Proteomic Characterization of Undifferentiated Small Round Cell Sarcomas with EWSR1- and CIC::DUX4-Translocations Reveals Diverging Tumor Biology and Distinct Diagnostic Markers.

Undifferentiated small round cell sarcomas of bone and soft tissue (USRS) are a group of tumors with heterogenic genomic alterations sharing similar morphology. In the present study, we performed a comparative large-scale proteomic analysis of USRS (n=42) with diverse genomic translocations including classic Ewing sarcomas with EWSR1::FLI1 fusions (n=24) or EWSR1::ERG - fusions (n=4), sarcomas with an EWSR1 - rearrangement (n=2), CIC::DUX4 fusion (n=8), as well as tumors classified as USRS with no genetic data available (n=4). Proteins extracted from formalin-fixed, paraffin-embedded (FFPE) pretherapeutic biopsies were analyzed qualitatively and quantitatively using shot gun mass spectrometry (MS). More than 8000 protein groups could be quantified using data-independent acquisition. Unsupervised hierarchical cluster analysis based on proteomic data allowed stratification of the 42 cases into distinct groups reflecting the different molecular genotypes. Protein signatures that significantly correlated with the respective genomic translocations were identified and used to generate a heatmap of all 42 sarcomas with assignment of cases with unknown molecular genetic data to either the EWSR1- or CIC-rearranged groups. MS-based prediction of sarcoma subtypes was molecularly confirmed in two cases where next-generation sequencing was technically feasible. MS also detected proteins routinely used in the immunohistochemical approach for the differential diagnosis of USRS. BCL11B highly expressed in Ewing sarcomas and Bach2 as well as ETS-1 highly expressed in CIC::DUX4-associated sarcomas, were among proteins identified by the present proteomic study and were chosen for immunohistochemical confirmation of MS data in our study cohort. Differential expression of these 3 markers in the two genetic groups were further validated in an independent cohort of n= 34 USRS. Finally, our proteomic results point towards diverging signaling pathways in the different USRS subgroups.

[Bone marrow edema syndromes of the knee]. / Knochenmarködem-Syndrome am Kniegelenk.

Bone marrow edema represents a common finding on magnetic resonance imaging (MRI) of the knee and other joints, which can occur as a primary pathology or as a secondary phenomenon of various bone and joint pathologies. This article reviews the terminology, definition, pathology and differential diagnosis of bone marrow edema of the knee taking into consideration current concepts.

Soft tissue tumor imaging in adults: European Society of Musculoskeletal Radiology-Guidelines 2023-overview, and primary local imaging: how and where?

OBJECTIVES: Early, accurate diagnosis is crucial for the prognosis of patients with soft tissue sarcomas. To this end, standardization of imaging algorithms, technical requirements, and reporting is therefore a prerequisite. Since the first European Society of Musculoskeletal Radiology (ESSR) consensus in 2015, technical achievements, further insights into specific entities, and the revised WHO-classification (2020) and AJCC staging system (2017) made an update necessary. The guidelines are intended to support radiologists in their decision-making and contribute to interdisciplinary tumor board discussions. MATERIALS AND METHODS: A validated Delphi method based on peer-reviewed literature was used to derive consensus among a panel of 46 specialized musculoskeletal radiologists from 12 European countries. Statements were scored online by level of agreement (0 to 10) during two iterative rounds. Either "group consensus," "group agreement," or "lack of agreement" was achieved. RESULTS: Eight sections were defined that finally contained 145 statements with comments. Overall, group consensus was reached in 95.9%, and group agreement in 4.1%. This communication contains the first part consisting of the imaging algorithm for suspected soft tissue tumors, methods for local imaging, and the role of tumor centers. CONCLUSION: Ultrasound represents the initial triage imaging modality for accessible and small tumors. MRI is the modality of choice for the characterization and local staging of most soft tissue tumors. CT is indicated in special situations. In suspicious or likely malignant tumors, a specialist tumor center should be contacted for referral or teleradiologic second opinion. This should be done before performing a biopsy, without exception. CLINICAL RELEVANCE: The updated ESSR soft tissue tumor imaging guidelines aim to provide best practice expert consensus for standardized imaging, to support radiologists in their decision-making, and to improve examination comparability both in individual patients and in future studies on individualized strategies. KEY POINTS: • Ultrasound remains the best initial triage imaging modality for accessible and small suspected soft tissue tumors. • MRI is the modality of choice for the characterization and local staging of soft tissue tumors in most cases; CT is indicated in special situations. Suspicious or likely malignant tumors should undergo biopsy. • In patients with large, indeterminate or suspicious tumors, a tumor reference center should be contacted for referral or teleradiologic second opinion; this must be done before a biopsy.

