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Objective: To assess the feasibility, accuracy, and safety of ultrasound (US)-guided coaxial core-needle biopsy (CNB) for histomolecular diagnosis of extra-ocular orbital soft tissue tumours as a minimally invasive alternative to surgical biopsy., Methods: This retrospective study was conducted at a single Comprehensive Cancer Center and included all consecutive patients referred to our center between 2015 and 2023 for the diagnosis and treatment of orbital soft tissue tumours. All patients underwent US-guided transconjunctival coaxial CNB using a semiautomatic 18-gauge biopsy gun. Pathological analysis included morphological analysis, immunostainings, and molecular biology techniques when required., Results: A total of 26 patients were included consisting of 21 adults (median age: 64 years, range: 24-93 years), 1 adolescent (17 years), and 4 children (aged 4 weeks, 5 weeks, 26 months, and 6 years). Tumour largest diameters ranged from 11 to 57 mm (median 23 mm). The overall feasibility of CNB was 88% (23/26), and it was 100% (5/5) in children. The histological accuracy was 91% (21/23), and its safety was 96% (25/26). Molecular biology analyses were requested in 9 out of 23 cases and were successful in all instances. The final diagnoses included hematological malignancies (n = 8), carcinomas (n = 5), metastases (n = 4), sarcomas (n = 4), and benign mesenchymal tumours (n = 5)., Conclusions: This study supports the use of US-guided coaxial CNB for the pathological and molecular diagnosis of orbital soft tissue tumours in both children and adults. This technique shows promise as a minimally invasive alternative to open surgical biopsy., (Copyright © 2024 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

CREB gene family (ATF1, CREB1, CREM) fusions with either EWSR1 or FUS gene partners drive the pathogenesis of a wide range of neoplasms, including various soft tissue tumors, intracranial myxoid mesenchymal tumors (IMMTs), hyalinizing clear cell carcinoma (HCCC), and rare mesotheliomas. Recently, a SMARCA2::CREM fusion was reported in one case each of IMMT and HCCC. In this study, we expand the clinicopathologic and molecular spectrum of these neoplasms by describing three additional cases with SMARCA2::CREM and one with a novel SMARCA4::CREM fusion, highlighting the recurrent potential of additional CREB gene fusion partners beyond FET family members. To evaluate if these fusions define a new pathologic entity, we performed a comprehensive genomic and methylation analysis and compared the results to other related tumors. Tumors occurred in children and young adults (median age 20 years) and spanned a broad anatomic distribution, including soft tissue, intracranial, head and neck, and prostatic urethra. Microscopically, the tumors shared an undifferentiated round to epithelioid cell phenotype and a hyalinized fibrous stroma. Immunohistochemically, a polyphenotypic profile was observed, with variable expression of SOX10, desmin, and/or epithelial markers. No targetable genomic alterations were found using panel-based DNA sequencing. By DNA methylation and transcriptomic analyses, tumors grouped closely to FET::CREB entities, but not with SMARCA4/SMARCB1-deficient tumors. High expression of CREM by immunohistochemistry was also documented in these tumors. Patients experienced local recurrence (n = 2), locoregional lymph node metastases (n = 2), and an isolated visceral metastasis (n = 1). Overall, our study suggests that SMARCA2/4::CREM fusions define a distinct group of neoplasms with round cell to epithelioid histology, a variable immunoprofile, and a definite risk of malignancy. Larger studies are needed to further explore the pathogenetic relationship with the FET::CREB family of tumors. © 2024 The Pathological Society of Great Britain and Ireland., (© 2024 The Pathological Society of Great Britain and Ireland.)

MYCN-amplified RB1 wild-type (MYCN amp RB1 +/+ ) retinoblastoma is a rare and aggressive subtype, often resistant to standard therapies. Identifying unique MRI features is crucial for diagnosing this subtype, as biopsy is not recommended. This study aimed to differentiate MYCN amp RB1 +/+ from the most prevalent RB1 -/- retinoblastoma using pretreatment MRI and radiomics. Ninety-eight unilateral retinoblastoma patients (19 MYCN cases and 79 matched controls) were included. Tumors on T2-weighted MR images were manually delineated and validated by experienced radiologists. Radiomics analysis extracted 120 features per tumor. Several combinations of feature selection methods, oversampling techniques and machine learning (ML) classifiers were evaluated in a repeated fivefold cross-validation machine learning pipeline to yield the best-performing prediction model for MYCN. The best model used univariate feature selection, data oversampling (duplicating MYCN cases), and logistic regression classifier, achieving a mean AUC of 0.78 (SD 0.12). SHAP analysis highlighted lower sphericity, higher flatness, and greater gray-level heterogeneity as predictive for MYCN amp RB1 +/+ status, yielding an AUC of 0.81 (SD 0.11). This study shows the potential of MRI-based radiomics to distinguish MYCN amp RB1 +/+ and RB1 -/- retinoblastoma subtypes., (© 2024. The Author(s).)

