Bone marrow disease in rhabdomyosarcoma visualized by 2-[18F]fluorodeoxyglucose positron emission tomography/computed tomography.

Bone marrow metastases-noted in 6% of patients with rhabdomyosarcoma-have been linked to very poor outcomes. Bilateral bone marrow sampling from iliac crests has been the gold standard for bone marrow examination in rhabdomyosarcoma, but sampling errors due to patchy bone marrow involvement may limit its sensitivity. Here, we report the case of a 6-year-old boy with embryonal rhabdomyosarcoma of the skull base and multiple 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG)-avid bone marrow metastases visualized by positron emission tomography and computed tomography (2-[18F]FDG PET/CT). His bone marrow aspirates were tumor-free. This case illustrates the diagnostic value of 2-[18F]FDG PET/CT in the detection of bone marrow metastases in rhabdomyosarcoma patients, which may re-shape the definition of bone marrow disease and, ultimately, alter disease staging and risk stratification.

[Bone-RADS: Diagnostic algorithm for management of incidental solitary bone lesions]. / Bone-RADS: Diagnostischer Algorithmus zum Management von inzidentellen solitären Knochenläsionen.

The bone reporting and data system (Bone-RADS) is a guideline of the Society of Skeletal Radiology for the standardized assessment of incidentally found solitary bone lesions. It consists of basic definitions and continuative algorithms for the radiological diagnosis of bone lesions in computed tomography (CT) and magnetic resonance imaging (MRI). This Continuing Medical Education (CME) article gives a compact summary of the Bone-RADS classification for users. After reading this article Bone-RADS can be used by anyone. The authors have compiled the critical comments and obstacles at the end of the article.

Successful Secondary Endovascular Intervention in Pediatric Patients with Venous Thromboembolic Events.

BACKGROUND: In the past, pediatric patients with venous thromboembolic events (VTE) were treated with low-molecular-weight heparin (LMWH) which was successful in around 70% of the cases. However, anticoagulation alone might not restore patency in all patients, and advanced therapeutic options to prevent postthrombotic syndrome are needed. During recent years, endovascular interventions have become a treatment option for pediatric patients with persistent thrombotic occlusion, not only in life- or limb-threatening VTE. METHODS: We evaluated 12 consecutive patients (11-17 years) with newly diagnosed VTE being treated at our department during the last 4 years (2017-2020). In case follow-up examination showed persistent venoocclusion under anticoagulation, patients received secondary interventional therapy like recanalization, percutaneous transluminal angioplasty with or without catheter-directed thrombolysis, and stenting. Patients with no clinical signs of venoocclusion or regredient thrombosis in imaging examination received anticoagulation alone. RESULTS: Six of 12 (50%) patients underwent catheter intervention. Median time from diagnosis to intervention was 4 months (0-12 months). Reintervention was necessary in one (8%) case and complete recanalization failed in one (8%) case. There were no major bleeding events or other major postinterventional complications, no acute or late local recurrence, and all patients reported clinical improvement after the procedure. CONCLUSION: If endovascular intervention is used in teenage patients with persistent symptomatic VTE, reduction of postthrombotic symptoms is possible, even if intervention is performed secondary to failure of anticoagulation. Multidisciplinary treatment decisions can be based on the clinical course and follow-up imaging.

Laboratory Findings, Medical Imaging, and Clinical Outcome in Children with Cerebral Sinus Venous Thrombosis.