Diagnostic Delay in Patients with Osteoid Osteoma.

PURPOSE: To assess diagnostic delay in patients with osteoid osteoma and to analyze influencing factors. MATERIALS AND METHODS: All patients treated for osteoid osteoma at our tertiary referral center between December 1997 and February 2021 were retrospectively identified (n = 302). The diagnosis was verified by an expert panel of radiologists and orthopedic surgeons. The exclusion criteria were post-interventional recurrence, missing data on symptom onset, and lack of pretherapeutic CT images. Clinical parameters were retrieved from the local clinical information system. CT and MR images were assessed by a senior specialist in musculoskeletal radiology. RESULTS: After all exclusions, we studied 162 patients (mean age: 24 ±â€Š11 years, 115 men). The average diagnostic delay was 419 ±â€Š485 days (median: 275 days; range: 21-4503 days). Gender, patient age, presence of nocturnal pain, positive aspirin test, extent of bone sclerosis, and location of the tumor within bone and relative to joints did not influence diagnostic delay (p > 0.05). It was, however, positively correlated with nidus size (r = 0.26; p < 0.001) and was shorter with affection of long tubular bones compared to all other sites (p = 0.04). If osteoid osteoma was included in the initial differential diagnoses, the diagnostic delay was also shorter (p = 0.007). CONCLUSION: The diagnostic delay in patients with osteoid osteoma is independent of demographics, clinical parameters, and most imaging parameters. A long average delay of more than one year suggests low awareness of the disease among physicians. Patients with unclear imaging findings should thus be referred to a specialized musculoskeletal center or an expert in the field should be consulted in a timely manner. KEY POINTS: · In this retrospective study of 162 patients treated for osteoid osteoma, the median diagnostic delay was 275 days (range: 21-4503 days).. · Gender, age, presence of nocturnal pain, positive aspirin test, extent of bone sclerosis, and location of the tumor did not influence the diagnostic delay (p > 0.05).. · Diagnostic delay was positively correlated with nidus size (r = 0.26; p < 0.001) and was shorter with affection of long tubular bones compared to all other sites (376 ±â€Š485 vs. 560 ±â€Š462 days; p = 0.04)..

Coronal extrusion of the lateral meniscus does not increase after pullout repair of the posterior root of the lateral meniscus at short-term follow-up.

PURPOSE: Posterior lateral meniscus root (PLMR) tears are injuries that commonly occur together with anterior cruciate ligament (ACL) tears. The aim of this study was to evaluate the clinical and radiological outcome of PLMR repair accompanying ACL reconstruction. Specifically, PLMR healing rates, meniscal extrusion behavior and their influence on patient-reported outcome measures (PROMs) were analyzed. It was hypothesized that PLMR repair shows satisfactory healing rates and coronal meniscal extrusion does not increase significantly following PLMR repair. METHODS: Patients that underwent PLMR repair between 2014 and 2019 were evaluated at least 12 months postoperatively. At follow-up, magnetic resonance imaging (MRI) was performed in order to evaluate the PLMR healing behavior (complete vs. partial vs. no healing) as well as the coronal and sagittal meniscal extrusion in comparison with the preoperative MRI. Additionally, patient-reported outcome measures (PROMs; Lysholm score, International Knee Documentation Committee subjective knee form [IKDC]) were compiled. Pre- and postoperative meniscal extrusion were tested for statistical significance using the paired t test. The Kruskal-Wallis test was used to compare extrusion values and PROMs in relation to different healing states. A correlation analysis was conducted using the Pearson correlation coefficient between differences in meniscal extrusion and PROMs. RESULTS: Out of 25 patients, 18 patients (72.0%; 11 male and seven female) were available for final assessment at a mean follow-up of 40.8 ± SD 17.5 months. One revision PLMR repair was performed five months after the initial repair. In 14 cases (77.8%), healing of the lateral meniscus was observed (6 × complete, 8 × partial). Coronal extrusion of the lateral meniscus did not increase significantly following PLMR repair (2.0 ± 1.5 mm vs. 2.1 ± 1.3 mm; p = 0.645). Sagittal extrusion increased significantly (25.7 ± 2.4 mm vs. 27.0 ± 1.4 mm; p < 0.001). The healing status of the PLMR showed no significant association with meniscal extrusion or PROMs (p > 0.05). But a higher increase in coronal meniscal extrusion negatively affected PROMs (Lysholm score: p = 0.046, r = - 0.475; IKDC: p = 0.003, r = - 0.651). CONCLUSION: High healing rates of the PLMR and no significant increase in coronal extrusion may be expected following combined PLMR repair and ACL reconstruction. But a greater increase in postoperative coronal meniscal extrusion correlates with less favorable clinical results. A greater increase in sagittal extrusion was observed, but this did not influence the clinical outcome. LEVEL OF EVIDENCE: Retrospective Case Series; IV.