Objectives: To assess the diagnostic accuracy of nerve thickening on MRI to predict early-stage postlaminar optic nerve invasion (PLONI) in retinoblastoma. Furthermore, this study aimed to incorporate measurements into a multiparametric model for radiological determination of PLONI., Methods: In this retrospective multicenter case-control study, high-spatial-resolution 3D T2-weighted MR images were used to measure the distal optic nerve. Histopathology was the reference standard for PLONI. Two neuroradiologists independently measured the optic nerve width, height, and surface at 0, 3, and 5 mm from the most distal part of the optic nerve. Subsequently, PLONI was scored on contrast-enhanced T1-weighted and 3D T2-weighted images, blinded for clinical data. Optic nerve measurements with the highest diagnostic accuracy for PLONI were incorporated into a prediction model for radiological determination of PLONI., Results: One hundred twenty-four retinoblastoma patients (median age, 22 months [range, 0-113], 58 female) were included, resulting in 25 retinoblastoma eyes with histopathologically proven PLONI and 206 without PLONI. ROC analysis of axial optic nerve width measured at 0 mm yielded the best area under the curve of 0.88 (95% confidence interval: 0.79, 0.96; p < 0.001). The optimal width cutoff was ≥ 2.215 mm, with a sensitivity of 84% (95% CI: 64, 95%) and specificity of 83% (95% CI: 75, 89%) for detecting PLONI. Combining width measurements with the suspicion of PLONI on MRI sequences resulted in a prediction model with an improved sensitivity and specificity of respectively up to 88% and 92%., Conclusion: Postlaminar optic nerve thickening can predict early-stage postlaminar optic nerve invasion in retinoblastoma., Clinical Relevance Statement: This study provides an additional tool for clinicians to help determine postlaminar optic nerve invasion, which is a risk factor for developing metastatic disease in retinoblastoma patients., Key Points: • The diagnostic accuracy of contrast-enhanced MRI for detecting postlaminar optic nerve invasion is limited in retinoblastoma patients. • Optic nerve thickening can predict postlaminar optic nerve invasion. • A prediction model combining MRI features has a high sensitivity and specificity for detecting postlaminar optic nerve invasion., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

This retrospective multicenter study examines therapy-induced orbital and ocular MRI findings in retinoblastoma patients following selective intra-arterial chemotherapy (SIAC) and quantifies the impact of SIAC on ocular and optic nerve growth. Patients were selected based on medical chart review, with inclusion criteria requiring the availability of posttreatment MR imaging encompassing T2-weighted and T1-weighted images (pre- and post-intravenous gadolinium administration). Qualitative features and quantitative measurements were independently scored by experienced radiologists, with deep learning segmentation aiding total eye volume assessment. Eyes were categorized into three groups: eyes receiving SIAC (Rb-SIAC), eyes treated with other eye-saving methods (Rb-control), and healthy eyes. The most prevalent adverse effects post-SIAC were inflammatory and vascular features, with therapy-induced contrast enhancement observed in the intraorbital optic nerve segment in 6% of patients. Quantitative analysis revealed significant growth arrest in Rb-SIAC eyes, particularly when treatment commenced ≤ 12 months of age. Optic nerve atrophy was a significant complication in Rb-SIAC eyes. In conclusion, this study highlights the vascular and inflammatory adverse effects observed post-SIAC in retinoblastoma patients and demonstrates a negative impact on eye and optic nerve growth, particularly in children treated ≤ 12 months of age, providing crucial insights for clinical management and future research.

