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Background/Objectives : Musculoskeletal neoplasms are rare and challenging diseases. Their geographic pattern varies worldwide, and no studies analyze their distribution in Italy. The aim of this study was to investigate a possible association between clinical variables to a period of diagnosis and geographic origin in Italy. Moreover, we wanted to describe the survival rate of bone osteosarcoma (OS) and Ewing sarcoma (EwS) from the Rizzoli Orthopaedic Institute (IOR) experience. Methods : We retrospectively reviewed 3098 diagnoses of high-grade bone OS and EwS made at the IOR in the past 40 years (1982-2021). Incidence, measures of associations, and survival rates have been analyzed. Results : The time of diagnosis and geographic origin were associated either with each other or with age and stage of tumor. Overall, the 10-year survival rate was 54% (95% CI 52-56) and 53% (95% CI 50-56) for bone OS and EwS, respectively. Multivariate analyses showed that adverse factors at diagnosis are age, location, stage, and time of diagnosis, in both cohorts. Conclusions : We confirmed known prognostic factors, and owing to the large cohort, we highlight their importance in clinical practice. No differences were observed in patient survival associated with different areas of Italy, although geographic origin was associated with most clinical variables analyzed, suggesting a further factor to investigate. Given the above-mentioned results, a Sarcoma Specialist Network with a recognized expertise is determinably in charge of the management of sarcomas.

Background: Pseudotumors are defined as exuberant non-neoplastic inflammatory masses. This condition can be associated with hip and knee arthroplasty but has not been reported in Total Ankle Arthroplasty (TAA). This paper reports a pseudotumor that formed following TAA, highlighting its clinical presentation, management, and histopathology. Methods: A 55-year-old male with end-stage post-traumatic ankle osteoarthritis underwent TAA using a mobile-bearing prosthesis. The procedure was reported to be successful, with no immediate complications. Results: Three years postoperatively, following a period of symptom resolution, the patient presented with progressively worsening ankle pain, swelling, and limited weight-bearing ability. Imaging revealed indirect signs of a periarticular mass and loosening components. Revision surgery involved prosthesis explantation and mass excision for histological and microbiological analysis, followed by concomitant tibio-talo-calcaneal fusion with a retrograde nail. The histopathology identified a pseudotumor characterized by chronic inflammation, fibrous tissue, and necrotic debris, with no evidence of infection. The postoperative recovery was uneventful, with pain resolution and successful fusion confirmed at a one-year follow-up. Conclusions: In patients experiencing unexplained pain or symptoms following TAA, the possibility of a pseudotumor, although rare, should be considered. Prompt and comprehensive clinical and radiographic evaluation is crucial to raise suspicion and prevent this condition from being overlooked.

Epithelioid sarcoma (ES) is a rare tumor hallmarked by the loss of INI1/SMARCB1 expression. Apart from this alteration, little is known about the biology of ES. Despite recent advances in treatment, the prognosis of ES remains unsatisfactory. To elucidate the molecular underpinnings of ES, and to identify diagnostic biomarkers and potential therapeutic vulnerabilities, we performed an integrated omics profiling (RNA sequencing and methylation array) of 24 primary, untreated ESs. Transcriptome and methylome analysis identified 2 distinct molecular clusters that essentially corresponded to the morphologic variants of ES, classic ES (C-ES) and the more aggressive proximal ES (P-ES). The P-ES group was characterized by hyperactivation of GATA3 and MYC pathways, with extensive epigenetic rewiring associated with EZH2 overexpression. Both DNA methylation and gene expression analysis indicated a striking similarity with the "MYC subgroup" of atypical teratoid/rhabdoid tumor, another SMARCB1-deficient tumor, implying a shared molecular background and potential therapeutic vulnerabilities. Conversely, the C-ES group exhibited an endothelial-like molecular profile, with expression of vascular genes and elevated proangiogenic SOX17 signaling. Immunohistochemistry validated the overexpression of the chromatin regulators GATA3 (9/12 vs 0/16) and EZH2 (7/7 vs 2/6) in P-ESs, and of the vascular factors SOX17 (8/8 vs 1/10) and N-cadherin (5/9 vs 0/10) in C-ESs. Therefore, these molecules emerge as potential diagnostic tools to fill the gap represented by the lack of ES subtype-specific biomarkers. In summary, our study shows that P-ES and C-ES represent distinct molecular entities defined by MYC/GATA3 and SOX17/endothelial molecular traits, respectively. Besides providing insights into the biology of ES, our study pinpoints subtype-specific biomarkers and potential therapeutic vulnerabilities., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To depict histological and imaging features of myoepithelial carcinoma of the bone and soft tissue., Materials and Methods: We retrospectively examined histological features in 22 patients with myoepithelial carcinoma of the bone (4 patients) and soft tissue (18 patients) at a single institution. Imaging analysis of 15 patients (bone, 3 patients; soft tissue, 12 patients;) with preoperative images involved classifying lytic bone lesions via the modified Lodwick-Madewell classification; the growth patterns of soft tissue lesions were classified as well-defined, focally invasive, or diffusely invasive., Results: Local recurrence occurred in eight out of 22 patients (36.3%). Four of 22 patients (18.2%) had metastasis at presentation, whereas 11 of 22 patients (50.0%) had distant metastasis during follow-up. Severe cytological pleomorphism was observed in 14 of 22 patients (63.6%), and 10 of 22 tumors (45.5%) showed ≥ 10 mitoses/10 high-power fields. Vascular invasion was observed in 10 of 22 patients (45.5%). Extracapsular/extraskeletal infiltration into the surrounding tissues was assessed in 20 patients, with 14 of them (70%) showing infiltration beyond the tumor border. Regarding imaging of bone lesions, two patients had Ludwick type IIIB, whereas one patient had type II. The growth pattern of soft tissue lesions was well-defined in two patients (16.7%), focally invasive in seven patients (58.3%), and diffusely invasive in three (25.0%) out of 12 patients., Conclusion: Myoepithelial carcinoma of the bone and soft tissue presents high risk of local recurrence and distant metastasis. Histological and imaging features might be important to understand the aggressive behavior of the tumor., (© 2024. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Objective: No consensus exists for tumor volume response criteria in patients with Ewing sarcoma. This study aimed to identify an optimal cutoff for predicting a good histological response by analyzing tumor volume changes and tumor necrosis after neoadjuvant chemotherapy., Materials and Methods: We performed a retrospective analysis of 184 Ewing sarcoma patients, analyzing tumor volume changes before and after neoadjuvant chemotherapy. Patients were divided into two groups based on histological response: good (tumor necrosis ≥ 95%) and poor (tumor necrosis < 95%) responders. The receiver operating characteristic (ROC) area under the curve (AUC) method was used to determine the optimal thresholds for predicting the histological response. Additionally, the prognostic value of this cutoff for relapse-free survival was assessed., Results: Out of 184 patients, 83 (45%) had tumor necrosis ≥ 95%, while 101 (55%) had tumor necrosis < 95%. ROC analysis identified the optimal cutoff for a good histological response as over 65% tumor volume reduction (AUC = 0.69; p < 0.001). Patients with volume reduction of ≥ 65% had a higher likelihood of a good histological response than those with lesser reductions (p = 0.004; odds ratio = 2.61). Multivariable analysis indicated a correlation between poor histological response and reduced relapse-free survival (hazard ratio = 2.17; p = 0.01), while tumor volume reduction itself did not impact survival., Conclusion: We reported that a tumor volume reduction of ≥ 65% was able to predict a good histological response in Ewing sarcoma patients. We recommend preoperative tumor volume assessment to identify patients at greater risk for poor histological response who could benefit from more intensive chemotherapy protocols or additional radiotherapy., (© 2024. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Osteosarcoma and Ewing sarcoma are bone tumors mostly diagnosed in children, adolescents, and young adults. Despite multimodal therapy, morbidity is high and survival rates remain low, especially in the metastatic disease setting. Trials investigating targeted therapies and immunotherapies have not been groundbreaking. Better understanding of biological subgroups, the role of the tumor immune microenvironment, factors that promote metastasis, and clinical biomarkers of prognosis and drug response are required to make progress. A prerequisite to achieve desired success is a thorough, systematic, and clinically linked biological analysis of patient samples, but disease rarity and tissue processing challenges such as logistics and infrastructure have contributed to a lack of relevant samples for clinical care and research. There is a need for a Europe-wide framework to be implemented for the adequate and minimal sampling, processing, storage, and analysis of patient samples. Two international panels of scientists, clinicians, and patient and parent advocates have formed the Fight Osteosarcoma Through European Research consortium and the Euro Ewing Consortium. The consortia shared their expertise and institutional practices to formulate new guidelines. We report new reference standards for adequate and minimally required sampling (time points, diagnostic samples, and liquid biopsy tubes), handling, and biobanking to enable advanced biological studies in bone sarcoma. We describe standards for analysis and annotation to drive collaboration and data harmonization with practical, legal, and ethical considerations. This position paper provides comprehensive guidelines that should become the new standards of care that will accelerate scientific progress, promote collaboration, and improve outcomes., (©2024 The Authors; Published by the American Association for Cancer Research.)