[Tophaceous gout as a differential diagnosis of preauricular tumor]. / Tophöse Gicht als Differenzialdiagnose eines präaurikulären Tumors.

Primary gout is a hereditary disorder in nucleotide metabolism. In addition to typical manifestations in the feet, hands, and large joints, there may be rare manifestations in the head and neck. We report a case of tophaceous gout in the temporomandibular joint in a patient who presented with preauricular swelling and progressive hearing impairment. Physical examination showed obliteration of the auditory canal and imaging revealed a destructive process involving the skull base. The diagnosis was confirmed by imaging and biopsy.

Differentiating Enchondromas and Atypical Cartilaginous Tumors in Long Bones with Computed Tomography and Magnetic Resonance Imaging.

The differentiation between the atypical cartilaginous tumor (ACT) and the enchondromas is crucial as ACTs require a curettage and clinical as well as imaging follow-ups, whereas in the majority of cases enchondromas require neither a treatment nor follow-ups. Differentiating enchondromas from ACTs radiologically remains challenging. Therefore, this study evaluated imaging criteria in a combination of computed tomography (CT) and magnetic resonance (MR) imaging for the differentiation between enchondromas and ACTs in long bones. A total of 82 patients who presented consecutively at our institution with either an ACT (23, age 52.7 ±18.8 years; 14 women) or an enchondroma (59, age 46.0 ± 11.1 years; 37 women) over a period of 10 years, who had undergone preoperative MR and CT imaging and subsequent biopsy or/and surgical removal, were included in this study. A histopathological diagnosis was available in all cases. Two experienced radiologists evaluated several imaging criteria on CT and MR images. Likelihood of an ACT was significantly increased if either edema within the bone (p = 0.049), within the adjacent soft tissue (p = 0.006) or continuous growth pattern (p = 0.077) were present or if the fat entrapment (p = 0.027) was absent on MR images. Analyzing imaging features on CT, the likelihood of the diagnosis of an ACT was significantly increased if endosteal scalloping >2/3 (p < 0.001), cortical penetration (p < 0.001) and expansion of bone (p = 0.002) were present and if matrix calcifications were observed in less than 1/3 of the tumor (p = 0.013). All other imaging criteria evaluated showed no significant influence on likelihood of ACT or enchondroma (p > 0.05). In conclusion, both CT and MR imaging show suggestive signs which can help to adequately differentiate enchondromas from ACTs in long bones and therefore can improve diagnostics and consequently patient management. Nevertheless, these features are rare and a combination of CT and MR imaging features did not improve the diagnostic performance substantially.

[Surgical treatment of chest wall tumors]. / Chirurgische Therapie von Brustwandtumoren.

The term chest wall tumor summarizes a heterogeneous group of malignant and benign tumors, whereby primary and secondary chest wall tumors are differentiated. The incidence of secondary chest wall tumors is higher than that of primary tumors. Primary chest wall tumors can arise from any anatomic structure of the chest wall. Surgical resection is usually the treatment of choice. Resection status and tumor differentiation are relevant prognostic factors. Treatment of secondary chest wall tumors is performed depending on the patient's symptoms and prognosis of the underlying disease. Lung carcinomas infiltrating the chest wall can be resected primarily or secondarily as part of multimodal therapeutic strategies. Anatomic lung resections combined with chest wall resection have a higher mortality than standard resections. Chest wall reconstruction after resection has the goal of reducing paradoxical respiratory motion, although not every chest wall defect requires reconstruction.

