Clear cell sarcoma of the kidney in Austrian children: Long-term survival after relapse.

INTRODUCTION: Clear cell sarcoma of the kidney (CCSK) is a rare malignant childhood renal tumour. Recently, the central nervous system (CNS) was found to be the most frequent site of relapse associated with a poor outcome. Optimal treatment strategies are scarce. PATIENTS AND METHODS: Retrospective data analysis of all Austrian children with CCSK. They were enrolled in the Austrian-Hungarian Wilms Tumour Study (AHWTS) 1989, the SIOP93-01 or the SIOP2001 study between 1990 and 2019. Demographic, diagnostic, treatment-related variables and survival data were analysed. RESULTS: We identified 12 children with CCSK (M = 7, F = 5; median age 1.6 years). All had localised disease (stage I: 2; stage II: 2; stage III: 8) at diagnosis, and a first complete remission (CR1) was achieved in 12/12. Six patients are in an ongoing CR1 (median follow-up 10 years). Six other patients had a relapse (local 1; brain 5) a median time of 2.4 years from diagnosis. Two patients died of the disease 4 months and 2.8 years after first relapse. Four of five patients with CNS relapse are in CR2 with a median follow-up time of 9.3 years after relapse diagnosis. Relapse treatment included a combination of chemotherapy, radiation and surgery. Two children received high-dose chemotherapy followed by autologous stem cell rescue, and one child received intrathecal mafosphamide. Long-term side effects after treatment were impaired tubular renal function (n = 4), cardiomyopathy (n = 1) and growth disorders (n = 1). CONCLUSIONS: In this series, the brain was the most common site of relapse. Long-term survival after recurrence was achievable with intensive multimodal therapy.

Heterogeneous MYCN amplification in neuroblastoma: a SIOP Europe Neuroblastoma Study.

BACKGROUND: In neuroblastoma (NB), the most powerful prognostic marker, the MYCN amplification (MNA), occasionally shows intratumoural heterogeneity (ITH), i.e. coexistence of MYCN-amplified and non-MYCN-amplified tumour cell clones, called heterogeneous MNA (hetMNA). Prognostication and therapy allocation are still unsolved issues. METHODS: The SIOPEN Biology group analysed 99 hetMNA NBs focussing on the prognostic significance of MYCN ITH. RESULTS: Patients <18 months (18 m) showed a better outcome in all stages as compared to older patients (5-year OS in localised stages: <18 m: 0.95 ± 0.04, >18 m: 0.67 ± 0.14, p = 0.011; metastatic: <18 m: 0.76 ± 0.15, >18 m: 0.28 ± 0.09, p = 0.084). The genomic 'background', but not MNA clone sizes, correlated significantly with relapse frequency and OS. No relapses occurred in cases of only numerical chromosomal aberrations. Infiltrated bone marrows and relapse tumour cells mostly displayed no MNA. However, one stage 4s tumour with segmental chromosomal aberrations showed a homogeneous MNA in the relapse. CONCLUSIONS: This study provides a rationale for the necessary distinction between heterogeneous and homogeneous MNA. HetMNA tumours have to be evaluated individually, taking age, stage and, most importantly, genomic background into account to avoid unnecessary upgrading of risk/overtreatment, especially in infants, as well as in order to identify tumours prone to developing homogeneous MNA.

Monitoring of plexiform neurofibroma in children and adolescents with neurofibromatosis type 1 by [18 F]FDG-PET imaging. Is it of value in asymptomatic patients?

