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Cellular myxoma is a benign soft tissue tumor frequently associated with GNAS mutation that may morphologically resemble low-grade myxofibrosarcoma. This study aimed to identify the undescribed methylation profile of cellular myxoma and compare it to myxofibrosarcoma. We performed molecular analysis on twenty cellular myxomas and nine myxofibrosarcomas and analyzed the results using the methylation-based DKFZ sarcoma classifier. A total of 90% of the cellular myxomas had GNAS mutations (four loci had not been previously described). Copy number variations were found in all myxofibrosarcomas but in none of the cellular myxomas. In the classifier, none of the cellular myxomas reached the 0.9 threshold. Unsupervised t-SNE analysis demonstrated that cellular myxomas form their own clusters, distinct from myxofibrosarcomas. Our study shows the diagnostic potential and the limitations of molecular analysis in cases where morphology and immunohistochemistry are not sufficient to distinguish cellular myxoma from myxofibrosarcoma, particularly regarding GNAS wild-type tumors. The DKFZ sarcoma classifier only provided a valid prediction for one myxofibrosarcoma case; this limitation could be improved by training the tool with a more considerable number of cases. Additionally, the classifier should be introduced to a broader spectrum of mesenchymal neoplasms, including benign tumors like cellular myxoma, whose distinct methylation pattern we demonstrated.
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Variations de nombre de copies de segment d'ADN , Méthylation de l'ADN , Fibrosarcome , Myxome , Humains , Myxome/génétique , Myxome/diagnostic , Myxome/anatomopathologie , Fibrosarcome/génétique , Fibrosarcome/anatomopathologie , Fibrosarcome/diagnostic , Fibrosarcome/métabolisme , Adulte d'âge moyen , Femelle , Sujet âgé , Mâle , Adulte , Mutation , Diagnostic différentiel , Sous-unités alpha Gs des protéines G/génétique , Chromogranine/génétique , Sujet âgé de 80 ans ou plus , Tumeurs des tissus mous/génétique , Tumeurs des tissus mous/diagnostic , Tumeurs des tissus mous/anatomopathologieRÉSUMÉ
OBJECTIVE: We aim to evaluate the efficacy of CT-guided percutaneous radiofrequency ablation (RFA) and surgical treatment in osteoid osteoma (OO) treated at the Medical University of Graz. MATERIALS AND METHODS: In a single-institution study, we analysed data from January 2005 to January 2021 of patients with histological/radiological diagnosis of OO. CT and MRI scans were reviewed for typical findings. Means (with SD) and medians (with IQR) were reported for normally and non-normally distributed variables. Differences between groups were assessed using chi-squared tests and t-tests. RESULTS: One hundred nineteen patients (mean age: 21.6 ± 10.9 years; 63.9% males) with confirmed OO were retrospectively evaluated. 73 and 43 patients underwent RFA and surgery, respectively. In three cases, RFA combined with surgery was performed. Pre-intervention, 103 patients (88.8%) had undergone CT, and 101 had an MRI (87.1%). The nidus was confirmed in 82.5% of cases with CTs (85/103) and 63.4% with MRIs (64/101). The majority of nidi were located cortically (n = 96; 82.8%), most frequently in the femur (38 patients, 33.3%) with a median size of 8.0 mm (IQR: 5.0-12.0 mm). Median symptom duration before treatment was 6.0 (IQR: 4.0-13.0) months. The complication rate was 12.1% (14/116; 15.1% RFA vs. 7.0% surgery; p = 0.196). In total, 11.2% of patients had persistent symptoms after one week with clinical success rates of RFA and surgery, 86.3% and 90.7% (p = 0.647), respectively. CONCLUSION: Compared to surgical treatment, CT-guided percutaneous RFA is a safe, minimally invasive, reliable, and efficient treatment option for OO. CRITICAL RELEVANCE STATEMENT: This article critically assesses the diagnosis and treatment of osteoid osteoma, emphasising accurate imaging, and detailing a non-invasive option for effective management. KEY POINTS: ⢠This study analyses 116 cases of OO at one institution, focusing on symptom persistence, recurrence in short-term follow-up, and complications in two study groups. ⢠Surgery showed higher, though not statistically significant, success despite comparable symptom persistence; CT displayed typical OO features more than MRI, regardless of the intramedullary, cortical and subperiosteal location as well as the site of the affected bone. ⢠CT-guided RFA is an effective therapeutic alternative for OO compared to surgical intervention. In case of atypical OO appearance, RFA is not the first-line treatment.