Epicondylopathia humeri radialis. / Epicondylopathia humeri radialis (Epicondylitis radialis) ­ Diagnostik und Therapie unter Berücksichtigung der aktuellen S2k-Leitlinie.

BACKGROUND: Lateral epicondylitis is a common orthopaedic condition often massively restricting the quality of life of the affected patients. There are a wide variety of treatment options - with varying levels of evidence. METHOD: The following statements and recommendations are based on the current German S2k guideline Epicondylopathia radialis humeri (AWMF registry number: 033 - 2019). All major German specialist societies participated in this guideline, which is based on a systematic review of the literature and a structured consensus-building process. OUTCOMES: Lateral epicondylitis should be diagnosed clinically and can be confirmed by imaging modalities. The Guidelines Commission issues recommendations on clinical and radiological diagnostic workup. The clinical condition results from the accumulated effect of mechanical overload, neurologic irritation and metabolic changes. Differentiating between acute and chronic disorder is helpful. Prognosis of non-surgical regimens is favourable in most cases. Most cases spontaneously resolve within 12 months. In case of unsuccessful attempted non-surgical management for at least six months, surgery may be considered as an alternative, if there is a corresponding structural morphology and clinical manifestation. At present, it is not possible to recommend a specific surgical procedure. CONCLUSION: This paper provides a summary of the guideline with extracts of the recommendations and statements of its authors regarding the pathogenesis, prevention, diagnostic workup as well as non-surgical and surgical management.

Ultrasound-based examination of the medial ligament complex shows gender- and age-related differences in laxity.

PURPOSE: Ultrasound (US) examination of the medial joint space of the knee has played a subordinate diagnostic role up till now. The purpose of the present study was to describe mean values of medial joint width and to investigate the impact of gender, age, and body mass index (BMI) on medial joint laxity in healthy knees using modern, dynamic US in a standardized fashion in unloaded and standardized loaded conditions. METHODS: A total of 65 subjects with 79 healthy knees were enrolled in this study. All volunteers underwent clinical examination of the knee. The medial knee joint width was determined using US in a supine position at 0° and 30° of knee flexion in unloaded and standardized loaded (= 15 Dekanewton, daN) conditions using a specific device. Mean values were described and correlations between medial knee joint width and gender, age, and BMI were assessed. RESULTS: Thirty-two females and 33 males were enrolled in this study. The mean medial joint width in 0° unloaded was 5.7 ± 1.2 mm and 7.4 ± 1.4 mm loaded. In 30° of knee flexion, the mean medial joint width was 6.1 ± 1.1 mm unloaded and 7.8 ± 1.2 mm loaded. The average change between unloaded and loaded conditions in 0° was 1.7 ± 1.0 mm and in 30° 1.7 ± 0.9 mm. A significant difference between genders was evident for medial joint width in 0° and 30° of flexion in unloaded and loaded conditions (p < 0.05). With rising age, a significant increased change of medial joint space width between unloaded and loaded conditions could be demonstrated in 0° (p = 0.032). No significant correlation between BMI and medial joint width in US could be found. CONCLUSION: Mean values of medial joint width in unloaded and standardized loaded conditions using a fixation device could be demonstrated. Based on the results of this study, medial knee joint width in US is gender- and age-related in healthy knees. These present data may be useful for evaluating patients with acute or chronic pathologies to the medial side of the knee. LEVEL OF EVIDENCE: III.

Preoperative Evaluation of Myxofibrosarcoma: Prognostic Value and Reproducibility of Different Features on MRI.

BACKGROUND/AIM: Myxofibrosarcoma (MFS) is characterized by an infiltrative growth pattern. This study aimed to determine the correlation between overall survival (OS) and morphological features of MFS as well as examine the reproducibility of these findings on preoperative magnetic resonance imaging (MRI). PATIENTS AND METHODS: Fifty-eight MFS patients underwent preoperative MR imaging with the following features analysed: i) tumour size, ii) localization, iii) margins, iv) morphology, v) signal characteristics, vi) contrast enhancement, vii) presence and extent of perilesional oedema, and viii) presence of the tail sign. RESULTS: Only circumscribed perilesional oedema was associated with a significantly better survival compared to diffuse oedema (p=0.010), which was found in the majority of cases. The tail sign was found in less than 50% of the cases. Cohen's kappa coefficients confirmed a relatively high interrater variability. CONCLUSION: Perilesional diffuse oedema on MR imaging of MFS is significantly correlated with a poor overall survival. The interrater variability in interpretation of MR examinations varies from slight to substantial agreement. Preoperative MR imaging with detailed planning of the resection seem to be a logical approach to achieve negative resection margins and recurrence-free survival.

