[Bone and soft tissue tumours in children : Proposal for a rational diagnostic approach]. / Knochen- und Weichteiltumoren im Kindesalter : Vorschlag für ein rational-diagnostisches Vorgehen.

CLINICAL/METHODOLOGICAL ISSUE: Bone and soft tissue tumours are often incidental findings in children. Because they are usually benign tumours, nonspecialised radiologists generally have little experience in the diagnosis and differentiation from malignant tumours. Various imaging techniques are used in the diagnosis of skeletal tumours. STANDARD RADIOLOGICAL METHODS: Imaging techniques used to evaluate bone and soft tissue tumours include sonography, computed tomography (CT) and magnetic resonance imaging (MRI). METHODOLOGICAL INNOVATIONS: An algorithm to determine malignancy of bone and soft tissue tumours in children is proposed. PERFORMANCE: By using the presented algorithms, further diagnostic procedures such as biopsies can be avoided in the majority of children with bone and soft tissue tumours. Aggressive bone lesions and unclear soft tissue tumours are guided to biopsy to confirm diagnosis. ACHIEVEMENTS: The algorithms presented are based on the proposals of European professional societies and have been adapted by the authors for use in children and adolescents. PRACTICAL RECOMMENDATIONS: In the clarification of soft tissue tumours, sonography is the first diagnostic tool; depending on the sonographic findings, MRI is the technique for further clarification. Biopsy confirmation of the diagnosis in unclear cases or in cases of probable malignancy should be carried out in a paediatric oncology centre.

Rapid, complete and sustained tumour response to the TRK inhibitor larotrectinib in an infant with recurrent, chemotherapy-refractory infantile fibrosarcoma carrying the characteristic ETV6-NTRK3 gene fusion.

BACKGROUND: The ETV6-NTRK3 gene fusion is present in the majority of cases of infantile fibrosarcoma (IFS) and acts as a potent oncogenic driver. We report the very rapid, complete, and sustained response of an advanced, chemotherapy-refractory, recurrent IFS to targeted treatment with the oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib. PATIENT AND METHODS: A male infant born with a large congenital IFS of the tongue had the tumour surgically resected at age 4 days. Within 2 months, he developed extensive lymph node recurrence that progressed during two cycles of vincristine-doxorubicin-cyclophosphamide chemotherapy. At screening, a large right cervical mass was clinically visible. Magnetic resonance imaging (MRI) revealed bilateral cervical and axillary lymph node involvement as well as infiltration of the floor of the mouth. The largest lesion measured 5.5×4.5×4.4 cm (ca. 55 cm3). The patient started outpatient oral larotrectinib at 20 mg/kg twice daily at age 3.5 months. RESULTS: After 4 days on treatment, the parents noted that the index tumour was visibly smaller and softer. The rapid tumour regression continued over the following weeks. On day 56 of treatment, the first scheduled control MRI showed the target lesion had shrunk to 1.2×1.2×0.8 cm (ca. 0.6 cm3), corresponding to a complete response according to the Response Evaluation Criteria In Solid Tumors version 1.1. This response was maintained over subsequent follow-up visits, and on day 112 at the second control MRI the target lymph node was completely normal. At last follow-up, the disease remained in complete remission after 16 months on larotrectinib, with negligible toxicity and no safety concerns. CONCLUSION(S): Selective TRK inhibition by larotrectinib offers a novel, highly specific and highly effective therapeutic option for IFS carrying the characteristic ETV6-NTRK3 gene fusion. Its use should be considered when surgery is not feasible. (NCT02637687).

Rapid, complete and sustained tumour response to the TRK inhibitor larotrectinib in an infant with recurrent, chemotherapy-refractory infantile fibrosarcoma carrying the characteristic ETV6-NTRK3 gene fusion.

