Xanthogranulomatous Epithelial Tumors and Keratin-Positive Giant Cell Rich Tumors of Soft Tissue and Bone: Two Sides of the Same Coin.

Xanthogranulomatous epithelial tumor is a recently described soft tissue tumor characterized by subcutaneous location, partial encapsulation, a xanthogranulomatous inflammatory cell infiltrate, and keratin-positive mononuclear cells. It shares some morphologic features with keratin-positive, giant cell-rich soft tissue tumors. Both have recently been shown to harbor HMGA2::NCOR2 fusions. The relationship between these tumors and their differential diagnosis with other osteoclast-containing soft tissue tumors is discussed.

Pigmented villonodular synovitis/giant cell tumor in the knee.

PURPOSE OF REVIEW: Pigmented villonodular synovitis (PVNS) is a rare diagnosis in pediatric patients and commonly presents with symptoms of swelling and pain. Early diagnosis is important to prevent secondary degeneration into the subchondral bone. This review will analyze the etiology, clinical signs/symptoms, diagnosis, treatment, and recent literature on PVNS in the pediatric population. RECENT FINDINGS: Many theories of PVNS etiology have been described in the literature; however, an inflammatory response has been most widely accepted. PVNS can occur in any joint, but most commonly in the knee. The most common treatment for PVNS is synovectomy, and long-term follow-up is necessary to detect disease persistence or recurrence. SUMMARY: Although uncommon, PVNS does occur in the pediatric population and this diagnosis should be included in the differential of atraumatic joint swelling and pain.

CSF1 expression in xanthogranulomatous epithelial tumor/keratin-positive giant cell-rich tumor.

"Xanthogranulomatous epithelial tumor" (XGET) and "keratin-positive giant cell-rich soft tissue tumor" (KPGCT), two recently described mesenchymal neoplasms, likely represent different aspects of a single entity. Both tumors are composed of only a small minority of tumor cells surrounded by large numbers of non-neoplastic inflammatory cells and histiocytes, suggesting production of a paracrine factor with resulting "landscape effect," as seen in tenosynovial giant cell tumor. Recent evidence suggests that the paracrine factor in XGET/KPGCT may be CSF1, as in tenosynovial giant cell tumor. We hypothesized that CSF1 is overexpressed in XGET/KPGCT. To test our hypothesis, we performed quantitative real time PCR (qPCR) for CSF1 expression and CSF1 RNAscope chromogenic in situ hybridization (CISH) on 6 cases of XGET/KPGCT. All cases were positive with CSF1 CISH and showed increased expression of CSF1 by qPCR. Our findings provide additional evidence that the CSF1/CSF1R pathway is involved in the pathogenesis of XGET/KPGCT. These findings suggest a possible role for CSF1R inhibition in the treatment of unresectable or metastatic XGET/KPGCT.

Sonographic features of diffuse giant cell tumor of the tendon sheath in the shoulder: A case report.

A middle-aged woman presented to our hospital with a chief complaint of a mass on the left shoulder for 1 year. The initial lump was small with no pain or tenderness, and the patient had not sought medical attention for numbness in the left shoulder. Clinical examination showed a mass on the left shoulder measuring 11 × 8 × 3 cm approximately with no apparent skin damage or ecchymosis. No limitations in left shoulder joint movements were observed, and the patient exhibited normal movement of the left elbow joint, wrist joint, and metacarpophalangeal joint. Moreover, the left radial artery was palpable.

Partial sternectomy with reconstruction of a giant cell tumor of the sternum, a case report, Saudi, Arabia.

BACKGROUND: Giant cell tumor (GCT) is a relatively common and locally aggressive benign bone tumor that rarely affects the sternum. CASE PRESENTATION: We report a case of giant cell tumor of the sternum in a 28-year-old Saudi with painful swelling at the lower part of the sternum. Subtotal sternectomy and reconstruction with a neosternum using two layers of proline mesh, a methyl methacrylate prosthesis, and bilateral pectoralis muscle advancement flaps were performed. CONCLUSIONS: Giant cell tumor of the sternum is a rare diagnosis. Surgical resection with negative margins is the ideal management. To avoid defects or instability of the chest wall, reconstruction of the chest wall with neosternum should be considered.

Bone SPECT/CT in Advanced Diffuse Tenosynovial Giant Cell Tumor of the Wrist.

ABSTRACT: Tenosynovial giant cell tumor, previously known as pigmented villonodular synovitis, is a benign low-grade fibrohistiocytic proliferation with hemosiderin deposits in synovial joints. Mostly affecting the knee, it can also manifest in other synovial joints, infrequently also in the wrist. Tenosynovial giant cell tumor typically causes intense radionuclide uptake in all phases in planar bone scintigraphy, making a differentiation from other bone tumors or osteomyelitis difficult, especially in cases associated with extensive bone destruction. We present a case of an unusually advanced and extended tenosynovial giant cell tumor of the wrist in bone scintigraphy, SPECT/CT, radiograph, and MRI.

