Giant Cell Tumor Research Articles

Denosumab in irresectable giant cell tumour of the cervical spine

Denosumab in irresectable giant cell tumour of the cervical spine

Pleomorphic Liposarcoma Cytologically Detected in Hemosiderotic Pleural Effusion: Pitfalls Mitigated by Cytologic Clues and Cellblock Immunocytochemistry.

Sarcomatous serous effusions are uncommon and diagnostically challenging. Dedifferentiated and pleomorphic liposarcomas are rare tumors in pleural effusions revealing highly pleomorphic tumor cells mimicking carcinoma, mesothelioma, melanoma, and other sarcomas. Hematothoracic effusions further complicate the cytologic diagnosis. Correct cytologic recognition is important. We report pleomorphic liposarcoma cytologically detected in effusion fluid in a 56-year-old man who presented with a massive unilateral pleural effusion. ThinPrep showed hemorrhagic effusion fluid characterized by lysed red blood cells, foamy macrophages, and siderophages intermixed with highly pleomorphic predominantly naked mononuclear and giant nuclei. The aggregated siderophages and vacuolated macrophages could be mistaken for tumor cells, whereas the bare nuclei may be missed as nonspecific degenerate changes. Cellblock sections showed highly pleomorphic mononuclear and multinucleated giant tumor cells with diagnostic lipoblasts, intermixed with foamy macrophages and siderophages. Cellblock immunocytochemistry showed staining for vimentin and S-100 protein in the tumor cells. Other lineage-specific immunomarkers were negative. CD68 and calretinin revealed frequent background macrophages and scarce mesothelial cells. The tumor cells were negative for MDM2 and CDK4. The entertained cytopathologic diagnosis was pleomorphic liposarcoma. Core needle biopsy was procured from the mass. The histopathologic features and immunoprofile of the tissue specimen matched the cytopathologic and immunocytochemical findings confirming the cytologic diagnosis of pleomorphic liposarcoma. Pleomorphic liposarcoma is an unexpected cytologically challenging finding in effusions, particularly when compounded by pitfalls introduced by hemosiderotic fluid. Attention to certain cytologic clues mitigate pitfalls. Cellblock is a valuable diagnostic tool when integrated with relevant negative and positive immunocytochemical markers.

Chondroid Synoviocytic Neoplasm: A Clinicopathologic, Immunohistochemical, and Molecular Genetic Study of a Distinctive Tumor of Synoviocytes

Tumors resembling tenosynovial giant cell tumor (TGCT) but additionally forming chondroid matrix 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, in the age group of 31 to 80 years (median, 50 years) and involved the TMJ 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 chromogenic in situ hybridization (8/13) but at best weakly positive for CSF1 by immunohistochemistry (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); and MALAT1::FN1, PDGFRA::USP35, and TIMP3::ZCCHC7 (1 case each). Three tumors contained more than 1 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.

A multivariate analysis on characteristics of hand and wrist tumours: a multiethnic study.

Hand tumours are frequently encountered in clinical practice. However, large-scale epidemiological data of soft tissue tumours in the hand are infrequently published. Epidemiological data provide diagnostic cues to guide the workup and management of hand tumours. Assessing significant independent demographic factors and tumour characteristics associated with hand tumours is essential in health care. A retrospective review of patients who underwent excision of hand tumours in Singapore General Hospital between 2004 and 2015 was conducted. The data collected included age, gender, ethnicity, histological diagnosis, malignancy and location of tumour. Generalised linear latent and mixed models (GLLAMM) analyses were performed. A total of 4476 tumours were identified from 4226 patients with a mean age of 51.3 (range 8-101) years and male to female ratio of 1 to 1.15. Most patients were Chinese (75%), followed by Malay (9%), Indian (8%) and others (8%). The most common hand tumours excised were ganglions (43%) (majority in the wrist), followed by giant cell tumours (9%) (commonly in the digits). Most soft tissue tumours were benign (97%), with only 3% of malignant cases. The GLLAMM analyses revealed further potential factors on the status of malignancy, tumour origin and tumour location. Most soft tissue tumours in the hand and wrist are benign. This can guide workup and counselling of patients before the operation. While malignant tumours are uncommon, they have the potential for significant morbidity and mortality if not appropriately evaluated or treated. The application of GLLAMM analyses showed that age, ethnicity and gender were significant predictors of malignancy.

