Imaging findings of COPA Syndrome.

BACKGROUND: Autosomal dominant mutations in the coatomer-associated protein alpha (COPA) gene cause an immune dysregulation disorder associated with pulmonary hemorrhage, lymphoid hyperplasia, arthritis, and glomerulonephritis. OBJECTIVE: To describe the thoracic, musculoskeletal, and renal imaging findings of COPA syndrome with a focus on the evolution of the pulmonary findings. MATERIALS AND METHODS: With approval of the Institutional Review Board, consensus retrospective review of findings on chest radiography and computed tomography (CT), musculoskeletal radiography and magnetic resonance imaging (MRI), and renal ultrasound (US) was performed for pediatric COPA syndrome patients. COPA syndrome patients < 18 years of age presenting between 1992 and 2019 were identified from an institutional rheumatology registry. RESULTS: Twelve pediatric COPA syndrome patients (mean age of 6.5 years at first imaging exam; 6 females) were identified. Imaging exams available for review included 45 chest CT exams on 12 patients, 37 musculoskeletal exams on 4 patients, and 10 renal US exams on 5 patients. All 12 had abnormal chest CT exams, with findings including ground-glass opacities (12/12), cysts (8/12), septal thickening (9/12), nodules (8/12), fibrosis (7/12), crazy-paving (2/12), consolidation (1/12), hilar/mediastinal lymphadenopathy (11/12), and chest wall deformity (5/12). Nine had at least one follow-up chest CT, which showed improvement in nodules (7/9), ground-glass opacities (4/9), and lymphadenopathy (9/9), but worsening of septal thickening (3/9), cyst formation (3/9), and fibrosis (3/9). Four had musculoskeletal imaging revealing synovitis (2/4), bone erosions (1/4), tenosynovitis (1/4), enthesitis (1/4), and subcutaneous nodules (1/4). Five had at least one renal US, revealing renal size abnormalities (4/5) and cortical hyperechogenicity (3/5). CONCLUSION: The most prevalent imaging finding of COPA syndrome is diffuse lung disease related to early childhood-onset recurrent pulmonary hemorrhage and lymphoid hyperplasia that may progress to pulmonary fibrosis. Other imaging findings manifesting later in childhood or adolescence relate to arthritis and glomerulonephritis.

Imaging of pediatric pulmonary tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

Pediatric pulmonary malignancy can be primary or metastatic, with the latter being by far the more common. With a few exceptions, there are no well-established evidence-based guidelines for imaging pediatric pulmonary malignancies, although computed tomography (CT) is used in almost all cases. The aim of this article is to provide general imaging guidelines for pediatric pulmonary malignancies, including minimum standards for cross-sectional imaging techniques and specific imaging recommendations for select entities.

Vascular Anomaly Syndromes in the ISSVA Classification System: Imaging Findings and Role of Interventional Radiology in Management.

Vascular anomalies encompass a spectrum of tumors and malformations that can cause significant morbidity and mortality in children and adults. Use of the International Society for the Study of Vascular Anomalies (ISSVA) classification system is strongly recommended for consistency. Vascular anomalies can occur in isolation or in association with clinical syndromes that involve complex multifocal lesions affecting different organ systems. Thus, it is critical to be familiar with the differences and similarities among vascular anomalies to guide selection of the appropriate imaging studies and possible interventions. Syndromes associated with simple vascular malformations include hereditary hemorrhagic telangiectasia, blue rubber bleb nevus syndrome, Gorham-Stout disease, and primary lymphedema. Syndromes categorized as vascular malformations associated with other anomalies include Klippel-Trenaunay-Weber syndrome, Parkes Weber syndrome, Servelle-Martorell syndrome, Maffucci syndrome, macrocephaly-capillary malformation, CLOVES (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and scoliosis, skeletal, and spinal anomalies) syndrome, Proteus syndrome, Bannayan-Riley-Ruvalcaba syndrome, and CLAPO (capillary malformations of the lower lip, lymphatic malformations of the face and neck, asymmetry of the face and limbs, and partial or generalized overgrowth) syndrome. With PHACES (posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects and/or coarctation of the aorta, eye abnormalities, and sternal clefting or supraumbilical raphe) syndrome, infantile hemangiomas associated with other lesions occur. Diagnostic and interventional radiologists have important roles in diagnosing these conditions and administering image-guided therapies-embolization and sclerotherapy, and different ablation procedures in particular. The key imaging features of vascular anomaly syndromes based on the 2018 ISSVA classification system and the role of interventional radiology in the management of these syndromes are reviewed. Online supplemental material is available for this article. ©RSNA, 2022.