A Mass on the Sole Revealing a Giant-Cell Tumor of the Tendon Sheath.

A 61-year-old woman presented with a 3-year history of painless soft-tissue mass on the right sole. The patient reported gradual growth, with a rapid increase in size over the past few months, leading to difficulty in walking. She had no history of past trauma. Examination revealed a 4-cm ovoid mass located over the ball of the foot. It was firm in consistency, with well-defined margins, a smooth surface, and an overlying normal skin (Figure 1). An ultrasound image revealed an eccentric, hypoechoic, nonvascular subcutaneous lobular mass. A magnetic resonance imaging (MRI) of the foot revealed a well-defined mass arising from the flexor tendon sheath of the right foot. The lesion was heterogeneously hyperin-tense on T1- and T2-weighted images with an avid contrast enhancement. All of the surrounding soft tissues indicated normal signal intensity patterns. There was no associated bony destruction. Histopathologic examination after complete excision of the mass established a well-circumscribed lesion composed of osteoclast-like giant cells and mononuclear cells in a hyalinized stroma, consistent with a giant cell tumor of the tendon sheath (GCT-TS) (Figure 2). There was no recurrence during a 6-month follow-up period (Figure 3).

Tenosynovial giant cell tumour of the finger: a case report.

Giant cell tumour most commonly occuring in epiphysis of the long bone, present and with pain, tenderness and swelling. It is a solitary lesion with restricted movement and tenderness over the lesion. The tendon sheath is where tenosynovial giant cell tumours typically develop. Because of its remarkably peculiar position, we present a case of giant cell tumour (GCT) tenosynovial of bone in the middle phalaynx in a 33-year-old female with complaints of swelling, pain in ring finger of left hand since 2 months which is rarely seen. After clinical, radiological, pathological investigations tenosynovial giant cell tumour was diagnosed. Following fine needle aspiration cytology, histopathology was utilized to confirm the tumour's diagnosis which was later treated as resection of excision of the tumour with allo/autograft reconstruction. Our case report showed no evidence of recurrence in 2 years of follow-up. Hence our case report proves that early and complete resection of the tumour shows evidence of regain of complete range of motion and decrease recurrence rate.

Cytomorphologic panorama of giant cell tumour of tendon sheath.

BACKGROUND: Giant Cell Tumour of Tendon Sheath (GCTTS) is a slow growing benign soft tissue tumour arising from synovium of tendon sheath or joint. These tumours occur more frequently in upper limbs, especially hands. In the present study, we aimed to evaluate the cytomorphological spectrum of GCTTS. METHODS: This retrospective study includes a total of 56 cases of GCTTS diagnosed over a period of 8 years. The clinical and radiological details of these cases were retrieved from the cytopathology records and detailed cytomorphological features were studied and analysed. Histopathological correlation was done in 16/56 cases, where follow-up was available. RESULTS: The mean age of patients at the time of presentation was 32 years and were predominantly females (68%). The most common site of GCTTS was fingers (76%), followed by foot, wrist and toes. The most consistent finding on cytology was stromal cells (100%) of polygonal, spindle and plasmacytoid morphology with interspersed multinucleated osteoclastic giant cells (100%), followed by binucleated stromal cells (75%), xanthoma cells (61%) and hemosiderin laden macrophages (52%). Presence of proteinaceous fluid background was also observed in 50% of the cases. CONCLUSION: GCTTS can be diagnosed with certainty on FNAC based on characteristic cytomorphological features in an appropriate clinical and radiological setting. FNAC plays a pivotal role in diagnosing GCTTS and differentiating it from other giant cell rich lesions, thus obviating the need of tissue biopsy for diagnosis, which in turn helps the clinician in timely and adequate management of the patient.

Multimodal management of tenosynovial giant cell tumors (TGCT) in the landscape of new druggable targets.

Tenosynovial giant cell tumor (TGCT) is a rare, benign, locally aggressive synovial based neoplastic process that can result in functional debilitation and end-stage arthrtitis. Although surgical resection is the primary treatment modality, novel systemic therapies are emerging as part of the multimodal armamentarium for patients with unresectable or complex disease burden. This review discusses the pathogenesis of TGCT, potential druggable targets and therapeutic approaches. It also evaluates the safety and efficacy of different systemic therapies.

Giant Cell Tumour of Tendon Sheath of Distal Phalanx of Thumb: A Case Report.