CSF1R Inhibition in Patients with Advanced Solid Tumors or Tenosynovial Giant Cell Tumor: A Phase I Study of Vimseltinib.

Tenosynovial giant cell tumor (TGCT) is a locally aggressive neoplasm caused by dysregulation of the colony-stimulating factor 1 (CSF1) gene and overexpression of the CSF1 ligand. Surgery is the standard of care for most patients, but there are limited treatment options for patients with TGCT not amenable to surgery. This study evaluates vimseltinib, an investigational, oral, switch-control tyrosine kinase inhibitor designed to selectively and potently inhibit the CSF1 receptor. This first-in-human, multicenter, open-label phase I/II study of vimseltinib in patients with malignant solid tumors (N = 37) or TGCT not amenable to surgery (N = 32) followed a pharmacologically guided 3 + 3 study design (NCT03069469). The primary objectives were to assess safety and tolerability, determine the recommended phase II dose, and characterize the pharmacokinetics; exploratory objectives included pharmacodynamics and efficacy. Vimseltinib was well tolerated; the majority of non-laboratory treatment-emergent adverse events were of grade 1/2 severity. There was no evidence of cholestatic hepatotoxicity or drug-induced liver injury. The recommended phase II dose was determined to be 30 mg twice weekly (no loading dose), and vimseltinib plasma exposure increased with the dose. In patients with TGCT, the median treatment duration was 25.1 months (range, 0.7-46.9), and the objective response rate as assessed by independent radiological review using RECIST version 1.1 was 72%. Vimseltinib demonstrated long-term tolerability, manageable safety, dose-dependent exposure, and robust antitumor activity in patients with TGCT not amenable to surgery.

Pexidartinib Upfront in a Case of Tenosynovial Giant Cell Tumor: Proof of Concept for a Treatment Paradigm Shift.

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 factor1 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. A 32-year-old man presented with intra-articular diffuse TGCT with pain and received noncurative treatment for 5years (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 800mg/day. After dose reductions to pexidartinib at 400mg/day and then 200mg/day as a result of creatine phosphokinase elevations, the patient achieved a complete response after 2years 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. Our case is unique because it provides support for pexidartinib use as upfront therapy for TGCT, instead of surgery, in selected cases.

Combined preoperative denosumab and adjuvant microwave ablation for high-risk giant cell tumor of bone: a retrospective study in a single center

BackgroundGiant cell tumor of bone (GCTB) is a locally aggressive neoplasm with a high propensity for recurrence following intralesional curettage. The introduction of denosumab, a RANKL inhibitor, has shown potential in facilitating joint-sparing surgery. However, concerns exist regarding its impact on local recurrence rates. This study aimed to evaluate the efficacy and safety of combined preoperative denosumab with adjuvant microwave ablation (MWA) for the treatment of high-risk GCTB.MethodsWe conducted a retrospective review of 19 patients with high-risk GCTB who underwent preoperative denosumab treatment followed by curettage and adjuvant MWA. The primary outcome measure was the local recurrence rate, with secondary outcomes including functional status assessed by the Musculoskeletal Tumor Society (MSTS) score and safety profile of the treatment.ResultsIn this retrospective analysis, we evaluated the outcomes of 19 patients with high-risk GCTB treated with preoperative denosumab and adjuvant MWA. The median follow-up duration was 33.1 months, 3 patients (15.8%) experienced local recurrence at a median of 21.6 months postoperatively and the local recurrence-free survival was 81.2% at two years. Notably, no patient developed lung metastasis, and all recurrences were successfully managed with repeat curettage and MWA, with a mean MSTS score of 27.3. No patient required joint replacement due to tumor recurrence, resulting in a 100% joint preservation rate.ConclusionThe combination of preoperative denosumab and adjuvant MWA is a feasible and effective strategy for the management of high-risk GCTB, providing effective local control with preserved joint function. This approach may offer a surgical alternative for young patients where joint preservation is paramount.