[Parosteal low-grade osteosarcoma with focal differentiation]. / Parossales Low-grade-Osteosarkom mit fokaler Dedifferenzierung.

This case study deals with the case of a 16-year-old male patient with a low-grade parosteal osteosarcoma of the distal femur with focal differentiation. Case history, disease course, and surgery as well as the pathological workup with final diagnosis are presented. Relevant radiologic and pathologic differential diagnoses und diagnostic pitfalls are explained in detail and discussed. Additionally, postoperative treatment options are illustrated.

Diagnosis of peripheral bone and prosthetic joint infections: overview on the consensus documents by the EANM, EBJIS, and ESR (with ESCMID endorsement).

OBJECTIVES: Peripheral bone infection (PBI) and prosthetic joint infection (PJI) are two different infectious conditions of the musculoskeletal system. They have in common to be quite challenging to be diagnosed and no clear diagnostic flowchart has been established. Thus, a conjoined initiative on these two topics has been initiated by the European Society of Radiology (ESR), the European Association of Nuclear Medicine (EANM), the European Bone and Joint Infection Society (EBJIS), and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). The purpose of this work is to provide an overview on the two consensus documents on PBI and PJI that originated by the conjoined work of the ESR, EANM, and EBJIS (with ESCMID endorsement). METHODS AND RESULTS: After literature search, a list of 18 statements for PBI and 25 statements for PJI were drafted in consensus on the most debated diagnostic challenges on these two topics, with emphasis on imaging. CONCLUSIONS: Overall, white blood cell scintigraphy and magnetic resonance imaging have individually demonstrated the highest diagnostic performance over other imaging modalities for the diagnosis of PBI and PJI. However, the choice of which advanced diagnostic modality to use first depends on several factors, such as the benefit for the patient, local experience of imaging specialists, costs, and availability. Since robust, comparative studies among most tests do not exist, the proposed flowcharts are based not only on existing literature but also on the opinion of multiple experts involved on these topics. KEY POINTS: • For peripheral bone infection and prosthetic joint infection, white blood cell and magnetic resonance imaging have individually demonstrated the highest diagnostic performance over other imaging modalities. • Two evidence- and expert-based diagnostic flowcharts involving variable combination of laboratory tests, biopsy methods, and radiological and nuclear medicine imaging modalities are proposed by a multi-society expert panel. • Clinical application of these flowcharts depends on several factors, such as the benefit for the patient, local experience, costs, and availability.

Neoadjuvant image-guided helical intensity modulated radiotherapy of extremity sarcomas - a single center experience.

BACKGROUND: Advanced radiotherapy (RT) techniques allow normal tissue to be spared in patients with extremity soft tissue sarcoma (STS). This work aims to evaluate toxicity and outcome after neoadjuvant image-guided radiotherapy (IGRT) as helical intensity modulated radiotherapy (IMRT) with reduced margins based on MRI-based target definition in patients with STS. METHODS: Between 2010 to 2014, 41 patients with extremity STS were treated with IGRT delivered as helical IMRT on a tomotherapy machine. The tumor site was in the upper extremity in 6 patients (15%) and lower extremity in 35 patients (85%). Reduced margins of 2.5 cm in longitudinal direction and 1.0 cm in axial direction were used to expand the MRI-defined gross tumor volume, including peritumoral edema, to the clinical target volume. An additional margin of 5 mm was added to receive the planning target volume. The full total dose of 50 Gy in 2 Gy fractions was sucessfully applied in 40 patients. Two patients received chemotherapy instead of surgery due to systemic progression. All patients were included into a strict follow-up program and were seen interdisciplinarily by the Departments of Orthopaedic Surgery and Radiation Oncology. RESULTS: Thirty eight patients that received total RT total dose and subsequent resection were analyzed for outcome. After a median follow-up of 38.5 months cumulative OS, local PFS and systemic PFS at 2 years were determined at 78.2, 85.2 and 54.5%, respectively. Two of 6 local recurrences were proximal marginal misses. Negative resection margins were achieved in 84% of patients. The rate of major wound complications was comparable to previous IMRT studies with 36.8%. RT was overall tolerable with low toxicity rates. CONCLUSIONS: IMRT-IGRT offers neoadjuvant treatment for extremity STS with reduced safety margins and thus low toxicity rates. Wound complication rates were comparable to previously reported frequencies. Two reported marginal misses suggest a word of caution for reduction of longitudinal safety margins.