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Autotransplantation of a mature tooth usually leads to pulpal necrosis. Root canal treatment is recommended to prevent related inflammatory complications a few weeks after surgery. Extraoral root-end resection may facilitate reperfusion and obviate root canal treatment, but cannot be pictured with conventional dental radiography at this point in time. In the case of a lower mature transplanted molar, contrast-enhanced magnetic resonance imaging proved to be a feasible method for visualizing pulp revascularization just 4 weeks after autotransplantation. Consequently, root canal treatment was obviated. Nevertheless, the tooth had to be extracted 18 months postoperatively due to external cervical root resorption, probably caused by the extraction trauma. This allowed the histological processing and examination of the newly generated intracanal tissue. Uninflamed fibrovascular connective tissue was found, while odontoblasts or cementoblast-like cells were absent. These findings indicated that it was most likely stem cells from the bone marrow and the periodontal ligament that drove the regeneration.
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BACKGROUND: In the ongoing development of bioresorbable implants, there has been a particular focus on magnesium (Mg)-based alloys. Several Mg alloys have shown promising properties, including a lean, bioresorbable magnesium-zinc-calcium (Mg-Zn-Ca) alloy designated as ZX00. To our knowledge, this is the first clinically tested Mg-based alloy free from rare-earth elements or other elements. Its use in medial malleolar fractures has allowed for bone healing without requiring surgical removal. It is thus of interest to assess the resorption behavior of this novel bioresorbable implant. QUESTIONS/PURPOSES: (1) What is the behavior of implanted Mg-alloy (ZX00) screws in terms of resorption (implant volume, implant surface, and gas volume) and bone response (histologic evaluation) in a sheep model after 13 months and 25 months? (2) What are the radiographic changes and clinical outcomes, including patient-reported outcome measures, at a mean of 2.5 years after Mg-alloy (ZX00) screw fixation in patients with medial malleolar fractures? METHODS: A sheep model was used to assess 18 Mg-alloy (ZX00) different-length screws (29 mm, 24 mm, and 16 mm) implanted in the tibiae and compared with six titanium-alloy screws. Micro-CT was performed at 13 and 25 months to quantify the implant volume, implant surface, and gas volume at the implant sites, as well as histology at both timepoints. Between July 2018 and October 2019, we treated 20 patients with ZX00 screws for medial malleolar fractures in a first-in-humans study. We considered isolated, bimalleolar, or trimalleolar fractures potentially eligible. Thus, 20 patients were eligible for follow-up. However, 5% (one patient) of patients were excluded from the analysis because of an unplanned surgery for a pre-existing osteochondral lesion of the talus performed 17 months after ZX00 implantation. Additionally, another 5% (one patient) of patients were lost before reaching the minimum study follow-up period. Our required minimum follow-up period was 18 months to ensure sufficient time to observe the outcomes of interest. At this timepoint, 10% (two patients) of patients were either missing or lost to follow-up. The follow-up time was a mean of 2.5 ± 0.6 years and a median of 2.4 years (range 18 to 43 months). RESULTS: In this sheep model, after 13 months, the 29-mm screws (initial volume: 198 ± 1 mm3) degraded by 41% (116 ± 6 mm3, mean difference 82 [95% CI 71 to 92]; p < 0.001), and after 25 months by 65% (69 ± 7 mm3, mean difference 130 [95% CI 117 to 142]; p < 0.001). After 13 months, the 24-mm screws (initial volume: 174 ± 0.2 mm3) degraded by 51% (86 ± 21 mm3, mean difference 88 [95% CI 52 to 123]; p = 0.004), and after 25 months by 72% (49 ± 25 mm3, mean difference 125 [95% CI 83 to 167]; p = 0.003). After 13 months, the 16-mm screws (initial volume: 112 ± 5 mm3) degraded by 57% (49 ± 8 mm3, mean difference 63 [95% CI 50 to 76]; p < 0.001), and after 25 months by 61% (45 ± 10 mm3, mean difference 67 [95% CI 52 to 82]; p < 0.001). Histologic evaluation qualitatively showed ongoing resorption with new bone formation closely connected to the resorbing screw without an inflammatory reaction. In patients treated with Mg-alloy screws after a mean of 2.5 years, the implants were radiographically not visible in 17 of 18 patients and the bone had homogenous texture in 15 of 18 patients. No clinical or patient-reported complications were observed. CONCLUSION: In this sheep model, Mg-alloy (ZX00) screws showed a resorption to one-third of the original volume after 25 months, without eliciting adverse immunologic reactions, supporting biocompatibility during this period. Mg-alloy (ZX00) implants were not detectable on radiographs after a mean of 2.5 years, suggesting full resorption, but further studies are needed to assess environmental changes regarding bone quality at the implantation site after implant resorption. CLINICAL RELEVANCE: The study demonstrated successful healing of medial malleolar fractures using bioresorbable Mg-alloy screws without clinical complications or revision surgery, resulting in pain-free ankle function after 2.5 years. Future prospective studies with larger samples and extended follow-up periods are necessary to comprehensively assess the long-term effectiveness and safety of ZX00 screws, including an exploration of limitations when there is altered bone integrity, such as in those with osteoporosis. Additional use of advanced imaging techniques, such as high-resolution CT, can enhance evaluation accuracy.