Validity of the Musculoskeletal Tumor Society Score for lower extremity in patients with bone sarcoma or giant cell tumour of bone undergoing bone resection and reconstruction surgery in hip and knee

BackgroundThe Musculoskeletal Tumor Society Score (MSTS) is widely used to evaluate functioning following surgery for bone and soft-tissue sarcoma. However, concerns have been raised about its content validity due to the lack of patient involvement during item development. Additionally, literature reports inconsistent results regarding data quality and structural validity. This study aimed to evaluate content, structural and construct validity of the Danish version of the MSTS for lower extremity (MSTS-LE).MethodsThe study included patients from three complete cohorts (n = 87) with bone sarcoma or giant cell tumour of bone who underwent bone resection and reconstruction surgery in hip and knee. Content validity was evaluated by linking MSTS items to frameworks of functioning, core outcome sets and semi-structured interviews. Data quality, internal consistency and factor analysis were used to assess the underlying structure of the MSTS. Construct validity was based on predefined hypotheses of correlation between the MSTS and concurrent measurements.ResultsContent validity analysis revealed concerns regarding the MSTS. The MSTS did not sufficiently cover patient-important functions, the item Emotional acceptance could not be linked to the framework of functioning, the items Pain and Emotional acceptance pertained to domains beyond functioning and items’ response options did not match items. A two-factor solution emerged, with the items Pain and Emotional acceptance loading highly on a second factor distinct from functioning. Internal consistency and construct validity showed values below accepted levels.ConclusionThe Danish MSTS-LE demonstrated inadequate content validity, internal consistency, and construct validity. In addition, our analyses did not support unidimensionality of the MSTS. Consequently, the MSTS-LE is not a simple reflection of the construct of functioning and the interpretation of a sum score is problematic. Clinicians and researcher should exercise caution when relying solely on MSTS scores for assessing lower extremity function. Alternative outcome measurements of functioning should be considered for the evaluation of postoperative function in this patient group.

Plexiform Variant of Ameloblastoma in Body of Mandible: Case Report and Review of Literature

Ameloblastoma is a benign but locally aggressive odontogenic epithelial neoplasm arising from remnants of dental lamina and dental organ [1,4]. This neoplasm is more prevalent between 2nd to 4th decade of life and mandible (11%) is more commonly involved than maxilla (1%) [2,5]. It has an aggressive behavior and recurrent course, It is rarely metastatic. Ameloblastoma represents 10% of odontogenic tumors and 1% of all tumors and cysts involving the maxillo mandibular region [1]. The World Health Organization (WHO) classification of 2017 describes ameloblastomas of the following four types: Solid/multicystic ameloblastoma (91%) unicystic ameloblastoma (6%); extraosseous/peripheral ameloblastoma (2%); and metastasizing ameloblastoma (1%). [3,8] A conclusive diagnosis can only be made by histopathology because it has wide range of histologic patterns and has radiographic characteristics with other lesions such the odontogenic keratocyst, giant cell tumour, aneurysmal bone cyst, and renal cell carcinoma metastasis.[5] Treatment for each type of ameloblastoma differs depending on its biological behaviour and rate of recurrence. This report presents a case of ameloblastoma involving the body of mandible with resorption of the root apices of canine, premolars and first molar. The lesion extends till the base of mandible with intact lower border. This was surgically excised preserving the lower border of mandible with safe sound margins of bone.

Multiportal Arthroscopy-assisted Surgical Resection of Diffuse-type Tenosynovial Giant Cell Tumors in the Ankle Joint Yields Favorable Clinical Outcomes: A Retrospective Study.