The partial loss of SMARCB1/INI1 expression has recently been reported in skull base conventional chordomas, with possible therapeutic implications. We retrospectively analyzed 89 patients with conventional spinal chordomas to investigate the differences in the immunohistochemical expression of SMARCB1/INI1 and the underlying genetic alterations in the SMARCB1 gene. Moreover, we assessed the correlation of clinicopathological features (age, gender, tumor size, tumor location, surgical margins, Ki67 labelling index, SMARCB1/INI1 pattern, previous surgery, previous treatment, type of surgery, and the Charlson Comorbidity Index) with patient survival. Our cohort included 51 males and 38 females, with a median age at diagnosis of 61 years. The median tumor size at presentation was 5.9 cm. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) rates were 90.8% and 54.9%, respectively. Partial SMARCB1/INI1 loss was identified in 37 (41.6%) patients with conventional spinal chordomas (27 mosaic and 10 clonal). The most frequent genetic alteration detected was the monoallelic deletion of a portion of the long arm of chromosome 22, which includes the SMARCB1 gene. Partial loss of SMARCB1/INI1 was correlated with cervical-thoracic-lumbar tumor location ( p = 0.033) and inadequate surgical margins ( p = 0.007), possibly due to the high degree of tumor invasiveness in this site. Among all the considered clinicopathological features related to patient survival, only tumor location in the sacrococcygeal region and adequate surgical margins positively impacted DFS. In conclusion, partial SMARCB1/INI1 loss, mostly due to 22q deletion, was detected in a significant number of patients with conventional spinal chordomas and was correlated with mobile spine location and inadequate surgical margins., Competing Interests: The authors declare no conflicts of interest.

Epithelioid hemangioma is recognized by the World Health Organization as a distinct benign neoplasm; however, it is characterized by locally aggressive and rarely metastasizing behavior. Epithelioid vascular tumors are rare bony vascular lesions with varying degrees of malignant potential that remain controversial because of their rarity, unusual morphological features, and unpredictable biological behavior. The application of new molecular tools, such as massive parallel sequencing technologies, have provided new diagnostic markers and an opportunity to further refine the classification of bone vascular neoplasms. Very few cases of EH of the spine have been reported in the literature; therefore, it is difficult to make evidence-based therapeutic decisions for these patients. We report herein our experience with eleven patients suffering from EH of the spine. The study population included three males and eight females treated in our center from 2016 to the present; the average age was 44.8 years (range 14-75 years). The surgical, clinical, and radiographic data were retrospectively analyzed. The mean follow-up was 34.8 months. All patients presented lytic vertebral body lesions, six of them with pathological fracture. The majority of patients (80%) presented myelo-radicular compression. All patients were surgically treated, and preoperative embolization was performed in all cases. In light of the literature review and the clinical experience of our center, we can consider EH a locally aggressive tumor that requires surgical treatment in case of symptoms. Here, we propose a treatment algorithm that could be useful in the management of patients with this rare disease.

