Multifocal Giant Cell Tumor of the Wrist: Radiologic-Pathologic Correlation and Review of Diagnostic Challenges
Ramkumar R
Senior Consultant plastic surgeon, Kauvery hospital, Vadapalani
Abstract
Background: Giant cell tumors of the tendon sheath (GCT-TS), a form of tenosynovial giant cell tumor (TGCT), are benign soft-tissue neoplasms usually presenting as solitary nodules, most often in the fingers. Multifocal occurrences in the wrist are exceedingly rare (reported in <5% of cases ) and can be diagnostically challenging due to overlap with diffuse synovial proliferative disorders.
Case Presentation: We report a 43-year-old female with multiple firm, non-tender masses on the volar and dorsal wrist, causing restricted motion. MRI demonstrated lobulated, hypointense lesions on T1- and T2-weighted sequences with prominent hemosiderin deposition. Lesions encased tendons and displaced neurovascular structures without bone erosion. En bloc resection was performed. Histopathology revealed sheets of mononuclear synovial cells with hemosiderin-laden macrophages and multinucleated giant cells, confirming multifocal GCT-TS.
Discussion: Key MRI features (uniform low signal on T1/T2, nodular morphology) correlated with pathological hemosiderin and fibrous stroma, distinguishing GCT-TS from common mimics (ganglion cysts, synovial sarcoma). Multifocal presentation in the wrist is unusual; a literature review found only isolated case reports and small series of multifocal hand/wrist GCT-TS . Complete surgical excision is curative but can be challenging due to tendon and neurovascular involvement. Recurrence rates range from ~5–20% in solitary lesions to higher in diffuse or incompletely excised tumors . Adjuvant therapies (e.g. external beam radiotherapy) may be considered for residual or recurrent disease.
Conclusion: Multifocal GCT-TS of the wrist, though rare, should be considered in patients with multiple wrist masses. MRI is indispensable for mapping lesion extent and guiding surgery, while histology provides definitive diagnosis. Early recognition and complete excision offer the best chance for cure, and careful follow-up is warranted given the risk of recurrence.
Introduction
Giant cell tumor of the tendon sheath (GCT-TS) is a benign proliferative tumor arising from the synovial lining of tendon sheaths, classified under localized-type tenosynovial giant cell tumors . It is the second most common soft-tissue tumor of the hand after ganglion cysts . Approximately 85% of GCT-TS present as solitary nodules in the fingers , typically along the flexor tendon sheaths or interphalangeal joints. In contrast, involvement of the wrist is uncommon, and multifocal lesions in the wrist are exceptionally rare . Such atypical presentations can mimic diffuse tenosynovial giant cell tumor (formerly pigmented villonodular synovitis, PVNS) or inflammatory arthropathies, leading to diagnostic uncertainty.
This report describes a rare case of multifocal GCT-TS of the wrist in a middle-aged female, with an emphasis on radiology-pathology correlation. We detail the magnetic resonance imaging (MRI) characteristics across multiple sequences and correlate them with histopathological findings, including cellular architecture and the presence of hemosiderin. We also discuss the broader clinical context, differential diagnoses, surgical management challenges, risk of recurrence, and adjuvant treatment considerations. A brief literature review is provided to assess the rarity of multifocal GCT-TS in the wrist and to compare our case with previously reported cases. Finally, we consider the suitability of this case for publication and identify potential journals in plastic surgery, orthopedics, or radiology that accept case reports.
Case Report
Clinical Presentation
A 43-year-old right-handed female presented with multiple firm, slow-growing swellings over the volar and dorsal aspects of the right wrist. The masses had been noticed for one year and were not associated with significant pain, though the patient reported mild stiffness and restricted range of motion in the wrist. There was no history of antecedent trauma, infection, or inflammatory joint disease. On examination, three distinct subcutaneous nodules were palpable: two on the volar radial side and one on the dorsal ulnar side of the wrist. All were non-tender, firm, and mildly mobile under the skin. No overlying skin changes or warmth were present. Neurological examination of the hand was normal, and there were no signs of systemic arthritis. The clinical differential diagnosis included ganglion cysts (given the wrist location), rheumatoid nodules (in the context of possible rheumatoid arthritis, though the patient lacked systemic signs), and a tenosynovial proliferative process such as PVNS (diffuse TGCT) given the presence of multiple lesions.
