Tumors resembling tenosynovial giant cell tumor (TGCT) but additionally forming chondroid matrix (C-TGCT) are rare and most often involve the temporomandibular joint (TMJ). We studied 21 tumors consisting of synoviocytes (large, eosinophilic mononuclear cells containing hemosiderin) and chondroid matrix to better understand these unusual neoplasms. The tumors occurred in 10 males and 11 females, ranging from 31-80 years (median, 50 years) and involved the temporomandibular joint region (16), extremities (4), and spine (1). As in conventional TGCT, all were composed of synoviocytes, small histiocytes, foamy macrophages, siderophages and osteoclast-like giant cells in variably hyalinized background. Expansile nodules of large, moderately atypical synoviocytes were present, in addition to \"chondroblastoma-like\", \"chondroma-like\", or \"phosphaturic mesenchymal tumor-like\" calcified matrix. The synoviocytes expressed clusterin (17/19) and less often desmin (3/15). The tumors were frequently CSF1-positive by CISH (8/13) but at best weakly positive for CSF1 by IHC (0/3). Background small histiocytes were CD163-positive (12/12). All were FGF23-negative (0/10). Cells within lacunae showed a synoviocytic phenotype (clusterin-positive; S100 protein and ERG-negative). RNA-seq was successful in 13 cases; fusions were present in 7 tumors, including FN1::TEK (5 cases), FN1::PRG4 (2 cases), MALAT1::FN1, PDGFRA::USP35 and TIMP3::ZCCHC7 (1 case each). Three tumors contained more than one fusion (FN1::PRG4 with TIMP3::ZCCHC7, FN1::TEK with FN1::PRG4, and FN1::TEK with MALAT1::FN1). Clinical follow up (17 patients; median follow up duration 38 months; range 4-173 months) showed 13 (76%) to be alive without evidence of disease and 4 (24%) to be alive with persistent/recurrent local disease. No metastases or deaths from disease were observed. We conclude that these unusual tumors represent a distinct category of synoviocytic neoplasia, which we term \"chondroid synoviocytic neoplasm\", rather than simply ordinary TGCT with cartilage. Despite potentially worrisome morphologic features, they appear to behave in at most a locally aggressive fashion.

BACKGROUND: Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive tumor of the joints, bursa, and tendon sheath that can cause considerable pain and substantial morbidity. Although surgery is the primary treatment for patients with TGCT, surgical resection is associated with high rates of recurrence, particularly for patients with diffuse TGCT. Pexidartinib, a colony-stimulating factor 1 receptor inhibitor, is approved by the US Food and Drug Administration for the treatment of adult patients with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery.
METHODS: A 32-year-old man presented with intra-articular diffuse TGCT with pain and received noncurative treatment for 5 years (2014-2019). In 2019, the patient was found to have extensive disease accompanied by pain and limited range of motion. The patient\'s case was presented to a sarcoma multidisciplinary tumor board, who determined that surgery would cause significant morbidity and macroscopic residual tumor. As a result of the extent of disease, young age, and otherwise good health, treatment with pexidartinib was started through a compassionate use program at 800 mg/day. After dose reductions to pexidartinib at 400 mg/day and then 200 mg/day as a result of creatine phosphokinase elevations, the patient achieved a complete response after 2 years of treatment; pain was reduced and mobility was restored. The patient reported no side effects related to pexidartinib treatment. Treatment was stopped in 2022 for future family planning. After pexidartinib therapy was interrupted, the patient\'s wife had a successful pregnancy and delivery; however, the disease showed a slow but constant clinical deterioration, with a reduction in the range of movement of the affected knee and an apparent increase in widespread TGCT nodules.
CONCLUSIONS: Our case is unique because it provides support for pexidartinib use as upfront therapy for TGCT, instead of surgery, in selected cases.

Tenosynovial giant cell tumor (TGCT) occurs in both diffuse and localized forms. While diffuse TGCT is an uncommon but well-described complication after total knee arthroplasty (TKA), localized TGCT has only once been previously described as a postoperative complication after TKA. We report on the diagnosis and management of a patient who developed postoperative localized TGCT after routine TKA and underwent uncomplicated removal. Postoperatively the patient noted a resolution of pain and mechanical symptoms. Early consideration of this rare occurrence after TKA can prevent significant pain and disability due to delayed diagnosis.