Giant cell tumour of tendon sheath is an uncommon benign soft tissue tumour. Histopathological examination plays a crucial role in the definitive diagnosis of giant cell tumour although pre-operative imaging supports its suspicion. We report a case of a giant cell tumour of the tendon sheath in a 26-year-old man as a painless, firm, localized, slow-growing benign soft tissue tumour of the thumb; managed by complete excision. The patient continues to do well at 7 months post-surgery with no complaints and no signs of recurrence. Giant cell tumour of the phalanges is a locally aggressive entity; therefore delayed or missed diagnosis of giant cell tumour especially of the thumb distal phalanx can be extremely debilitating. Hence, high degree of suspicion and early en bloc resection is the key to its management. Keywords: case reports; giant cell tumors; tendons; thumb.

Keratin-positive giant cell-rich tumors of soft tissue with HMGA2::NCOR2 fusions.

BACKGROUND: Giant cell tumor of soft tissue (GCT-ST) is a rare soft tissue neoplasm that is morphologically similar to but genetically distinct from giant cell tumor of bone. A novel keratin-positive GCT-ST (KPGCT-ST) harboring HMGA2::NCOR2 fusions was recently discovered. Fewer than 30 cases have been described; herein is reported an additional seven. METHODS: Cases diagnosed as GCT-ST were retrieved from institutional archives and consultation files. The histopathologic characteristics were assessed, and the electronic medical record was reviewed. RESULTS: Seven tumors were identified in six women and one man with a median age of 23 years. All patients underwent excision; no recurrences or metastases were noted during a median follow-up period of 7 months. Histopathologically, the tumors were characterized by a multinodular proliferation of keratin-positive mononuclear cells with evenly admixed osteoclast-like giant cells and absent neoplastic bone. A fibrous capsule with lymphoid cuffing was frequently seen. Foamy macrophages, inflammation, hemorrhage, and hemosiderin were variably present. The HMGA2::NCOR2 fusion was detected in all cases. CONCLUSIONS: Our findings support previously reported hypotheses that KPGCT-ST is a spectrum of the same entity as the recently described xanthogranulomatous epithelial tumor. Although follow-up data are limited, to date, KPGCT-ST appears to follow an indolent course.

Giant cell tumor of the patellar tendon sheath in childhood: case report.

The aim of this study was to report a rare case of a giant cell tumor of the patellar tendon sheath. This indicates the diagnostic procedures and treatment options for giant cell tumors of the patellar tendon. This study reported a case of a 13-year-old male patient with a giant cell tumor of the tendon sheath. In our case, open arthrotomy was performed with complete surgical excision of the lesion. Histopathological examination revealed a giant cell tumor. At the last follow-up, 2 years after surgery, no complications were reported. The giant cell tumor of the patellar tendon sheath is an uncommon benign tumor. It mimics common knee symptoms. A differential diagnosis is definitely a challenge. Available operation approaches have demonstrated similar results, which lead to symptom relief and a low recurrence rate.

Giant Cell Tumors With HMGA2::NCOR2 Fusion : Clinicopathologic, Molecular, and Epigenetic Study of a Distinct Entity.

Giant cell tumors (GCTs) with high mobility group AT-Hook 2 ( HMGA2 )::nuclear receptor corepressor 2 ( NCOR2 ) fusion are rare mesenchymal tumors of controversial nosology, which have been anecdotally reported to respond to CSFR1 inhibitors. Here, we performed a comprehensive study of 6 GCTs with HMGA2::NCOR2 fusion and explored their relationship with other giant cell-rich neoplasms. Tumors occurred in 4 females and 2 males ranging in age from 17 to 32 years old (median 24). Three lesions originated in subcutaneous soft tissue and 3 in bone. Tumor size ranged from 20 to 33 mm (median 27 mm). The lesions had a nodular/multinodular architecture and were composed of sheets of mononuclear "histiocytoid" cells with uniform nuclei intermingled with multinucleated giant cells. Mitotic activity was low and nuclear atypia and metaplastic bone were absent. Variable findings included necrosis, cystic degeneration, lymphocytic infiltrate (sometimes forming nodules), and xanthogranulomatous inflammation. On immunohistochemistry, all cases focally expressed pan-keratin and were negative with SATB2 and H3.3G34W. Whole RNA-sequencing was performed in all cases of GCT with HMGA2::NCOR2 fusion and a subset of giant cell-rich tumors (tenosynovial-GCT, n = 19 and "wild-type" GCT of soft tissue, n = 9). Hierarchical clustering of RNA-sequencing data showed that GCT with HMGA2::NCOR2 fusion formed a single cluster, independent of the other 2 entities. Methylome profiling showed similar results, but the distinction from "wild-type" GCT of soft tissue was less flagrant. Gene expression analysis showed similar levels of expression of the CSF1/CSFR1 axis between GCT with HMGA2::NCOR2 fusion and tenosynovial-GCT, supporting their potential sensitivity to CSFR1 inhibitors. Clinical follow-up was available for 5 patients (range: 10 to 64 mo; median 32 mo). Three patients (60%) experienced local recurrences, whereas none had distant metastases or died of disease. Overall, our study confirms and expands previous knowledge on GCT with HMGA2::NCOR2 fusion and supports its inclusion as an independent entity.

