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Xanthogranulomatous epithelial tumor (XGET)/Keratin-positive giant cell tumor (KP-GCT) represents a spectrum of recently described neoplasms characterized by a proliferation of distinctive mononuclear cells expressing keratin within a background of osteoclast-like giant cells, mixed inflammatory cells, and a variably prominent xanthogranulomatous component. Recent studies demonstrated a recurrent HMGA2::NCOR2 fusion in many cases. We herein describe a case of XGET/KP-GCT arising in the right femoral head of a 19-year-old male harboring a rare novel HMGA2::COL14A1 fusion., (© 2024 Wiley Periodicals LLC.)

Giant cell tumors originating in the larynx are extremely rare. This article presents a case of a recurrent postoperative giant cell tumor of the larynx（GCTL）. The patient, a 28-year-old male, underwent a total thyroidectomy in June 2022 due to a thyroid mass. The postoperative pathological diagnosis was giant cell tumor of soft tissues. The patient was readmitted in June 2023 due to the recurrence of the neck mass and underwent partial laryngectomy and partial hypopharyngectomy to completely remove the tumor. Based on postoperative pathology, immunohistochemistry（H3.3 G34W+）, and genetic testing, the neck mass was ultimately diagnosed as GCTL. The patient did not receive radiotherapy or chemotherapy, and at the 12-month postoperative follow-up, there was no evidence of tumor recurrence., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background: Different giant cell-rich tumors may occur in the jaws. Recently, a new condition known as keratin-positive giant-cell rich tumor harboring recurrent HMGA2::NCOR2 fusions has been described. Interestingly, the mononuclear cells of this tumor are immunoreactive with the AE1/AE3 keratin. Considering the similarities of central and peripheral giant cell granuloma of the jaws with the keratin-positive giant cell-rich tumor of the soft tissue and bone, we hypothesized whether the keratin-positive tumors could also occur in the maxillary bones., Methods and Results: An immunohistochemical investigation of AE1/AE3 in a cohort of 16 cases of peripheral and central giant cell granuloma of the jaws was carried out. None of the cases was keratin-positive., Conclusions: Although no immunopositivity for keratin was observed in the present giant cell granulomas cohort, we cannot completely exclude the possibility of keratin-positive giant cell-rich tumors occurring in the jaws. Therefore, oral pathologists should be aware about this condition and further studies using cohorts from different laboratories are necessary., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Xanthogranulomatous epithelial tumor (XGET) and HMGA2::NCOR2 fusion keratin-positive giant cell-rich tumor (KPGCT) are recently described morphologically overlapping rare neoplastic entities characterized by HMGA2::NCOR2 fusions, low-grade biological behavior, and a strong predilection for young females. To date, 47 cases have been reported with only four occurring in head and neck anatomic locations. In this study, we describe the clinicopathologic, immunohistochemical, and molecular findings of seven XGET/KPGCTs occurring in the head and neck region. The patients were six females and one male, aged 3.5-59 years old (median, 25 years). The tumors involved the ear, vocal cord, skull, neck soft tissue, and sinonasal cavity. Tumor sizes ranged from 1.5 to 6.7 cm. Histologically, the tumors were characterized by xanthogranulomatous histiocytes, osteoclast-like giant cells, and keratin-positive epithelioid cells. The XGET/KPGCTs involving the ear was remarkable for more cytologic atypia than previously described. Four cases had the HMGA2::NCOR2 fusion identified by NGS and three had HMGA2 gene locus alterations by FISH. Follow-up information was available for 3 of 7 patients (range 6-46 months). The patient with a vocal cord XGET/KPGCTs developed a local recurrence treated with excision. This study illustrates that XGET/KPGCTs involves the head and neck region as well, where it may be unexpected and hence under-recognized, and expands the anatomic locations of involvement to include unreported sites (ear, vocal cord, and sinonasal tract)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Abstract: Cutaneous sarcomatoid squamous cell carcinoma is well-described with histology resembling pleomorphic undifferentiated sarcoma featuring collagenous or myxoid stroma with or without elements of keratinizing squamous carcinoma. This report presents 2 cases of dedifferentiated squamous cell carcinoma (SCC) composed of sheets of malignant mononuclear cells with malignant osteoclast-like multinucleated giant cells, extravasated blood, and hemosiderin resembling cutaneous giant cell tumor (cGCT). In the first case, an exophytic facial mass of a 96-year-old woman removed by shave showing extensive cGCT-like tumor but with microscopic elements of SCC in situ and positivity for cytokeratin 5/6 in the malignant spindle cells and SCC. The second case involved a 32-year-old man with a pedunculated penile mass removed by shave biopsy, displaying malignant cytology resembling cGCT, focal staining for cytokeratin AE1/AE3 and p63, and CD68 highlighting the osteoclast-like giant cells. Molecular analysis revealed CDKN2A, TP53, and TERT. Upon reexcision, case 2 showed focally invasive keratinizing SCC associated with differentiated penile intraepithelial neoplasia and lichen sclerosus. Skin specimens with an exophytic mass histologically resembling cGCT but with malignant cytology should be meticulously evaluated for elements of SCC. Molecular analysis, detecting mutations like H3F3 or HMGA2-NCOR2 fusion, can aid in distinguishing cutaneous sarcomatoid squamous cell carcinoma from GCT bone or GCT soft tissue., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Giant cell tumour is a growth predominantly found in long bones of the body. Giant cell tumour has a rare occurrence in the head and neck. A case of a 31 year old male with no known comorbidities at the ENT Department, Shifa International Hospital, Islamabad presented with anterior neck swelling and hoarseness of voice. Patient was diagnosed as having Giant Cell Tumour of Larynx (GTCL) proven on FNA cytology and post-operative biopsy. GCTL is an uncommon entity with only 45 reported cases in the world.