Late pulmonary complications related to cancer treatment in children.

As the number of childhood cancer survivors increases, a heightened awareness and recognition of therapy-related late effects is becoming more important. Pulmonary complications are the third leading cause of late mortality in cancer survivors. Diagnosis of these complications on chest imaging helps facilitate prompt treatment to mitigate adverse outcomes. In this review, we summarize the imaging of late pulmonary complications of cancer therapy in children and highlight characteristic findings that should be recognized by radiologists.

Ultrasound for Midgut Malrotation and Midgut Volvulus: AJR Expert Panel Narrative Review.

Midgut volvulus in association with malrotation is a pediatric surgical emergency. Prompt and accurate diagnosis is necessary to avoid bowel ischemia and necrosis, thereby reducing morbidity and mortality. Historically, the fluoroscopic upper gastrointestinal series has been the preferred imaging modality for the evaluation of both midgut malrotation and volvulus, although the use of ultrasound (US) is increasing. In this Narrative Review, we describe the findings of midgut malrotation and volvulus on US, including practical tips for acquisition and interpretation; discuss the advantages and challenges of both imaging modalities; and propose a path and safeguards for possible transition to the use of US as the first-line modality for diagnosis based on our experience in imaging children with midgut malrotation and volvulus.

Acute appendicitis and SARS-CoV-2 in children: imaging findings at a tertiary children's hospital during the COVID-19 pandemic.

BACKGROUND: Evidence suggests severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may be associated with appendicitis or clinical symptoms that mimic appendicitis, but it is not clear if the findings or utility of imaging in pediatric patients with suspected appendicitis have changed since the onset of the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: To evaluate for potential differences in SARS-CoV-2 positive and SARS-CoV-2 negative pediatric patients imaged for suspected appendicitis to determine the reliability of the existing medical imaging approach for appendicitis in a population that contains both SARS-CoV-2 positive and SARS-CoV-2 negative pediatric patients. MATERIALS AND METHODS: Patients imaged for suspected appendicitis Apr. 1, 2020, to Dec. 31, 2020, were identified via an electronic medical records search. Differences in ultrasound (US) diagnostic performance, use of computed tomography (CT) following US, rates of appendicitis, imaging findings of appendicitis and perforation were compared between SARS-CoV-2 positive and SARS-CoV-2 negative tested patients, using pathology and surgery as reference standards for appendicitis and perforation, respectively. Fisher exact test and Student's t-test were used for statistical analysis. RESULTS: One thousand, six hundred and ninety-three patients < 18 years old met inclusion criteria, with 46% (772/1,693) female, 11 imaged with only CT and 1,682 with US. Comparing SARS-CoV-2 positive and SARS-CoV-2 negative patients, no statistically significant differences in sensitivity or specificity of US (P = 1 and P = 1, respectively), or in the US (P-values ranging from 0.1 to 1.0) or CT imaging findings (P-values ranging from 0.2 to 1.0) in appendicitis were found. Perforation rates were similar between SARS-CoV-2 positive (20/57, 35.1% perforated) and SARS-CoV-2 negative (359/785, 45.7% perforated) patients with appendicitis (P = 0.13). Use of CT following first-line US was similar, with 7/125 (5.6%) of SARS-CoV-2 positive imaged with CT after US and 127/1,557 (8.2%) of SARS-CoV-2 negative imaged with CT after US (P = 0.39). CONCLUSION: In pediatric patients with suspected appendicitis, no significant difference was found in the diagnostic performance of US, CT usage or perforation rates between SARS-CoV-2 positive and SARS-CoV-2 negative patients.

Role of anticoagulation in the management of tumor thrombus: A 10-year single-center experience.

BACKGROUND: Children with cancer diagnosis are overall at a higher risk of thrombosis. For a newly diagnosed blood clot, patients are commonly started on anticoagulants to prevent further extension and embolization of the clot. In the rare instance that a pediatric patient has a tumor thrombus, role of anticoagulation is less clear. PROCEDURE/METHODS: Patients under 21 years of age with a finding of tumor thrombus on imaging from 2010 to 2020 at Texas Children's Hospital were identified and their medical records were reviewed. RESULTS: A total of 50 patients were identified. Most thrombi were incidental findings at diagnosis; however, two patients presented with pulmonary embolism (PE). Inferior vena cava extension was noted in 36% of the patients, and 24% patients had an intracardiac tumor thrombus. Anticoagulation was initiated in 10 patients (20%). There was no difference in the rate of bland thrombus formation and/or embolization in patients who did or did not receive anticoagulation. However, three of the six patients with asymptomatic tumor thrombus who were started on anticoagulation had bleeding complications compared to only two patients in the no anticoagulation cohort (p < .05). CONCLUSION: Children with intravascular extension of solid tumors were not commonly started on anticoagulation at the time of diagnosis, irrespective of the extent of tumor thrombus. Furthermore, we observed a significant trend toward higher incidence of bleeding complications after initiation of anticoagulation for asymptomatic tumor thrombus. There is inadequate evidence at this time to support routine initiation of anticoagulation in pediatric patients with intravascular extension of solid tumors.