Diffuse-type tenosynovial giant cell tumors (Dt-TGCTs) commonly occur in the knee joint and tend to recur postoperatively. However, limited clinical data are available on ankle joint involvement especially associated multiportal arthroscopic treatment outcomes. The purpose of this study was to report the clinical results of multiportal arthroscopy-assisted resection of Dt-TGCTs of the ankle. We retrospectively reviewed the clinical data of 33 patients with Dt-TGCT of the ankle who underwent multiportal arthroscopic treatment between August 2011 and December 2020. Clinical follow-up included the visual analogue scale (VAS) score, American Orthopedic Foot and Ankle Society (AOFAS) score, Kofoed score, and recurrence rate to assess surgical outcomes. The number of patients who achieved the patient acceptable symptom state (PASS) based on the AOFAS score was also examined. Additionally, the patients were categorized into two groups based on the final surgical approach: Group A who underwent multiportal arthroscopic synovectomy and Group AO who underwent combined arthroscopic and open surgical excision. Intergroup comparisons were conducted. Intraoperative characteristics, such as the number of patients with involvement of the tarsal tunnel and fibularis tendon and the Outerbridge grading of cartilage damage, were recorded to assess the selection of surgical procedures. Among the 33 patients, 15 were assigned to Group A, and 18 were in Group AO. The median follow-up duration for the 33 patients was 77 months (range, 28-142 months). The median VAS score was 1 (range, 0-4), the AOFAS score was 96 (range, 65-100), and the Kofoed score was 96 (range, 67-100). A total of 27 patients (82%) achieved PASS based on AOFAS scores, while five patients (15%) had recurrence. No statistically significant difference was observed between the two groups in recurrence rate, follow-up VAS score, AOFAS score, Kofoed score, or number of patients who reached the PASS (p > 0.05). In the AO group, 16 cases of Dt-TGCT involved the tarsal tunnel, and 11 cases involved the fibularis tendon. All these patients exhibited extension beyond the joint. In contrast, only one patient in Group A had involvement of the tarsal tunnel. Statistically significant differences were observed between the groups (p < 0.001). This study demonstrated that, with the assistance of a multiportal arthroscopic approach, surgical excision of Dt-TGCT in the ankle resulted in favorable clinical outcomes with a relatively low recurrence rate. Additionally, patients with extra-articular involvement were more likely to require concomitant open surgery.

TFE3-rearranged perivascular epithelioid cell tumors: a clinicopathological analysis of eight cases

Objective: To investigate the clinicopathological, immunohistochemical and molecular genetic characteristics of TFE3-rearranged perivascular epithelioid cell tumor (PEComa). Methods: Eight cases of PEComa with TFE3 rearrangement diagnosed in the First Affiliated Hospital of Air Force Medical University from January 2014 to July 2022 were collected. Three were consultation cases and 5 were collected from our hospital; 7 cases were resection specimens and 1 case was a needle biopsy specimen. Routine histolopathological analysis, immunohistochemical staining, fluorescence in situ hybridization (FISH) and the next-generation sequencing were performed. Clinical data were collected and the prognosis was assessed. Results: The 8 patients consisted of 5 females and 3 males with a median age of 45 years (ranged from 25 to 65 years). The tumor location included 1 uterus, 1 liver, 1 urachus, 2 kidneys, 1 abdominal cavity, 1 colon, and 1 retroperitoneum (3 subsequent recurrences in the abdominal cavity, pelvis and ovary, and abdominal cavity, respectively). Morphologically, the tumor cells were uniform and epithelioid with translucent or eosinophilic cytoplasm. They were arranged in nests or sheets, most of which were separated by thin-walled blood vessels. There were no papillary structures, and no overt smooth muscle or fat components. Atypical features were seen in 3 cases, with bizarre nuclei and tumor giant cells. Large areas of necrosis were visible, and mitosis was common (up to 28/50 HPF). Melanin deposition was present in 3 cases. Immunohistochemical staining showed diffuse and strong positivity for TFE3 in 8/8 cases and for HMB45 in 6/8 cases; focal positivity for Cathepsin K and Melan-A in 6/8 cases and for SMA in 2/8 of cases. All cases were negative for CKpan, PAX8 and Desmin. TFE3 gene break-apart was detected by FISH in all 8 cases, 4 of which underwent next-generation sequencing, and it revealed that 2 cases presented with SFPQ::TFE3 fusion, 1 case with ASPSCR1::TFE3 fusion, and 1 case with no chimeric fusion. Seven cases were followed up for 4-94 months. All cases were alive; 4 cases were disease-free, 2 cases showed recurrence, and 1 case had metastasis at initial diagnosis. Conclusions: TFE3-rearranged PEComa has unique histomorphological, immunohistochemical and molecular characteristics. The biological behavior is aggressive, which could lead to recurrence and metastasis, and warrants close clinical follow-up.