INTRODUCTION: Cerebral sinus venous thrombosis (CSVT) is a rare disease, especially in children. Therefore, thrombophilia markers, risk factors, treatment strategy, and MRI, as well as clinical outcome need further investigation to support future diagnostic and therapeutic guidelines for children. METHODS: We retrospectively identified all children with CSVT treated in our center between January 1, 2000, and December 31, 2015. Risk factors and laboratory findings were investigated. Furthermore, outcome and treatment satisfaction were evaluated using magnetic resonance imaging (MRI) analyses and a modified questionnaire. RESULTS: All 43 patients, who agreed to participate, were treated with therapeutic levels of heparin; 86% of children had an increased risk for thromboembolic events upon onset of CSVT (acute disease: 58.1%, perinatal risk factors: 9.3%, medical intervention/immobility: 14%, chronic disease: 16.3%). Thrombophilia markers showed positive results (e.g., reduced values for protein C/S, factor-V-Leiden mutation) in 58% of children at the time of CSVT diagnosis but dropping to 20.9% over the course of the disease. Forty-two of 43 patients received MRI follow-ups and the outcome showed complete recanalization in 69% of the patients and partial recanalization in 31%. At the onset of CSVT, 88% of patients reported restrictions in everyday life due to CSVT; at follow-up this percentage declined to 18%. Satisfaction with the outcome among parents/patients according to the questionnaire was high with 1.7 (German school grades from 1 to 6). CONCLUSIONS: All 42 children with MRI follow-up demonstrated complete or partial recanalization under anticoagulation. This positive result underlines the need for future studies on anticoagulation to optimize therapy regimens of pediatric CSVT.

Unusual course of disease and genetic profile in Li-Fraumeni syndrome-associated osteosarcoma - a case report.

BACKGROUND: Osteosarcoma is a highly malignant tumour associated with numerous and complex genetic alterations like copy number alterations. Recent whole genome studies revealed distinct mutations in several candidate oncogenes. While clinical parameters stratify osteosarcoma patients in risk groups, genetic profiles have not yet been used to tailor tumour treatment. However, specific copy number alterations seem to have a prognostic impact in osteosarcoma treatment. Somatic TP53 gene mutation frequently occurs in sporadic osteosarcoma. When arising germline, TP53 mutation leads to Li-Fraumeni syndrome and may result in early life osteosarcoma. The effect of Li-Fraumeni syndrome on the genetic profile of osteosarcoma and the consideration of the syndrome during cancer treatment are topics of current research. CASE PRESENTATION: We report a 25-year-old female with pelvic osteosarcoma refusing continuation of therapy. She interrupted neo-adjuvant chemotherapy according to EURAMOS-1/COSS recommendations and declined local or further adjuvant therapy. Surprisingly, she remained in sustained remission for the osteosarcoma but eventually died from newly diagnosed breast cancer. After establishment of breast cancer, we detected TP53 germline mutation and investigated the osteosarcoma material with array-CGH. CONCLUSION: Genetic examination of the tumour evidenced several copy number alterations with striking differences to previously reported data. We discuss possible influences of the genetic profile on the unusual clinical course and the significance of Li-Fraumeni syndrome for the genetic profile. Specific loss of (proto-) oncogenes might have contributed to the unusual case. Further large-scale genetics of Li-Fraumeni patients combined with detailed clinical data will help to identify specific genetic risk profiles and improve treatment.

[Musculoskeletal manifestations of neurofibromatosis type 1 (von Recklinghausen's disease) and tuberous sclerosis (Bourneville's disease)]. / Muskuloskeletale Manifestationen der Neurofibromatose Typ 1 (M. von Recklinghausen) und der tuberösen Sklerose (M. Bourneville).

CLINICAL PROBLEM: Neurofibromatosis type 1 (NF1) and tuberous sclerosis (TS) are among the most common genetic diseases. Bone and soft tissue manifestations are common disease manifestations. STANDARD RADIOLOGICAL PROCEDURE AND EVALUATION: The standard radiological procedure is magnetic resonance imaging (MRI). All macroscopic disease manifestations can be diagnosed radiologically and observed during the course. Specific complications such as plexiform neurofibromas and malignant peripheral nerve sheath tumors (MPNST) in NF1 are readily visible on MRI. Differentiation of plexiform neurofibromas and MPNST is uncertain and requires follow-up. RECOMMENDATION FOR PRACTICE: MRI is the most important procedure for the investigation of soft tissue and bone manifestations of NF1 and TS.

Clinicopathologic characteristics, metastasis-free survival, and skeletal-related events in 628 patients with skeletal metastases in a tertiary orthopedic and trauma center.