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Objectives: Subcutaneous granuloma annulare (SGA) is a rare, self-limiting granulomatous disease in children, commonly diagnosed by histopathology following biopsy or surgical excision. This study aimed to identify imaging clues for SGA that could expedite accurate diagnosis and avoid the need for biopsy in children. Methods: We retrospectively analyzed complete hospital records of all children diagnosed with SGA at our institution from January 2001 to December 2020. Detailed disease history, imaging findings, management, and outcome were evaluated. Results: We identified 28 patients (20 girls) at a median age of 3.75 (range 1-12.5 years). Ten patients presented with multiple lesions. Most lesions were located on the lower extremities (n = 26/41). Ultrasound examinations were performed on all patients, and 12 (43%) patients also received an MRI. Surgical intervention was conducted in 18 (64%) patients either by incisional biopsy (n = 6) or total excision of the lump (n = 12). In all patients who did not undergo surgery, SGA resolved spontaneously. A careful review of the MRIs led to the discovery of a characteristic imaging shape of SGA lesions: the epifascial cap with a typical broad circular base laying on the fascia, extending towards the subdermal/dermal tissue. This distinctive shape was evident in every patient in our cohort. Conclusions: The "Epifascial Cap Sign" is a specific imaging sign for SGA, which to the best of our knowledge, helps distinguish this disease from other subcutaneous lesions. Recognition of this novel diagnostic sign combined with the historical and physical findings should enable clinicians to establish SGA diagnosis easily and diminish the need for further invasive diagnostic procedures.
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OBJECTIVES: There are various subcutaneous lesions in children and often there is difficulty in obtaining an accurate diagnosis by non-invasive diagnostic procedures. Subcutaneous granuloma annulare (SGA) is a rare granulomatous disease that, even after imaging, is often mistaken for a low-flow subcutaneous vascular malformation (SVM). This study aimed to accurately identify clinical and imaging clues to distinguish SGA from low-flow SVM. METHODS: We retrospectively analyzed complete hospital records of all children with a confirmed diagnosis of SGA and low-flow SVM who underwent MR imaging at our institution from January 2001 to December 2020. Their disease history, clinical and imaging findings, management, and outcome were evaluated. RESULTS: Among 57 patients with granuloma annulare, we identified 12 patients (nine girls) with a confirmed SGA diagnosis who underwent a preoperative MRI. Their median age was 3.25 years (range 2-5 years). Of 455 patients diagnosed with vascular malformations, 90 had malformations limited to the subcutaneous area. Among them only 47 patients with low-flow SVM were included in the study and further analyzed. Our SGA cohort had a female predilection (75%) and a short history of lump appearance of 1.5 months. SGA lesions were immobile and firm. Before MRI, patients underwent initial evaluation by ultrasound (100%) and X-ray (50%). Surgical tissue sampling was performed in all SGA patients to establish a diagnosis. All 47 patients with low-flow SVM were diagnosed correctly by MRI. A total of 45 patients (96%) underwent surgical resection of the SVM. A careful retrospective review of imaging findings of patients with SGA and SVM showed that SGA present as homogenous lesions in the shape of an epifascial cap with a typical broad fascial base extending towards the subdermal tissue in the middle of the lesion. In contrast, SVMs always present with variable-sized multicystic or tubular areas. CONCLUSIONS: Our study shows clear clinical and imaging differences between low-flow SVMs and SGA. SGA presents characteristically in the shape of a homogenous "epifascial cap," which distinguishes these lesions from multicystic heterogenous SVMs.
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Trichoblastic carcinosarcoma is a seldom biphasic adnexal tumor with malignant epithelial and mesenchymal components. The authors report the first tumor on the neck developed from preexistent trichoblastoma showing aggressive, recurrent behavior. An 82-year-old man presented with a solitary 3-cm exophytic lesion. Histology verified the diagnosis of trichoblastic carcinosarcoma. Four years earlier, a trichoblastic carcinoma arising in a preexisting trichoblastoma was excised at the same location. Despite successful surgical treatments, three local recurrences within 4 years were diagnosed. After the second relapse, the patient agreed on adjuvant radiation. Twelve months later, another relapse was excised in toto. In the last surgical specimen, only the mesenchymal component was found. Copy number variation analysis of the preexisting tumor and two recurrences revealed the same entity and additional chromosomal aberrations in the recurrences. Adnexal carcinosarcomas are seldom, yet presumably underdiagnosed biphasic tumors with aggressive growth potential. They should have adequate preoperative clarification with wide tumor excision, as radiosensitivity seems to be of limited effect.