Tenosynovial giant cell tumors (TGCTs) are benign histo-fibrocystic tumors originating from the synovium of joints, bursae, or tendon sheaths. They are categorized into localized and diffuse types, each with distinct clinical presentations and management approaches. The diffuse form, which is rare, generally affects a single joint and is characterized by joint swelling, pain, functional limitation, and often hemarthrosis. While MRI is commonly used for diagnosis, we present a case highlighting ultrasound\'s significance in diagnosing and managing TGCTs, particularly for identifying vascular complications. A 59-year-old female with a 10-year history of recurrent swelling, pain, and functional limitation of the right knee was evaluated for persistent symptoms and unilateral right peripheral edema. Ultrasound revealed multiple hypoechoic, vascularized masses with both homogeneous and heterogeneous echostructures and a significant suprapatellar effusion. An ultrasound-guided biopsy confirmed the diagnosis of a recurrent diffuse TGCT complicated by vascular compression of the popliteal vein. The patient underwent mass resections, total synovectomy, and radiotherapy to reduce the risk of recurrence.  Ultrasound is cost-effective and highly beneficial for the diagnosis, treatment planning, and monitoring of diffuse TGCTs. Total synovectomy combined with radiotherapy or intra-articular yttrium-90 injection is the preferred treatment to prevent recurrence and complications.

BACKGROUND: Tenosynovial giant cell tumor (TGCT) is a monoarticular fibrohistiocytic benign or locally aggressive soft tissue tumor that originates from the synovium of joints, bursae, and tendon sheaths. It has an inflammatory neoplastic nature, with a clinical presentation ranging from pain, swelling, stiffness, and limited range of movement to joint instability and blockage. Its uncommon incidence leads to a poorly understood pathogenesis. Localized forms of TGCT (LTGCT) can cause significant morbidity, interfere with daily patient activities, and decrease the patient\'s quality of life in challenging cases. This study aimed to investigate the immunohistochemical expression of PPARγ (peroxisome proliferator-activated receptor gamma) and P53 in LTGCT to understand the disease better and offer potential therapeutic targets.
METHODS: The study is cross-sectional, in which 27 LTGCT cases were collected from the Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt. Solitary and multiple LTGCT cases retrieved between January 2018 and December 2022 were included, and immunohistochemically stained with anti-PPARγ and P53 antibodies. The TGCT samples were excluded if they were insufficient for sectioning, processing, and interpretation, over-fixed, had process artifacts, or were of the diffuse TGCT type. Scoring of stain expression was performed by ImageJ (National Institutes of Health, Bethesda, MD) analysis using the threshold method and was expressed in percent area/high power field. Clinicopathological correlations were analyzed.
RESULTS: All the 27 collected LTGCT cases were located in the small joints of patients\' hands. Cases with solitary LGTCTs constituted 55.6% (n = 15), while 44.4% (n = 12) had multiple LTGCTs related to one affected site/case (e.g., multiple tumors in one finger). PPARγ was expressed in the cytoplasm of mononuclear and multinucleated tumor cells and foamy histiocytes, while P53 expression was mainly in mononuclear cells\' nuclei. PPARγ significantly correlated with P53 expression (r = 0.9 and P = 0.000). PPARγ (r = 0.4 and P = 0.02) and P53 (r = 0.5 and P = 0.01) were positively correlated with tumor size. Only P53 expression was positively correlated with tumor multiplicity (r = 0.4 and P = 0.03). Using the receiver operating characteristic curve test, the P53 cutoff score detecting the multiplicity of TGCTs was ≥20.5%, with a 75% sensitivity and 80% specificity.
CONCLUSIONS: PPARγ and P53 have a significant role in LTGCT growth, while P53 plays a role in tumor multiplicity. They can be possible targets in LTGCTs unfit for excision.

Giant cell tumor of soft tissue (GCTST) is a locally aggressive mesenchymal neoplasm of intermediate malignancy that predominantly occurs in the superficial soft tissue of the extremities. It is histologically similar to a giant cell tumor of bone (GCTB) and shows a mixture of round to oval mononuclear cells and osteoclast-like multinucleated giant cells. Currently, immunohistochemistry plays a very limited role in the diagnosis of GCTST. Primary or secondary malignant GCTST has recently been described and tumors exhibiting high-grade histological features demonstrate higher rates of distant metastasis. GCTST lacks the H3-3A gene mutations that are identified in the vast majority of GCTBs, suggesting a different pathogenesis. Surgery is the standard treatment for localized GCTST. Incomplete surgical resection is usually followed by local recurrence. Radiation therapy may be considered when the close proximity of critical structures prevents microscopically negative surgical margins. The systemic treatment options for advanced or metastatic disease are very limited. This review provides an updated overview of the clinicoradiological features, pathogenesis, histopathology, and treatment for GCTST. In addition, we will discuss the differential diagnosis of this peculiar neoplasm.