Imaging Findings
Magnetic resonance imaging (MRI) of the wrist was performed for lesion characterization and surgical planning. T1-weighted images revealed multiple lobulated masses of low signal intensity in the volar and dorsal wrist. In the volar flexor compartment, a 1.5 × 1.3 cm hypointense lesion was seen adjacent to the radial styloid, encasing the flexor pollicis longus (FPL) tendon and abutting the radial artery and vein. In the dorsal extensor compartment, nodular lesions were noted near the extensor tendons, including a 1.2 cm mass at the distal ulna near the triangular fibrocartilage complex. All lesions appeared dark on T2-weighted and proton-density fat-saturated (PDFS) sequences as well, with only faint heterogeneous internal signals. There was no significant joint effusion or bone marrow edema. Notably, none of the lesions caused cortical erosion or bone destruction, favoring a benign process. On fat-suppressed T2 or STIR images, the lesions demonstrated predominantly low signal with patchy areas of intermediate signal intensity. Post-contrast T1 fat-saturated sequences (gadolinium-enhanced) showed mild to moderate enhancement of the nodules, consistent with their solid nature and vascularity.
Surgical and Histopathologic Findings
Based on the imaging findings, the patient was taken for surgical exploration. A combined volar and dorsal approach to the wrist was utilized to allow complete excision of all identified lesions. Intraoperatively, three discrete nodular tumors were found: two volar lesions arising from the tendon sheath of the FPL and flexor carpi radialis (FCR), and one dorsal lesion arising near the extensor indicis proprius tendon. The tumors were lobulated, rubbery, and tan-brown in color, each enveloped by a thin pseudocapsule. They were firmly adherent to the tendon sheaths but did not infiltrate the tendons or adjacent bone. The radial artery and median nerve were carefully dissected free from the volar masses, which encased these structures without invading them. All nodules were excised en bloc with clear margins. The largest volar mass measured 1.5 cm, and the dorsal mass measured 1.2 cm. No satellite lesions were observed beyond the three main nodules.
Histopathological examination confirmed the diagnosis of multifocal localized TGCT (giant cell tumor of tendon sheath). Low-power views showed a well-defined lobulated tumor with a collagenous stroma. Higher-power sections revealed a characteristic triad of cell populations: mononuclear synovial-type cells, multinucleated giant cells, and hemosiderin-laden macrophages . The mononuclear cells were polygonal to round, with pale eosinophilic cytoplasm and bland oval nuclei, forming sheets in the lesion. Scattered osteoclast-like multinucleated giant cells were present throughout the stroma. Abundant hemosiderin pigment was observed within the cytoplasm of many cells and in the interstitium, consistent with prior microhemorrhage.
Mitotic figures were infrequent, and no atypical mitoses were seen. There was no evidence of necrosis or malignant features. Immunohistochemistry, performed to confirm the histiocytic nature of the lesion, showed the mononuclear cells to be diffusely positive for CD68 (a marker of macrophage lineage) and negative for cytokeratins, supporting a synovial origin. The proliferative index (Ki-67) was low (<5%), in line with a benign lesion. Histology did not reveal any features of diffuse-type TGCT/PVNS (which typically shows more villous architecture and diffuse synovial involvement).
Postoperatively, the patient recovered uneventfully. Wrist motion exercises were started two weeks after surgery. At 6-month follow-up, she had near-full range of motion in the wrist with only mild stiffness and no evidence of recurrence on clinical exam. The surgical wounds healed well, and there were no neurovascular deficits.
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Discussion
Radiologic-Pathologic Correlation
GCT-TS has several distinctive imaging characteristics that reflect its underlying pathology. On MRI, localized GCT-TS typically appears as a well-defined lobular mass that is isointense to skeletal muscle on T1-weighted images and low to heterogeneous on T2-weighted images . This MRI hypointensity is a hallmark feature resulting from the lesion’s content of fibrous tissue and hemosiderin. In our case, all lesions showed uniformly low signal on both T1 and T2 sequences with minor internal heterogeneity. Pathologically, the abundance of hemosiderin pigment within the tumor (from prior hemorrhage) accounts for the low signal (so-called “blooming”) on MRI, especially on gradient echo or fat-suppressed sequences . This radiologic appearance can help differentiate GCT-TS from other wrist masses: for example, ganglion cysts or lipomas typically appear hyperintense on T2 (due to fluid or fat content), and vascular tumors exhibit flow voids or high T2 signal. The presence of dark, solid-appearing nodules on all MRI sequences strongly favored a hemosiderin-rich lesion in this patient . Additionally, the lesions in our case showed mild post-contrast enhancement, consistent with a fibrous tumor that has moderate vascularity. This correlates with histology, where GCT-TS contains numerous capillaries and synovial cells but also fibrous stroma limiting diffuse enhancement.