Objectives: The neurotrophic tyrosine receptor kinase (NTRK) fusion transcript (FT) is a major genetic landmark of infantile fibrosarcoma (IFS) and cellular congenital mesoblastic nephroma (cCMN) but is also described in other tumours. The recent availability of NTRK-targeted drugs enhances the need for better identification. We aimed to describe the anatomic locations and imaging features of tumours with NTRK-FT in children., Case Series: Imaging characteristics of NTRK-FT tumours of 41 children (median age: 4 months; 63% <1 year old; range: 0-188) managed between 2001 and 2019 were retrospectively analysed. The tumours were located in the soft tissues (n = 24, including 19 IFS), kidneys (n = 9, including 8 cCMN), central nervous system (CNS) (n = 5), lung (n = 2), and bone (n = 1). The tumours were frequently deep-located (93%) and heterogeneous (71%) with necrotic (53%) or haemorrhagic components (29%). Although inconstant, enlarged intratumoural vessels were a recurrent finding (70%) with an irregular distribution (63%) in the most frequent anatomical locations., Conclusion: Paediatric NTRK-FT tumours mainly occur in infants with very variable histotypes and locations. Rich and irregular intra-tumoural vascularization are recurrent findings., Advances in Knowledge: Apart from IFS of soft tissues and cCMN of the kidneys, others NTRK-FT tumours locations have to be known, as CNS tumours. Better knowledge of the imaging characteristics may help guide the pathological and biological identification., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The aim of this study was to assess the clinical impact of indeterminate pulmonary nodules (no more than four pulmonary nodules of less than 5 mm or one nodule measuring between 5 and less than 10 mm by computed tomography [CT]) in children and adolescents with adult-type non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) at diagnosis., Methods: Patients with NRSTS treated in 11 centers as part of the European paediatric Soft Tissue Sarcoma Study Group (EpSSG) were retrospectively assessed. Local radiologists, blinded to clinical information except for patients' age and tumor histotype, reviewed the chest CT at diagnosis and filled out a case report form. Because patients with or without indeterminate nodules in the EpSSG NRSTS 2005 study received the same type of treatment, event-free survival (EFS) and overall survival (OS) between groups by log-rank test were compared., Results: Overall, 206 patients were examined: 109 (52.9%) were without any nodules, 78 (38%) had at least one indeterminate nodule, and 19 (9.2%) had nodules meeting the definition of metastases, which were then considered to be misclassified and were excluded from further analyses. Five-year EFS was 78.5% (95% CI, 69.4%-85.1%) for patients without nodules and 69.6% (95% CI, 57.9%-78.7%) for patients with indeterminate nodules (p = .135); 5-year OS was 87.4% (95% CI, 79.3%-92.5%) and 79.0% (95% CI, 67.5%-86.8%), respectively (p = .086)., Conclusions: This study suggests that survival does not differ in otherwise nonmetastatic patients with indeterminate pulmonary nodules compared to nonmetastatic patients without pulmonary nodules., Plain Language Summary: Radiologists should be aware of the classification of indeterminate pulmonary nodules in non-rhabdomyosarcoma soft tissue sarcomas and use it in their reports. More than a third of patients with non-rhabdomyosarcoma soft tissue sarcoma can be affected by indeterminate pulmonary nodules. Indeterminate pulmonary nodules do not significantly affect the overall survival of pediatric patients with non-rhabdomyosarcoma soft tissue sarcoma., (© 2023 American Cancer Society.)

Objectives: To validate associations between MRI features and gene expression profiles in retinoblastoma, thereby evaluating the repeatability of radiogenomics in retinoblastoma., Methods: In this retrospective multicenter cohort study, retinoblastoma patients with gene expression data and MRI were included. MRI features (scored blinded for clinical data) and matched genome-wide gene expression data were used to perform radiogenomic analysis. Expression data from each center were first separately processed and analyzed. The end product normalized expression values from different sites were subsequently merged by their Z-score to permit cross-sites validation analysis. The MRI features were non-parametrically correlated with expression of photoreceptorness (radiogenomic analysis), a gene expression signature informing on disease progression. Outcomes were compared to outcomes in a previous described cohort., Results: Thirty-six retinoblastoma patients were included, 15 were female (42%), and mean age was 24 (SD 18) months. Similar to the prior evaluation, this validation study showed that low photoreceptorness gene expression was associated with advanced stage imaging features. Validated imaging features associated with low photoreceptorness were multifocality, a tumor encompassing the entire retina or entire globe, and a diffuse growth pattern (all p < 0.05). There were a number of radiogenomic associations that were also not validated., Conclusions: A part of the radiogenomic associations could not be validated, underlining the importance of validation studies. Nevertheless, cross-center validation of imaging features associated with photoreceptorness gene expression highlighted the capability radiogenomics to non-invasively inform on molecular subtypes in retinoblastoma., Clinical Relevance Statement: Radiogenomics may serve as a surrogate for molecular subtyping based on histopathology material in an era of eye-sparing retinoblastoma treatment strategies., Key Points: • Since retinoblastoma is increasingly treated using eye-sparing methods, MRI features informing on molecular subtypes that do not rely on histopathology material are important. • A part of the associations between retinoblastoma MRI features and gene expression profiles (radiogenomics) were validated. • Radiogenomics could be a non-invasive technique providing information on the molecular make-up of retinoblastoma., (© 2023. The Author(s).)

Atypical teratoid rhabdoid tumors (ATRT) are divided into MYC, TYR and SHH subgroups, suggesting diverse lineages of origin. Here, we investigate the imaging of human ATRT at diagnosis and the precise anatomic origin of brain tumors in the Rosa26-Cre ERT2 ::Smarcb1 flox/flox model. This cross-species analysis points to an extra-cerebral origin for MYC tumors. Additionally, we clearly distinguish SHH ATRT emerging from the cerebellar anterior lobe (CAL) from those emerging from the basal ganglia (BG) and intra-ventricular (IV) regions. Molecular characteristics point to the midbrain-hindbrain boundary as the origin of CAL SHH ATRT, and to the ganglionic eminence as the origin of BG/IV SHH ATRT. Single-cell RNA sequencing on SHH ATRT supports these hypotheses. Trajectory analyses suggest that SMARCB1 loss induces a de-differentiation process mediated by repressors of the neuronal program such as REST, ID and the NOTCH pathway., (© 2023. Springer Nature Limited.)