BACKGROUND: Skeletal-related events (SREs) due to bone metastases (BM) significantly impact the morbidity and mortality of cancer patients. The present study sought to investigate clinicopathological characteristics, metastasis-free survival (MFS), and SREs in patients referred to a tertiary orthopedic and trauma center. METHODS: Data were retrieved from electronic health records (n=628). Survival curves were estimated utilizing the Kaplan-Meier method. The Cox regression model was used to determine factors influencing MFS based on estimated hazard ratios (HRs). RESULTS: Breast (55.8%) and lung (18.2%), and lung (32.9%) and prostate (16.8%) cancer were the most common cancer types in our cohort in women and men, respectively. Fifteen percent of patients presented with BM as the first manifestation of tumor disease, 23% had metastasis diagnosis on the same day of primary tumor diagnosis or within 3 months, and 62% developed BM at least 3 months after primary tumor diagnosis. Osteolytic BM were predominant (72.3%) and most commonly affecting the spine (23%). Overall median MFS was 45 months (32 (men) vs. 53 (women) months). MFS was shortest in the lung (median 15 months, 95% CI 8.05-19) and longest in breast cancer (median 82 months, 95% CI 65.29-94). Age (≥ 60 vs. < 60 years) and primary cancer grading of ≥2 vs. 1 revealed prognostic relevance. CONCLUSION: Women with breast or lung cancer, men with lung or prostate cancer, age ≥60 years, male sex, and primary cancer grading ≥2 are associated with increased risk for MBD. Intensified follow-up programs may reduce the risk of SREs and associated morbidity and mortality.

[Tumor-like bony lesions of the skeleton]. / Tumorähnliche Knochenläsionen des Skeletts.

Tumor-like bony lesions are, by definition bony lesions, which can be clinically, radiologically and histologically mistaken for real bone tumors. This article presents the aneurysmal bone cyst (ABC), solitary bone cyst (SBC), fibrous dysplasia, osteofibrous dysplasia Campanacci and non-ossifying fibroma (NOF). Many tumor-like bony lesions are often incidental findings. The combination of X­ray imaging specifically supplemented by magnetic resonance imaging (MRI) or computed tomography (CT) enables a diagnostic classification in the majority of cases.

[Tumor-like bony lesions of the skeleton]. / Tumorähnliche Knochenläsionen des Skeletts.

Tumor-like bony lesions are, by definition bony lesions, which can be clinically, radiologically and histologically mistaken for real bone tumors. This article presents the aneurysmal bone cyst (ABC), solitary bone cyst (SBC), fibrous dysplasia, osteofibrous dysplasia Campanacci and non-ossifying fibroma (NOF). Many tumor-like bony lesions are often incidental findings. The combination of X­ray imaging specifically supplemented by magnetic resonance imaging (MRI) or computed tomography (CT) enables a diagnostic classification in the majority of cases.

TIM-3 deficiency presenting with two clonally unrelated episodes of mesenteric and subcutaneous panniculitis-like T-cell lymphoma and hemophagocytic lymphohistiocytosis.

This report offers novel clinical and diagnostic aspects of the association between germline mutations in HAVCR2 and subcutaneous panniculitis-like T-cell lymphoma (SPTCL). The patient presented with panniculitis-like T-cell lymphoma involving mesenteric fatty tissue associated with hemophagocytic lymphohistiocytosis (HLH). Five years later, he developed a clonally unrelated SPTCL and underwent hematopoietic stem cell transplantation. Retrospectively, he was found to carry germline mutations in HAVCR2 associated with reduced T-cell immunoglobulin mucin-3 (TIM-3) expression. We show that mesenteric fatty tissue localization of SPTCL can be the presenting manifestation of TIM-3 deficiency, that this condition predisposes to recurrent lymphoma, and that flow cytometry is a possible screening tool.

Anatomical Reconstruction of the Acromion Using an Autologous Iliac Crest Graft for Treatment of Recurrent Chondroblastoma: A Case Report.