Another important imaging clue was the anatomic distribution and effect on adjacent structures. The multifocal nodules were located along tendon sheaths (flexor and extensor compartments) and caused displacement of tendons and vessels without invading them. This behavior is typical of localized GCT-TS, which often wraps around tendons in a constrictive manner . The absence of bone erosion in our case also supports the benign nature; while pressure erosion of bone can be seen in up to 5% of GCT-TS cases on radiographs , overt bony destruction is uncommon and its absence helps distinguish GCT-TS from aggressive tumors like synovial sarcoma or from diffuse TGCT involving joints. In summary, the MRI findings in this case – lobulated, low-signal masses adjacent to tendons with minimal joint involvement – were highly suggestive of tenosynovial giant cell tumor and this was confirmed on histopathology.
Clinical Differential Diagnosis
Multifocal nodular lesions around the wrist require careful differentiation from other synovial proliferative disorders or tumor mimics. Pigmented villonodular synovitis (PVNS), also known as diffuse-type TGCT, is a key consideration. PVNS typically presents with more diffuse synovial involvement within a joint (often the knee or ankle) rather than discrete masses, but in rare cases of diffuse TGCT of the wrist, one might see extensive synovial thickening and nodules throughout the wrist joint and tendon sheaths. Imaging can overlap since PVNS also demonstrates low T1/T2 signal from hemosiderin.
However, PVNS tends to involve an entire joint compartment (e.g., radiocarpal joint) with ill-defined proliferation, whereas localized GCT-TS produces encapsulated nodules . Our patient’s lesions were well-circumscribed and separable, favoring multifocal localized TGCT over diffuse PVNS. Other considerations included rheumatoid arthritis nodules or amyloid deposition in tendon sheaths, but the patient had no systemic disease signs, and those conditions have distinct clinical contexts. Synovial sarcoma is a malignant tumor that can occur near joints and tendons; it can sometimes present as multiple nodules if metastases or skip lesions occur. However, synovial sarcoma usually shows intermediate to high signal on T2 (not uniformly low), often contains calcifications, and occurs in younger patients; biopsy in our case clearly showed a benign process. Myxoid cysts (mucous cysts) on extensor tendons and fibroma of tendon sheath can also form nodules, but myxoid cysts have cystic fluid (bright on T2) and fibroma of tendon sheath, while solid, usually lacks the hemosiderin deposits of GCT-TS. In practice, the combination of clinical and imaging findings in this case (multiple solid masses with characteristic MRI signal) made GCT-TS the leading diagnosis before surgery. A definitive diagnosis, however, relied on histological examination, as biopsy or excision is necessary to distinguish these entities. In ambiguous cases, a preoperative core needle biopsy can be considered, but for resectable wrist masses like these, many surgeons proceed directly to excision both for diagnosis and therapy .
Pathogenesis and Multifocality
The pathogenesis of GCT-TS is not fully understood, and it has historically been debated whether it represents a reactive inflammatory process or a benign neoplasm. Modern evidence favors a neoplastic origin driven by an overexpression of colony-stimulating factor 1 (CSF-1) in tumor cells, leading to the recruitment of macrophages and giant cells . Clonal chromosomal abnormalities, such as trisomy 7 and translocations involving 1p13, have been identified in these tumors . In our patient, multiple separate lesions were present in the same wrist, raising the question of multifocal origin. Multifocal GCT-TS can occur in two scenarios: (1) the diffuse-type TGCT/PVNS, where nodules are part of a continuous synovial process (not truly independent lesions), or (2) true multifocal localized-type lesions, as seen here, where separate nodules arise in distinct locations without a contiguous synovial spread . The latter scenario is extremely uncommon. Possible mechanisms include synchronous neoplastic transformation at different sites in response to an unknown stimulus, or metaplastic synovial changes leading to multiple growth centers. Repetitive trauma or mechanical irritation has been postulated as a triggering factor in some cases, especially in the hand and wrist which undergo frequent motion . Our patient’s occupation (she was a tailor, involving repetitive hand movements) might conceivably have contributed to synovial hyperplasia, though this is speculative.