Aneurysmal bone cyst (ABC) is a rare and usually painful condition, representing about 1% of all bone tumors. A geographical lytic, expansile, and septated radiological pattern, with fluid-fluid levels on MRI, is classically displayed. ABC can be a primary bone lesion (70% of patients) or can arise in an underlying condition and is subsequently named "ABC-like changes" (30%). ABC-like changes are more frequently encountered in skeletal segments affected by chondroblastoma, fibrous dysplasia, giant cell tumor, osteoblastoma, non-ossifying fibroma, and osteosarcoma. In this article, we describe the first case of ABC-like changes developed in association with an ultra-rare sclerosing bone disease: melorheostosis. Melorheostosis is characterized by recognizable patterns on radiological studies with a pathological increased bone density and a cortical thickening within the periosteal or endosteal space, usually with a "dripping candle wax" appearance. More rarely, other different radiological patterns can be observed, such as "osteopatia striata-like," "osteoma-like," "myositis ossificans-like," and mixed patterns. Pain and limb hypotrophy are the most common clinical manifestations. We report the case of a Caucasian male with a clinic-radiological diagnosis of melorheostosis (with epiphyseal osteopoikilosis) since the age of twelve. At the age of nineteen, he suffered from increased pain in the proximal right thigh, and the radiological control revealed an expansive septated lesion at the right proximal femoral bone. The diagnosis of ABC-like changes developed in melorheostosis was obtained after CT-guided bone biopsy and confirmed by open-incisional biopsy., (© 2023. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Angiosarcoma (AS) represents a rare and aggressive vascular sarcoma, posing distinct challenges in clinical management compared to other sarcomas. While the current European Society of Medical Oncology (ESMO) clinical practice guidelines for sarcoma treatment are applicable to AS, its unique aggressiveness and diverse tumor presentations necessitate dedicated and detailed clinical recommendations, which are currently lacking. Notably, considerations regarding surgical extent, radiation therapy (RT), and neoadjuvant/adjuvant chemotherapy vary significantly in localized disease, depending on each different site of onset. Indeed, AS are one of the sarcoma types most sensitive to cytotoxic chemotherapy. Despite this, uncertainties persist regarding optimal management across different clinical presentations, highlighting the need for further investigation through clinical trials. The Italian Sarcoma Group (ISG) organized a consensus meeting on April 1st, 2023, in Castel San Pietro, Italy, bringing together Italian sarcoma experts from several disciplines and patient representatives from "Sofia nel Cuore Onlus" and the ISG patient advocacy working group. The objective was to develop specific clinical recommendations for managing localized AS within the existing framework of sarcoma clinical practice guidelines, accounting for potential practice variations among ISG institutions. The aim was to try to standardize and harmonize clinical practices, or at least highlight the open questions in the local management of the disease, to define the best evidence-based practice for the optimal approach of localized AS and generate the recommendations presented herein., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: None of the authors has any interests to report directly related to this manuscript. Outside the scope of this manuscript: Elena Palassini, Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Giacomo Giulio Baldi, consulting fees from Eli Lilly, Pharmamar, AboutEvents; honoraria from Pharmamar, Eli Lilly, Glaxo Smith Kline, Merck Sharp & Dome, Eisai, Istituto Gentili; support for attending meetings and/or travels from Novartis, Pharmamar, Eli Lilly; participation on advisory board from Pharmamar, Eli Lilly, Glaxo Smith Kline, Merck Sharp & Dome, Eisai. Sara Sulfaro, Marta Barisella, Giuseppe Bianchi, Domenico Campanacci, Marco Fiore, Marco Gambarotti, Massimiliano Gennaro, Carlo Morosi, no conflict of interests to declare. Federico Navarria, travel grants from Pharmamar, Boehringer Ingelheim. Claudia Sangalli, advisory board from Boehringer Ingelheim, Astra Zeneca. Rossella Bertulli, travel grants from PharmaMar. Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Alexia Bertuzzi, Roberto Biagini, Angela Bonadonna, Antonella Brunello, Dario Callegaro, no conflict of interests to declare. Ferdinando Cananzi, speaking fee from Istituto Gentili. Marco Cianchetti, Paola Collini(,) Danila Comandini, Annalisa Curcio, no conflict of interests to declare. Lorenzo D’Ambrosio, advisory board: PSI CRO Italy, GSK, AstraZeneca, Boehringer Ingelheim, Eisai. Meeting participation: GSK, AstraZeneca, PharmaMar. Martino De Pas, participation on advisory board from Glaxo Smith Kline, Boehringer Ingelheim. Trial support from: Pfizer, BluPrint Medicine, Gilead, Amgen, Merck. Angelo Paolo Dei Tos, no conflict of interests to declare. Virginia Ferraresi, Travel grants from PharmaMar, Gentili, Boehringer Ingelheim. Advisory Board: SERB Pharmaceuticals. Andrea Ferrari, Alessandro Franchi, no conflict of interests to declare. Anna Maria Frezza, Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Elena Fumagalli, Advisory Board from Deciphera Pharmaceuticals. Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Matteo Ghilli, Daniela Greto, no conflict of interests to declare. Giovanni Grignani, advisory board from Pharmamar, Incyte, Merck, Novartis, Deciphera,Bayer. Michele Guida, advisory board from Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre. Toni ibrahim, advisory board and consultation fees from Amgen, Glaxosmithkline, PharMamar and Istituto Gentili. Travel grants from Istitaka Gentili and Pharmamar. Marco Krengli, Roberto Luksch, Andrea Marrari, Marinella Mastore, Alessandra Merlini, no conflict of interests to declare. Giuseppe Maria Milano, Advisory board from Bayer, GSK, SERBS Pharmaceuticals. Piera Navarria, Maria Abbondanza Pantaleo, Antonina Parafioriti, no conflict of interests to declare. Ilaria Pellegrini, Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Elisabetta Pennacchioli, Marco Rastrelli, Elisabetta Setola, Salvatore Tafuto, Salvatore Turano, Sergio Valeri, Bruno Vincenzi, Viviana Vitolo, Andrei Ivanescu, Fiammetta Paloschi, no conflict of interests to declare. Paolo Giovanni Casali, Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Alessandro Gronchi, no conflict of interests to declare. Silvia Stacchiotti, personal financial interests (honoraria, consultancy or advisory role): Aadi, Astex Pharmaceuticals, Bavarian Nordic, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Deciphera, Epizyme, Gentili, GSK, Agenus, Ikena, MaxiVAX, Novartis, PharmaMar, Pharma Essentia, Rain Therapeutics, Servier. Support for attending meetings and/or travel Pharmamar; Institutional financial interests: Advenchen, Bayer, Blueprint, Daiichi Sankyo, Deciphera, Epizyme, Eli Lilly, GSK, Hutchinson, Inhibrx, Karyopharm, Novartis, PharmaMar, Rain Therapeutics, SpringWorks; unpaid Member of the Scientifc Advisory Board of the Chordoma Foundation, Member of the Scientifc Advisory Board of the Desmoid Foundation, Member of the Scientifc Advisory Board of the Epithelioid Hemangioendothelioma Group, Member of the Scientifc Advisory Board of the Leiomyosarcoma Foundation., (Copyright © 2024. Published by Elsevier Ltd.)