Mountain ultramarathon results in temporary meniscus extrusion in healthy athletes.

PURPOSE: In recent literature medial meniscus extrusion (MME) was demonstrated as an age, BMI and load dependent physiological phenomenon in healthy knees. The aim of the present study was to evaluate the influence of mountain ultramarathon running on the medial meniscus extrusion (MME) in healthy athletes. METHODS: Healthy athletes of the 2017 Gore-Tex® Transalpine run (seven stages with in total 270.5 km and 16453 m altitude) with asymptomatic knee, and no history of knee injuries or surgeries were included. All athletes underwent standard knee examination, MRI to exclude further knee pathologies and ultrasound imaging (USI) for measurement of MME before the competition. Extrusion in USI was determined in supine position (unloaded) and in standing position with full weight bearing and 20° of flexion (loaded). After the 1st, 3rd, and 7th stage ultrasound measurements were repeated directly after the competition. For evaluation of recovery, ultrasound measurement of MME was repeated 2 weeks after the race. Difference between ultrasound measurements of MME was assessed by unpaired t-test with significance set at p < 0.05. RESULTS: Eighteen athletes (mean age 37.4 ± 8.3 years, 5 females, 13 males) were included in the study. The mean USI MME before the race was 1.9 mm ± 0.3 mm in supine position and 2.4 mm ± 0.4 mm under full weight bearing. During the race the mean MME increased significantly compared to baseline measurements. After 7th stage the mean MME in supine position was 2.7 mm ± 0.7 mm and 3.1 mm ± 0.6 mm under full weight bearing. After 2 weeks of recovery medial meniscus demonstrated a complete reversibility of the extrusion to normal (N.S). CONCLUSION: Medial meniscus extrusion observed under extreme loads generated by a mountain ultramarathon is a temporary and reversible phenomenon in healthy athletes. This suggests, that the meniscus has viscoelastic capacities showing short-term adaptions to high loads, which are completely reversible over time. For clinical practice assessment of the MME by ultrasound might be favorable compared to MRI due to the ability of dynamic evaluation and the easy access. Furthermore, load should be taken in account when assessing the MME and the current cut-off value of 3 mm for meniscus pathologies should be reconsidered. LEVEL OF EVIDENCE: IV.

Three-material decomposition with dual-layer spectral CT compared to MRI for the detection of bone marrow edema in patients with acute vertebral fractures.

OBJECTIVES: To assess whether bone marrow edema in patients with acute vertebral fractures can be accurately diagnosed based on three-material decomposition with dual-layer spectral CT (DLCT). MATERIALS AND METHODS: Acute (n = 41) and chronic (n = 18) osteoporotic thoracolumbar vertebral fractures as diagnosed by MRI (hyperintense signal in STIR sequences) in 27 subjects (72 ± 11 years; 17 women) were assessed with DLCT. Spectral data were decomposed into hydroxyapatite, edema-equivalent, and fat-equivalent density maps using an in-house-developed algorithm. Two radiologists, blinded to clinical and MR findings, assessed DLCT and conventional CT independently, using a Likert scale (1 = no edema; 2 = likely no edema; 3 = likely edema; 4 = edema). For DLCT and conventional CT, accuracy, sensitivity, and specificity for identifying acute fractures (Likert scale, 3 and 4) were analyzed separately using MRI as standard of reference. RESULTS: For the identification of acute fractures, conventional CT showed a sensitivity of 0.73-0.76 and specificity of 0.78-0.83, whereas the sensitivity (0.93-0.95) and specificity (0.89) of decomposed DLCT images were substantially higher. Accuracy increased from 0.76 for conventional CT to 0.92-0.93 using DLCT. Interreader agreement for fracture assessment was high in conventional CT (weighted κ [95% confidence interval]; 0.81 [0.70; 0.92]) and DLCT (0.96 [0.92; 1.00]). CONCLUSIONS: Material decomposition of DLCT data substantially improved accuracy for the diagnosis of acute vertebral fractures, with a high interreader agreement. This may spare patients additional examinations and facilitate the diagnosis of vertebral fractures.