Ten rules for ordering chest CTs.

These "rules" are suggestions for clinicians who order chest computed tomography (CTs). The first three address CT scanning technique and the ordering details that we find cause the most confusion. The next three are on patient preparation, and specifically the use of sedation and anesthesia. Radiation risk is next, and we end with three, more philosophical, rules on how we can best work together as clinicians and imagers. This is not a complete or systematic review. You won't find detailed references (or any references for that matter), descriptions of the latest techniques, or lists of sample protocols. We hope that the reader will consult his or her imaging colleagues when more specific guidance is needed. The goal of this article is to provide simple answers to frequently asked questions and to address some of the concerns that arise when deciding how to perform a chest CT scan in a child. These are the opinions of the authors, two pediatric radiologists with special interest in chest imaging and 50 years combined experience in working with clinical colleagues to provide the best imaging care for their patients. We hope that sharing these thoughts will help to decrease confusion and increase understanding to the benefit of the children we serve.

Pulmonary manifestations and outcomes in paediatric ANCA-associated vasculitis: a single-centre experience.

OBJECTIVES: ANCA-associated vasculitis (AAV) usually involves the renal and respiratory systems, but the paediatric literature on pulmonary manifestations and outcomes is limited. We aimed to describe pulmonary manifestations and outcomes after therapy in a cohort of paediatric AAV (pAAV) patients. METHODS: A retrospective chart review of all patients <19 years presenting to our institution with AAV between 1/2008 and 2/2018 was conducted. Patient demographics, clinical presentation, diagnostic testing, therapy and pulmonary outcomes over the first 3 years after presentation were evaluated. RESULTS: A total of 38 patients were included; all had ANCA positivity by immunofluorescence. A total of 23 had microscopic polyangiitis (MPA), 13 had granulomatosis with polyangiitis and 2 had eosinophilic granulomatosis with polyangiitis. A total of 30 (79%) had pulmonary manifestations, with cough (73%) and pulmonary haemorrhage (67%) being the most common. Abnormalities were noted in 82% of chest CT scans reviewed, with nodules and ground-glass opacities being the most common. At 6, 12 and 36 months follow-up, respectively, 61.8%, 39.4% and 29% of patients continued to show pulmonary manifestations. Five MPA patients with re-haemorrhage are described in detail. CONCLUSION: MPA was more common than granulomatosis with polyangiitis, with pulmonary involvement being common in both. MPA patients had more severe pulmonary manifestations. Chest CT revealed abnormal findings in a majority of cases. A subgroup of young MPA patients experienced repeat pulmonary haemorrhage. Treatment modality and response were comparable in different subtypes of AAV, except for this young MPA group. Additional prospective studies are needed to better understand the different phenotypes of pAAV.

Pediatric thoracic mass lesions: Beyond the common.

Thoracic mass lesions can be categorized as originating in one of the three major compartments: a) chest wall and pleura, b) lung parenchyma and airways, c) mediastinum. While some of these, such as lymphoma, are common in both children and adults, others are rare and unique to childhood. The goal of this review is to familiarize radiologists with unusual but distinctive mass lesions of the pediatric thorax.

Management of severe pulmonary Langerhans cell histiocytosis in children.

Patients with pulmonary Langerhans cell histiocytosis (LCH) typically have a benign course but may have extensive cystic lung disease with rare life-threatening complications including multiple and recurrent pneumothoraces and respiratory failure. We report seven severely affected pediatric patients treated with chemotherapy, aggressive chest tube management, and pleurodesis of whom five survived. Patients with extraordinary amounts of pulmonary cystic disease and multiple pneumothoraces due to LCH can have remarkable, curative outcomes with early recognition, optimal LCH-directed therapy, and supportive care.

E-cigarette or vaping product use-associated lung injury in the pediatric population: imaging features at presentation and short-term follow-up.