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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

"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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (© 2023 Wiley Periodicals LLC.)

Spinal giant cell tumor (GCT) combined with secondary aneurysmal bone cyst (ABC) is a locally aggressive primary bone tumor. Total en bloc spondylectomy has never been reported to treat thoracic GCT combined with secondary ABC. We retrospectively reviewed two cases of spinal GCT combined with secondary ABC. A 41-year-old male patient was presented with back pain due to irregular expansive bone destruction involving the T6 vertebral body and intraspinal space-occupying lesion. Total en bloc spondylectomy of T6 vertebra was performed with good neurological status after the surgery. A 29-year-old female patient was presented with right scapular region pain due to irregular expansive bone destruction involving the T5 vertebral body and intraspinal space-occupying lesion. Total en bloc spondylectomy of T5 vertebra was performed with good neurological status after the surgery. Adjuvant radiation therapy was applied after the surgery without local recurrence at the 12-month or 24-month follow-up. Spinal GCT combined with secondary ABC appears to have a high local recurrence rate. Therefore, total en bloc spondylectomy should be applied to treat thoracic GCT combined with secondary ABC.

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., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2023 The Authors. Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.)

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., (© 2023. BioMed Central Ltd., part of Springer Nature.)

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 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., (© 2023 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

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., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

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., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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.

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., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.

Background: In this article on giant cell tumor of tendon sheath (GCTTS), we intend to summarize and analyze the clinical and pathological features of GCTTS hoping to improve clinical management and patient treatment., Methods: The study retrospectively reviewed 216 patients of GCTTS, registered at the Affiliated Hospital of Southwest Medical University from January 2010 to December 2020. These cases were diagnosed by surgical excision. The clinicopathological features and the prognosis were reviewed in the light of the current literature., Results: Of these 216 GCTTS patients, 72 were males (33.3%) and 144 females (66.7%), with a ratio male-to-female of 1:2. The patients' age ranged from 5 to 82, the average being 41.5 years at diagnosis. A total of 96 cases (44.4%) occurred in the hand region, followed by 35 cases (16.2%) in the knee, 32 cases (14.8%) in the foot, 25 cases (11.6%) in the ankle, 12 cases (5.6%) in the wrist, 12 cases (5.6%) in the leg, 2 cases (0.9%) in the head, 1 case (0.5%) in the forearm, and 1 case (0.5%) inside and outside the spinal channel. Histopathology mainly revealed large synovial-like monocytes, small monocytes, and osteoclast-like giant cells., Conclusion: Our results confirm that GCTTS predominantly occurs in the hands of young women. Complete surgical resection with long-term follow-up is the preferred management., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: To compare total en bloc spondylectomy with marginal margins against piecemeal spondylectomy with intralesional margins in the surgical treatment of Enneking stage III spinal giant cell tumor (GCT) in terms of local recurrence., Methods: A retrospective survival analysis of patients with Enneking stage III GCT who underwent TES with marginal margins or total piecemeal spondylectomy with intralesional margins was performed between January 2006 and April 2020. Local recurrence-free survival (LRFS) was the time between the date of surgery and recurrence. Factors with p-values < 0.05 in the univariate analysis were included in the multivariate analysis using proportional hazard analysis., Results: Sixty patients (25 men and 35 women) with a mean age of 35.6 (range 11-71) years were included. The mean follow-up duration was 93 (range 24-198) months. Two patients were lost to follow-up 6 and 14 years after the procedure. Over a 10-year period, the recurrence rate was 13.3%. The 2-, 5-, and 10-year LRFS rates were 95%, 88%, and 78%, respectively. Univariate analysis identified total piecemeal spondylectomy and no adjuvant radiotherapy as prognostic factors for LRFS. Multivariate Cox-regression models showed a significant association between local recurrence and total piecemeal spondylectomy and no adjuvant radiotherapy., Conclusion: TES with marginal margins is better than total piecemeal spondylectomy with intralesional margins owing to its lower postoperative recurrence rate. Adjuvant radiotherapy should be administered to reduce postoperative recurrence rates., (© 2022. The Author(s).)