Rare Presentation of Giant Cell Tumors of the Tendon Sheath: Bilateral Involvement of Tendoachilles.

Giant cell tumor of tendon sheath arises from the synovium of tendon sheaths, joints, or bursa, mostly affects adults between 30 and 50 years of age, and is slightly more common in females. It corresponds to a localized form of pigmented villonodular synovitis (PVNS). Typically occur in the hand where they represent the second most common type of soft tissue tumors after synovial ganglions. Bilateral giant cell tumor of tendon sheath of tendoachilles is a rare presentation. We report the case of a 22-years-old female presenting with pain in both ankles without any history of trauma. On clinical examination, tenderness on both tendoachilles and local indurations were observed. Ultrasonography showed focal thickening of Achilles tendon bilaterally, and Doppler demonstrated increased flow in peritendinous area. MRI findings showed that most of the tumor had intermediate signal intensity and portions of the tumor had low signal intensity. Fine needle aspiration cytology confirmed the diagnosis of giant cell tumor of tendon sheath. Excision biopsy was done with no recurrence on subsequent follow-up.

Outcomes of Surgery for Benign Tumours in The Upper Extremity.

Benign tumours of the upper extremity are common in hand surgeons' practice. The most commonly diagnosed are giant-cell tumours of the tendon sheath and lipomas. THE OBJECTIVE: of this study was an investigation into the distribution of tumours in the upper limb, their symptomatology and outcomes of surgery, particularly regarding the rate of recurrence. MATERIAL AND METHODS: A total of 346 patients, 234 women (68%) and 112 men (32%), who had undergone surgery for tumours located in the upper extremity which were not ganglion cysts were enrolled into the study. The follow-up assessment was performed at a mean of 21 months (range 12-36) post-operatively. RESULTS: The most common tumour in this study was giant cell tumour of the tendon sheath - 96 cases (27.7%), followed by lipoma - 44 cases (12.7%). Most lesions - 231 (67%) were localized in the digits. A total of 79 (23%) recurrences were noted, the most common after surgery for rheumatoid nodules - 43.3% and the giant-cell tumours of the tendon sheath - 31.3%. The independent factors increasing risk of recurrence following the tumour's resection were: histological type of the lesion - the giant-cell tumour of the tendon sheath (p=0.0086) and the rheumatoid nodule (p=0.0027), as well as a combination of incomplete (non-radical) and not "en block" resection of tumours. A brief review of the literature referring to the presented material is offered.

Resection and reconstruction with and without neoadjuvant denosumab in campanacci grade III giant cell tumors of proximal humerus: a retrospective comparative study.

BACKGROUND: Giant cell tumors (GCT) of the proximal humerus are rarely reported case that requires complex surgeries due to involvement of the shoulder joint. Therefore, we report the first retrospective comparative study where the postoperative functional outcomes, recurrence rate and complications in patients who underwent arthrodesis of shoulder after resection of grade III GCT with and without neoadjuvant denosumab are compared. METHODS: A retrospective review of eight cases of grade III GCT of proximal humerus receiving resection and fibular strut graft and arthrodesis between January 2014 and December 2019 is performed. They were stratified into two groups: one group of four patients received once-weekly denosumab 120 mg for 4-weeks before resection and reconstruction, while the other group of four patients did not receive denosumab before surgery. Primary outcomes included the functional outcomes assessed by revised Musculoskeletal tumor society (MSTS) score and shoulder pain and disability index (SPDI) at 6-weeks and 12-months postoperatively while secondary outcomes included complications and recurrences. RESULTS: There was no significant difference in terms of SPDI at 6 weeks and 12 months, MSTS at 12 months, complications, recurrence among denosumab and non-denosumab groups. At 6-weeks follow-up, a significantly better pain score in SPDI and MSTS was acquired in the denosumab group. CONCLUSIONS: Resection and reconstruction with or without neoadjuvant denosumab for Grade III GCT of proximal humerus had similar functional outcomes and with no major differences in recurrence and complications. Hence, postoperative pain relief while long-term benefits were not discovered with the use of neoadjuvant denosumab.