Background: A BCL6 corepressor (BCOR) gene alteration is a genetic signature of rare subsets of sarcomas. The identification of this alteration has recently contributed to the definition of new entities in the current WHO (2020) classification of soft tissue and bone tumours. We retrospectively examined cases of BCOR-rearranged sarcoma (BRS) to assess the reliability of the BCOR FISH analysis using an IVD (in vitro diagnostic) probe., Methods: We investigated and compared the molecular diagnostic strategies and features by collecting 17 data from patients with a BCOR gene rearrangement detected using quantitative-Reverse Transcription-Polymerase Chain Reaction (qRTPCR), Next-Generation Sequencing (NGS) and Fluorescence in situ hybridization (FISH)., Results: We describe fourteen BCOR::CCNB3 sarcomas, one spindle cell sarcoma with a novel BCOR::MAML1 fusion, one spindle cell sarcoma with a novel BCOR::AHR fusion, and one ossifying fibromyxoid tumour with a BCOR::ZC3H7B fusion. FISH analysis of all, except one, BCOR::CCNB3 sarcoma, showed a FISH break-apart pattern with mild signal separation. The MAML1::BCOR sarcoma showed large-space split signals, while in the two patients with AHR::BCOR and ZC3H7B::BCOR fusions, no BCOR rearrangement was observed using FISH., Conclusions: Our study indicates that BCOR FISH analysis using an IVD probe, may be useful to detect the presence of a BCOR rearrangement, including both translocations and inversions; however, negative results, in some cases, can occur., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Multiple osteochondromas is genetic disorder characterized by the formation of multiple benign cartilage-capped bone tumors, named osteochondromas, during skeletal development. The most feared complication is the secondary peripheral chondrosarcoma, a malignant cartilaginous neoplasm that arises from the chondroid cap of pre-existent osteochondromas. We conducted a retrospective cohort study on patients diagnosed and followed up from 1960 to 2019 to describe the clinical and pathological features of individuals affected by peripheral chondrosarcoma in multiple osteochondromas, to evaluate follow up information and individual outcome and to compare the results with literature. Data, including age, gender, site, histological grade, cartilage cap thickness, surgical treatments, surgical margins, genotype mutational status as well as treatment details were captured from the hospital electronic health records and from Registry of Multiple Osteochondromas. In addition, a complete histological review of all hematoxylin and eosin (H&E)-stained sections has been performed by expert pathologists., Results: One hundred five of the screened cases were included in the present study. The age at diagnosis of SPC ranges from 13 to 63, with median age at diagnosis of 34 years. The site most frequently affected by malignant degeneration was the pelvis (46 patients, 44%) with higher incidence in male patients (32 males vs.14 females). The second one was lower limbs (including femur, fibula, or tibia), identified in 35 patients. Histological information - available for 103 patients - showed: 59 patients with grade 1; 40 patients had a grade 2 and 4 patients had a grade 3. The most common surgical treatment was the complete resection, followed by debulking, amputation and partial resection. Most of cases did not have recurrence of the disease. Outcome in disease-free survival highlights that a worse course of the disease was associated with histological grade 2 or 3, and partial resection surgery. In most of analyzed cases (94%) a pathogenic variant was identified., Conclusions: In conclusion, the present study gives an overview of the secondary peripheral chondrosarcomas, confirming that this disease represents an impacting complication for multiple osteochondromas patients and suggests that malignant transformation can occur also in younger patient, in a not irrelevant number of cases., (© 2024. The Author(s).)

Competing Interests: None declared

Introduction: Extraskeletal Ewing sarcoma (EEwS) is a rare malignant tumor, and current international recommendations indicate systemic and local treatment like bone Ewing sarcoma (BEwS); to the best of our knowledge, very few studies tried to explore the clinical and genetic characteristics of this tumor, and the most appropriate treatment strategy remains uncertain., Methods: We reviewed 35 EEwS cases enrolled at Rizzoli Orthopedic Institute in Bologna, Italy, between 1988-2022. We performed RNA sequencing in 18 Ewing sarcoma cases, including 12 BEwSs and 6 EEwSs. We analyzed overall survival (OS), local relapse-free survival (LRFS), and metastasis-free survival (MFS) and the risk factors associated to survival., Results: Unsupervised hierarchical clustering showed no differences in the transcriptional profile between EEwS and BEwS. Five-year OS was 67% (95% confidence interval [CI]: 47-80), 5-year LRFS was 61% (95% CI: 43-75), and 5-year MFS was 55% (95% CI: 38-70). Recurrent tumors, larger than 8 cm, and elevated lactate dehydrogenase (LDH) serum value resulted to be negative prognostic factors., Conclusions: The finding/detection of a genetic profile that is indistinguishable between EEwS and BEwS confirms the view that the two subgroups belong to the same tumor entity and supports the use of a single therapeutic approach for Ewing sarcoma, regardless of the site of origin. Statistical evaluation showed that size bigger than 8 cm, elevated LDH, and recurrent tumors had a worse prognosis, suggesting a risk-stratification method for identifying patients for specific therapy treatment. However, larger, multicenter, prospective trials are called for to validate our findings., (© 2024 S. Karger AG, Basel.)