BACKGROUND: Cases of e-cigarette or vaping product use-associated lung injury (EVALI) have rapidly reached epidemic proportions, yet there remain limited reports within the literature on the associated imaging findings. OBJECTIVE: We describe the most common imaging findings observed on chest computed tomography (CT) and chest radiograph (CXR) at presentation and at short-term follow-up at our major pediatric hospital. MATERIALS AND METHODS: A retrospective review of the electronic medical records was performed on all patients with suspected EVALI who were treated at a major pediatric hospital and 11 patients were included for analysis. Two board-certified pediatric radiologists then categorized the CXRs as either normal or abnormal, and further performed a systematic review of the chest CTs for imaging findings in the lungs, pleura and mediastinum. Interrater discordance was reconciled by consensus review. RESULTS: The 11 patients (9 males:2 females) ranged in age from 14 to 18 years. Gastrointestinal and constitutional symptoms were present in all patients, whereas shortness of breath and cough were reported in 5/11 and 6/11 patients, respectively. The CXR was abnormal in 10/11 patients, whereas all chest CTs were abnormal. The most common CT findings included consolidation, ground-glass opacities, interlobular septal thickening, lymphadenopathy and crazy-paving pattern. Almost all patients demonstrated subpleural sparing, and less than half also demonstrated peribronchovascular sparing. There was complete or near-complete resolution of imaging abnormalities in 5/6 patients with a median follow-up duration of 114 days. CONCLUSION: Pulmonary opacities with subpleural and peribronchovascular sparing was a commonly observed pattern of EVALI in the pediatric population at this institution. A CXR may not be sufficiently sensitive in diagnosing EVALI, and radiologists and clinicians should exercise caution when excluding EVALI based on the lack of a pulmonary opacity. Caution should also be exercised when excluding EVALI solely based on the lack of respiratory symptoms. Despite extensive pulmonary involvement at presentation, findings may resolve on short-term follow-up imaging.

Guidance for computed tomography (CT) imaging of the lungs for patients with cystic fibrosis (CF) in research studies.

Numerous issues must be addressed when developing standard operating procedures for clinical research studies involving chest computed tomography of lung disease in patients with cystic fibrosis (CF). Study success depends on the provision of adequate funding and the identification of personnel with the necessary expertise to conduct the study, along with clear guidelines that detail the CT operating procedure at each site, including breathing maneuvers, and image reconstruction. Close coordination of the quality assurance process between sites and the central review organization is required to maintain protocol adherence. The data transfer process must ensure the integrity and security of the data to comply with patient privacy regulations, and study outcome measures are best assessed with a scoring system or other structured method of imaging data analysis. The recommendations provided are designed to serve as a valuable reference guide for planning clinical research studies of patients with CF involving chest CT.

Imaging of DICER1 syndrome.

DICER1 syndrome is a highly pleiotropic tumor predisposition syndrome that has been increasingly recognized in the last 10 years. Diseases in the syndrome result from mutations in both copies of the gene DICER1, a highly conserved gene that is critically implicated in micro-ribonucleic acid (miRNA) biogenesis and hence modulation of messenger RNAs. In general, susceptible individuals carry an inherited germline mutation that disables one copy of DICER1; within tumors, a very characteristic second mutation alters function of the other gene copy. About 20 hamartomatous, hyperplastic or neoplastic conditions comprise DICER1 syndrome. Most are not life-threatening, but some are aggressive malignancies. There are many unaffected carriers because penetrance is generally low; however, clinically occult thyroid nodules and lung cysts are frequent. Rare diseases of early childhood were the first recognized conditions in DICER1 syndrome, while other conditions affect adolescents and adults. The hallmarks of DICER1 syndrome are certain rare tumors including pleuropulmonary blastoma; cystic nephroma; ovarian Sertoli-Leydig cell tumor; sarcomas of the cervix, kidneys and cerebrum; pituitary blastoma; ciliary body medulloepithelioma; and nasal chondromesenchymal hamartoma. Radiologists are often the first practitioners to observe these diverse manifestations and play a primary role in recognizing DICER1 syndrome.

Emergent high fatality lung disease in systemic juvenile arthritis.