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Carcinosarcome , Maladies du système pileux , Tumeurs basocellulaires , Tumeurs cutanées , Mâle , Humains , Sujet âgé de 80 ans ou plus , Variations de nombre de copies de segment d'ADN , Récidive tumorale locale/diagnostic , Récidive tumorale locale/génétique , Tumeurs cutanées/diagnostic , Tumeurs cutanées/génétique , Tumeurs cutanées/chirurgie , Maladies du système pileux/anatomopathologie , Carcinosarcome/diagnostic , Carcinosarcome/génétique , Carcinosarcome/chirurgieRÉSUMÉ
Male breast cancer (MBC) is rare and usually presents as a locally advanced disease. Stromal tumor-infiltrating lymphocytes (sTILs) are associated with a better response to neoadjuvant chemotherapy and improved prognosis in all molecular subtypes of female breast cancer, but their role in MBC is less clear. We studied sTILs and the expression of programmed cell death ligand 1 (PD-L1) and pan-TRK in MBC. We retrospectively studied 113 cases of MBC surgically treated between 1988 and 2015. The tumors were evaluated for histological type and grade, stage, intrinsic subtype and sTILs. We performed immunohistochemistry for PD-L1 (clone SP142) and pan-TRK (clone EPR17341) on tissue microarrays. Pan-TRK positive cases were further analyzed by next-generation sequencing. The median age was 69 years (range 60−77). Invasive carcinoma of no special type was found in 94.7% of cases, of which 53.1% were grade 2. Estrogen receptor was positive in 92% of the tumors, progesterone receptor in 85.8%, androgen receptor in 70.8%; 4.4% were human epidermal growth factor receptor 2 (HER2)-positive, and 55.8% HER2-low. 40.7% of tumors were luminal A and 51.3% luminal B, 4.4% HER2-enriched and 3.5% triple negative carcinoma. sTILs density was <50% in 96.4% of the tumors, >50% in 3.6% of the tumors. PD-L1 immune cell score >1% was found in 7.1% of the tumors (all of luminal subtype). A weak focal cytoplasmic pan-TRK staining was present in 8.8% but without NTRK fusion. Neither sTILs nor PD-L1 had statistically significant outcomes. Our findings suggest that a subset of MBC patients harbors an immunological environment characterized by increased sTILs with PD-L1 expression. These patients may potentially benefit from immune checkpoint inhibitor therapy. Frequent HER2-low may offer novel anti-HER2 treatment options.
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Tumeur du sein de l'homme , Tumeurs du sein , Tumeurs du sein triple-négatives , Femelle , Humains , Mâle , Adulte d'âge moyen , Sujet âgé , Tumeur du sein de l'homme/métabolisme , Lymphocytes TIL , Antigène CD274/génétique , Antigène CD274/métabolisme , Microenvironnement tumoral , Études rétrospectives , Tumeurs du sein/métabolisme , Marqueurs biologiques tumoraux/métabolisme , Tumeurs du sein triple-négatives/anatomopathologieRÉSUMÉ
Magnesium (Mg)-based implants are highly attractive for the orthopedic field and may replace titanium (Ti) as support for fracture healing. To determine the implant-bone interaction in different bony regions, we implanted Mg-based alloy ZX00 (Mg < 0.5 Zn < 0.5 Ca, in wt%) and Ti-screws into the distal epiphysis and distal metaphysis of sheep tibiae. The implant degradation and osseointegration were assessed in vivo and ex vivo after 4, 6 and 12 weeks, using a combination of clinical computed tomography, medium-resolution micro computed tomography (µCT) and high-resolution synchrotron radiation µCT (SRµCT). Implant volume loss, gas formation and bone growth were evaluated for both implantation sites and each bone region independently. Additionally, histological analysis of bone growth was performed on embedded hard-tissue samples. We demonstrate that in all cases, the degradation rate of ZX00-implants ranges between 0.23 and 0.75 mm/year. The highest degradation rates were found in the epiphysis. Bone-to-implant contact varied between the time points and bone types for both materials. Mostly, bone-volume-to-total-volume was higher around Ti-implants. However, we found an increased cortical thickness around the ZX00-screws when compared with the Ti-screws. Our results showed the suitability of ZX00-screws for implantation into the distal meta- and epiphysis.
