitigation Strategy (REMS) Program,[28] and two other oral CSF-1R inhibitors, pimicotinib and vimseltinib are being developed in phase 3 trials.[29][30]

There is insufficient and contradictory evidence on radiation therapy, in the form of radiosynoviorthesis (yttrium injections) or external beam, before or after surgery and thus no recommendation for its use in TGCT can be made. [31]

For asymptomatic patients, active surveillance is the preferred method.[32][33] Active surveillance includes monitoring with MRI in intervals (e.g., every 6 months) to ensure the delay in treatment does not pose a potential harm.[34] This should be carefully weighed against the potential for over treatment.

Epidemiology

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.[7] 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 

See also

References

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    PMID 25679002
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  11. PMID 16407111
    . 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.
  12. S2CID 29544370
    . 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.
  13. PMID 21765227
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  27. PMID 28716061
    . 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.
  28. ^ "FDA approves pexidartinib for tenosynovial giant cell tumor". FDA. 20 December 2019.
  29. ^ "CTG Labs - NCBI".
  30. ^ "CTG Labs - NCBI".
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External links

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