Diffuse tenosynovial giant cell tumor (D-TGCT), previously known as pigmented villonodular synovitis (PVNS), is a benign, aggressive, and distracting proliferative synovial lesion. D-TGCT is commonly seen in large joints such as the knee and hip. We present the case of a 57-year-old female who initially presented with swelling on the left midfoot that increased over four years. Clinically, a ganglion was suspected on the left midfoot and an MRI showed a heterogeneous lobulated soft tissue mass on the superior aspect of the tarsal midfoot measuring 5.8 x 2.4 x 4.2 cm. The mass causing remodeling and bony erosion was more appreciated at the medial aspect of the talus bone and extended to the sinus tarsi and talocalcaneal joint space. Surgical excision of the mass was performed, and pathology reports found lobulated soft tissue lesions composed of mononuclear cells, multinucleated giant cells, sheets of foamy macrophages, inflammatory cells, and hemosiderin-laden macrophages. This case represents D-TGCT without atypia or malignancy based on the findings.

UNASSIGNED: Giant cell tumor of the tendon sheath (GCTTS), also termed Tenosynovial giant cell tumor (TGCT), is a locally aggressive tumor which originates from tendon sheaths or bursas. Around 3-5% of these tumors arise from foot and ankle. Localized lesions in this area are often manifested as firm masses or nodules with slow but continuous progression through months and years. Pain associated with weight-bearing, as well as limitations in joint motions, may be reported, depending on tumor\'s location. Surgery is the treatment of choice for the definitive removal of GCTTSs with the aim to eradicate the neoplasm and restore the lower limb\'s functionality.
UNASSIGNED: Thirteen cases suffering from GCTTS of the foot and ankle underwent surgical resection at our institution between 2017 and 2022. For each case we recorded pre-operative and post-operative symptoms, as well as their pre-operative and post-operative functional status according to both MSTS and AOFAS scores. Eventual complications and local recurrences were reported.
UNASSIGNED: Each patient experienced an at least mild pain before surgical treatment. The mean pre-operative MSTS and AOFAS scores were 22.8 and 70.7, respectively. The mean tumor size was 17.7 mm. Each patient received a resection with wide margins. Two cases (15.4%) had local recurrences. None had major complications at their latest follow-up. After the surgery, the mean post-operative MSTS and AOFAS scores increased to 28.3 and 92.2, respectively.
UNASSIGNED: Resection with wide margins for foot and ankle GCTTS is effective in restoring the patients\' lower limb functionality and is associated with reasonable local recurrence rates.
UNASSIGNED: Gigantiniᶙ ląsteliᶙ sausgysliᶙ apvalkalo navikas (trumpinys GCTTS), kuris taip pat vadinamas tenosinoviniu gigantiniᶙ ląsteliᶙ naviku (trumpinys TGCT), yra lokalus agresyvus navikas, visᶙ pirma pasireiškiantis sausgyslės apvalkale arba bursoje. Maždaug 3–5 % šiᶙ navikᶙ atsiranda pėdoje arba kulkšnyje. Lokalūs šios srities pažeidimai dažnai pasireiškia susidarančia kieta mase arba gumbeliais, kuriᶙ lėtas, tačiau nuolatinis progresavimas gali trukti mėnesius ar net metus. Pacientᶙ galimi nusiskundimai – skausmas, atsiradęs nešant svorį, ir sąnariᶙ judesiᶙ ribotumas; tai priklauso nuo naviko vietos. GCTTS užtikrintai pašalinti būtina operacija. Tokiu būdu sunaikinama neoplazma ir atkuriamas apatinės galūnės funkcionalumas.
UNASSIGNED: Mūsᶙ institucijoje nuo 2017 iki 2022 metᶙ buvo nustatyta 13 GCTTS atvejᶙ pėdoje ar kulkšnyje, kai prireikė chirurginės rezekcijos. Kiekvienu atveju registravome priešoperacinius ir pooperacinius simptomus. Taip pat fiksavome priešoperacinį ir pooperacinį funkcinį statusą pagal tiek MSTS, tiek ir AOFAS skaliᶙ vertinimus. Pateikėme ataskaitą apie vėlesnes komplikacijas ir vietinį išplitimą.
UNASSIGNED: Prieš chirurginį gydymą kiekvienas pacientas patyrė bent jau nestiprᶙ skausmą. Vidutiniai priešoperaciniai MSTS ir AOFAS skaliᶙ vertinimai buvo atitinkamai 22,8 ir 70,7. Vidutinis naviko dydis – 17,7 mm. Kiekvienam pacientui buvo atlikta rezekcija su didelėmis pakraščio zonomis. Dviem atvejais (15,4 %) navikai vėl susiformavo. Nė vienam pacientui vėlesnio stebėjimo laikotarpiu nepasireiškė jokiᶙ sudėtingesniᶙ komplikacijᶙ. Atlikus operaciją, vidutiniai pooperaciniai MSTS ir AOFAS skaliᶙ balai išaugo atitinkamai iki 28,3 ir 92,2.
UNASSIGNED: Rezekcija su didelėmis pakraščio zonomis pėdos ar kulkšnies GCTTS atveju efektyviai padeda atkurti pacientᶙ apatiniᶙ galūniᶙ funkcionalumą ir yra susijusi su priimtinai nežymiu naviko išplitimo procentu.