PURPOSE: About 10% of patients with neurofibromatosis type 1 (NF-1) develop malignant peripheral nerve sheath tumours (MPNST) mostly arising in plexiform neurofibroma (PN); 15% of MPNST arise in children and adolescents. 2-[18 F]fluoro-2-deoxy-d-glucose ([18 F]FDG)-PET (where PET is positron emission tomography) is a sensitive method in differentiating PN and MPNST in symptomatic patients with NF-1. This study assesses the value of [18 F]FDG-PET imaging in detecting malignant transformation in symptomatic and asymptomatic children with PN. METHODS: Forty-one patients with NF-1 and extensive PN underwent prospective [18 F]FDG imaging from 2003 to 2014. Thirty-two of the patients were asymptomatic. PET data, together with histological results and clinical course were re-evaluated retrospectively. Maximum standardised uptake values (SUVmax) and lesion-to-liver ratio were assessed. RESULTS: A total of 104 examinations were performed. Mean age at first PET was 13.5 years (2.6-22.6). Eight patients had at least one malignant lesion; four of these patients were asymptomatic. Two of four symptomatic patients died, while all patients with asymptomatic malignant lesions are alive. All malignant tumours could be identified by PET imaging in both symptomatic and asymptomatic patients. All lesions judged as benign by [18 F]FDG imaging and clinical judgment were either histologically benign if removed or remained clinically silent during follow-up. SUVmax of malignant and benign lesions overlapped, but no malignant lesion showed FDG uptake ≤3.15. Asymptomatic malignant lesions were detected with a sensitivity of 100%, a negative predictive value of 100% and a specificity of 45.1%. CONCLUSION: Malignant transformation of PN also occurs in asymptomatic children and adolescents. Detection of MPNST at early stages could increase the possibility of oncologically curative resections.

Thoracic Actinomycosis With Infiltration of the Spine: An Oncological Pitfall.

Thoracic actinomycosis with involvement of the vertebral column and chest wall is rare in children and may resemble malignant tumors. A 12-year-old girl was admitted to our clinic having B-symptoms, cachexia, and painful scoliosis (Karnofsky index 20%). Imaging showed a large thoracic left-sided paravertebral tumor with infiltration of the vertebrae, destruction of the chest wall and multiple intrapulmonary nodules. Initially, Ewing sarcoma was suspected and chemotherapy started without previous biopsies. Definite diagnosis of actinomycosis was established later upon histopathologic examination and successfully treated by ß-lactam antibiotics. Collectively, this case illustrates that actinomycosis can be an oncological pitfall and possible differential diagnosis.

Outcome of two patients with bilateral nephroblastomatosis/Wilms tumour treated with an add-on 13-cis retinoic acid therapy - Case report.

Although the fate of nephrogenic rests varies, they are known to be precursors of Wilms tumour. Thus, nephrogenic rests require adequate treatment to prevent malignant transformation. We added 13-cis retinoic acid to the standard chemotherapy with vincristine and actinomycin-D in two patients with bilateral nephrogenic rests/nephroblastomatosis. Patient 1 also had a history of Wilms tumour. 46 (patient 1) and 81 (patient 2) months after end of treatment, both patients show stable conditions with no signs of relapse or progressive disease. Our observation supports further investigation of retinoic acid in patients with nephrogenic rests and nephroblastomatosis.

The genetic tumor background is an important determinant for heterogeneous MYCN-amplified neuroblastoma.

Amplification of MYCN is the signature genetic aberration of 20-25% of neuroblastoma and a stratifying marker associated with aggressive tumor behavior. The detection of heterogeneous MYCN amplification (hetMNA) poses a diagnostic dilemma due to the uncertainty of its relevance to tumor behavior. Here, we aimed to shed light on the genomic background which permits hetMNA in neuroblastoma and tied the occurrence to other stratifying markers and disease outcome. We performed SNP analysis using Affymetrix Cytoscan HD arrays on 63 samples including constitutional DNA, tumor, bone marrow and relapse samples of 26 patients with confirmed hetMNA by MYCN-FISH. Tumors of patients ≤18m were mostly aneuploid with numeric chromosomal aberrations (NCAs), presented a prominent MNA subclone and carried none or a few segmental chromosomal aberrations (SCAs). In older patients, tumors were mostly di- or tetraploid, contained a lower number of MNA cells and displayed a multitude of SCAs including concomitant 11q deletions. These patients often suffered disease progression, tumor dissemination and relapse. Restricted to aneuploid tumors, we detected chromosomes with uniparental di- or trisomy (UPD/UPT) in almost every sample. UPD11 was exclusive to tumors of younger patients whereas older patients featured UPD14. In this study, the MNA subclone appears to be constraint by the tumor environment and thus less relevant for tumor behavior in aggressive tumors with a high genomic instability and many segmental aberrations. A more benign tumor background and lower tumor stage may favor an outgrowth of the MNA clone but tumors generally responded better to treatment.