A review of the literature underscores the rarity of multifocal GCT-TS in the wrist. In a 20-year institutional series by Montero et al., only 12 cases of multifocal wrist GCT-TS were identified . Similarly, other reports have documented only isolated instances of multiple lesions in the hand. For example, Phalen et al. described a few patients with two separate nodules in the hand , and Reilly et al. reported three cases of multifocal hand involvement in a large series . In a series of 207 GCT-TS cases of the hand and wrist, only one patient (0.5%) had two tumors in separate locations . These data confirm that while GCT-TS is relatively common as a single lesion in the finger or hand, the occurrence of multiple independent lesions in the same region is exceptionally unusual . Our case appears to represent one of the rare documented instances of true multifocal localized TGCT in the wrist.
This distinction is important, as multifocal localized GCT-TS needs to be differentiated from diffuse TGCT (PVNS) which has a different clinical course and treatment approach.
Management Challenges and Recurrence Risk
The mainstay of treatment for localized GCT-TS is surgical excision. Complete excision with clear margins offers the best chance of cure. However, surgery can be challenging, particularly in a multifocal case involving critical structures. In our patient, the volar tumors were intimately associated with the radial artery and median nerve, requiring meticulous dissection to avoid injury. Likewise, the dorsal lesion surrounded the extensor tendons. Achieving complete resection without sacrificing important tendons or neurovascular bundles required fine surgical technique. Intraoperatively, it was confirmed that each nodule had a thin pseudocapsule and did not infiltrate adjacent tendons, which facilitated removal. If a lesion had invaded a tendon (as is reported in some cases ), partial tendon resection or grafting might be necessary. In this case, no tendon resection was required, and all structures were preserved.
Recurrence is a well-recognized concern with GCT-TS. Reported recurrence rates vary widely in the literature, largely depending on whether lesions are localized or diffuse and on the completeness of excision. For truly localized, well-circumscribed GCT-TS in the hand, recurrence rates are often cited in the range of 5% to 15% . Al-Qattan’s classification differentiates Type I lesions (single nodule with a capsule) from Type II (multilobulated or diffuse lesions without a single capsule), finding that Type II lesions have significantly higher recurrence . In one series, no Type I tumors recurred, whereas about 38% of Type II did . In general, incompletely excised or diffuse-type tumors have recurrence rates that can reach 20–50% . Our patient’s tumors would be considered Type I (localized nodules each surrounded by a capsule), and we achieved margin-negative resection, which should confer a low risk of recurrence. Indeed, at 6 months post-op she remains disease-free; however, longer surveillance is needed as recurrences can manifest after a year or more. We plan to follow her with periodic clinical exams and an MRI at 1-year post-surgery to ensure no regrowth.
For recurrent or difficult-to-excise GCT-TS, adjuvant treatments have been explored. One option is external beam radiotherapy to the affected area after surgery. While radiotherapy is not routinely used for localized GCT-TS due to the benign nature of the disease, it has shown utility in controlling diffuse or infiltrative disease and in cases with multiple recurrences . Coroneos et al. reported that none of 10 patients with infiltrative GCT-TS who received postoperative radiation developed recurrence at 3-year follow-up . In cases of diffuse TGCT (PVNS) of large joints, low-dose radiotherapy or yttrium-90 radiosynovectomy has been used to reduce recurrence, though concerns about long-term side effects remain. In the wrist, delivering radiation must be balanced against potential stiffness or radiation-induced tissue changes, but modern protocols (e.g., 35 Gy in fractions) have been well tolerated in the hand . We considered radiotherapy for our patient if residual disease was found; since resection was complete, it was not indicated. Another emerging therapy is targeted molecular treatment. Pexidartinib, a CSF-1R inhibitor, was approved by the FDA in 2019 as the first systemic treatment for TGCT that is not amenable to surgery . It has shown significant tumor reduction in diffuse TGCT, though it is typically reserved for cases where surgery would be morbid or ineffective (due to the risk of liver toxicity and other side effects of the drug). For a localized multifocal case like ours, pexidartinib was not indicated, but it represents a promising option for unresectable or refractory TGCT in the future.