Aim: Real-world treatment patterns in tenosynovial giant cell tumor (TGCT) patients remain unknown. Pexidartinib is the only US FDA-approved treatment for TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Objective: To characterize drug utilization and treatment patterns in TGCT patients. Methods: In a retrospective observational study using IQVIA\'s linked prescription and medical claims databases (2018-2021), TGCT patients were stratified by their earliest systemic therapy claim (pexidartinib [N = 82] or non-FDA-approved systemic therapy [N = 263]). Results: TGCT patients treated with pexidartinib versus non-FDA-approved systemic therapies were predominantly female (61 vs 50.6%) and their median age was 47 and 54 years, respectively. Pexidartinib-treated patients had the highest 12-month probability of remaining on treatment (54%); 34.1% of pexidartinib users had dose reduction after their first claim. Conclusion: This study provides new insights into the unmet need, utilization and treatment patterns of systemic therapies for the treatment of TGCT patients.
Treatment patterns in patients with tenosynovial giant cell tumors in the USAThis database study is the first investigation of how drugs are used to treat patients with tenosynovial giant cell tumor (TGCT) in the real world. We researched adult TGCT patients from IQVIA\'s prescription and medical claims databases who started treatment with pexidartinib (N = 82) or other non-US FDA-approved systemic therapies (N = 263). The patients included in this analysis were mostly women (61.0 and 50.6%) and their median age was 47 and 54 years for pexidartinib and other non-FDA-approved systemic therapies, respectively. The patients treated with pexidartinib were most likely to remain on treatment (54.0%) at the end of the first year. Most patients (79.3%) started pexidartinib treatment at a total daily dose of 800 mg/day, as per the product label. Only 34.1% of patients had reduced medication dose during follow-up. Of note, this study found that TGCT patients were treated with other systemic therapies which remain unproven to be safe and effective in medical studies of TGCT. Given the unmet need, and with pexidartinib being the only approved systemic treatment in USA, there is an opportunity for the larger population of adult TGCT patients to benefit from its use. Further research is needed to identify barriers for access to pexidartinib and treatment of TGCT patients.

We present a rare case of histiocytic sarcoma (HS) occurring in the foot of a 12-year-old male, initially misdiagnosed as localized tenosynovial giant cell tumor (TSGCT). HS is an exceptionally uncommon hematologic malignant neoplasm, with its occurrence in children and extranodal sites being even rarer. To our knowledge, this is the first reported case of extranodal HS in the foot, emphasizing comprehensive MRI findings. Initially, the patient was diagnosed with TSGCT based on histological results following surgical resection. However, after recurrence and subsequent surgical resection, histological and immunochemical analyses led to a revised diagnosis of HS. This report focuses on the MRI findings of HS, highlighting the distinctions from localized TSGCT. While both conditions share histopathological similarities, immunohistochemical tests are crucial for accurate diagnosis. The report underscores the importance of differentiating HS for appropriate treatment.