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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background: Localized tenosynovial giant cell tumor (GCT) or giant cell tumor of tendon sheath (GCTTS), is a benign nodular lesion that arises from the synovium of the tendon sheath of the hands and foot. GCTTS is characterized by the presence of multinucleated giant cells and proliferation of synovial-like mononuclear cells. A clinical diagnosis of GCTTS is kept as a differential when a firm, nodular mass shows decreased signal intensity on both T1-and T2-weighted MR imaging. Treatment is usually marginal excision of the mass., Material and Methods: It is a retrospective study, observed in the past 3 years at a tertiary care hospital. Those cases were included in the study in which histopathological confirmation was available or if clinico-radiological features were confirmatory of the diagnosis of GCTTS when correlated with cytological features., Results: There was a total of 24 cases, out of which 16 were females and 8 males. The tumor was located in the upper limb in 21 cases and in 3 cases the tumor was present in the lower limb. In the upper limb, 18 cases were on the right side and three cases were on the left side. In the lower limb, 1 case was present on the left and 2 on the right side. The cytomorphology consisted of mononuclear stromal cells, multinucleated giant cells, and hemosiderin-laden macrophages in variable numbers., Conclusion: It is important to accurately diagnose and categorize giant cell-containing lesions because their prognosis depends on the exact categorization of the tumor., (© 2022 Wiley Periodicals LLC.)

Giant cells may be found in a wide variety of reactive and neoplastic soft tissue lesions. Because of their distinct histomorphology, they often stand out in procured samples such as fine needle aspirates. The giant cells themselves may be benign or neoplastic. However, the presence, type, and quantity of giant cells are usually not specific and in some cases can even be misleading when making a diagnosis. The aim of this review is to guide the practicing cytopathologist in narrowing their differential diagnosis when encountering one of these challenging giant cell-rich lesions of the soft tissue., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Giant cell tumor (GCT) of bone is essentially benign but locally aggressive, and the rate of local recurrence is high when the resection is not enough. En bloc resection is recommended as an ideal solution for GCT to decrease the risk of local recurrence, but it remains challenging for cervical GCT. In this technical case report, we present a case of extensively infiltrating GCT of the cervical spine completely encasing the vertebral artery (VA) on one side. The tumor was distributed to layers A-D, sectors 3-8 based on the Weinstein-Boriani-Biagini staging. Combined posterior and anterior surgical approach for the cervical spine was successfully performed and followed by postoperative adjuvant pharmacological therapy. This kind of multimodal management may be one of the solutions for advanced cervical GCT.

Pancreatic giant cell tumors (PGCTs), undifferentiated pancreatic carcinoma are rare tumors of the pancreas. PGCTs consist of osteoclastic, pleomorphic and mixed variants. PGCT is usually diagnosed at an advanced stage. PGCT has a worse prognosis than pancreatic ductal adenocarcinoma. Although surgery can be curative, there is no standard treatment approach for advanced PGCT. We present a case of PGCT that is resistant to standard therapy and progresses in a short time., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: We present a case report of a triple location Giant Cell Tumor of tendon sheath appearance on the same flexor tendon sheath of a single digit. There have been scarce descriptions of multiple Giant Cell Tumors of tendon sheath. Multiple tumors may predispose patients to a higher recurrence rate; therefore, recognition and treatment of this rare entity is important.