Fetal diffusion tensor quantification of brainstem pathology in Chiari II malformation.

OBJECTIVES: This prenatal MRI study evaluated the potential of diffusion tensor imaging (DTI) metrics to identify changes in the midbrain of fetuses with Chiari II malformations compared to fetuses with mild ventriculomegaly, hydrocephalus and normal CNS development. METHODS: Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were calculated from a region of interest (ROI) in the midbrain of 46 fetuses with normal CNS, 15 with Chiari II malformations, eight with hydrocephalus and 12 with mild ventriculomegaly. Fetuses with different diagnoses were compared group-wise after age-matching. Axial T2W-FSE sequences and single-shot echo planar DTI sequences (16 non-collinear diffusion gradient-encoding directions, b-values of 0 and 700 s/mm(2), 1.5 Tesla) were evaluated retrospectively. RESULTS: In Chiari II malformations, FA was significantly higher than in age-matched fetuses with a normal CNS (p = .003), while ADC was not significantly different. No differences in DTI metrics between normal controls and fetuses with hydrocephalus or vetriculomegaly were detected. CONCLUSIONS: DTI can detect and quantify parenchymal alterations of the fetal midbrain in Chiari II malformations. Therefore, in cases of enlarged fetal ventricles, FA of the fetal midbrain may contribute to the differentiation between Chiari II malformation and other entities. KEY POINTS: • FA in the fetal midbrain is elevated in Chiari II malformations. • FA is not elevated in hydrocephalus and mild ventriculomegaly without Chiari II. • Measuring FA may help distinguish different causes for enlarged ventricles prenatally. • Elevated FA may aid in the diagnosis of open neural tube defects. • Elevated FA might contribute to stratification for prenatal surgery in Chiari II.

Peripheral nerve tractography in soft tissue tumors: a preliminary 3-tesla diffusion tensor magnetic resonance imaging study.

INTRODUCTION: This diffusion tensor magnetic resonance imaging (DTI) study aimed to clarify the relationship of peripheral nerves and soft tissue tumors (STTs) in 3D to optimize subsequent treatment. METHODS: Twenty-six consecutive STT patients (histologically malignant, n=10; intermediate, n=3; and benign, n=13) underwent 3-Tesla MRI using an echoplanar DTI sequence. Deterministic tractography was performed. Fractional anisotropy (FA) values were measured within peritumoral and distant regions of interest. RESULTS: Tractography depicted the 3D course of the sciatic (n=12), femoral (n=2), tibial (n=7), fibular (n=2), median (n=1), musculocutaneous (n=1), and ulnar (n=1) nerves in a regular (n=8 of 18, 44.4%) or thinned (n=7 of 18, 38.9%) fashion. The lowest peritumoral FA values, abrupt thinning, and/or complete discontinuity of trajectories were found in 2 cases with histologically proven tumoral nerve infiltration. CONCLUSIONS: DTI clarifies the 3D topography between major peripheral nerves and STTs and may be helpful in the assessment of peripheral nerve infiltration by malignant tumors.

Use of diagnostic dynamic contrast-enhanced (DCE)-MRI for targeting of soft tissue tumour biopsies at 3T: preliminary results.