Introduction: The aim of the study was to describe the successful conservative management of diffuse infiltrating retinoblastoma (DIR). Identification of RB1 pathogenic variant was done after cell-free DNA (cfDNA) analysis in aqueous humor., Case Presentation: Herein, we report 2 patients with unilateral, non-familial DIR with anterior and posterior involvement. Both patients underwent liquid biopsy for tumor cfDNA analysis in aqueous humor. Treatment consisted of a combination of systemic and intra-arterial chemotherapy, with consecutive intracameral and intravitreal injections of melphalan. One patient also required iodine-125 brachytherapy. In both cases, tumor cfDNA analysis revealed biallelic somatic alterations of the RB1 gene. These alterations were not found in germline DNA. Both patients retained their eyes and had a useful vision after a follow-up of 2 years., Conclusion: In selected cases, conservative management of DIR is safe and effective. Tumor cfDNA analysis in aqueous humor is an effective technique to disclose RB1 somatic alterations that guide the germline molecular explorations and improve genetic counseling after conservative treatment., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 S. Karger AG, Basel.)

Purpose: To confirm the overall benignity of fat-containing soft tissue tumors (STT) on a pediatric cohort and to define the clinical and imaging features that warrant a biopsy., Methods: A retrospective monocentric study was conducted on patients aged less than 25 years consecutively referred for fat-containing STT to our Comprehensive Cancer Center between 1998 and 2022. Tumor imaging characteristics at diagnosis (US, CT, or MRI) were correlated with pathology., Results: The database extraction identified 63 fat-containing tumors with clinical, histologic, and imaging data available for review. In total, 58 (92%) were benign tumors: 36 lipoblastomas and lipomas, 12 fibrous hamartomas of infancy (FHI), 5 lipofibromatosis, 2 lipomas arborescens, 2 lipomatosis and 1 spindle-cell lipoma. Five patients (8%) were diagnosed with liposarcoma. Factors significantly correlated with malignancy were age >10 years old ( p < 0.001), having a cancer-predisposing condition ( p < 0.001), a percentage of fat <25% ( p = 0.002), and a presence of myxoid zones ( p < 0.001) on imaging., Conclusion: Most fat-containing STT in children may be classified as benign tumors based on clinics and imaging. The indication for biopsy could be limited to patients aged 10 years or more with either a cancer-predisposing condition or imaging features demonstrating either a low-fat component (<25%) or the presence of myxoid zones.

Background MYCN -amplified RB1 wild-type ( MYCN A RB1 +/+ ) retinoblastoma is a rare but clinically important subtype of retinoblastoma due to its aggressive character and relative resistance to typical therapeutic approaches. Because biopsy is not indicated in retinoblastoma, specific MRI features might be valuable to identify children with this genetic subtype. Purpose To define the MRI phenotype of MYCN A RB1 +/+ retinoblastoma and evaluate the ability of qualitative MRI features to help identify this specific genetic subtype. Materials and Methods In this retrospective, multicenter, case-control study, MRI scans in children with MYCN A RB1 +/+ retinoblastoma and age-matched children with RB1 -/- subtype retinoblastoma were included (case-control ratio, 1:4; scans acquired from June 2001 to February 2021; scans collected from May 2018 to October 2021). Patients with histopathologically confirmed unilateral retinoblastoma, genetic testing ( RB1/MYCN status), and MRI scans were included. Associations between radiologist-scored imaging features and diagnosis were assessed with the Fisher exact test or Fisher-Freeman-Halton test, and Bonferroni-corrected P values were calculated. Results A total of 110 patients from 10 retinoblastoma referral centers were included: 22 children with MYCN A RB1 +/+ retinoblastoma and 88 control children with RB1 -/- retinoblastoma. Children in the MYCN A RB1 +/+ group had a median age of 7.0 months (IQR, 5.0-9.0 months) (13 boys), while children in the RB1 -/- group had a median age of 9.0 months (IQR, 4.6-13.4 months) (46 boys). MYCN A RB1 +/+ retinoblastomas were typically peripherally located (in 10 of 17 children; specificity, 97%; P < .001) and exhibited plaque or pleomorphic shape (in 20 of 22 children; specificity, 51%; P = .011) with irregular margins (in 16 of 22 children; specificity, 70%; P = .008) and extensive retina folding with vitreous enclosure (specificity, 94%; P < .001). MYCN A RB1 +/+ retinoblastomas showed peritumoral hemorrhage (in 17 of 21 children; specificity, 88%; P < .001), subretinal hemorrhage with a fluid-fluid level (in eight of 22 children; specificity, 95%; P = .005), and strong anterior chamber enhancement (in 13 of 21 children; specificity, 80%; P = .008). Conclusion MYCN A RB1 +/+ retinoblastomas show distinct MRI features that could enable early identification of these tumors. This may improve patient selection for tailored treatment in the future. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Rollins in this issue.