BACKGROUND: The ETV6-NTRK3 gene fusion is present in the majority of cases of infantile fibrosarcoma (IFS) and acts as a potent oncogenic driver. We report the very rapid, complete, and sustained response of an advanced, chemotherapy-refractory, recurrent IFS to targeted treatment with the oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib. PATIENT AND METHODS: A male infant born with a large congenital IFS of the tongue had the tumour surgically resected at age 4 days. Within 2 months, he developed extensive lymph node recurrence that progressed during two cycles of vincristine-doxorubicin-cyclophosphamide chemotherapy. At screening, a large right cervical mass was clinically visible. Magnetic resonance imaging (MRI) revealed bilateral cervical and axillary lymph node involvement as well as infiltration of the floor of the mouth. The largest lesion measured 5.5×4.5×4.4 cm (ca. 55 cm3). The patient started outpatient oral larotrectinib at 20 mg/kg twice daily at age 3.5 months. RESULTS: After 4 days on treatment, the parents noted that the index tumour was visibly smaller and softer. The rapid tumour regression continued over the following weeks. On day 56 of treatment, the first scheduled control MRI showed the target lesion had shrunk to 1.2×1.2×0.8 cm (ca. 0.6 cm3), corresponding to a complete response according to the Response Evaluation Criteria In Solid Tumors version 1.1. This response was maintained over subsequent follow-up visits, and on day 112 at the second control MRI the target lymph node was completely normal. At last follow-up, the disease remained in complete remission after 16 months on larotrectinib, with negligible toxicity and no safety concerns. CONCLUSION(S): Selective TRK inhibition by larotrectinib offers a novel, highly specific and highly effective therapeutic option for IFS carrying the characteristic ETV6-NTRK3 gene fusion. Its use should be considered when surgery is not feasible. (NCT02637687).

[Pediatric radiology in oto-rhino-laryngology]. / Pädiatrische Radiologie in der Hals-Nasen-Ohren-Heilkunde.

Head and neck diseases in children and adolescents pose special diagnostic and differential diagnostic challenges to ENT surgeons as well as to radiologists. Both disciplines have to adapt the latest radiological and interventional technologies to the needs of the paediatric patient in order to enable a minimally invasive but successful diagnostic procedure. High quality sonography by an experienced examiner often is the only imaging technique that is required in children and adolescents. Radiographs are rarely indicated in paediatric head and neck diseases. MRI, compared to computed tomography, has the advantage of the lack of radiation exposure. Additionally, because of current advances in high resolution techniques to delineate very small details or in visualization of different tissue characteristics it has become an integral part of the pre-and post-operative imaging. However, children should not be denied an adequate diagnostic procedure even if it includes a sedation, an intervention or an exposure to radiation. The responsible use of the diagnostic options under consideration of the therapeutic consequences is essential. It is most likely to be successful in a close interdisciplinary cooperation of paediatric ENT specialists and radiologists as well as paediatric anaesthesiologists in selected cases. Although benign diseases predominate in children and adolescents, the possibility of a malignancy has to be considered in case of atypical clinical and radiological findings. In many of these young patients the outcome and the probability of survival are directly connected to the initial diagnostic and therapeutic strategies, which should therefore be in accordance with the current guidelines in oncological therapy studies. Our collection of clinical cases consists of representative examples of useful diagnostic approaches in common and age specific diagnoses as well as in rare diseases and malformations. It shows the significance of a special knowledge in embryology and normal postnatal development for the differentiation of normal variants from pathological findings. Only in considering the results of imaging studies in their clinical context, we may succeed in detecting a syndrome behind a single malformation or in adequately caring for a patient with a chronic disease such as cystic fibrosis.

Osteosarcoma of the mobile spine.

BACKGROUND: The aims of this analysis were to investigate features and outcome of high-grade osteosarcomas of the mobile spine. PATIENTS AND METHODS: Since 1977, 20 Cooperative Osteosarcoma Study Group patients had a diagnosis of high-grade osteosarcomas of the mobile spine and were included in this retrospective analysis of patient-, tumor- and treatment-related variables and outcome. RESULTS: The median age was 29 years (range 5-58). Most frequent tumor sites were thoracic and lumbar spine. All but three patients had nonmetastatic disease at diagnosis. Treatment included surgery and chemotherapy for all patients, 13 were also irradiated. Eight patients failed to achieve a macroscopically complete surgical remission (five local, one primary metastases, two both), six died, two are alive, both with radiotherapy. Of 12 patients with complete remission at all sites, three had a recurrence (two local, one metastases) and died. The median follow-up of the 11 survivors was 8.7 years (range 3.1-22.3), 5-year overall and event-free survival rates were 60% and 43%. Age <40 years, nonmetastatic disease at diagnosis and complete remission predicted for better overall survival (OS, P < 0.05). CONCLUSIONS: Osteosarcomas of the mobile spine are rare. With complete resection (and potentially radiotherapy) and chemotherapy, prognosis may be comparable with that of appendicular osteosarcomas.