Background: A giant cell tumor (GCT) is a benign neoplasm characterized by mixture of mononuclear cells and multinucleated cells. A GCT of soft tissue (GCT-ST) is developed in various extraosseous sites, but GCT-ST of the gastrointestinal tract is very rare. GCT-ST usually has a benign course, but rare cases reported malignant potential of the tumor. Therefore, complete resection is required to prevent local recurrence or distant metastasis., Case Presentation: A 53-year-old woman was admitted for follow-up colonoscopy who underwent the colorectal endoscopic submucosal dissection (ESD) of a laterally spreading tumor at the hepatic flexure 6 months ago. A colonoscopy showed a polypoid mass about 3.5 × 2.5 cm at the previous ESD site. As endoscopic finding showed a smooth multi-nodular tumor without submucosal invasion, we performed endoscopic mucosal resection. Based on pathological and immunohistochemical findings, the lesion was diagnosed as a GCT-ST in the colon. Follow-up colonoscopy performed 6 months later revealed no evidence of recurrence., Conclusion: This is the first report of a GCT-ST identified in the colon. Although GCT-ST generally has a benign clinical course, complete resection should be performed to prevent local recurrence and metastasis., (© 2022. The Author(s).)

This study is aimed to unravel the status of local and circulating β-catenin in different primary bone tumors and its relevance to tumor types, severity, and chemotherapy. The β-catenin mRNA expression level and the expression of the protein (intensity level) were evaluated in tumor tissue and peripheral blood mononuclear cells of 150 patients with different types of primary bone tumors (78 malignant and 72 benign tumors) using Real-Time PCR and immunohistochemistry. The β-catenin mRNA expression level and the expression of the protein were increased in bone tumors which was positively correlated with the tumor malignancy. Amongst osteosarcoma, Ewing's Sarcoma, chondrosarcoma, osteochondroma, Giant Cell Tumor, and exostosis tumors, the osteosarcoma, and Giant Cell Tumor groups showed the highest level of β-catenin expression. The β-catenin expression in malignant bone tumors was significantly correlated with tumor grade, size, metastasis, tumor recurrent, and the level of response to chemotherapy. A similar pattern of β-catenin gene expression and its association with tumor characteristics was detected in the patient's peripheral blood cells. The simultaneous increase in the expression of the β-catenin gene and protein in tumor tissue and in circulating blood cells and its relationship with tumor severity indicates the possible promoting role of β-catenin in primary bone tumor pathogenesis., (© 2022. The Author(s).)

Giant cell tumor of the calcaneal bone is a very rare entity and generally seen in the 30 to 40 years age group. We report a case of a 17-year-old male with giant cell tumor of the calcaneus, presented with left heel pain without another obvious physical abnormality. Radiographs showed a lobulated, well-defined, lytic lesion of the calcaneus with narrow transitional zone without periosteal reaction, no extraosseal spread, and no lung metastases. Arthroscopic procedure was done directly for both diagnostic and curative procedures. All soft, grayish lesions were completely removed arthroscopically using direct lateral portals and the suspected reactive zones debrided using high-speed burr and injected with corticosteroid. Histopathology confirmed the suspected diagnosis. The postoperative clinical course was uneventful with immediate pain relief and full weight bearing and movement allowed soon. The patient had no recurrent pain as well as recurrent radiographic lesions, and normal joint mobility 9 months postoperatively. Considering the accessibility of the lesion, giant cell tumor of the calcaneal bone can be successfully treated arthroscopically using direct lateral approach.Levels of Evidence: Therapeutic, Level IV: Retrospective, case report .