Aims: Low-grade central osteosarcoma (LGCOS), a rare type of osteosarcoma, often has misleading radiological and pathological features that overlap with those of other bone tumours, thereby complicating diagnosis and treatment. We aimed to analyze the clinical, radiological, and pathological features of patients with LGCOS, with a focus on diagnosis, treatment, and outcomes., Methods: We retrospectively analyzed the medical records of 49 patients with LGCOS (Broder's grade 1 to 2) treated between January 1985 and December 2017 in a single institute. We examined the presence of malignant features on imaging (periosteal reaction, cortical destruction, soft-tissue invasion), the diagnostic accuracy of biopsy, surgical treatment, and oncological outcome., Results: Based on imaging, 35 of 49 patients (71.4%) exhibited malignant features. Overall, 40 of 49 patients (81.6%) had undergone a biopsy before en-bloc resection: 27 of 40 patients (67.5%) were diagnosed on the first biopsy, which was more accurate when carried out by open rather than needle biopsy (91.3% vs 35.3% diagnostic accuracy, respectively; p < 0.001). Of the 40 patients treated by en-bloc resection, surgical margins were wide in 38 (95.0%) and marginal in two (5.0%). Furthermore, nine of 49 patients (18.4%) underwent curettage (intralesional margin) without previous biopsy. All patients with a positive margin developed local recurrence. Distant metastases occurred in five of 49 patients (10.2%). The mean five-year overall survival (OS) and distant relapse-free survival (D-RFS) were 89.3% (SD 5.1%) and 85.7% (SD 5.5%), respectively. Univariate analysis showed that the occurrence of distant metastasis was a poor prognostic factor for OS (hazard ratio 11.54, 95% confidence interval (CI) 1.92 to 69.17; p < 0.001). Local recurrence was a poor prognostic factor for D-RFS (HR 8.72, 95% CI 1.69 to 45.0; p = 0.002)., Conclusion: The diagnosis of LGCOS can be challenging because it may present with non-malignant features and has a low diagnostic accuracy on biopsy. If precisely diagnosed, LGCOS can be successfully treated by surgical excision with wide margins., Competing Interests: None declared., (© 2024 The British Editorial Society of Bone & Joint Surgery.)

Background: Myxofibrosarcoma is a rare malignant soft tissue sarcoma characterised by multiple local recurrence and can become of higher grade with each recurrence. Consequently, myxofibrosarcoma represents a burden for patients, a challenge for clinicians, and an interesting disease to study tumour progression. Currently, few myxofibrosarcoma preclinical models are available., Methods: In this paper, we present a spontaneously immortalised myxofibrosarcoma patient-derived cell line (MF-R 3). We performed phenotypic characterization through multiple biological assays and analyses: proliferation, clonogenic potential, anchorage-independent growth and colony formation, migration, invasion, AgNOR staining, and ultrastructural evaluation., Results: MF-R 3 cells match morphologic and phenotypic characteristics of the original tumour as 2D cultures, 3D aggregates, and on the chorioallantoic membrane of chick embryos. Overall results show a clear neoplastic potential of this cell line. Finally, we tested MF-R 3 sensitivity to anthracyclines in 2D and 3D conditions finding a good response to these drugs., Conclusions: In conclusion, we established a novel patient-derived myxofibrosarcoma cell line that, together with the few others available, could serve as an important model for studying the molecular pathogenesis of myxofibrosarcoma and for testing new drugs and therapeutic strategies in diverse experimental settings., (© 2023. The Author(s).)

Aim: Myoepithelial carcinoma occurs mainly in salivary glands but rarely can also occur in soft tissues or bone. In this paper, we evaluated the role of surgical margins, radiotherapy, and chemotherapy in myoepithelial carcinoma of soft tissue and bone (MC-SB) treated at our Institute., Methods: Medical records of 33 patients presenting with MC-SB between 1998 and 2015 at our institution were retrospectively analysed, and diagnosis and treatment were studied., Results: The median follow-up was 58.5 months. Twenty patients had tumours originating in soft tissues and 13 in bone. Eight patients (24.2%) had metastases at diagnosis, the remaining 25 had localised disease. Thirty-two underwent resection of the primary lesion. In 29 surgical margins were evaluated: wide in 28 with 10/28 who recurred (35.7%) and marginal resection in 1 who also recurred. Six patients received adjuvant radiotherapy. Metastases developed in 15/25 patients (60%) with localised disease at onset. Chemotherapy was administered in patients with metastatic advanced disease. Cisplatin+doxorubicin was administered in six patients as first-line chemotherapy with an objective response in 5/6 patients with a median 4-month duration. Five-year overall survival rate was 62.6% in patients with localised tumours and 12.5% in those metastatic at diagnosis., Conclusions: MC-SB showed a high incidence of local recurrences and metastases. Despite different chemotherapy regimens, the outcome remains poor in patients with metastatic disease. Due to the absence of a standard protocol, we encourage treatment by multidisciplinary teams in referral centres with renowned expertise., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Myxofibrosarcoma (MFS) is a malignant soft tissue sarcoma (STS) that originates in the body's connective tissues. It is characterized by the presence of myxoid (gel-like) and fibrous components and typically affects patients after the fifth decade of life. Considering the ongoing trend of increasing lifespans across many nations, MFS is likely to become the most common musculoskeletal sarcoma in the future. Although MFS patients have a lower risk of developing distant metastases compared with other STS cases, MFS is characterized by a high frequency of local recurrence. Notably, in 40-60% of the patients where the tumor recurs, it does so multiple times. Consequently, patients may undergo multiple local surgeries, removing the risk of potential amputation. Furthermore, because the tumor relapses generally have a higher grade, they exhibit a decreased response to radio and chemotherapy and an increased tendency to form metastases. Thus, a better understanding of MFS is required, and improved therapeutic options must be developed. Historically, preclinical models for other types of tumors have been instrumental in obtaining a better understanding of tumor development and in testing new therapeutic approaches. However, few MFS models are currently available. In this review, we will describe the MFS models available and will provide insights into the advantages and constraints of each model.