CASE: A 38-year-old man presented with recurrent chondroblastoma of the acromion after primary curettage and bone grafting. The patient underwent revision surgery with resection of the acromion and reconstruction using an autologous iliac crest graft. He had regained normal shoulder function without recurrence at a follow-up of 17 months. CONCLUSIONS: This case demonstrates a rare location of chondroblastoma and successful anatomical and functional reconstruction. The described surgical procedure could be considered for large tumorous lesions of the acromion, for which curettage would be insufficient, and to preserve and reconstruct a functionally intact shoulder girdle.

Long-Term Clinical and MRI Results of Matrix-Assisted Autologous Chondrocyte Implantation for Articular Cartilage Defects of the Knee.

OBJECTIVE: To evaluate the long-term clinical and radiological outcome of matrix-assisted autologous chondrocyte implantation (mACI) for articular cartilage defects in the knee joint. DESIGN: Clinical evaluation was assessed in 21 patients with full-thickness cartilage defects, International Cartilage Repair Society (ICRS) grade IV. Clinical scoring was performed preoperatively and 12 years after transplantation using the International Knee Documentation Committee (IKDC) score, the Lysholm score, the Knee injury and Osteoarthritis Outcome Score (KOOS), and the Noyes sports activity rating scale. Morphologic evaluation of the repair tissue was assessed by magnetic resonance imaging (MRI) in 14 patients using the Kreuz-Henderson score. RESULTS: Clinical evaluation revealed significant improvement in the IKDC, the Lysholm, the KOOS, and the Noyes score. Morphological evaluation by MRI showed moderate to complete defect filling in 10 of 14 patients, demonstrating normal to nearly normal values in mean 74.29% of all assessed parameters. Significant correlation of the parameter cartilage signal and clinical outcome was found with the IKDC, Lysholm, and KOOS subscales ADL (activities of daily living) and QoL (quality of life). CONCLUSIONS: The clinical and radiological outcomes 12 years after transplantation suggest the confirmation of the promising results of the mid-term follow-up. This study therefore provides first indications that the implantation of mACI might be a suitable option for long-term cartilage repair. Future controlled studies need to address the exact parameters influencing the long-term outcome of mACI.

Clinical and radiographical ten years long-term outcome of microfracture vs. autologous chondrocyte implantation: a matched-pair analysis.

PURPOSE: To compare the clinical and radiographical long-term outcome of microfracture (MFX) and first-generation periosteum-covered autologous chondrocyte implantation (ACI-P). METHODS: All subjects (n = 86) who had been treated with knee joint ACI-P or microfracture (n = 76) with a post-operative follow-up of at least ten years were selected. Clinical pre- and post-operative outcomes were analyzed by numeric analog scale (NAS) for pain, Lysholm, Tegner, IKDC, and KOOS score. Radiographical evaluation was visualized by magnetic resonance imaging (MRI). Assessment of the regenerate quality was performed by the magnetic resonance observation of cartilage repair tissue (MOCART) and modified knee osteoarthritis scoring system (mKOSS). Relaxation time (RT) of T2 maps enabled a microstructural cartilage analysis. RESULTS: MFX and ACI of 44 patients (24 females, 20 males; mean age 38.9 ± 12.1 years) resulted in a good long-term outcome with low pain scores and significant improved clinical scores. The final Lysholm and functional NAS scores were significantly higher in the MFX group (Lysholm: MFX 82 ± 15 vs. ACI-P 71 ± 18 p = 0.027; NAS function: MFX 8.1 ± 3.5 vs. ACI-P 6.0 ± 2.5; p = 0.003). The MOCART score did not show any qualitative differences. KOSS analysis demonstrated that cartilage repair of small defects resulted in a significant better outcome. T2-relaxation times were without difference between groups at the region of the regenerate tissue. CONCLUSION: This study did not demonstrate coherent statistical differences between both cartilage repair procedures. MFX might be superior in the treatment of small cartilage defects.

Sporting Activity Is Reduced 11 Years After First-Generation Autologous Chondrocyte Implantation in the Knee Joint.