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BACKGROUND: Awareness of the potential global overtreatment of patients with appendiceal neuroendocrine tumours (NETs) of 1-2 cm in size by performing oncological resections is increasing, but the rarity of this tumour has impeded clear recommendations to date. We aimed to assess the malignant potential of appendiceal NETs of 1-2 cm in size in patients with or without right-sided hemicolectomy. METHODS: In this retrospective cohort study, we pooled data from 40 hospitals in 15 European countries for patients of any age and Eastern Cooperative Oncology Group performance status with a histopathologically confirmed appendiceal NET of 1-2 cm in size who had a complete resection of the primary tumour between Jan 1, 2000, and Dec 31, 2010. Patients either had an appendectomy only or an appendectomy with oncological right-sided hemicolectomy or ileocecal resection. Predefined primary outcomes were the frequency of distant metastases and tumour-related mortality. Secondary outcomes included the frequency of regional lymph node metastases, the association between regional lymph node metastases and histopathological risk factors, and overall survival with or without right-sided hemicolectomy. Cox proportional hazards regression was used to estimate the relative all-cause mortality hazard associated with right-sided hemicolectomy compared with appendectomy alone. This study is registered with ClinicalTrials.gov, NCT03852693. FINDINGS: 282 patients with suspected appendiceal tumours were identified, of whom 278 with an appendiceal NET of 1-2 cm in size were included. 163 (59%) had an appendectomy and 115 (41%) had a right-sided hemicolectomy, 110 (40%) were men, 168 (60%) were women, and mean age at initial surgery was 36·0 years (SD 18·2). Median follow-up was 13·0 years (IQR 11·0-15·6). After centralised histopathological review, appendiceal NETs were classified as a possible or probable primary tumour in two (1%) of 278 patients with distant peritoneal metastases and in two (1%) 278 patients with distant metastases in the liver. All metastases were diagnosed synchronously with no tumour-related deaths during follow-up. Regional lymph node metastases were found in 22 (20%) of 112 patients with right-sided hemicolectomy with available data. On the basis of histopathological risk factors, we estimated that 12·8% (95% CI 6·5 -21·1) of patients undergoing appendectomy probably had residual regional lymph node metastases. Overall survival was similar between patients with appendectomy and right-sided hemicolectomy (adjusted hazard ratio 0·88 [95% CI 0·36-2·17]; p=0·71). INTERPRETATION: This study provides evidence that right-sided hemicolectomy is not indicated after complete resection of an appendiceal NET of 1-2 cm in size by appendectomy, that regional lymph node metastases of appendiceal NETs are clinically irrelevant, and that an additional postoperative exclusion of metastases and histopathological evaluation of risk factors is not supported by the presented results. These findings should inform consensus best practice guidelines for this patient cohort. FUNDING: Swiss Cancer Research foundation.
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Tumeurs de l'appendice , Tumeurs neuroendocrines , Mâle , Humains , Femelle , Adulte , Tumeurs neuroendocrines/chirurgie , Tumeurs neuroendocrines/anatomopathologie , Appendicectomie/effets indésirables , Appendicectomie/méthodes , Études rétrospectives , Tumeurs de l'appendice/chirurgie , Tumeurs de l'appendice/diagnostic , Tumeurs de l'appendice/anatomopathologie , Études de cohortes , Métastase lymphatique , Europe , Colectomie/effets indésirablesRÉSUMÉ
BACKGROUND: To prevent further spread of the disease and secondary deformity, musculoskeletal tuberculosis (TB) remains a challenge in terms of early diagnosis and treatment. This study gives an overview on TB trends in Austria (pulmonary and extrapulmonary TB) (A) and analyses a retrospective series of musculoskeletal TB cases diagnosed and treated at an Austrian tertiary centre (B). METHODS: (A) We analysed data obtained from the Austrian national TB registry to provide information on TB patients´ demographics and manifestation sites between 1995 and 2019. (B) Furthermore, we performed an observational study of all patients with a confirmed diagnosis of musculoskeletal TB who were admitted to the Department of Orthopaedics and Trauma, Medical University of Graz (2005-2019). Demographic, diagnostic, clinical and follow-up data were retrieved from the medical records. RESULTS: (A) From 1995 to 2019, a significant linear reduction in overall Austrian tuberculosis incidence rates occurred (p < 0.001). In the period investigated, Austria recorded a total of 307 patients with musculoskeletal TB. (B) Our retrospective case-series included 17 individuals (9 males, 8 females; average follow-up 48.4 months; range 0-116). There was a biphasic age distribution with a peak in elderly native Austrians (median 69, range 63-92), and a second peak in younger patients with a migration background (median 29, range 18-39). Sites of manifestation were the spine (n = 10), peripheral joints (n = 5), and the soft tissues (n = 2). Diagnosis was based on histology (n = 13), PCR (n = 14), and culture (n = 12). Eleven patients underwent surgery (64.7%). Secondary deformities were frequent (n = 9), and more often observed in patients with spinal TB (n = 6). CONCLUSION: Musculoskeletal TB should be considered if untypical joint infections or nonspecific bone lesions occur in younger patients with a migration background or in patients with specific risk factors.