Background: Neurotrophic tyrosine receptor kinase (NTRK) gene-fusion targeted molecules revolutionized the paradigm of treatment of a limited subgroup of cancers of various histologies. Entrectinib and larotrectinib obtained unprecedented response rates in patients with cancer harboring NTRK rearrangements. This evidence recently led to the agnostic approval of these drugs, and evidence (confirmation) of their activity in a broader disease setting is emerging. Here, we report the case of a patient affected by EML4-NTRK3 rearranged undifferentiated spindle cell bone sarcoma treated with larotrectinib, and we argue (discuss about) the incidence and clinical presentation of NTRK gene-fusion positive bone sarcomas, the potential use of upfront treatment with NTRK inhibitors in neoadjuvant setting, and the role of a multidisciplinary tumor board. Despite the rarity of these rearrangements in patients with primitive bone sarcomas, the therapy with NTRK inhibitors represents a highly effective strategy to be pursued in selected cases even in neoadjuvant settings. The management of these very rare cancers should always be discussed in a multidisciplinary board of reference centers., Competing Interests: EP has served on advisory boards for Daiichy Sankyo, Deciphera Pharmaceuticals, Eusa Pharma, and SynOx Therapeutics outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Palmerini, Frega, Gambarotti, Frisoni, Cesari, Bazzocchi, Miceli, Donati, Fanti, Nanni, Benini, Longhi, Paioli, Marrari, Hakim, Righi and Ibrahim.)

Lung cancer is the second most frequently diagnosed cancer in the world, and surgery is an integral part of the treatment for spinal metastases. The aims of this retrospective study were to assess the overall survival of surgically treated patients affected by lung cancer spinal metastases and identify any factors related to a better survival rate. We recruited 56 consecutive patients (34 male and 22 female) surgically treated for metastatic lung cancer in the spine from 2009 to 2019. Surgical indications were based on a previously published and validated flow chart following a multidisciplinary evaluation. We assessed the localization of vertebral metastases, the presence of other bone or visceral metastases, neurological status according to the Frankel score, ambulatory autonomy, and general status, measured with the Karnofsky performance scale. The expected prognosis was retrospectively assessed according to the revised Tokuhashi score. The median survival was 8.1 months, with over a third of patients surviving more than 1 year. We observed a global improvement in all clinical parameters after surgical treatment. The Tokuhashi predictive score did not correlate with survival after surgery. The results of this study suggest that the surgical treatment of symptomatic spinal metastases from lung cancer can improve quality of life, even in patients with a shorter life expectancy, by controlling pain and improving autonomy., Competing Interests: The authors declare no conflicts of interest. The funder had no role in the design of the study; the collection, analyses, or interpretation of data; the writing of the manuscript; or the decision to publish the results.

Background: Undifferentiated small round cell sarcomas (URCSs) represent a diagnostic challenge, and their optimal treatment is unknown. We aimed to define the clinical characteristics, treatment, and outcome of URCS patients., Methods: URCS patients treated from 1983 to 2019 at 21 worldwide sarcoma reference centres were retrospectively identified. Based on molecular assessment, cases were classified as follows: (1) CIC-rearranged round cell sarcomas, (2) BCOR::CCNB3-rearranged round cell sarcomas, (3) unclassified URCSs. Treatment, prognostic factors and outcome were reviewed., Results: In total, 148 patients were identified [88/148 (60%) CIC-rearranged sarcoma (median age 32 years, range 7-78), 33/148 (22%) BCOR::CCNB3-rearranged (median age 17 years, range 5-91), and 27/148 (18%) unclassified URCSs (median age 37 years, range 4-70)]. One hundred-one (68.2%) cases presented with localised disease; 47 (31.8%) had metastases at diagnosis. Male prevalence, younger age, bone primary site, and a low rate of synchronous metastases were observed in BCOR::CCNB3-rearranged cases. Local treatment was surgery in 67/148 (45%) patients, and surgery + radiotherapy in 52/148 (35%). Chemotherapy was given to 122/148 (82%) patients. At a 42.7-month median follow-up, the 3-year overall survival (OS) was 92.2% (95% CI 71.5-98.0) in BCOR::CCNB3 patients, 39.6% (95% CI 27.7-51.3) in CIC-rearranged sarcomas, and 78.7% in unclassified URCSs (95% CI 56.1-90.6; p < 0.0001)., Conclusions: This study is the largest conducted in URCS and confirms major differences in outcomes between URCS subtypes. A full molecular assessment should be undertaken when a diagnosis of URCS is suspected. Prospective studies are needed to better define the optimal treatment strategy in each URCS subtype., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aim: To present our experience on osteosarcomas of the hands and review the existing literature pertaining osteosarcomas in this extremely rare location., Methods: and results: Seven cases of osteosarcomas of the hands were reviewed, and a literature search of all primary osteosarcomas of the hands was performed. All tumors occurred in adults (mean age, 41 years) and were located mainly around the metacarpophalangeal joints. All patients presented with localized long-lasting pain as main symptom. The mean size at diagnosis was 33 mm. Three tumors were low-grade central osteosarcomas, 1 low-grade central chondroblastoma-like osteosarcoma and 3 high-grade osteosarcomas. All tumors were positive for mouse double-minute 2 homolog (MDM2) immunohistochemistry. Three cases yielded results with fluorescence in-situ amplification for MDM2 (12q15)/CEP12. At last follow-up, one patient with a high-grade osteosarcoma was dead of disease. The literature review revealed similar demographic and site distribution of osteosarcomas within the hands than our series and an unusually high proportion of low-grade central and parosteal osteosarcomas when compared to the proportion of these infrequent neoplasms in the whole skeleton., Conclusions: osteosarcomas of hands present in older individuals compared to the population affected by conventional osteosarcomas of all sites. Importantly from a diagnostic, therapeutic and prognostic points of view, around 40% of osteosarcomas of the hands are low-grade osteosarcomas of the central or parosteal types., Competing Interests: Conflict of interest Authors declare no present or potential conflicts of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