Combined dynamic contrast-enhancement and serial 3D-subtraction analysis in magnetic resonance imaging of osteoid osteomas.

The purpose of this study was to retrospectively correlate the results of dynamic contrast-enhanced magnetic resonance imaging (MRI) with histological and clinical diagnoses in patients with osteoid osteomas. Fifty-four patients with the MR diagnosis of osteoid osteoma were studied. MRI (1.5 Tesla) consisted of thin-section STIR sequences, dynamic 3D T1 gradient echo sequences during application of contrast material, and high-resolution postcontrast T1 spin echo sequences with fat saturation (maximum voxel size 0.6 x 0.6 x 3.0 mm). Evaluation was focused on serial image subtraction during the early phase after contrast injection and on time-intensity curves. The surrounding edema was helpful in finding the nidus in each lesion. In 49 of 54 patients (90.7%), the diagnosis of osteoid osteoma was certain or highly probable (sensitivity 1.0, positive predictive value 0.91). A total of 38 of 54 osteoid osteomas were histologically proven. Five MRI diagnoses were regarded as false positives. A similar proportion has been reported for computed tomography. Tailored high-resolution MR examinations with dynamic contrast enhancement can reliably diagnose osteoid osteomas and exactly localize the nidus without radiation exposure. We propose a stepwise approach with STIR sequences, dynamic contrast-enhanced scanning, and high-resolution postcontrast T1 spin echo sequences with fat saturation.

Andermann syndrome can be a phenocopy of hereditary motor and sensory neuropathy--report of a discordant sibship with a compound heterozygous mutation of the KCC3 gene.

Andermann syndrome is a rare autosomal recessive disorder characterized by agenesis of the corpus callosum (ACC), progressive motor-sensory neuropathy, mental retardation and facial features. We report on two siblings with the clinical picture of a demyelinating hereditary motor and sensory neuropathy (HMSN), where only the presence of ACC in the younger brother pointed to the diagnosis of Andermann syndrome. Mutation analysis of the KCC3 (SLC12A6) gene showed a compound heterozygous mutation; a maternal missense mutation c.1616G>A (p.G539D) and a paternal splice mutation c.1118+1G>A in both siblings. We hypothesize that mutations of the KCC3 gene may result in non-syndromic childhood onset HMSN.

Congenital intrahepatic portosystemic shunt: prenatal diagnosis and possible influence on fetal growth.

Congenital intrahepatic portosystemic shunts (IPSS) are abnormal vascular communications within the liver between branches of the portal vein and the hepatic veins. They have been recognized as an important disorder in children and should be differentiated from metabolic diseases, the symptoms of which may be similar. Several cases of prenatal diagnosis of abnormalities of the fetal venous system have been described in the literature, but the significance and prognosis of isolated congenital IPSS in prenatal life have not been reported and have only been derived from children. We present a case of congenital IPSS in which there was severe intrauterine growth restriction with a concomitant atypical fetal Doppler pattern. Findings on Doppler ultrasound indicate that the prenatal diagnosis of congenital IPSS is now feasible.

[Contrast-enhanced MR angiography (CEMRA) in peripheral arterial occlusive disease (PAOD): conventional moving table technique versus hybrid technique]. / Kontrastverstärkte MR-Angiographie (CEMRA) bei peripherer AVK (pAVK): konventionelle Tischverschiebetechnik versus Hybrid-Technik.

PURPOSE: In peripheral arterial occlusive disease (PAOD), angiographic evaluation of the entire aortopedal arterial system is mandatory. In a randomized study, two different protocols of CEMRA were evaluated prospectively to compare their diagnostic quality and clinical usefulness. PATIENTS AND METHODS: 80 patients (males n = 60, females n = 20, median age = 70 years, diabetics n = 27) with PAOD were examined with a 1.5 T system (40 mT/m) using a dedicated phased array peripheral vascular coil. Protocol A consisted of a single injection of Gd-BOPTA with consecutive craniocaudal image acquisition and protocol B of two injections, with the first injection of Gd-BOPTA followed by image acquisition of the popliteocrural and pedal segments and the second injection followed by acquiring the aortoiliac and femoral segments (hybrid technique). The evaluation of the arterial system was directed to the iliac, femoral, popliteocrural and pedal arteries. RESULTS: The visualization of the entire aortopedal vascular system was of diagnostically good or satisfactory quality in 16 of 40 patients using protocol A and in 29 of 40 patients using protocol B (iliac 40 vs. 37, femoral 40 vs. 40, popliteocrural 35 vs. 37, pedal 16 vs. 29); without the pedal station the number increased to 35 of 40 patients for both protocols. The reason of diagnostic limitations was an arteriovenous overlap in 24 of 80 cases, with 19 of 40 cases for protocol A and 5 of 40 for protocol B, located exclusively in the cruropedal region. CONCLUSION: Moving table hybrid CEMRA is superior to conventional technique in craniocaudal direction by producing less venous overlap of arteries and is especially more suitable for the diagnostic evaluation of the cruropedal region.