OBJECTIVES: To test the feasibility and accuracy of MR-guided soft tissue tumour biopsy at 3T, using the dynamic contrast-enhanced (DCE) information from staging MRI for intralesional targeting. METHODS: After obtaining written informed consent for this institutional review board-approved study, 53 patients with suspected soft tissue tumours prospectively underwent preoperative staging MRI at 3T, including DCE, and subsequent MR-guided core needle biopsy. In 44/53 cases, DCE was heterogeneous and was used for intralesional biopsy targeting. Surgical, whole-specimen histology was used as the gold standard in 43/44 patients and revealed 42 soft tissue tumours (24 men; 18 women; mean age, 52 years; range, 19 - 84). RESULTS: Final surgical histology revealed eight benign lesions, six tumours of intermediate dignity, and 28 malignancies. All malignancies had shown heterogeneous DCE. The diagnostic yield of the biopsies was 100% (42/42). Histological accuracy rates of biopsy were 100% in predicting the dignity (42/42; 95% CI [0.916 - 1.000]), 95.2% for the tissue-specific entity (40/42; 95% CI [0.847 - 0.987]), and 90.5% for the tumour grade (38/42; 95% CI [0.779 - 0.962]). CONCLUSIONS: Our preliminary study indicates that biopsy of soft tissue tumours can be performed accurately and safely with DCE targeted MR-guidance at 3T, using a combined staging/biopsy MRI protocol. KEY POINTS: • MR-guided soft tissue tumour biopsy using DCE for intralesional targeting is feasible. • Targeting by staging-MRI allows reliable planning of the biopsy approach. • The method seems accurate and safe as a combined staging/biopsy procedure in outpatients. • DCE-targeted biopsy seems useful in challenging large and heterogeneous tumours.

Diffusion tensor tractography for the surgical management of peripheral nerve sheath tumors.

OBJECT Peripheral nerve sheath tumors (PNSTs) are uncommon but bear a significant risk of malignancy. High-resolution MRI is the standard technique for characterizing PNSTs. However, planning the appropriate extent of resection and subsequent reconstructive strategies is highly dependent on the intraoperative findings because preoperative MRI evaluation can be insufficient. Diffusion tensor tractography (DTT) represents a recently developed advanced MRI technique that reveals the microstructure of tissues based on monitoring the random movement of water molecules. DTT has the potential to provide diagnostic insights beyond conventional MRI techniques due to its mapping of specific fibrillar nerve structures. Here, DTT was applied to evaluate PNSTs and to examine the usefulness of this method for the correct delineation of tumor and healthy nerve tissue and the value of this information in the preoperative planning of surgical interventions. METHODS In this prospective study, patients with the clinical symptoms of a PNST were investigated using DTT 3-Tesla MRI scans. Image data processing and tractography were performed using the FACT (fiber assessment by continuous tracking) algorithm and multiple-regions-of-interest approach. The surgical findings were then compared with the results of the DTT MRI scans. Preoperative fascicle visualization and the correlation with the intraoperative findings were graded. RESULTS In a 21-month period, 12 patients with PNSTs were investigated (7 female and 5 male patients with a mean age of 46.2 ± 19.2 years). All patients underwent surgical removal of the tumor. Schwannoma was the most common benign histopathological finding (n = 7), whereas 2 malignant lesions were detected. In 10 of 12 patients, good preoperative nerve fascicle visualization was achieved using DTT scans. In 9 of 10 patients with good preoperative fascicle visualization, good intraoperative correlation between the DTT scans and surgical anatomy was found. CONCLUSIONS DTT properly visualizes the peripheral nerve fascicles and their correct anatomical relation to PNST. DTT represents a promising new method for the preinterventional planning of nerve tumor resection.

Initially localized synovial sarcoma in adults: a retrospective single-center analysis of 26 patients registered at the Department of Oncology, University of Vienna between 2004 and 2013.

