Medical Therapy
In August 2019, pexidartinib was approved by the US Food and Drug Administration (FDA) for tenosynovial giant cell tumor (TGCT), the first systemic therapy to be approved for this condition. Pexidartinib inhibits colony stimulating factor-1 receptor (CSF1R), a tyrosine kinase receptor. By binding to CSF1R expressed on monocytes, macrophages, and osteoclasts, pexidartinib prevents activation of interleukin-34. Blocking the production of inflammatory mediators by macrophages and monocytes is thought to inhibit tumor cell proliferation.
Approval of pexidartinib was based on the phase 3 ENLIVEN study, the first placebo-controlled study of a systemic therapy for TGCT. [39] The primary endpoint, overall response rate (ORR), showed significant improvement. At week 25, patients treated with pexidartinib (n = 61) had an ORR of 38%, compared with 0% for placebo-treated patients (n = 59). The complete response rate was 15% and the partial response rate was 23%. Of the 23 responders followed for a minimum of 6 months after the initial response, 22 maintained their response for 6 or more months. All 13 responders followed for a minimum of 12 months after the initial response maintained their response for 12 or more months.
Additionally, the ENLIVEN study documented statistically significant improvements in secondary end points (eg, mean changes in range of motion, physical function, and worst stiffness). [39] Liver toxicities were documented with pexidartinib that necessitated dosage reduction or discontinuance.
In October 2022, the FDA approved a lower dose to reduce the risk of increasing pexidartinib serum concentrations that could lead to adverse effects, including hepatotoxicity.
Surgical Therapy
Marginal excision of giant cell tumor (GCT) of the tendon sheath (see the images below) has typically been the treatment of choice; systemic pharmacotherapy (pexidartinib) is now available (see Medical Therapy). A patient's poor medical health and the presence of life-threatening illnesses are contraindications for the surgical resection of these tumors.
An 11-year-old girl presented with this firm nonfluctuant mass over her posterior medial left ankle that had been present for 5 months and had not increased in size. The mass was not transilluminating. Findings on frozen section were consistent with a benign giant cell tumor of the tendon sheath. The mass was marginally excised.
Giant cell tumor of the tendon sheath after marginal excision from an 11-year-old girl who presented with a firm nonfluctuant mass over her posterior medial left ankle that had been present for 5 months and had not increased in size.
The tumor may involve the tendon sheath, volar plate, capsular ligaments, and joints. Dorsal sites frequently involve the joints or tendinous attachments to bone. Volar sites are more frequently present near the joints, presumably because the fibrous flexor-tendon sheath is thinner at the level of the joints. In a review of 115 cases, 20% had extra-articular joint involvement.
In the digits, these tumors are often intimately associated with the flexor or extensor tendon. If no intimate association exists, a stalk of tissue often connects the tumor to the tendon sheath. If the mass is relatively large, smaller satellite lesions extending into the surrounding tendon sheath and synovium may be found.
Because the mass is frequently associated with the tendon sheath or synovial joint, complete excision can be difficult. Often, partial excision of the joint capsule or tendon sheath is necessary for complete removal of the tumor.
Meticulous dissection and exploration are essential because satellite lesions are common. A Freer elevator or other blunt probe is often helpful in teasing these satellite lesions from beneath the surrounding tendons or other structures. Care should be taken to avoid puncturing these lesions because seeding of adjacent soft-tissue structures may be possible. Occasionally, bony debridement with a curette or rongeur is necessary if adjacent bony erosion is present.
Jones et al [17] noted an association between these lesions and arthritis at the distal interphalangeal (DIP) joint. If such arthritis is present, debridement or fusion may be necessary to completely eradicate the process. If the tumor involves the skin, consider the excision of an elliptical area of skin along with the mass. Skin excision may necessitate secondary skin grafting. Rarely, tendon reconstruction may be necessary if tumor excision compromises the associated tendon. Even with careful dissection, reported recurrence rates are in the range of 9-44%.
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Image in a 44-year-old right hand–dominant man who presented with a mass on the volar radial aspect of his left index finger. The mass was painless and had been slowly growing for 1.5 years.
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Radiograph demonstrates cortical erosion from the pressure effect of the adjacent mass on the radial aspect of the proximal phalanx.
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Radiograph demonstrates the bony erosion associated with some giant cell tumors of the tendon sheath and shows the unmineralized soft-tissue shadow of the mass.
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Radiograph demonstrates cortical erosion from the pressure effect of the overlying giant cell tumor of the tendon sheath. This apple-core effect is indicative of a primary soft-tissue mass that is causing external erosion, which should not be confused with a primary bone process such as periosteal chondroma.
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Radiograph demonstrates cortical erosion from the pressure effect of the overlying giant cell tumor of the tendon sheath.
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Histologic findings of a giant cell tumor of the tendon sheath.
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High-power photomicrograph depicts the histologic findings of a giant cell tumor of the tendon sheath.
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Typical T2-weighted MRI appearance of a giant cell tumor of the tendon sheath. Most of the tumor has intermediate signal intensity, and portions of the tumor have low signal intensity; the latter finding likely reflects signal attenuation due to hemosiderin deposition.
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Typical T1-weighted MRI appearance of a giant cell tumor of the tendon sheath. Portions of the tumor have decreased signal intensity.
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Typical T1-weighted MRI findings in a giant cell tumor of the tendon sheath overlying the metacarpophalangeal joint. Note the low-signal-intensity areas.
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Corresponding T2-weighted MRI findings in the tumor shown in the image above. Note the areas of low signal intensity.
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Intraoperative excision of the giant cell tumor of the tendon sheath, which has the typical golden-yellow color secondary to hemosiderin deposition. The radial digital nerve is dissected free and slightly volar to the mass.
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After excision, the bone is curetted, leaving the exposed radial aspect of the proximal phalanx, as shown here.
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Giant cell tumor of the tendon sheath after marginal excision.
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Typical microscopic appearance of a giant cell tumor of the tendon sheath. Sheets of rounded or polygonal cells blend with hypocellular collagenized zones; variable numbers of giant cells are present.
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High-power photomicrograph of giant cell tumor of the tendon sheath shows occasional numerous mononuclear cells, scattered giant cells, and hemosiderin-containing xanthoma cells.
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An 11-year-old girl presented with this firm nonfluctuant mass over her posterior medial left ankle that had been present for 5 months and had not increased in size. The mass was not transilluminating. Findings on frozen section were consistent with a benign giant cell tumor of the tendon sheath. The mass was marginally excised.
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Giant cell tumor of the tendon sheath after marginal excision from an 11-year-old girl who presented with a firm nonfluctuant mass over her posterior medial left ankle that had been present for 5 months and had not increased in size.