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Tuberculose ostéoarticulaire , Mâle , Femelle , Humains , Sujet âgé , Autriche/épidémiologie , Études rétrospectives , Tuberculose ostéoarticulaire/épidémiologie , Tuberculose ostéoarticulaire/diagnostic , Facteurs de risque , EnregistrementsRÉSUMÉ
In the last decade, new tumor entities have been described, including EWSR1/FUS::NFATC2-rearranged neoplasms of different biologic behavior. To gain further insights into the behavior of these tumors, we analyzed a spectrum of EWSR1/FUS::NFATC2-rearranged neoplasms and discuss their key diagnostic and molecular features in relation to their prognosis. We report five patients with EWSR1/FUS::NFATC2-rearranged neoplasms, including one simple bone cyst (SBC), two complex cystic bone lesions lacking morphological characteristics of SBC, and two sarcomas. In three cases, fluorescence in situ hybridization (FISH) and in all cases copy number variation (CNV) profiling and fusion analyses were performed. All patients were male, three cystic lesions occurred in children (aged 10, 14, and 17 years), and two sarcomas in adults (69 and 39 years). Fusion analysis revealed two FUS::NFATC2 rearrangements in two cystic lesions and three EWSR1::NFATC2 rearrangements in one complex cystic lesion and two sarcomas. EWSR1 FISH revealed tumor cells with break-apart signal without amplification in one complex cystic lesion and EWSR1 amplification in both sarcomas was documented. CNV analysis showed simple karyotypes in all cystic lesions, while more complex karyotypes were found in NFATC2-rearranged sarcomas. Our study supports and expands previously reported molecular findings of EWSR1/FUS::NFATC2-rearranged neoplasms. The study highlights the importance of combining radiology and morphologic features with molecular aberrations. The use of additional molecular methods, such as CNV and FISH in the routine diagnostic workup, can be crucial in providing a correct diagnosis and avoiding overtreatment.
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Tumeurs osseuses , Sarcomes , Tumeurs des tissus mous , Femelle , Humains , Mâle , Tumeurs osseuses/diagnostic , Tumeurs osseuses/génétique , Tumeurs osseuses/anatomopathologie , Variations de nombre de copies de segment d'ADN , Hybridation fluorescente in situ , Facteurs de transcription NFATC/génétique , Protéines de fusion oncogènes/génétique , Protéine EWS de liaison à l'ARN/génétique , Protéine FUS de liaison à l'ARN/génétique , Sarcomes/diagnostic , Sarcomes/génétique , Tumeurs des tissus mous/diagnostic , Facteurs de transcription , Enfant , Adolescent , Adulte , Sujet âgéRÉSUMÉ
INTRODUCTION: The aim of this study was to externally validate the 2013-SPRING model, a survival prediction tool for patients treated surgically for bone metastases in a retrospective patient cohort from a single institution. Moreover, subgroup analyses on patients treated with (A) endoprostheses or (B) osteosynthesis, as well as (C) upper limb and (D) lower limb metastases, were performed. METHODS: Altogether, 303 cancer patients (mean age: 67.6 ± 11.1 years; 140 males (46.2%)) with bone metastases to the extremities, treated surgically between March 2000 and June 2018 at a single tertiary sarcoma centre, were retrospectively included. Median follow-up amounted to 6.3 (interquartile range (IQR): 2.3-21.8) months, with all patients followed-up for at least one year or until death. The 2013-SPRING model was applied to assess the prognostication accuracy at 3, 6 and 12 months. Models were validated with area under the curve receiver operator characteristic (AUC ROC; the higher the better), as well as Brier score. RESULTS: Of the 303 patients, 141 had been treated with osteosynthesis (46.5%), and the remaining 162 patients with endoprosthesis (53.5%). Sixty-five (21.5%) metastases were located in the upper limbs, and two hundred and thirty-eight (78.5%) in the lower limbs. Using the 2013-SPRING model for the entire cohort, the accuracy of risk of death prediction at 3, 6 and 12 months, determined by the AUC ROC, was 0.782 (95% CI: 0.729-0.843), 0.810 (95% CI: 0.763-0.858) and 0.802 (95% CI: 0.751-0.854), respectively. Corresponding Brier scores were 0.170, 0.178 and 0.169 at 3, 6 and 12 months. In the subgroup analyses, predictive accuracy of the 2013-SPRING model was likewise encouraging, albeit being slightly higher in the osteosynthesis subgroup as compared with the endoprosthesis subgroup, and also higher in the upper limb in comparison to the lower limb metastasis subgroup. CONCLUSIONS: The current validation study of the 2013-SPRING model shows that this model is clinically relevant to use in an external cohort, also after stratification for surgical procedure and metastasis location.
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Primary sarcomas of the lung are extremely uncommon. A diverse group of round cell sarcomas has been reported to originate in this location, including Ewing sarcoma, desmoplastic small round cell tumor, rhabdomyosarcoma, and poorly differentiated synovial sarcoma. The rarity of these tumors presents a potential pitfall; without careful study, they may easily be misidentified as the significantly more common poorly differentiated carcinoma. While histomorphology is a key aspect of correctly identifying a sarcoma, ancillary testing has become increasingly important in making a definitive diagnosis, as more and more recurrent genetic alterations are discovered and new entities are defined. We present three cases of primary round cell sarcomas of the lung that proved diagnostically challenging, describe the features and ancillary testing that led to the correct diagnoses, and discuss classic and evolving entities among sarcomas with round cell morphology.