BACKGROUND: Little is known about long-term sporting activity after periosteal autologous chondrocyte implantation (ACI-P) and its correlation to clinical, morphological, and ultrastructural cartilage characteristics on magnetic resonance imaging (MRI). PURPOSE: To evaluate long-term sporting activity after ACI-P and to correlate with clinical and MRI findings. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients who underwent ACI-P for isolated cartilage defects of the knee joint between 1997 and 2001 were analyzed for sporting ability for 3 different time points: lifetime until the onset of pain, the year before ACI-P, and 11 years (range, 9.0-13.4 years) postoperatively. Sporting activity was assessed and patients' level of activity scaled using standardized questionnaires. MRI scans of the affected knee joint at follow-up were analyzed using the MOCART (magnetic resonance observation of cartilage repair tissue) score and T2 mapping. RESULTS: Seventy of 86 patients (81% follow-up rate) consisting of 25 female and 45 male patients, with a mean age of 33.3 ± 10.2 years at the time of surgery, mean defect size of 6.5 ± 4.0 cm2, and 1.17 treated defects per patient, agreed to participate in the study at a mean 10.9 ± 1.1 years after ACI-P. Fifty-nine patients (69% of total; 84% of follow-up) agreed to MRI, allowing the complete evaluation of 71 transplant sites. Before the onset of symptoms (lifetime), 95.7% of patients played a mean 6.0 sporting activities at a competitive level. In the year before ACI-P, 81.4% of patients played a mean 3.4 sporting activities in 2.4 sessions during 5.4 hours per week at a recreational level. At follow-up, 82.9% of the patients played a mean 3.0 sporting activities in 1.8 sessions during 3.0 hours per week at a recreational level. In contrast to objective factors, 65.6% of the patients felt that their subjective sporting ability had improved or strongly improved after ACI-P, whereas 12.9% felt that their situation had declined or strongly declined, and 21.4% stated that their sporting ability had undergone no change because of surgery. Factors of sporting activity correlated significantly with clinical long-term outcomes. MRI analysis with a mean repair tissue T2 relaxation time of 35.2 milliseconds and mean MOCART score of 44.9 showed no conclusive significant correlation to sporting activity. Level of performance was the only sporting activity factor to show a weak correlation with subgroups of the MOCART score. CONCLUSION: The premorbid level of sporting and recreational activities cannot be achieved 11 years after ACI-P. The MRI results determined at this time point did not conclusively correlate with long-term sporting activity.

Treatment of a Focal Articular Cartilage Defect of the Talus with Polymer-Based Autologous Chondrocyte Implantation: A 12-Year Follow-Up Period.

Autologous chondrocyte implantation (ACI) is a first-line treatment option for large articular cartilage defects. Although well-established for cartilage defects in the knee, studies of the long-term outcomes of matrix-assisted ACI to treat cartilage defects in the ankle are rare. In the present report, we describe for the first time the long-term clinical and radiologic results 12 years after polymer-based matrix-assisted ACI treat a full-thickness talar cartilage defect in a 25-year-old male patient. The clinical outcome was assessed using the visual analog scale and Freiburg ankle score, magnetic resonance imaging evaluation using the Henderson-Kreuz scoring system and T2 mapping. Clinical assessment revealed improved visual analog scale and Freiburg ankle scores. The radiologic analysis and T2 relaxation time values indicated the formation of hyaline-like repair tissue. Polymer-based autologous chondrocytes has been shown to be a safe and clinically effective long-term treatment of articular cartilage defects in the talus.

Non-ossifying fibroma: natural history with an emphasis on a stage-related growth, fracture risk and the need for follow-up.

BACKGROUND: The aim of this study was to assess and present the radiological morphology of the non-ossifying fibroma (NOF), to describe the life span according to the Ritschl-stages in an effort to determine critical stages with regard to pathological fractures and discuss the need for a follow-up. METHODS: Reports of a consecutive series of 87 patients with 103 NOFs and a mean follow-up of 27 months were analysed according to the Ritschl-stages with regard to age at time of diagnosis, localisation, duration of stage and symptoms. RESULTS: Mean patient age in our series was 20 years and lesions most frequently affected the long bones of the lower extremity. Nineteen lesions were categorized in stage A, 53 in stage B, 17 in stage C and 14 in stage D. Most lesions were detected incidentally. In six of ten clinically symptomatic patients with an average age of ten years a pathological fracture occurred, and four of them were located in the tibia. All of these were in stage B with a mean length of 44 mm, an average expansion in relation to the bone-diameter of 75 % in transversal and 87 % in sagittal plane. Duration of the stages was variable. In the critical stage B the mean was 21 months. CONCLUSION: The non-ossifying fibroma follows a characteristic radiomorphological course with variable duration of each stage. Stage B lesions were found to be at an increased risk of fracture, and the age range over which fractures occur was wide. No fractures were detected in the other three stages. Follow-up, including clinical survey and imaging, at six to twelve month intervals may therefore be considered in the case of larger stage B lesions until stage C is reached.