BACKGROUND: Synovial sarcoma is a rare subgroup of all soft-tissue sarcomas. The aim of this retrospective single-center analysis was to investigate the outcome of patients with initially localized disease. PATIENTS AND METHODS: Twenty-six patients were enrolled in this retrospective single-center analysis. Baseline characteristics, treatment and outcome were evaluated. RESULTS: In 13 patients (50%), the tumor was located in the lower extremity and in 4 patients (15%) in the upper extremity. Surgical resection was done in all but 2 patients (92%). Re-resection was done in 7 patients (27%). Fourteen patients (54%) received adjuvant chemotherapy. After a median follow-up of 23.3 months (range: 2.6-150.3), median disease-free survival was not reached at the time of analysis. Eight patients (31%) relapsed after initial therapy. Surgery was done in 2 patients, amputation in 1 patient, palliative chemotherapy was administered in 3 and radiation therapy in 2 patients. Median overall survival (OS) for all patients was not reached at the time of analysis. The estimated 5-year OS rate was 62%. CONCLUSION: Patients with initially localized synovial sarcoma who were included in this retrospective single-center analysis have an estimated 5-year OS rate of 62%.

Distinctive outcome in patients with non-uterine and uterine leiomyosarcoma.

BACKGROUND: Leiomyosarcomas represent the largest subtype of soft tissue sarcomas. Two subgroups can be distinguished, non-uterine (NULMS) and uterine leiomyosarcomas (ULMS). The aim of this retrospective study was to evaluate differences in clinical features and outcome between these two subgroups. METHODS: Outcome and clinical-pathological parameters between 50 patients with NULMS and 45 patients with ULMS were assessed, and compared between both groups. Univariate and multivariable survival analyses were performed. RESULTS: Patients with ULMS presented with larger tumors when compared to patients with NULMS (p < 0.001). More patients with ULMS initially presented with metastatic disease (67% vs. 36%, p = 0.007). Most common metastatic site was lung for both subtypes (28% and 38%). Five-year overall survival (OS) rates of 82.6% and 41.2% and median OS times of 92.6 (range: 79.7-105.4) and 50.4 (range: 34.8-66.0) months were observed in patients with NULMS and ULMS, respectively (p = 0.006). In multivariate analysis, initial metastatic disease remained an independent prognostic factor in terms of OS (p < 0.0001). CONCLUSION: At time of diagnosis ULMS were larger and more often metastasized. Therefore patients with ULMS showed unfavorable outcome when compared to NULMS. Later diagnosis might be caused by differences in symptoms and clinical presentation or a more aggressive biological tumor behavior.

Follow-up of pediatric celiac disease: value of antibodies in predicting mucosal healing, a prospective cohort study.

BACKGROUND: In diagnosing celiac disease (CD), serological tests are highly valuable. However, their role in following up children with CD after prescription of a gluten-free diet is unclear. This study aimed to compare the performance of antibody tests in predicting small-intestinal mucosal status in diagnosis vs. follow-up of pediatric CD. METHODS: We conducted a prospective cohort study at a tertiary-care center. 148 children underwent esophohagogastroduodenoscopy with biopsies either for symptoms ± positive CD antibodies (group A; n = 95) or following up CD diagnosed ≥ 1 year before study enrollment (group B; n = 53). Using biopsy (Marsh ≥ 2) as the criterion standard, areas under ROC curves (AUCs) and likelihood-ratios were calculated to estimate the performance of antibody tests against tissue transglutaminase (TG2), deamidated gliadin peptide (DGP) and endomysium (EMA). RESULTS: AUCs were higher when tests were used for CD diagnosis vs. follow-up: 1 vs. 0.86 (P = 0.100) for TG2-IgA, 0.85 vs. 0.74 (P = 0.421) for TG2-IgG, 0.97 vs. 0.61 (P = 0.004) for DPG-IgA, and 0.99 vs. 0.88 (P = 0.053) for DPG-IgG, respectively. Empirical power was 85% for the DPG-IgA comparison, and on average 33% (range 13-43) for the non-significant comparisons. Among group B children, 88.7% showed mucosal healing (median 2.2 years after primary diagnosis). Only the negative likelihood-ratio of EMA was low enough (0.097) to effectively rule out persistent mucosal injury. However, out of 12 EMA-positive children with mucosal healing, 9 subsequently turned EMA-negative. CONCLUSIONS: Among the CD antibodies examined, negative EMA most reliably predict mucosal healing. In general, however, antibody tests, especially DPG-IgA, are of limited value in predicting the mucosal status in the early years post-diagnosis but may be sufficient after a longer period of time.