Objective: Distinguishing tumor recurrence from therapy-induced imaging changes (TIIC) on brain MRI in children treated for primary malignant brain tumors may be challenging. The authors aimed to assess the diagnostic ability of multimodal MRI in differentiating TIIC from tumor recurrence., Methods: The authors retrospectively included children with abnormal supratentorial brain MRI findings after treatment for primary malignant brain tumors (regardless of their localization) with complete resection and radiotherapy. A total of 18 patients with TIIC and 25 patients with tumor recurrence were compared, according to structural, apparent diffusion coefficient (ADC), and arterial spin labeling (ASL) imaging data accrued over time. TIIC were defined by a new MRI scan that was stable for at least 1 year or had regressed, or by histopathology findings in specimens obtained when the anomaly was surgically treated., Results: The time interval between completion of radiotherapy and the appearance of abnormal brain MRI findings was significantly shorter in the TIIC group compared with the tumor recurrence group (median 6 vs 35 months; p < 0.001). TIIC appeared as foci of increased T2-weighted signal intensity, without nodule, associated with variable contrast enhancement. Tumor recurrence appeared as a well-defined nodule with intermediate signal intensity on T2-weighted images with nodular contrast enhancement. Relative ADC values were significantly higher in the TIIC group (median 1.43 vs 0.88; p < 0.001). Relative ASL-cerebral blood flow (CBF) values were significantly lower in the TIIC group (median 0.27 vs 0.43; p = 0.04). On follow-up MRI, TIIC could progress, regress, or remain stable. In most instances (72%), they decreased in size or remained stable at 4 years of follow-up., Conclusions: MRI features of TIIC include foci of increased signal intensity without a demonstrable nodule on T2-weighted images, high ADC values, and lower ASL-CBF values, whereas tumor recurrence appears as a well-defined nodule with low ADC values and higher ASL-CBF values.

Aims: NTRK gene fusions have been described in a wide variety of central nervous system (CNS) and soft tissue tumours, including the provisional tumour type 'spindle cell neoplasm, NTRK-rearranged' (SCN-NTRK), added to the 2020 World Health Organisation Classification of Soft Tissue Tumours. Because of histopathological and molecular overlaps with other soft tissue entities, controversy remains concerning the lineage and terminology of SCN-NTRK., Methods and Results: This study included 16 mesenchymal tumours displaying kinase gene fusions (NTRK fusions and one MET fusion) initially diagnosed as infantile fibrosarcomas (IFS), SCN-NTRK and adult-type fibrosarcomas from the soft tissue, viscera and CNS. We used immunohistochemistry, DNA methylation profiling, whole RNA-sequencing and ultrastructural analysis to characterise them. Unsupervised t-distributed stochastic neighbour embedding analysis showed that 11 cases (two CNS tumours and nine extra-CNS) formed a unique and new methylation cluster, while all tumours but one, initially diagnosed as IFS, clustered in a distinct methylation class. All the tumours except one formed a single cluster within the hierarchical clustering of whole RNA-sequencing data. Tumours from the novel methylation class co-expressed CD34 and S100, had variable histopathological grades and frequently displayed a CDKN2A deletion. Ultrastructural analyses evidenced a myofibroblastic differentiation., Conclusions: Our findings confirm that SCN-NTRK share similar features in adults and children and in all locations combine an infiltrative pattern, distinct epigenetic and transcriptomic profiles, and ultrastructural evidence of a myofibroblastic lineage. Further studies may support the use of new terminology to better describe their myofibroblastic nature., (© 2022 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Purpose: To investigate the prevalence and magnetic resonance imaging (MRI) phenotype of retinoblastoma-associated orbital cellulitis. Additionally, this study aimed to identify postlaminar optic nerve enhancement (PLONE) patterns differentiating between inflammation and tumor invasion., Design: A monocenter cohort study assessed the prevalence of orbital cellulitis features on MRI in retinoblastoma patients. A multicenter case-control study compared MRI features of the retinoblastoma-associated orbital cellulitis cases with retinoblastoma controls., Participants: A consecutive retinoblastoma patient cohort of 236 patients (311 eyes) was retrospectively investigated. Subsequently, 30 retinoblastoma cases with orbital cellulitis were compared with 30 matched retinoblastoma controls without cellulitis., Methods: In the cohort study, retinoblastoma MRI scans were scored on presence of inflammatory features. In the case-control study, MRI scans were scored on intraocular features and PLONE patterns. Postlaminar enhancement patterns were compared with histopathologic assessment of postlaminar tumor invasion. Interreader agreement was assessed, and exact tests with Bonferroni correction were adopted for statistical comparisons., Main Outcome Measures: Prevalence of retinoblastoma-associated orbital cellulitis on MRI was calculated. Frequency of intraocular MRI features was compared between cases and controls. Sensitivity and specificity of postlaminar optic nerve patterns for detection of postlaminar tumor invasion were assessed., Results: The MRI prevalence of retinoblastoma-associated orbital cellulitis was 6.8% (16/236). Retinoblastoma with orbital cellulitis showed significantly more tumor necrosis, uveal abnormalities (inflammation, hemorrhage, and necrosis), lens luxation (all P &lt; 0.001), and a larger eye size (P = 0.012). The inflammatory pattern of optic nerve enhancement (strong enhancement similar to adjacent choroid) was solely found in orbital cellulitis cases, of which none (0/16) showed tumor invasion on histopathology. Invasive pattern enhancement was found in both cases and controls, of which 50% (5/10) showed tumor invasion on histopathology. Considering these different enhancement patterns suggestive for either inflammation or tumor invasion increased specificity for detection of postlaminar tumor invasion in orbital cellulitis cases from 32% (95% confidence interval [CI], 16-52) to 89% (95% CI, 72-98)., Conclusions: Retinoblastoma cases presenting with orbital cellulitis show MRI findings of a larger eye size, extensive tumor necrosis, uveal abnormalities, and lens luxation. Magnetic resonance imaging contrast-enhancement patterns within the postlaminar optic nerve can differentiate between tumor invasion and inflammatory changes., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Pre- and post-pubertal testicular tumors are two distinct entities in terms of epidemiology, diagnosis and treatment. Most pre-pubertal tumors are benign; the most frequent are teratomas, and the most common malignant tumors are yolk-sac tumors. Post-pubertal tumors are similar to those found in adults and are more likely to be malignant. Imaging plays a pivotal role in the diagnosis, staging and follow-up. The appearance on ultrasonography (US) is especially helpful to differentiate benign lesions that could be candidates for testis-sparing surgery from malignant ones that require radical orchidectomy. Some specific imaging patterns are described for benign lesions: epidermoid cysts, mature cystic teratomas and Leydig-cell tumors. Benign tumors tend to be well-circumscribed, with decreased Doppler flow on US, but malignancy should be suspected when US shows an inhomogeneous, not-well-described lesion with internal blood flow. Imaging features should always be interpreted in combination with clinical and biological data including serum levels of tumor markers and even intra-operative frozen sections in case of conservative surgery to raise any concerns of malignity. This review provides an overview of imaging features of the most frequent testicular and para-testicular tumor types in children and the value of imaging in disease staging and monitoring children with testicular tumors or risk factors for testicular tumors.