The histological diagnosis of sarcoma can be difficult as it sometimes requires the combination of morphological and immunophenotypic analyses with molecular tests. A total of 2705 tissue samples of sarcoma consecutively collected from 2006 until 2020 that had undergone molecular analysis were assessed to evaluate their diagnostic utility compared with histological assessments. A total of 3051 molecular analyses were performed, including 1484 gene fusions tested by c/qRT-PCR, 992 gene rearrangements analysed by FISH, 433 analyses of the gene status of MDM2, 126 mutational analyses and 16 NGS analysis. Of the samples analysed, 68% were from formalin-fixed, paraffin-embedded tissue and 32% were from frozen tissue. C/qRT-PCR and FISH analyses were conclusive on formalin-fixed, paraffin-embedded tissue in 74% and 76% of samples, respectively, but the combination of the two methods gave us conclusive results in 96% and 89% of frozen and formalin-fixed, paraffin-embedded tissues, respectively. We demonstrate the utility of c/qRT-PCR and FISH for sarcoma diagnosis and that each has advantages in specific contexts. We conclude that it is possible to accurately predict the sarcoma subtype using a panel of different subtype-specific FISH probes and c/qRT-PCR assays, thereby greatly facilitating the differential diagnosis of these tumours.

Objective: Chondroblastoma-like osteosarcoma (CBLOS) is a rare and poorly understood variant of OS. We examined the clinicopathological, immunohistochemical and molecular features of six CBLOSs to highlight the differences with conventional high-grade OS (CHGOS) and CB, including CB with aggressive features., Methods: We performed histone 3.3 mutation analysis by gene sequencing and/or immunohistochemistry in all cases, while whole exome sequencing (WES) was performed on two CB-like osteosarcomas and 11 conventional high-grade OS., Results: CBLOSs were predominantly localised at acral sites and involved mainly male subjects with a mean age of 29 years. One patient who had metastases at presentation died of disease, while another patient who developed multiple local recurrences and lung metastases was alive with no evidence of disease (ANED) at 294 months. The remaining patients were ANED after a mean interval of 70.8 months. Histologically, all CBLOS presented aggressive features, including nuclear atypia and infiltrative growth. Immunohistochemistry with H3F3 K36M mutant antibody was negative in all CBLOSs, and none of the five tumours tested by gene sequencing had H3F3B mutations. Conversely, all CBs presented the H3F3B K36M variant and were positive for immunostaining with the H3F3 K36M antibody. Two CBLOSs analysed by WES differed in amount and type of mutation from 11 cases of CHGOS. Moreover, CBLOSs showed lower copy number alteration (CNA) score values than CHGOSs., Conclusions: CBLOS presents a different genetic background and a less aggressive clinical behaviour in comparison with CHGOS. Search of the H3F3B K36M mutation is useful in the differential diagnosis with CB., (© 2022 John Wiley & Sons Ltd.)