[Ultrasound appendix imaging in mucoviscidosis patients]. / Sonographische Appendixdarstellung bei Mukoviszidosepatienten.

PURPOSE: The aim of this study was to determine the presentation of the appendix in patients with cystic fibrosis (CF) compared to a healthy control group and patients with acute appendicitis using high resolution graded compression sonography. METHOD: 59 CF patients (mean age 11 years), 54 healthy children (mean age 9 years) and 322 patients with histologically proven acute appendicitis were evaluated by sonography. A blind ending tubular structure in longitudinal sections and a target-like figure in cross sections without peristalsis was considered as appendix. The maximum distance between the outer echolucent layers was calculated as diameter. RESULTS: In 20%, 67% and 90% of the cases, the appendix was identified in the CF-group, healthy children, and patients with acute appendicitis. The mean diameters were 9.8, 3.9, and 10.9 mm respectively. These differences were statistically significant (p < 0.001 and p < 0.012). CONCLUSION: The appendiceal mucocele in cystic fibrosis is an uncommon but important differential diagnosis of the acute appendicitis.

Typical patterns of bone involvement in whole-body MRI of patients with chronic recurrent multifocal osteomyelitis (CRMO).

PURPOSE: The diagnosis of CRMO often involves a long patient history. We evaluated the spectrum of bone involvement in whole-body magnetic resonance imaging (WB-MRI) and assessed its potential contribution to a more rapid diagnosis. MATERIALS AND METHODS: WB-MRI (1.5 T, coronal STIR sequences) in 53 children and adolescents (mean age 11 years, 4.8 - 15.1) with histologically (n = 37) or clinically (n = 16) confirmed CRMO were retrospectively reviewed by two experienced pediatric radiologists. RESULTS: WB-MRI revealed multifocal lesions in all but one patients. Only 26 of them had presented with multifocal complaints. We detected 1 - 27 geographic lesions/patient (mean 9.7). 510 of 513 lesions were significantly hyperintense compared to normal bone marrow. The pelvis, lower extremities, shoulders and spine were most frequently involved. 40 patients (75 %) had bilateral symmetrical involvement of bones. Most of the lesions were located in tubular bones, in 87 % adjacent to one or both sides of a growth plate. 32 % of lesions showed periosteal involvement. Of 456 affected bones, 33 (7.2 %) were deformed, 6 (18 %) were vertebra plana. CONCLUSION: In the absence of more specific diagnostic criteria, WB-MRI can, in synopsis with clinical findings, substantially contribute to a rapid diagnosis of CRMO. It discovers the typical pattern of multifocal and bilateral bone involvement more often than has been reported for targeted MRI. It readily reveals the characteristic proximity of lesions to growth plates, the sacroiliac joint and triradiate cartilage and helps to uncover asymptomatic spinal complications.

Controversies in childhood osteosarcoma.

Osteosarcoma, the most frequent bone cancer of children and adolescents, will almost always result in death due to pulmonary metastatic disease unless treated by surgery and effective multidrug chemotherapy. Imaging of the primary tumor is by X-ray and magnetic resonance imaging. Imaging of the chest is by computed tomography, but many questions regarding the interpretation of small, nonspecific findings and how to deal with them remain. The diagnosis must be confirmed by a well-placed biopsy. Chemotherapy is usually initiated prior to definitive surgery. Treatment generally includes high-dose methotrexate, doxorubicin, and cisplatin, with some regimens also incorporating ifosfamide. While limb-saving resections have become standard after completion of skeletal growth, reconstruction in the growing child poses much greater challenges. The use of modern, expandable endoprostheses, but also rotation-plasties and even amputation may all be valid options in selected cases. Histologic response of the primary to preoperative chemotherapy has been identified as an important prognostic factor. Various imaging methods can help to predict tumor response to preoperative chemotherapy, yet all have their limitations. Results of a randomized trial assessing if modifying postoperative treatment based on the extent of response will improve results, EURAMOS-1, are pending. The debate about whether biologic agents or targeted therapies added to chemotherapy might improve outcomes is ongoing. Follow-up to detect late-effects of treatment and recurrences of osteosarcoma must be continued for several decades.