BCOR-ITD tumours form an emerging family of aggressive entities with an internal tandem duplication (ITD) in the last exon of the BCOR gene. The family includes cerebral tumours, termed central nervous system BCOR-ITD (CNS BCOR-ITD), and sarcomatous types described in the kidney as clear cell sarcoma of the kidney (CCSK), in the endometrium as high-grade endometrial stromal sarcoma, and in the bone and soft tissue as undifferentiated round cell sarcoma or primitive myxoid mesenchymal tumour of infancy. Based on a series of 33 retrospective cases, including 10 CNS BCOR-ITD and 23 BCOR-ITD sarcomas, we interrogated the homogeneity of the entity regarding clinical, radiological, and histopathological findings, and molecular signatures. Whole-transcriptomic sequencing and DNA methylation profiling were used for unsupervised clustering. BCOR-ITD tumours mostly affected young children with a median age at diagnosis of 2.1 years (range 0-62.4). Median overall survival was 3.9 years and progression-free survival was 1.4 years. This dismal prognosis is shared among tumours in all locations except CCSK. Histopathological review revealed marked differences between CNS BCOR-ITD and BCOR-ITD sarcomas. These two groups were consistently segregated by unsupervised clustering of expression (n = 22) and DNA methylation (n = 21) data. Proximity between the two groups may result from common somatic changes within key pathways directly related to the novel activity of the ITD itself. Conversely, comparison of gene signatures with single-cell RNA-Seq atlases suggests that the distinction between BCOR-ITD sarcomas and CNS BCOR-ITD may result from differences in cells of origin., (© 2022 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd.)