In summary, complete surgical excision remains the gold standard for localized GCT-TS, even in multifocal scenarios. Ensuring all nodules are removed is critical to minimizing recurrence. Adjuvant radiotherapy can be considered in select aggressive cases or if any lesion cannot be safely resected without residual tumor. The advent of targeted therapies adds to the armamentarium for diffuse or inoperable cases, although such treatments would rarely be needed for localized hand/wrist tumors that are surgically accessible. Our case highlights that with careful preoperative imaging to map all lesions, a strategic surgical approach, and awareness of possible multifocal disease, excellent outcomes can be achieved in this rare presentation of wrist GCT-TS.
Literature Review: Multifocal GCT-TS of the Wrist
To contextualize the rarity of our case, we performed a literature review of multifocal giant cell tumor of tendon sheath in the wrist and hand. The vast majority of GCT-TS cases are solitary; multiple lesions in the same hand/wrist are extremely uncommon. Early reports by Ushijima et al. and Phalen et al. in the 1970s–1980s documented only a handful of patients with more than one GCT-TS lesion . More recently, Montero et al. (2018) presented a series of multifocal GCT-TS, noting 12 cases involving the wrist over two decades. In those cases, patients often had lesions in both volar and dorsal compartments, similar to our patient, and MRI was invaluable in identifying all foci preoperatively . Zhao et al. (2019) reported a case of GCT-TS in the dorsal wrist with tendon involvement, but that was a solitary lesion with tendon damage , highlighting that even single lesions can be aggressive. We found only a few case reports specifically describing synchronous multifocal GCT-TS in the hand or wrist. Altaykan et al. (2009) reported a case with two separate nodules on the flexor tendon of a single finger . Park (2015) described two masses on the flexor pollicis longus of the thumb, and Hitora et al. (2004) documented two tumors in a finger (at metacarpophalangeal and interphalangeal joints) . In all these instances, the lesions were managed surgically and had outcomes similar to solitary tumors.
Comparing outcomes, patients with multifocal GCT-TS do not necessarily fare worse than those with solitary lesions, provided all disease is removed. However, the literature suggests a slightly higher tendency for recurrence if any lesion is missed or if the disease represents an underlying diffuse process. In our review, we did not find unique histological differences in multifocal cases; they showed the same benign histopathology. Multifocal cases often required a more extensive surgical exposure or multiple incisions to address all tumor sites. Notably, no cases of malignant transformation of multifocal GCT-TS have been reported – malignant tenosynovial giant cell tumor is exceptionally rare on its own and typically arises de novo, not from benign lesions turning cancerous .
In summary, literature confirms that our case of true multifocal GCT-TS in the wrist represents a rare clinical scenario. Including our patient, only a limited number of such cases have been published. The successful management in reported cases, as in ours, hinges on thorough imaging to detect all lesions and complete surgical excision. Our case contributes to this body of literature by demonstrating another occurrence in the wrist and reinforcing that multifocal localized GCT-TS, while rare, is a distinct entity that can be managed successfully with standard treatment.
Conclusion
Multifocal giant cell tumor of the tendon sheath in the wrist is a rare entity that underscores the importance of a meticulous radiologic-pathologic approach to diagnosis. This case illustrates how high-resolution MRI, with attention to characteristic low-signal features and lesion distribution, can accurately suggest the diagnosis and map the extent of disease for surgical planning. Histopathology remains the gold standard for confirmation, revealing the benign yet proliferative nature of these tumors. For the practicing surgeon or radiologist, it is crucial to distinguish multifocal GCT-TS from its mimics, such as diffuse PVNS or other soft tissue tumors, as management and prognosis differ. Complete surgical excision of all nodules is curative in the majority of cases and was successfully achieved in our patient, resulting in restoration of function and no signs of recurrence to date. Given the known recurrence rates, diligent follow-up is recommended. This case adds to the limited literature on multifocal GCT-TS of the hand/wrist, reinforcing that although uncommon, multiple localized tenosynovial tumors can occur and should be recognized.
Early diagnosis and intervention can prevent tendon or joint damage and lead to excellent outcomes.
In the broader perspective, our report highlights the collaborative role of radiology and pathology in diagnosing soft tissue tumors. The radiology-pathology correlation in GCT-TS is particularly striking: what is seen on MRI directly reflects the tumor’s composition. Recognizing this correlation can increase diagnostic confidence and influence management strategies (for instance, prompting a surgeon to look for additional nodules if multifocal disease is suspected). As advanced systemic therapies emerge for TGCT, cases like this also remind us that surgery remains highly effective for localized disease. Future research or case compilations may further elucidate why multifocal presentations occur and whether any adjuvant measures could reduce the risk of recurrence in such cases.