Medial meniscus extrusion increases with age and BMI and is depending on different loading conditions.

PURPOSE: Meniscus extrusion has always been described as an indirect sign of meniscus pathology and is associated with a loss of function of the affected meniscus. The current cut-off value of 3 mm displacement is indicated as abnormal and has been determined on magnetic resonance images (MRI) and ultrasound (US). However, it has to be considered that there is no description of the physiological meniscus extrusion in healthy knees depending on age or different weight-bearing conditions. It was hypothesized that in healthy knees there is a physiological age and BMI dependent meniscal extrusion, and meniscus extrusion depends on different loading conditions. METHODS: Healthy volunteers with non-symptomatic knee, and no history of knee injuries or operations were included in this prospective cross-sectional study. Exclusion criteria were age < 18years, subjective or objective instability, malalignment and positive medial meniscus test. Secondary exclusion criteria were osteoarthritis ICRS grade 3-4 or signs of meniscus tear on MRI. Every patient underwent standard knee examination following measurement of medial meniscus extrusion (MME) using US. In US extrusion was determined in supine position (unloaded) and in standing position with full weight-bearing and 20° of flexion (loaded). MRI was performed in a neutral knee position to compare ultrasound measurements with the current gold standard. Based on the power calculation of preliminary results a minimum of 70 volunteers was needed. RESULTS: 75 patients were enrolled to this study. The mean US MME was 1.1 mm ± 0.5 mm in supine position and 1.9 mm ± 0.9 mm under full weight-bearing. The mean US Δ-extrusion was 0.8 mm ± 0.6 mm. With rising age, a significant increased MME in US and MRI could be demonstrated (p < 0.001). Furthermore, elevated BMI was significantly correlated to increased US MME under full weight-bearing (p = 0.002) and to US Δ-extrusion (p = 0.003). CONCLUSION: Based on the results of this study, medial meniscus extrusion is an age-depending phenomenon in healthy knees and depends on various load-bearing conditions. Ultrasound examination of the MME might be favorable compared to MRI due to the ability of dynamic evaluation. As a consequence, the current cut-off value of 3 mm for meniscus pathologies should be reconsidered. LEVEL OF EVIDENCE: III.

PD-L1 and PD-1 and characterization of tumor-infiltrating lymphocytes in high grade sarcomas of soft tissue - prognostic implications and rationale for immunotherapy.

Therapies targeting programmed death 1-(PD-1) or its ligand (PD-L1), promoting antitumor T-cell activity have been successfully introduced into clinical practice. Clinical response correlates with PD-L1 expression by tumor cells or immune cells within the tumor microenvironment. The PD-L1/PD-1 axis and tumor microenvironment has been rarely studied in high-grade sarcomas of soft tissue (hSTS), a group of rare, genetically heterogenous and clinically aggressive tumors. We examined PD-L1 protein and CD274/PD-L1 gene copy number variations in 128 primary resected, therapy-naive hSTS using immunohistochemistry and fluorescence-in-situ hybridization. Frequency of tumoral PD-L1 expression varied widely in different disease subentities, with highest rates of positivity (40%) seen in undifferentiated pleomorphic sarcomas (UPS) and rare positivity detected in synovial sarcomas (6%). Amplification of the CD274/PD-L1 gene occurred in 14% of UPS and was rare in other subtypes. PD-L1 protein expression was significantly more frequent in CD274/PD-L1 amplified cases (p = 0.015). The subgroup of UPS was further characterized regarding the interaction between PD-L1 and the immunologic tumor microenvironment. High density of CD3+ and CD8+ tumor infiltrating lymphocytes (TILs) was significantly correlated with the presence of PD-L1 expression and seen more frequently in tumors with lower TNM stage (p = 0.024). Both, PD-L1 expression and high density lymphocytic infiltration were independent prognostic factors for a favorable overall (p = 0.001, HR 6.105 (2.041-8.258)), disease-specific (p = 0.003, HR 10.536 (2.186-50.774)) and disease-free survival (p = 0.020, HR 3.317 (1.209-9.106); values for CD8) in this particular subgroup of hSTS, whereas PD-L1 expression in TILs or CD274/PD-L1 gene amplification were not associated with outcome. These findings represent novel insights into the immune landscape of soft tissue sarcomas, in particular UPS and strengthen the rationale for immunotherapy, including targeting the PD-1/PD-L1 axis in these tumors.