Benign bone tumors in North East Indian population – A hospital-based study

Background: Primary bone tumors are relatively uncommon and constitute only 0.2–0.5% of all tumors in all ages in most series reported worldwide. Benign bone tumors are more common than the malignant bone tumors. Not many studies on benign bone tumors in the North Eastern Indian population are published in the available literature. Aims and Objectives: The current study was done with the aim to find out the epidemiological data on benign bone tumors in patients of the North-East Indian population who were admitted to the orthopedic department of a teaching institute. Materials and Methods: A hospital-based retrospective study with prospective effect was conducted on benign bone tumors in patients admitted to the Department of Orthopedics at our teaching institute from 2016 to 2020. Patients of all ages and both sexes with suspicion of bone tumors based on history and clinical examination were subjected to roentgenographic evaluation, including computed tomography (CT) scan and/or magnetic resonance imaging. Pre-operative core needle biopsy under C-arm/CT guidance or incisional biopsy was done for histological diagnosis, followed by appropriate intervention. Soft-tissue tumors and malignant bone tumors were excluded. Patients were followed up for recurrence, complications, and functional recovery. Results: Forty patients of bone tumors were treated out of 2288 patients admitted to the department (incidence of 1.75%). 29 were benign bone tumors with an incidence of 1.27%. Of 10–20 years age group was most commonly affected. Male preponderance with M: F=6.25:1. Femur (n=16) was the most commonly affected bone. Presenting features were swelling (n=18), pain (n=11), and pathological fracture (n=5). osteochondroma (n=15) was most common followed by giant cell tumor of bone (n=6). Treatment ranged from intralesional steroid to wide marginal excision based on histopathological diagnosis, the extent of tumor, anatomical location, and presenting symptoms. All patients were rehabilitated to activities of daily living at the final follow-up. No recurrence or any long-term complications were reported. Conclusion: This study gives epidemiological data on benign bone tumors, which can be used for setting up or upgrading dedicated oncological or oncosurgery institutes. A multicentric study on a large population in the future is suggested to obtain a larger data bank.

Lymphocyte Infiltration Score and Spatial Characteristics Refined the Prognosis and Denosumab Treatment Responsiveness Indicators for Giant Cell Tumor of Bone.

The prognostic value of lymphocyte infiltration score (LIS) and its nearest neighbor distance to tumor cells (NNDTC) in giant cell tumor of bone (GCTB) is currently not well established. This study aims to characterize LIS and NNDTC and examine their correlation with denosumab treatment responsiveness, clinicopathologic features, and patient prognosis. Using multiplexed quantitative immunofluorescence, LIS was evaluated in 253 tumor specimens, whereas NNDTC was computed using HALO software. Subsequently, we analyzed the association of these parameters with patient outcomes (progression-free survival [PFS] and overall survival [OS]), clinicopathologic features, and denosumab treatment responsiveness. Low LIS was indicative of both poor PFS and OS (both P < .001). In addition, LIS was significantly associated with sex (P = .046), Enneking staging (P < .001), Ki-67 expression (P = .007), and denosumab treatment responsiveness (P = .005). Lower CD8+ (tumor interior [TI]) NNDTC, and CD3+ (TI) NNDTC were associated with worse PFS (P = .003 and .038, respectively), whereas lower CD8+ (TI) NNDTC was associated with worse OS (P = .001), but CD8+ (tumor infiltrating margin) NNDTC had the opposite effect (P = .002). Moreover, NNDTC showed a correlation with several clinicopathologic features. Importantly, LIS outperformed Enneking and Campanacci staging systems in predicting the clinical outcomes of GCTB. These findings suggest that LIS is a reliable predictive tool for clinically relevant outcomes and response to denosumab therapy in patients with GCTB. These parameters may prove to be useful in guiding prognostic risk stratification and therapeutic optimization for patients.