Background: NUT carcinoma (NC), defined by the presence of the NUTM1 rearrangement, is an aggressive tumour associated with poor prognosis. This rare cancer is underdiagnosed and difficult to treat., Objective and Methods: The primary objective of this review is to describe the clinical, radiological and laboratory features of NC in young patients. The secondary objective is to propose a consensual strategy for the French very Rare Tumour group (FRACTURE group)., Results: NUT-specific antibody immunostaining in cases of undifferentiated or poorly differentiated carcinoma may demonstrate the specific NUT gene rearrangement. NCs are frequently advanced stage at diagnosis and the outcome remains poor despite a global strategy that generally includes conventional combination chemotherapy with wide local therapy (surgery, radiotherapy). Chemosensitivity is frequently only transient., Conclusion: Recent data have shown that new targeted drugs (histone deacetylase and bromodomain and extra-terminal protein inhibitors) are promising, but their role has yet to be evaluated in NC. Centralized data review is necessary to improve our knowledge of paediatric NC. We propose a multimodal strategy based on published data and their personal experience., (Copyright © 2022 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background and Purpose: A new brain tumor entity occurring in early childhood characterized by a somatic BCL6 corepressor gene internal tandem duplication was recently described. The aim of this study was to describe the radiologic pattern of these tumors and correlate this pattern with histopathologic findings., Materials and Methods: This retrospective, noninterventional study included 10 children diagnosed with a CNS tumor, either by ribonucleic acid-sequencing analysis or deoxyribonucleic acid methylation analysis. Clinical, radiologic, and histopathologic data were collected. A neuropathologist reviewed 9 tumor samples. Preoperative images were analyzed in consensus by 7 pediatric radiologists., Results: All tumors were relatively large (range, 4.7-9.2 cm) intra-axial peripheral masses with well-defined borders and no peritumoral edema. All tumors showed mild and heterogeneous enhancement and marked restriction on DWI of the solid portions. Perfusion imaging showed a relatively lower CBF in the tumor than in the adjacent normal parenchyma. Nine of 10 tumors showed areas of necrosis, with the presence of hemorrhage in 8/10 and calcifications in 4/7. Large intratumoral macroscopic veins were observed in 9/10 patients. No intracranial or spinal leptomeningeal dissemination was noted at diagnosis., Conclusions: CNS tumors with a BCL6 corepressor gene internal tandem duplication present as large intra-axial peripheral masses with well-defined borders, no edema, restricted diffusion, weak contrast enhancement, frequent central necrosis, hemorrhage and calcifications, intratumoral veins, and no leptomeningeal dissemination at the time of diagnosis. Knowledge of these imaging characteristics may aid in histologic, genomic, and molecular profiling of brain tumors in young children., (© 2022 by American Journal of Neuroradiology.)

Retinoblastoma mimickers, or pseudoretinoblastoma, are conditions that show similarities with the pediatric cancer retinoblastoma. However, false-positive retinoblastoma diagnosis can cause mistreatment, while false-negative diagnosis can cause life-threatening treatment delay. The purpose of this study is to identify the MR imaging features that best differentiate between retinoblastoma and the most common pseudoretinoblastoma diagnoses: Coats' disease and persistent fetal vasculature (PFV). Here, six expert radiologists performed retrospective assessments (blinded for diagnosis) of MR images of patients with a final diagnosis based on histopathology or clinical follow-up. Associations between 20 predefined imaging features and diagnosis were assessed with exact tests corrected for multiple hypothesis testing. Sixty-six patients were included, of which 33 (50%) were retinoblastoma and 33 (50%) pseudoretinoblastoma patients. A larger eye size, vitreous seeding, and sharp-V-shaped retinal detachment were almost exclusively found in retinoblastoma ( p < 0.001-0.022, specificity 93-97%). Features that were almost exclusively found in pseudoretinoblastoma included smaller eye size, ciliary/lens deformations, optic nerve atrophy, a central stalk between optic disc and lens, Y-shaped retinal detachment, and absence of calcifications ( p < 0.001-0.022, specificity 91-100%). Additionally, three newly identified imaging features were exclusively present in pseudoretinoblastoma: intraretinal macrocysts ( p < 0.001, 38% [9/24] in Coats' disease and 20% [2/10] in PFV), contrast enhancement outside the solid lesion ( p < 0.001, 30% [7/23] in Coats' disease and 57% [4/7] in PFV), and enhancing subfoveal nodules (38% [9/24] in Coats' disease). An assessment strategy was proposed for MR imaging differentiation between retinoblastoma and pseudoretinoblastoma, including three newly identified differentiating MR imaging features.

Soft tissue sarcomas in children are rare tumor, representing around 6 to 7% of children cancer. They spread mostly sporadically (90%) and therefore are rarely associated to an underlying constitutional genetic disease (10%). About half of those sarcomas are rhabdomyosarcomas and the others are a very heterogenous histologic group with various bio-pathologies and prognosis. Clinical presentation is mainly a soft tissue lump often difficult to distinguish from more frequent benign causes (malformative, infectious, benign, or pseudotumor). Inappropriate initial diagnosis work-up has a strong impact on soft tissue sarcomas' prognosis. Adapted complementary investigations (first ultrasound and MRI) are important to compile arguments for a malign origin and to indicate a biopsy. However, predictive value of imaging exams still remains imperfect, and histological analysis by percutaneous image-guided biopsy and sometimes by surgical biopsy is often necessary. Authors realize an update on optimal diagnostic pathway including molecular tests in presence of a soft tissue mass in a child., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