Peripheral neuroblastic tumors with genotype-phenotype discordance: a report from the Children's Oncology Group and the International Neuroblastoma Pathology Committee.

BACKGROUND: Of 4,706 peripheral neuroblastic tumors (pNTs) registered on the Children's Cancer Group and Children's Oncology Group Neuroblastoma Study between 1989 and 2010, 51 cases (1.1%) had genotype-phenotype discordance characterized by MYCN amplification (indicating poor prognosis) and Favorable Histology (indicating better prognosis). PROCEDURE: To distinguish prognostic subgroups in the genotype-phenotype discordant pNTs, two subgroups, "conventional" and "bull's eye," were identified based on the nuclear morphology. The "conventional" tumors (35 cases) included: Neuroblastoma, poorly differentiated subtype (NB-PD, 26 cases) with "salt-and-pepper" nuclei; neuroblastoma, differentiating subtype (4 cases); ganglioneuroblastoma, intermixed (3 cases); and ganglioneuroma, maturing subtype (2 cases). The "bull's eye" tumors included NB-PD with prominent nucleoli (16 cases). Clinicopathologic characteristics of these two subgroups were analyzed. N-myc protein expression was tested immunohistochemically on available tumors. RESULTS: No significant difference was found between these two subgroups in the distribution of prognostic factors such as age at diagnosis, clinical stage, histopathology category/subtype, mitosis-karyorrhexis index, ploidy, 1p LOH, and unbalanced 11q LOH. However, prognosis of the patients with "conventional" tumors (5-year EFS 85.7 ± 12.2%; OS 89.3 ± 10.3%) was significantly better than those with "bull's eye" tumors (EFS 31.3 ± 13.0%; OS 42.9 ± 16.2%; P = 0.0010 and 0.0008, respectively). Immunohistochemically all (11/11) tested "conventional" tumors were negative, and 10/11 tested "bull's eye" tumors were positive for N-myc protein expression. CONCLUSIONS: Based on the presence or absence of prominent nucleoli (the putative site of RNA synthesis/accumulation leading to N-myc protein expression), two prognostic subgroups, "conventional" with a better prognosis and "bull's eye" with a poor prognosis, were distinguished among the genotype-phenotype discordant pNTs.

A combined transcriptome and bioinformatics approach to unilateral ureteral obstructive uropathy in the fetal sheep model.

PURPOSE: Fetal obstructive uropathy is a leading cause of loss of renal function. Characterizing the molecular fingerprint of cellular responses to obstruction in a fetal model of complete unilateral ureteral obstruction may help elucidate the activated mechanisms and suggest new therapeutic interventions. MATERIAL AND METHODS: Unilateral ureteral obstruction was created in 3 sheep fetuses at day 60 of gestation. For transcriptome analysis total RNA was extracted from vital renal biopsies 2 weeks after intervention from obstructed kidneys and from control kidneys of untreated twins. cDNA preparation, hybridization to the GeneChip® Bovine Genome Array and array scanning were done according to manufacturer protocols. Bioinformatics analysis was used to derive functional biological processes linked to obstructive uropathy. Quantitative reverse-transcriptase-polymerase chain reaction and immunohistochemistry were used to validate microarray results. RESULTS: Seven biological processes were identified as significantly affected by differentially regulated features that characterize unilateral ureteral obstruction, namely protein metabolism and modification, other metabolism, neuronal activity, ligand mediated signaling, amino acid metabolism, coenzyme/prosthetic group metabolism and rRNA metabolism. Literature mining identified 17 candidate genes previously reported as key in the context of unilateral ureteral obstruction, related pathological mechanisms or other kidney diseases. CONCLUSIONS: Combined transcriptome and bioinformatics analysis allowed the identification of enriched processes in the fetal sheep model of unilateral ureteral obstruction that are likely associated with renal damage but to our knowledge have not been previously identified. Future clarification of these molecular fingerprints may eventually provide therapeutic targets and early predictive markers involved in the pathogenesis of fetal uropathy.