Background: The differential diagnosis of giant cell-rich bone tumors comprises a broad spectrum of lesions with prominent reactive osteoclast-like and/or neoplastic giant cells, with substantial differences in biologic behavior and clinical management. Evaluation of giant cell-rich bone tumors on small biopsies can be challenging especially in specimens with limited representative material. An accurate diagnosis requires a high level of skill on the part of both radiologist and pathologist as correlation with clinical and radiologic characteristics is critical. The objective of the study was to assess the utility of touch preparations (TP), immunohistochemistry (IHC) for mutation-specific markers H3G34W and H3K36M, and fluorescence in situ hybridization (FISH) for USP6 rearrangements and MDM2 amplification in the diagnostic workup of core needle biopsy specimens., Methods: A total of 27 core needle biopsies with TPs from patients with primary giant cell-rich bone tumors (16 giant cell tumors of bone (GCTBs) (including 3 with lung metastasis), 3 chondroblastomas (CBs), 4 primary aneurysmal bone cysts (ABCs), 2 non-ossifying fibromas (NOFs), 1 low grade osteosarcoma (OS), and 1 conventional OS with tumor giant cells were analyzed with IHC for H3G34W and H3K36M and in select cases FISH for USP6 rearrangements and MDM2 amplification., Results: In all cases the core biopsies were sufficient for histologic examination and diagnostic workup. 16 of 16 GCTBs were positive for H3G34W and negative for H3K36M, and 3 of 3 CBs were positive for H3K36M and negative for H3G34W. All other cases were negative for H3G34W and H3K36M. 4 of 4 primary ABCs showed rearrangement of USP6 by FISH and the low grade OS showed amplification of MDM2 by FISH., Conclusions: On-site adequacy assessment of TPs proved to be an accurate, simple, and fast method for obtaining sufficient material for complete diagnostic workup. The application of IHC for H3G34W and H3K36M and FISH for detection of rearrangements of USP6 and amplification of MDM2 can improve the diagnostic accuracy in core needle biopsy specimens., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Background/aim: Chimeras involving the high-mobility group AT-hook 2 gene (HMGA2 in 12q14.3) have been found in lipomas and other benign mesenchymal tumors. We report here a fusion of HMGA2 with the nuclear receptor co-repressor 2 gene (NCOR2 in 12q24.31) repeatedly found in tumors of bone and the first cytogenetic investigation of this fusion., Materials and Methods: Six osteoclastic giant cell-rich tumors were investigated using G-banding, RNA sequencing, reverse transcription polymerase chain reaction, Sanger sequencing, and fluorescence in situ hybridization., Results: Four tumors had structural chromosomal aberrations of 12q. The pathogenic variant c.103&#95;104GG>AT (p.Gly35Met) in the H3.3 histone A gene was found in a tumor without 12q aberration. In-frame HMGA2-NCOR2 fusion transcripts were found in all tumors. In two cases, the presence of an HMGA2-NCOR2 fusion gene was confirmed by FISH on metaphase spreads., Conclusion: Our results demonstrate that a subset of osteoclastic giant cell-rich tumors of bone are characterized by an HMGA2-NCOR2 fusion gene., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Giant cell tumor of soft tissue (GCT-ST), histologically resembling the GCT of the bone, is a rare tumor. The tumor has been categorized to have low malignancy. Few reports of local recurrence or distant metastasis and the use of chemotherapeutic agents for metastatic GCT-ST exist. Herein, we report the efficacy of pazopanib in a 78-year-old Japanese woman with GCT in the intrinsic back musculature with both post-operative local recurrence and lung metastasis. The patient visited the hospital with a three-month history of a palpable mass in the intrinsic back musculature. Following magnetic resonance imaging, the tumor predominantly exhibited slight hyperintensity on T2-weighted images and intense heterogeneous enhancement on contrast-enhanced T1-weighted images. A percutaneous needle biopsy was performed, and the pathological diagnosis was GCT-ST. The patient underwent surgery, and three months later she presented with not only local recurrence but also multiple lung metastases. The patient was immediately treated with pazopanib 400 mg once daily. One month after initiating treatment, a partial response in the pulmonary lesions was observed, and stable disease (SD) effects lasted for 11 months without severe adverse effects. Therefore, pazopanib treatment for metastatic malignant giant cell tumor of soft tissue achieved reasonable success.

Tenosynovial Giant Cell Tumor (TGCT) is a group of typically benign lesions arising from the synovium of joints, bursae and tendon sheaths. Depending on their growth pattern and clinical course, they are divided into localized and diffuse types. It is predominantly caused by a mutation in the stromal cells of the synovial membrane leading to overexpression of the colony stimulating factor 1 that recruits CSF1R-expressing cells of the mononuclear phagocyte lineage into the tumor mass. The lesions contain mainly histiocyte-like and synovial cells accompanied by varying numbers of multinucleated giant cells, mononuclear cells, foam cells, inflammatory cells and hemosiderin deposits. The gold standard for detect- ing and monitoring the disease is MRI, where the characteristic hemosiderin accumulation can be best appreciated, but it is a histological examination that is most conclusive. The main treatment is surgical resection of all pathological tissue, but radio- and chemotherapy are also viable options for certain groups of patients.