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Sarcomes , Tumeurs des tissus mous , Humains , Anatomopathologistes , Marqueurs biologiques tumoraux/génétique , Diagnostic différentiel , Sarcomes/diagnostic , Sarcomes/génétique , Tumeurs des tissus mous/anatomopathologie , Poumon/anatomopathologieRÉSUMÉ
Soft tissue sarcomas (STS) represent a small group of adult solid malignancies, with risk factors such as environmental factors, genetic predisposition, and prior radiotherapy. In STS patients with a novel swelling, differential diagnoses include recurrence, second primary cancer, metastasis from unknown primary cancer, and radiation-associated STS, the latter usually occurring approximately 10 years after radiotherapy. We present the case of a 64-year-old male patient with pleomorphic rhabdomyosarcoma, who underwent resection and radiotherapy. The patient presented again 5 years later with painful swelling in the area of the prior sarcoma, raising suspicion of recurrence. Resection was performed and a diagnosis of pleomorphic sarcoma (not otherwise specified [NOS]) was made. The patient was treated with radiotherapy and remained sarcoma-free for the following 7 years. A molecular analysis of both neoplasms, using RNA next-generation sequencing, did not detect any specific fusions. Due to the lack of rhabdomyoblastic differentiation in the second sarcoma and the low likelihood of a second primary in the same previously irradiated location, the diagnosis of a radiation-associated STS was suggested. This short report illustrates the difficult diagnostic work-up of a presumably radiation-associated STS, as these neoplasms lack characteristic morphological and immunohistochemical features. In our case, the suggested diagnosis may have pointed against another course of radiotherapy in an already irradiation-harmed region. Therefore, a relatively low latency period between surgery, radiotherapy, and diagnosis of another STS should not automatically point towards recurrence and may prompt further in-depth investigation.
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Seconde tumeur primitive , Rhabdomyosarcome , Sarcomes , Tumeurs des tissus mous , Adulte , Humains , Mâle , Adulte d'âge moyen , Seconde tumeur primitive/diagnostic , Seconde tumeur primitive/génétique , Rhabdomyosarcome/diagnostic , Rhabdomyosarcome/thérapie , Sarcomes/diagnostic , Sarcomes/thérapie , Tumeurs des tissus mous/diagnostic , Tumeurs des tissus mous/thérapieRÉSUMÉ
Diffuse gastric carcinoma (DGC) is characterized by poorly cohesive cells, highly invasive growth patterns, poor prognosis and resistance to the majority of available systemic therapeutic strategies. It has been previously reported that the Wnt/ß-catenin signaling pathway serves a prominent role in the tumorigenesis of gastric carcinoma. However, the mechanism underlying the dysregulation of this pathway in DGC has not been fully elucidated. Therefore, the present study aimed to investigate the expression profiles of Wnt antagonists, secreted frizzled-related protein 1 (SFRP1) and secreted frizzled-related protein 3 (SFRP3), and dishevelled protein family members, dishevelled segment polarity protein 2 (DVL2) and dishevelled segment polarity protein 3 (DVL3), in DGC tissues. The association between the expression levels of these factors and the clinicopathological parameters of the patients was determined. Protein and mRNA expression levels in 62 DGC tumor tissues and 62 normal gastric mucosal tissues obtained from patients with non-malignant disease were measured using immunohistochemical and reverse transcription-quantitative PCR (RT-qPCR) analysis. Significantly lower protein expression levels of SFRP1 (P<0.001) and SFRP3 (P<0.001), but significantly higher protein expression levels of DVL2 (P<0.001) and DVL3 (P<0.001) were observed in DGC tissues compared with in control tissues by immunohistochemistry. In addition, significantly lower expression levels of SFRP1 (P<0.05) and higher expression levels of DVL3 (P<0.05) were found in in DGC tissues compared with those in normal gastric mucosal tissues using RT-qPCR. According to correlation analysis between the SFRP1, SFRP3, DVL2 and DVL3 protein expression levels and the clinicopathological characteristics of patients with DGC, a statistically significant correlation was found between the SFRP3 volume density and T stage (r=0.304; P=0.017) and between the SFRP3 volume density and clinical stage (r=0.336; P=0.008). In conclusion, the findings of the present study suggested that the Wnt signaling pathway components SFRP1, SFRP3, DVL2 and DVL3 may be aberrantly expressed in DGC tissues, implicating their possible role in the development of this malignant disease. The present data also revealed a positive relationship between SFRP3 protein expression and the clinical and T stage of DGC.