Notch signalling is off and is uncoupled from HES1 expression in Ewing's sarcoma.

Notch can act as an oncogene or as a tumour suppressor and thus can either promote or inhibit tumour cell growth. To establish Notch status in Ewing's sarcoma family of tumours (ESFT), we investigated the Notch pathway by gene expression profiling meta-analysis or immunohistochemistry in samples obtained from 96 and 24 ESFT patients, respectively. We found that although Notch receptors were highly expressed, Notch did not appear to be active, as evidenced by the absence of Notch receptors in cell nuclei. In contrast, we show that Notch receptors known to be active in colon adenocarcinoma, hepatocarcinoma, and pancreatic carcinoma stain cell nuclei in these tumours. High expression of the Notch effector HES1 transcription factor, usually used as a surrogate marker for active Notch, was also restricted to outside of the nucleus in the majority of ESFT, and analysis of HES1 gene targets indicated HES1 to be transcriptionally inactive. Neither forced activation nor pharmacological or genetic blocking of Notch affected HES1 expression in ESFT cells, indicating HES1 expression to be uncoupled from the Notch pathway. Additional functional studies in ESFT cell lines confirmed Notch to be switched off. Finally, unlike experiments in which HES1 expression was modulated, experimental activation of Notch in ESFT cell lines via several means blocked cell proliferation and reduced their clonogenic potential in soft agar. These indicate that HES1 is uncoupled from Notch in ESFT, that EWS-FLI1-mediated inhibition of Notch contributes to ESFT aggressive cell growth, and support a role for Notch in ESFT tumour suppression, at least partly through the Notch effector HEY1.

Fetal akinesia and associated abnormalities on prenatal MRI.

OBJECTIVE: In view of the increasing role of magnetic resonance imaging (MRI) as an adjunct to prenatal ultrasonography (US), this study sought to demonstrate the visualization of fetal akinesia and associated abnormalities on MRI. METHODS: This retrospective study included six fetuses with akinesia and associated abnormalities, depicted on fetal MRI after suspicious prenatal US. The whole fetus was assessed for musculoskeletal abnormalities and associated pathological conditions elsewhere. Fetal outcome data were compared with prenatal imaging. US and MRI findings were also compared. RESULTS: Akinesia resulting in arthrogryposis was seen in 6/6 fetuses, with abnormal musculature in 5/6 fetuses. Associated brain abnormalities were found in 2/6 fetuses; facial abnormalities in 3/6; lung hypoplasia in 3/6; and polyhydramnios in 2/6. There were 5/6 pregnancies that were terminated and one individual died neonatally. MRI and brain autopsy were concordant in 4/6 cases. MRI and body autopsy were concordant in 1/6 cases and in 5/6 cases, autopsy revealed additional abnormalities. In addition to US, MRI correctly identified central nervous system findings in four cases and lung hypoplasia in three cases. CONCLUSION: Our MRI results demonstrate fetal akinesia and associated abnormalities, which may have an impact on perinatal management, as an adjunct to prenatal US.

Systematic review of the immunological landscape of Wilms tumors.

Results of immunotherapy in childhood solid cancer have been so far, with the exception of neuroblastoma, quite disappointing. Lack of knowledge of the immune contexture of these tumors may have contributed to the failure of immunotherapies so far. Here, we systematically reviewed the literature regarding the immunology of Wilms tumor (WT), one of the most frequent pediatric solid tumors of the abdomen. In Wilms tumor patients the high cure rate of >90%, achieved by the combination of surgery and radio-chemotherapy, is at the expense of a high early and late toxicity. Moreover, treatment-resistant entities, such as diffuse anaplastic tumors or recurrent disease, still pose unsolved clinical problems. Successful immunotherapy could represent a novel and possibly less-toxic treatment option. Employing the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) method of literature search, we analyzed the current knowledge of the immunological landscape of Wilms tumors in terms of tumor microenvironment, prognostic implications of single biomarkers, and immunotherapy response.