The esthesioneuroblastoma (ENB) is characterized as a rare malignant sinonasal tumor of neuroectodermal origin. Its starting point is the olfactory epithelium located in the upper part of the nasal cavities. Different nomenclatures have been proposed, but the most common are "esthesioneuroblastoma" and "olfactory neuroblastoma". ENBs have a bimodal distribution and mainly occur in teenagers, young adults and people aged 50-60. It is a very rare tumor in pediatrics since only around 100 cases have been reported so far. Within ENBs, we can distinguish tumors with different biological behavior ranging from localized forms with slow evolution to aggressive and metastatic forms at onset. In addition, precisely diagnosing undifferentiated tumors and distinguishing them from other etiologies of sinonasal tumors are sometime difficult. Added to its very low incidence, these characteristics make the study of ENB complicated. The standard treatment currently includes broad surgery followed by radiation therapy in localized resectable tumors. Neoadjuvant chemotherapy is indicated in large unresectable tumors and in metastatic forms. However, in certain indications, such as high-grade operable tumors, the role of perioperative chemotherapy remains to be defined. The objective of this analysis is to detail current knowledge regarding ENBs' epidemiological, biological, clinical and radiological characteristics as well as how to manage ENB in young patients., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Ninety percent of childhood renal tumors are Wilms tumors (nephroblastoma). While the Children's Oncology Group (COG) recommends primary surgery, the International Society of Paediatric Oncology (SIOP) recommends neoadjuvant chemotherapy, which can be initiated without histological confirmation if the presentation is typical for Wilms tumor. This review article describes the clinical, biological and radiologic criteria used by the SIOP community to consider diagnostic biopsy, i.e. when the renal origin is doubtful, when a pseudotumor is suspected or when a non-Wilms histology may be anticipated.

Background: In anterior pituitary deficiency, patients with non visible pituitary stalk have more often multiple deficiencies and persistent deficiency than patients with visible pituitary stalk., Objective: To compare the diagnostic value of a high-resolution heavily T2-weighted sequence to 1.5-mm-thick unenhanced and contrast-enhanced sagittal T1-weighted sequences to assess the presence of the pituitary stalk in children with ectopic posterior pituitary gland., Materials and Methods: We retrospectively evaluated the MRI data of 14 children diagnosed with ectopic posterior pituitary gland between 2010 and 2014. We evaluated the presence of a pituitary stalk using a sagittal high-resolution heavily T2-weighted sequence and a 1.5-mm sagittal T1-weighted turbo spin-echo sequence before and after contrast medium administration., Results: A pituitary stalk was present on at least one of the sequences in 10 of the 14 children (71%). T2-weighted sequence depicted the pituitary stalk in all 10 children, whereas the 1.5-mm-thick T1-weighted sequence depicted 2/10 (20%) before contrast injection and 8/10 (80%) after contrast injection (P=0.007)., Conclusion: Compared with 1.5-mm-thick contrast-enhanced T1-weighted sequences, high-resolution heavily T2-weighted sequence demonstrates better sensitivity in detecting the pituitary stalk in children with ectopic posterior pituitary gland, suggesting that contrast injection is unnecessary to assess the presence of a pituitary stalk in this setting.

We report a case of sudden onset of respiratory distress caused by pulmonary edema due to laryngospasm. The diagnosis was established by the clinical context and chest X-ray. A CT-scan was performed to narrow down the differential diagnosis and to confirm the diagnosis. Postextubation pulmonary edema due to laryngospasm is a rare entity with a typical clinical and radiographic presentation.

The standard procedure to study temporal encoding of sound waveforms in the auditory system has been Fourier analysis of responses to periodic stimuli. We introduce a new metric--correlation index (CI)--which is based on a simple counting of spike coincidences. It can be used for responses to aperiodic stimuli and does not require knowledge of the stimulus. Moreover, the basic procedure of comparing spiketimes in spiketrains is more physiological than currently used methods for temporal analysis. The CI is the peak value of the normalized shuffled autocorrelogram (SAC), which provides a quantitative summary of temporal structure in the neural response to arbitrary stimuli. We illustrate the CI and SACs by comparing temporal coding in the auditory nerve and output fibers of the cochlear nucleus.

Purpose: To illustrate the benefit of limbal stem cell transplantation in three eyes with severe ocular surface failure due to chemical burns., Methods: In two patients with monocular corneal scarring and vascularization after chronic chemical burns, a limbal tissue autograft was transferred from the unaffected fellow eye. A complete superficial keratectomy was performed on the host eye. One patient with bilateral ocular surface disorder received an eccentrically trephined corneolimbal allograft. To prevent immunologic rejection of the transplanted limbus, this patient was treated with systemic Ciclosporin A., Results: Postoperatively the limbal autografts grew a normal epithelium on the recipient eye with less vascularization and scarring. Our two patients reported a significant reduction in symptoms (redness, pain, photophobia) and an improved visual acuity. The corneolimbal allograft has remained clear for five months postoperatively., Conclusion: In strictly unilateral conditions of limbal deficiency, transplantation of healthy limbal tissue from the normal fellow eye may result in a stable ocular surface and a quiet and comfortable eye. Transplantation of an eccentrically trephined corneolimbal allograft under systemic Ciclosporin A cover may be an option in the rehabilitation of patients with severe bilateral stem cell deficiencies.

There are almost no hardware problems. Before buying a computer, one should carefully investigate the number of different tasks to be automated. The major problem is the kind of software to use for this tasks. It is obvious that the software possibilities determine the choice of the hardware type.