RÉSUMÉ
PURPOSE: Drug screening programmes have revealed epidermal growth factor receptor inhibitors (EGFRis) as promising therapeutics for chordoma, an orphan malignant bone tumour, in the absence of a known genetic driver. Concurrently, the irreversible EGFRi afatinib (Giotrif®) is being evaluated in a multicentric Phase II trial. As tyrosine kinase inhibitor (TKI) monotherapies are invariably followed by resistance, we aimed to evaluate potential therapeutic combinations with EGFRis. METHODS: We screened 133 clinically approved anticancer drugs as single agents and in combination with two EGFRis (afatinib and erlotinib) in the clival chordoma cell line UM-Chor1. Synergistic combinations were analysed in a 7 × 7 matrix format. The most promising combination was further explored in clival (UM-Chor1, MUG-CC1) and sacral (MUG-Chor1, U-CH1) chordoma cell lines. Secretomes were analysed for receptor tyrosine kinase ligands (EGF, TGF-α, FGF-2 and VEGF-A) upon drug treatment. RESULTS: Drugs that were active as single agents (n = 45) included TKIs, HDAC and proteasome inhibitors, and cytostatic drugs. Six combinations were analysed in a matrix format: n = 4 resulted in a significantly increased cell killing (crizotinib, dabrafenib, panobinostat and doxorubicin), and n = 2 exhibited no or negligible effects (regorafenib, venetoclax). Clival chordoma cell lines were more responsive to combined EGFR-MET inhibition. EGFR-MET cross-talk (e.g. via TGF-α secretion) likely accounts for the synergistic effects of EGFR-MET inhibition. CONCLUSION: Our screen revealed promising combinations with EGFRis, such as the ALK/MET-inhibitor crizotinib, the HDAC-inhibitor panobinostat or the topoisomerase-II-inhibitor doxorubicin, which are part of standard chemotherapy regimens for various bone and soft-tissue sarcomas.
Sujet(s)
Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Chordome/traitement médicamenteux , Tests de criblage d'agents antitumoraux , , Afatinib/pharmacologie , Afatinib/usage thérapeutique , Antinéoplasiques/pharmacologie , Antinéoplasiques/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/pharmacologie , Communication autocrine , Lignée cellulaire tumorale , Crizotinib/pharmacologie , Crizotinib/usage thérapeutique , Agrément de médicaments , Récepteurs ErbB/antagonistes et inhibiteurs , Récepteurs ErbB/métabolisme , Facteur de croissance des hépatocytes/métabolisme , Humains , Ligands , Inhibiteurs de protéines kinases/pharmacologie , Protéines proto-oncogènes c-met/métabolisme , Facteur de croissance transformant alpha/métabolisme , États-Unis , Food and Drug Administration (USA) , Facteur de croissance endothéliale vasculaire de type A/métabolismeRÉSUMÉ
BACKGROUND: Molecular diagnosis has become an established tool in the characterisation of adult soft-tissue sarcomas (STS). FoundationOne® Heme analyses somatic gene alterations in sarcomas via DNA and RNA-hotspot sequencing of tumour-associated genes. METHODS: We evaluated FoundationOne® Heme testing in 81 localised STS including 35 translocation-associated and 46 complex-karyotyped cases from a single institution. RESULTS: Although FoundationOne® Heme achieved broad patient coverage and identified at least five genetic alterations in each sample, the sensitivity for fusion detection was rather low, at 42.4%. Nevertheless, potential targets for STS treatment were detected using the FoundationOne® Heme assay: complex-karyotyped sarcomas frequently displayed copy-number alterations of common tumour-suppressor genes, particularly deletions in TP53, NF1, ATRX, and CDKN2A. A subset of myxofibrosarcomas (MFS) was amplified for HGF (n = 3) and MET (n = 1). PIK3CA was mutated in 7/15 cases of myxoid liposarcoma (MLS; 46.7%). Epigenetic regulators (e.g. MLL2 and MLL3) were frequently mutated. CONCLUSIONS: In summary, FoundationOne® Heme detected a broad range of genetic alterations and potential therapeutic targets in STS (e.g. HGF/MET in a subset of MFS, or PIK3CA in MLS). The assay's sensitivity for fusion detection was low in our sample and needs to be re-evaluated in a larger cohort.
RÉSUMÉ
Background and purpose - Cat scratch disease (CSD) is a self-limiting disease caused by Bartonella (B.) henselae. It is characterized by granulomatous infection, most frequently involving lymph nodes. However, it can present with atypical symptoms including musculoskeletal manifestations, posing a diagnostic challenge. We describe the prevalence and demographics of CSD cases referred to a sarcoma center, and describe the radiological, histological, and molecular findings.Patients and methods - Our cohort comprised 10 patients, median age 27 years (12-74) with clinical and radiological findings suspicious of sarcoma.Results - 7 cases involved the upper extremities, and 1 case each involved the axilla, groin, and knee. B. henselae was found in 6 cases tested using polymerase chain reaction and serology in 5 cases. 9 cases were soft tissue lesions and 1 lesion involved the bone. 1 patient had concomitant CSD with melanoma metastasis in enlarged axillary lymph nodes. On MRI, 5 soft tissue lesions were categorized as probably inflammatory. In 3 cases, with still detectable lymph node structure and absent or initial liquefaction, the differential diagnosis included lymph node metastasis. A sarcoma diagnosis was suggested in 4 cases. The MRI imaging features of the bone lesion were suspicious of a bone tumor or osteomyelitis.Interpretation - Atypical imaging findings cause a diagnostic challenge and the differential diagnosis includes malignant neoplasms (such as sarcoma or carcinoma metastasis) and other infections. The distinction between these possibilities is crucial for treatment and prognosis.