Background: Periosteal chondrosarcomas are among the rarest types of chondrosarcomas dealt with in few small series of cases. In this study, we aimed to present our experience with this chondrosarcoma, seek for prognostic factors for OS and DFS and survey the status of IDH1 and IDH2., Results: 55 periosteal chondrosarcomas were retrospectively identified. Median age was 37 years, there was a male predominance (62%). The great majority of cases involved the metaphysis of long bones of the extremities. The median size of the tumors was 7.5 cm. Thirty patients underwent to subtotal surgical resection, 22 to tangential resection and the remaining 3 to amputation. The margins, reported in 54 cases, were wide/radical in 38 patients (70.4%), marginal in 9 (16.7%) and intralesional in 7 (12.9%). Histologically, 23 (42%) were grade 1; 27 (49%), grade 2; 3 (5%), grade 3 and 2 (4%) were dedifferentiated. A third of cases in which mutational analysis was feasible harbored heterozygous mutations in codon 132 of IDH1. Fifty-four cases were included for follow-up (median, 137 months). Four patients had local recurrences and six patients developed metastasis to the lungs. All patients that developed metastasis died of disease, two died of unrelated causes and 46 were alive without disease. OS and DFS was not found to be statistically associated with clinical and pathological parameters considered., Conclusions: periosteal chondrosarcomas exhibit a low-grade behavior that can be adequately treated with marginal excisions. Clinical and morphologic parameters do not seem to predict their outcome., Competing Interests: Declaration of competing interest All authors affirm that we have no actual or potential conflicts of interest, including any financial, personal, or other relationships with other people or organizations., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: According to retrospective osteosarcoma series, ABCB1/P-glycoprotein (Pgp) overexpression predicts for poor outcomes. A prospective trial to assess a risk-adapted treatment strategy using mifamurtide in Pgp+ patients was performed., Methods: This was a phase 2, multicenter, uncontrolled trial including patients 40 years old or younger with nonmetastatic extremity high-grade osteosarcoma stratified according to Pgp expression. All patients received high-dose methotrexate, doxorubicin, and cisplatin (MAP) preoperatively. In Pgp+ patients, mifamurtide was added postoperatively and combined with MAP for a good histologic response (necrosis ≥ 90%; good responders [GRs]) or with high-dose ifosfamide (HDIFO) at 3 g/m 2 /d on days 1 to 5 for a histologic response < 90% (poor responders [PRs]). Pgp- patients received MAP postoperatively. After an amendment, the cumulative dose of methotrexate was increased from 60 to 120 g/m 2 (from 5 to 10 courses). The primary end point was event-free survival (EFS). A postamendment analysis was performed., Results: In all, 279 patients were recruited, and 194 were included in the postamendment analysis: 70 (36%) were Pgp-, and 124 (64%) were Pgp+. The median follow-up was 51 months. For Pgp+ patients, 5-year EFS after definitive surgery (null hypothesis, 40%) was 69.8% (90% confidence interval [CI], 62.2%-76.2%): 59.8% in PRs and 83.7% in GRs. For Pgp- patients, the 5-year EFS rate was 66.4% (90% CI, 55.6%-75.1%)., Conclusions: This study showed that adjuvant mifamurtide, combined with HDIFO for a poor response to induction chemotherapy, could improve EFS in Pgp+ patients. Overall, the outcomes compared favorably with previous series. Mifamurtide and HDIFO as salvage chemotherapy are worth further study., (© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Ewing sarcoma (ES) is an aggressive neoplasm with variable morphology. It has no specific immunoprofile or molecular signature. Neither CD99, NKX2.2 nor PAX7 immunoreactivity alone is completely specific, although diagnostic specificity improves when combined. The purpose of the present study was to investigate the immunohistochemical (IHC) expression of PAX7 in a large series of genetically confirmed ES. Existing results for CD99 and NKX2.2 immunoexpression, morphological findings and molecular studies (fusion gene subtypes) were retrieved from a previous study. Survival analyses were performed in cases with available clinical follow-up. PAX7 was positive in 95.5% of ES with diffuse staining (> 50%) in all positive cases and moderate or strong intensity for most cases. Nineteen ES displayed both PAX7 and CD99 immunoreactivity but lacked NKX2.2 immunoexpression. No relationships could be found between PAX7 expression and the histological types or ES gene fusion subtypes. Univariant/multivariate analysis showed that lack of PAX7 and/or NKX2.2 immunoexpression constitute independent poor prognostic factors for progression free survival (PFS) and overall survival (OS). In conclusion, IHC for CD99, NKX2.2, and PAX7 may be useful in daily practice for ES diagnosis, particularly in hospitals lacking facilities for molecular studies. In addition, the combination of strong CD99 membranous positivity and nuclear PAX7 and NKX2.2 immunoreactivity seems to be very reliable for ES diagnosis when supported by a corroborating histomorphologic and clinical picture. Although PAX7 is not entirely specific for ES, it seems to have a more extensive and strong nuclear immunoreactivity than NKX2.2 expression, even in tumors with decalcification artifact. Considering the prognostically significant data herein reported, we strongly recommend validation in prospective ES series that include localized and disseminated tumors., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Primary spindle cell and pleomorphic sarcomas of bone represent an exceedingly rare group of mesenchymal malignancies that include soft tissue histotypes, as malignant peripheral nerve sheath tumor. Outside the head and neck region, only 36 cases of primary malignant peripheral nerve sheath tumor of bone have been described. We retrieved from our archives eight cases of primary malignant peripheral nerve sheath tumor of bone arising outside the head and neck region, describing their clinical, radiological, and morphologic features. Our series, in which all but one patient died of diseases after a median of seven months, confirms that primary malignant peripheral nerve sheath tumors of bone are aggressive tumors. Pathologists should be aware of this rare histotype. More aggressive and active adjuvant treatments should be investigated., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: To evaluate the diagnostic accuracy of SSX and SSX::SS18 antibodies in decalcified surgical specimens and outcome of synovial sarcomas (SS) of bone., Methods and Results: Twenty-five cases were classified as bone SS (prevalence 0.32% among malignant primary bone sarcoma). Median age was 34 years (range = 9-79). Twenty-four of 25 patients presented with non-metastatic tumours, one with lung metastases. The majority of tumours involved the long bones of extremities with metaphyseal origin. Mean size of the tumour was 7.1 cm. Twenty cases (80%) were monophasic and five (20%) were biphasic. SS18::SSX fusion-specific antibody had 92% sensitivity and 99% specificity for primary bone SS, whereas SSX C-terminus antibody had 100% sensitivity and 94% specificity. Fluorescence in-situ hybridisation (FISH) analysis was feasible in nine (36%) cases and detected SS18 rearrangement in all nine cases. All patients underwent surgical removal of their primary tumour, with adequate margins in 18 (72%) patients. Chemotherapy with metothrexate, cisplatin, doxorubicin and ifosfamide was used in the seven patients. Two patients with inadequate surgical margins received radiotherapy. With a median follow-up of 80 months (range = 6-428), 5- and 10-year overall survival (OS) was 66.6% and 47.9%, respectively, and 5 and 10 years' disease-free survival (DFS) was 36.8% [95% confidence interval (CI) = 18.0-55.7%] and 32.2% (95% CI = 14.6-51.2%), respectively. A significant improvement in 10 years' DFS in patients undergoing chemotherapy compared with patients who did not was observed (P = 0.039)., Conclusions: Our series highlights the utility of SS18::SSX fusion-specific and SSX C-terminus antibodies to support the diagnosis of SS. Adjustment chemotherapy was associated with improved prognosis in this series., (© 2021 John Wiley & Sons Ltd.)

Aim: The aim of this study was to establish how reliable FISH CIC analysis using an IVD (in vitro diagnostic) commercial probe is., Methods and Results: A series of 19 CIC-DUX4 sarcomas were evaluated. The samples presenting CIC-DUX4 fusion transcript detected by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Sanger sequencing and/or Next Generation Sequencing were selected for Fluorescent in Situ Hybridization (FISH) CIC analysis with CIC break-apart IVD probe and compared to molecular analysis. CIC FISH analysis showed 26% of false negatives., Conclusion: Our results indicate that, in the setting of CIC-DUX4 fusion positive small round cell sarcomas, CIC FISH using IVD commercial probe may lead to false-negative results. This novel study evaluates the diagnostic use of a commercial IVD CIC probe for FISH., (Copyright © 2022. Published by Elsevier GmbH.)