Deep learning-based detection of primary bone tumors around the knee joint on radiographs: a multicenter study.

Most primary bone tumors are often found in the bone around the knee joint. However, the detection of primary bone tumors on radiographs can be challenging for the inexperienced or junior radiologist. This study aimed to develop a deep learning (DL) model for the detection of primary bone tumors around the knee joint on radiographs. From four tertiary referral centers, we recruited 687 patients diagnosed with bone tumors (including osteosarcoma, chondrosarcoma, giant cell tumor of bone, bone cyst, enchondroma, fibrous dysplasia, etc.; 417 males, 270 females; mean age 22.8±13.2 years) by postoperative pathology or clinical imaging/follow-up, and 1,988 participants with normal bone radiographs (1,152 males, 836 females; mean age 27.9±12.2 years). The dataset was split into a training set for model development, an internal independent and an external test set for model validation. The trained model located bone tumor lesions and then detected tumor patients. Receiver operating characteristic curves and Cohen's kappa coefficient were used for evaluating detection performance. We compared the model's detection performance with that of two junior radiologists in the internal test set using permutation tests. The DL model correctly localized 94.5% and 92.9% bone tumors on radiographs in the internal and external test set, respectively. An accuracy of 0.964/0.920, and an area under the receiver operating characteristic curve (AUC) of 0.981/0.990 in DL detection of bone tumor patients were for the internal and external test set, respectively. Cohen's kappa coefficient of the model in the internal test set was significantly higher than that of the two junior radiologists with 4 and 3 years of experience in musculoskeletal radiology (Model vs. Reader A, 0.927 vs. 0.777, P<0.001; Model vs. Reader B, 0.927 vs. 0.841, P=0.033). The DL model achieved good performance in detecting primary bone tumors around the knee joint. This model had better performance than those of junior radiologists, indicating the potential for the detection of bone tumors on radiographs.

Comprehensive Molecular Characterization of a Large Series of Calcified Chondroid Mesenchymal Neoplasms Widening Their Morphologic Spectrum.

Recently, FN1 fusions to receptor tyrosine kinase genes have been identified in soft tissue tumors with calcified chondroid matrix named calcifying chondroid mesenchymal neoplasms (CCMNs). We collected 33 cases of CCMN from the French network for soft tissue and bone tumors. We performed whole-exome RNA sequencing, expression analysis, and genome-wide DNA methylation profiling in 33, 30, and 20 cases of CCMN compared with a control group of tumors, including noncalcified tenosynovial giant cell tumor (TGCT). Among them, 15 cases showed morphologic overlap with soft tissue chondroma, 8 cases with tophaceous pseudogout, and 10 cases with chondroid TGCT. RNA-sequencing revealed a fusion of FN1 in 76% of cases (25/33) with different 5' partners, including most frequently FGFR2 (14 cases), TEK or FGFR1. Among CCMN associated with FGFR1 fusions, 2 cases had overexpression of FGF23 without tumor-induced osteomalacia. Four CCMN had PDGFRA::USP8 fusions; 3 of which had histologic features of TGCT and were located in the hip, foot, and temporomandibular joint (TMJ). All cases with FN1::TEK fusion were located at TMJ and had histologic features of TGCT with or without chondroid matrix. They formed a distinct cluster on unsupervised clustering analyses based on whole transcriptome and genome-wide methylome data. Our study confirms the high prevalence of FN1 fusions in CCMN. In addition, through transcriptome and methylome analyses, we have identified a novel subgroup of tumors located at the TMJ, exhibiting TGCT-like features and FN1::TEK fusions.