Diagnostic accuracy of ultrasound-guided core needle biopsy versus incisional biopsy in soft tissue sarcoma: an institutional experience.

Core needle biopsy (CNB) is gaining in importance due to its advantages in the matter of patient morbidity, time and cost. Nevertheless, controversies still exist regarding the biopsy technique of choice for the accurate diagnosis of soft tissue sarcoma (STS). This retrospective cohort study compared the diagnostic performance between ultrasound-guided CNB and incisional biopsy (IB), both performed by orthopedic surgeons. The aims of the study were to answer the following questions: (1) Is ultrasound-guided CNB a highly reliable modality for diagnosing STSs? (2) Is CNB equally useful to IB for identifying histologic subtype? (3) Had patients who underwent CNB a reduced risk of complications? One-hundred and fifty-three patients who underwent resection of soft tissue sarcoma were classified into two groups according to biopsy technique prior to surgery; CNB group (n = 95) and IB group (n = 58). The final surgical specimens were in 40 patients liposarcoma (myxoid, pleomorphic and dedifferentiated), 39 undifferentiated pleomorphic sarcoma (UPS), 33 myxofibrosarcoma, 10 synovial sarcoma, 10 leiomyosarcoma and in the remaining 21 patients different soft tissue sarcoma entities. Sarcoma location of 71 patients was in the thigh, 19 in the lower leg, 22 in the upper arm and shoulder area; 10 in the knee and gluteal region, 9 in the thoracic region, the residual 12 in other body areas. Malignancy was correctly diagnosed in 87% (83 of 95) for the CNB group and 93% (54/58) for the IB group. Correct identification rate of histologic subtype was 80% (76 of 95) in the CNB group and 83% (48 of 58) in the IB group. There were no significant differences in the correct diagnosis rates of malignancy and subtype between the two techniques. No complications were seen in the CNB group, whereas 2 patients in whom IB was performed developed pulmonary embolism and 1 patient surgical site infection. Ultrasound-guided CNB is highly accurate and not inferior to IB in diagnosing the dignity of lesions and histologic subtype in patients with suspected STSs.

Long-Term Outcome and Role of Biology within Risk-Adapted Treatment Strategies: The Austrian Neuroblastoma Trial A-NB94.

We evaluated long-term outcome and genomic profiles in the Austrian Neuroblastoma Trial A-NB94 which applied a risk-adapted strategy of treatment (RAST) using stage, age and MYCN amplification (MNA) status for stratification. RAST ranged from surgery only to intensity-adjusted chemotherapy, single or multiple courses of high-dose chemotherapy (HDT) followed by autologous stem cell rescue depending on response to induction chemotherapy, and irradiation to the primary tumor site. Segmental chromosomal alterations (SCAs) were investigated retrospectively using multi- and pan-genomic techniques. The A-NB94 trial enrolled 163 patients. Patients with localized disease had an excellent ten-year (10y) event free survival (EFS) and overall survival (OS) of 99 ± 1% and 93 ± 2% whilst it was 80 ± 13% and 90 ± 9% for infants with stage 4S and for infants with stage 4 non-MNA disease both 83 ± 15%. Stage 4 patients either >12 months or ≤12 months but with MNA had a 10y-EFS and OS of 45 ± 8% and 47 ± 8%, respectively. SCAs were present in increasing frequencies according to stage and age: in 29% of localized tumors but in 92% of stage 4 tumors (p < 0.001), and in 39% of patients ≤ 12 months but in 63% of patients > 12 months (p < 0.001). RAST successfully reduced chemotherapy exposure in low- and intermediate-risk patients with excellent long-term results while the outcome of high-risk disease met contemporary trials.