Clinical outcome and T2 assessment following autologous matrix-induced chondrogenesis in osteochondral lesions of the talus.

PURPOSE: Scientific evidence for the treatment of osteochondral lesions (OCLs) of the talus is limited. The aim of this study was an evaluation of the clinical outcome after a one-step autologous subchondral cancellous bone graft and autologous matrix-induced chondrogenesis (AMIC) in medial OCLs of the talus and the assessment of the repair tissue (RT). METHODS: Seventeen patients (eight women, nine men; mean age, 38.8 ± 15.7 years) with an OCL of the medial talus underwent surgery. Clinical and radiological assessment was performed after a mean follow-up of 39.5 ± 18.4 months, including established scoring systems (American Orthopaedic Foot and Ankle Society [AOFAS] Score, Foot Function Index [FFI], visual analogue scale [VAS]), evaluation of Magnetic Resonance Observation of Cartilage Repair Tissue scoring system (MOCART Score) and T2 mapping. RESULTS: Preoperative pain (7.8 ± 2.1) significantly improved to an average of 3.2 ± 2.4 postoperatively. AOFAS Score averaged 82.6 ± 13.4, MOCART Score 52.7 ± 15.9. Mean T2 relaxation time of the RT was 41.6 ± 6.3 ms and showed no significant differences to the surrounding cartilage (mean, 38.8 ± 8.5; p = 0.58). MOCART Score significantly correlated with the AOFAS Score (rho = 0.574, p = 0.040). T2 relaxation time of the RT significantly correlated with the MOCART Score (rho = 0.593, p = 0.033). CONCLUSIONS: The one-step autologous subchondral cancellous bone grafting and AMIC leads to a significant reduction in postoperative pain and satisfying postoperative functional outcome in mid-term follow-up. Magnetic resonance imaging (MRI) assessment demonstrated a good quality of regenerative tissue similar to the MRI ultrastructure of the surrounding cartilage.

Evaluation and analysis of graft hypertrophy by means of arthroscopy, biochemical MRI and osteochondral biopsies in a patient following autologous chondrocyte implantation for treatment of a full-thickness-cartilage defect of the knee.

Graft hypertrophy represents a characteristic complication following autologous chondrocyte implantation (ACI) for treatment of cartilage defects. Although some epidemiological data suggest that incidence is associated with first-generation ACI using autologous chondrocyte implantation, it has also been reported in other technical modifications of ACI using different biomaterials. Nevertheless, it has not been described in autologous, non-periosteum, implant-free associated ACI. In addition, little is known about histological and T2-relaxation appearance of graft hypertrophy. The present case report provides a rare case of extensive graft hypertrophy following ACI using an autologous spheres technique with clinical progression over time. Detailed clinical, MR tomographic and histological evaluation has been performed, which demonstrates a high quality of repair tissue within the hypertrophic as well as non-hypertrophic transplanted areas of the repair tissue. No expression of collagen type X (a sign of chondrocyte hypertrophy), only slight changes of the subchondral bone and a nearly normal cell-matrix ratio suggest that tissue within the hypertrophic area does not significantly differ from intact and high-quality repair tissue and therefore seems not to cause graft hypertrophy. This is in contrast to the assumption that histological hypertrophy might cause or contribute to an overwhelming growth of the repair tissue within the transplantation site. Data presented in this manuscript might contribute to further explain the etiology of graft hypertrophy following ACI.