Extra-articular tenosynovial giant cell tumor with novel FBN1::CSF1 fusion masquerading as a floor of mouth inflammatory process

Extra-articular tenosynovial giant cell tumor with novel FBN1::CSF1 fusion masquerading as a floor of mouth inflammatory process

Malignant Phyllodes Tumour with Heterologous Osteosarcomatous differentiation and Osteoclast-like giant cells: Case Report of an uncommon neoplasm

Background: Phyllodes tumour (PT), an uncommon fibroepithelial neoplasm accounts for less than 1% of all primary tumours of the breast. MPT with osseous differentiation often gets misdiagnosed on imaging as benign giant calcifications resulting in treatment delay. We describe a rare case of MPT with heterologous osteosarcomatous differentiation and osteoclast-like giant cells and review the literature to discuss clinical-radiological findings, differential diagnosis and treatment options. Case Presentation: A 34-year-old female presented with a right breast lump. Mammography showed a high-density irregular mass with amorphous dense calcification, suggesting neoplastic aetiology. Preoperative core needle biopsy raised the possibility of a phyllodes tumour versus giant cell tumour. Wide local excision was performed to confirm the diagnosis which revealed the presence of a biphasic tumour with osteoid-like matrix and numerous osteoclastic giant cells. Immunohistochemistry was used to rule out metaplastic carcinoma or carcinosarcoma. The stromal cells were negative for panCK and P63 and positive for vimentin, CD10 and BCL-2. The osseous component was positive for Osteonectin and SATB2. Thus, a final diagnosis of malignant phyllodes tumour with heterologous osteosarcomatous differentiation and osteoclast-like giant cells was made. Conclusion: MPT with osteosarcomatous differentiation is a rare and challenging entity associated with a poor clinical outcome. Accurate diagnosis requires a multidisciplinary approach involving breast surgeons, pathologists and radiologists with careful histopathological examination. Wide local excision with close surveillance is crucial for timely detection of tumour recurrence and metastasis.

Study of Multimodality Imaging Features of Brown Tumor or Osteitis Fibrosa Cystica

Introduction Brown tumor, also known as osteitis fibrosa cystica, is a rare but significant manifestation of hyperparathyroidism characterized by focal bone lesions resulting from excessive osteoclastic activity. Despite its rarity, Brown tumor poses diagnostic challenges due to its varied clinical presentations and radiographic features, often mimicking other bone lesions such as giant cell tumors or metastatic disease. Material and Methods In this study, we present a retrospective analysis of 6 cases of Brown tumor diagnosed and managed at our institution over a 12 months period from April 2022 to April 2023. Our objectives are to delineate the diverse clinical manifestations of Brown tumor, discuss diagnostic modalities utilized, treatment strategies employed, and evaluate patient outcomes. Results Five out of our six patients were females. Also 5 out of our 6 patients were under the age of 25. 2 patients presented to us with multiple lytic lesions and other 4 patients had solitary lesions. 1 patient out of 6 presented to us with pathological fracture. Only 2 out of the 6 patients had a positive sestamibi scan but Ultrasonography (USG) of the neck and MRI of the neck showed the presence of parathyroid adenoma in all the cases. Preoperative average of VAS score in this patients was 67 which was decreased to as low as 24. We performed paired t-tests on the blood investigation values and Visual Analog Scale (VAS) scores for all patients. The results were statistically significant, with values returning to normal three months post-surgery. Conclusion When radiographic evidence of a lytic lesion and hypercalcemia are present, Brown tumor should always be considered in the differential diagnosis. Brown tumor has a distinctive imaging appearance, with solid components displaying intermediate to low intensity on T1- and T2-weighted images, while the cystic components appear hyperintense on T2-weighted images and exhibit fluid-fluid levels. MRI of the neck corroborates the ultrasound findings and detects parathyroid adenomas as hyperintense nodes on T2-weighted images. Parathyroidectomy yields excellent results, enabling conservative management of lytic lesions.