Incidental findings in paranasal sinuses and mastoid cells: a cross-sectional magnetic resonance imaging (MRI) study in a pediatric radiology department.

PURPOSE: Misdiagnosis of "sinusitis" is still frequent in children, although mucosal swelling in the paranasal sinuses of children has been reported as a common incidental finding. Recent radiological publications on the problem are rare. We prospectively evaluated the mucosal thickening in the paranasal sinuses and mastoid cells of children who underwent MRI of the head for reasons other than sinusitis or mastoiditis. MATERIALS AND METHODS: 147 patients, 0.2 - 22.7 years, median 8.9. Axial and sagittal T2 TSE images were evaluated by two experienced pediatric radiologists. Categories for the degree of mucosal swelling were for the maxillary, frontal and sphenoid sinuses: no swelling, minor: < 5 mm, or major: ≥ 5 mm; for ethmoid cells and mastoid cells: not present, minor: ≤ 50 % of cells, or major: > 50 %. RESULTS: 61 % of children had one or more salient findings in their paranasal sinuses or mastoid cells. 48 % had mucosal swelling in their paranasal cavities, 25 % in their mastoid cells. The prevalence was higher among children less than 10 years of age (60 % and 42 %) and among children with current upper respiratory tract infection (71 % and 35 %). There was no correlation to a history of headache, snoring, asthma and allergies, or to gender or place of residence. CONCLUSION: Mucosal swelling in paranasal sinuses and in mastoid cells is a frequent incidental finding in children. Even major mucosal swelling in a paranasal sinus is not necessarily a sign of infection. In radiological reports the terms "sinusitis" and "mastoiditis" should therefore be used with great caution. The initiation of treatment should be based on clinical symptoms and not on radiological abnormalities alone.

[Comparison of the diagnostic value of X-ray versus MRI in paediatric spine injuries]. / Stellenwert des konventionellen Röntgenbilds versus MRT in der Diagnostik kindlicher Wirbelsäulenverletzungen.

AIM: The evaluation of paediatric thoracic or lumbar compression fractures can be challenging. The anatomy of the growing spine often makes a correct diagnosis by plain radiography difficult. The aim of our study was to compare the diagnostic reliability of X-Ray and that of magnetic resonance imaging in the evaluation of acute compression fractures of the paediatric spine. METHOD: From January to December 2008 20 patients (12 boys, 8 girls) who were treated because of clinically suspected compression fractures of the vertebra were included in our study. The average age was 8.3 years. In all cases a radiograph in two planes and an MRI of the lumbar and thoracic spine were obtained. Two orthopaedic surgeons and one radiologist retrospectively assessed the radiographs. The results were compared with the MRI findings. RESULTS: In six cases the MRI was normal, in one case there was only a bone bruise without compression of the vertebra. 13 children had two or more than two minor compression fractures (29 fractures altogether). The 5th and 6th thoracic vertebra predominated. In only two cases there was a corresponding result of all three physicians and the MRI. In 4 cases the observers agreed on the localisation of the fracture. There was no agreement about the number of fractured vertebrae. CONCLUSION: An exact evaluation of minor compression fractures of the pediatric spine with plain X-ray was not satisfactory.

[Appendicitis in childhood]. / Appendizitis im Kindesalter.

From 1989 to 1995 high-resolution ultrasonography (US) was performed in 3,546 children (age: 1-17 years) with clinically suspected appendicitis. A total of 518 patients underwent laparotomy; 420 had histologically proven acute or perforated appendicitis (prevalence 11.8%). In these children, the sensitivity, specificity and overall accuracy of US examination were 90%, 97% and 96% respectively. The use of US in clinically doubtful acute abdomen may allow earlier diagnosis of acute appendicitis; in 1995 the rate of unnecessary appendectomy was reduced to 13%.