Childhood Tumors around the Knee Revisited: Predilection Sites for Most Entities Confirmed.

Background: The diagnostic work-up of musculoskeletal tumors is a multifactorial process. During the early phase, differential diagnoses are made using basic radiological imaging. In this phase, part of the decision making is based on the patient's age, as well as the incidence and predilection sites of different entities. Unfortunately, this information is based on older and fragmented data. In this study, we retrospectively evaluated all soft-tissue and bone tumors around the knee in children treated at our tertiary center in the last 20 years, with the aim of verifying the data used today. Methods: In this retrospective study, the databank of our tertiary center was used to give an overview of treated tumors around the knee in children. Results: We were able to include 224 children with bone and soft-tissue tumors around the knee. The cohort consisted of 184 bone tumors, of which 144 were benign and 40 malignant. The 40 soft-tissue tumors comprised 30 benign and 10 malignant masses. The most common lesions were osteochondromas (88) in the bone and tenosynovial giant-cell tumors (12) in the soft tissue. Conclusions: With this original work, we were able to verify and supplement earlier studies, as well as deepen our insight into these very rare diseases.

Free-hand ultrasound strain elastography in evaluation of soft tissue tumors.

The purpose of this study is to evaluate elastography in a wide spectrum of soft tissue superficial lesions by correlating the elastographic characteristics of these lesions with the elastographic score (ES) system established by Asteria. Forty patients with different superficial lesions of the soft tissues were studied, including lipomas, schwannomas, neuromas, epidermal inclusion cysts, "in transit" melanoma metastasis, arterio-venous malformation, and giant-cell tumor. An ultrasound examination was performed combined with color-Doppler and elastographic module. The B-mode criteria were echogenicity, margins, and structural homogeneity of the lesion. The color-Doppler criterion was irregular and mainly intra-nodular vascularization. ES 1-4 was attributed, in relation with the increasing tissue stiffness, according to the classification of Asteria adapted for soft tissues. Subsequently, we added to each single B-mode and color-Doppler criterion the ES 3 and 4, thus crossing two parameters of malignancy. All the presumptive diagnoses formulated were confirmed with the clinical data or with the histopathological result. The hypoechoic appearance had the best diagnostic performance. Sensitivity was 87%, specificity 71%, positive predictive value (PPV) 80%, negative predictive value (NPV) 80%, and diagnostic accuracy 80%. There was a good correlation with the clinical and biopsy data, the irregularity of margins the worst performance, the inhomogeneity an intermediate. Color-Doppler had sensitivity 74%, specificity 82%, PPV 85%, NPV 70% and diagnostic accuracy 77.5%. Elastography had sensitivity 87%, specificity 94%, PPV 95%, NPV 84%, and diagnostic accuracy 90%. The combination hypoechoic appearance + ES3/ES4 showed sensitivity 83%, specificity 100%, PPV 100%, NPV 81%,and diagnostic accuracy of 90%. The combination of irregularity of margins + ES3/ES4 showed sensitivity 43%, specificity 100%, PPV 100%, NPV 59%, and diagnostic accuracy of 67.5%. The combination of inhomogeneity of the lesion + ES3/ES4 showed sensitivity 65%, specificity 94%, PPV 94%, NPV 68%, and diagnostic accuracy of 78%. The combination of the color-Doppler with the ES3/ES4 showed sensitivity 69.5%, specificity 100%, PPV 100%, NPV 71%, and diagnostic accuracy of 82.5%.In the combined evaluation, there was a significant increase in specificity, allowing healthy subjects to be categorized as correctly negative, with a reduction in false positives which also translates into an increase in PPV. Elastography alone is not sufficient for a correct diagnostic classification and must be considered as an additional parameter in the study of soft-tissue lesions. Although there was a good agreement between B-mode malignancy criteria and ES3/ES4, there is no significant improvement in sensitivity. Ultrasound assessment, especially of superficial lesions, cannot be separated from an integrated approach that foresees the additional and routine use of the elastographic examination.