OBJECTIVE: To investigate the characteristics and risk factors of a novel parenchymal lung disease (LD), increasingly detected in systemic juvenile idiopathic arthritis (sJIA). METHODS: In a multicentre retrospective study, 61 cases were investigated using physician-reported clinical information and centralised analyses of radiological, pathological and genetic data. RESULTS: LD was associated with distinctive features, including acute erythematous clubbing and a high frequency of anaphylactic reactions to the interleukin (IL)-6 inhibitor, tocilizumab. Serum ferritin elevation and/or significant lymphopaenia preceded LD detection. The most prevalent chest CT pattern was septal thickening, involving the periphery of multiple lobes ± ground-glass opacities. The predominant pathology (23 of 36) was pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP), with atypical features including regional involvement and concomitant vascular changes. Apparent severe delayed drug hypersensitivity occurred in some cases. The 5-year survival was 42%. Whole exome sequencing (20 of 61) did not identify a novel monogenic defect or likely causal PAP-related or macrophage activation syndrome (MAS)-related mutations. Trisomy 21 and young sJIA onset increased LD risk. Exposure to IL-1 and IL-6 inhibitors (46 of 61) was associated with multiple LD features. By several indicators, severity of sJIA was comparable in drug-exposed subjects and published sJIA cohorts. MAS at sJIA onset was increased in the drug-exposed, but was not associated with LD features. CONCLUSIONS: A rare, life-threatening lung disease in sJIA is defined by a constellation of unusual clinical characteristics. The pathology, a PAP/ELP variant, suggests macrophage dysfunction. Inhibitor exposure may promote LD, independent of sJIA severity, in a small subset of treated patients. Treatment/prevention strategies are needed.

A novel approach using volumetric dynamic airway computed tomography to determine positive end-expiratory pressure (PEEP) settings to maintain airway patency in ventilated infants with bronchopulmonary dysplasia.

BACKGROUND: Positive end-expiratory pressure (PEEP) is a key mechanical ventilator setting in infants with bronchopulmonary dysplasia (BPD). Excessive PEEP can result in insufficient carbon dioxide elimination and lung damage, while insufficient PEEP can result in impaired gas exchange secondary to airway and alveolar collapse. Determining PEEP settings based on clinical parameters alone is challenging and variable. OBJECTIVE: The purpose of this study was to describe our experience using dynamic airway CT to determine the lowest PEEP setting sufficient to maintain expiratory central airway patency of at least 50% of the inspiratory cross-sectional area in children with BPD requiring long-term ventilator support. MATERIALS AND METHODS: We retrospectively identified all infants with BPD who underwent volumetric CT with a dynamic airway protocol for PEEP optimization from December 2014 through April 2019. Sixteen infants with BPD underwent 17 CT exams. Each CT exam consisted of acquisitions spanning the trachea and mainstem bronchi. We measured cross-sectional area of the trachea and mainstem bronchi and qualitatively assessed the amount of atelectasis. We documented changes in management as a result of the CT exam. RESULTS: The average effective dose was 0.1-0.8 mSv/scan. Of 17 CT exams, PEEP was increased in 9, decreased in 3 and unchanged after 5 exams. CONCLUSION: Dynamic airway CT shows promise to assist the clinician in determining PEEP settings to maintain airway patency in infants with BPD requiring long-term ventilator support. Further evaluation of the impact of this maneuver on gas exchange, cardiac output and other physiological measures is needed.

Treatment-Responsive Granulomatous-Lymphocytic Interstitial Lung Disease in a Pediatric Case of Common Variable Immunodeficiency.

Granulomatous-Lymphocytic Interstitial Lung disease (GLILD) is a granulomatous and lymphoproliferative condition occurring in ~25% of Common Variable Immunodeficiency (CVID) patients with the highest prevalence in the late teen to young adult years. GLILD was first described in adults and carries a poor prognosis with survival estimated to be reduced by half. Here we report a pediatric case of CVID-associated GLILD that presented with rapid deterioration over 3 months and responded to adult-based treatment with dual chemotherapeutic agents (rituximab and azathioprine), resulting in complete resolution of clinical findings and near complete resolution of radiologic findings. This case highlights the opportunity to achieve a favorable outcome in GLILD following appropriate diagnosis and therapy.

Clinico-radiologic features of pleuroparenchymal fibroelastosis in children.

BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) may be underdiagnosed clinically and radiographically in children with a remote history of cancer, leading to a delay in care and unnecessary lung biopsies. OBJECTIVE: To describe the characteristic clinical and radiologic findings of PPFE in a cohort of children to facilitate recognition and noninvasive diagnosis. MATERIALS AND METHODS: Clinical presentation, history of chemotherapy or radiation therapy, lung or bone marrow transplantation, and lung function testing and outcome were retrospectively extracted from the electronic medical records of eight children treated at our institution's pulmonary medicine clinic with histopathology confirmation of PPFE from 2008 to 2018. Two pediatric radiologists evaluated the chest imaging studies for the presence or absence of published radiologic findings of PPFE in adults, including platythorax, pneumothorax, upper lobe predominant pleural and septal thickening, and bronchiectasis. Platythorax indices were calculated from the normal chest CT exams of eight age- and gender-matched individuals obtained via the radiology search engine. RESULTS: The mean presentation age was 12.9 years (range: 7-16 years). Seven of the eight had a history of chemotherapy and radiation therapy for cancer. Three of the eight had undergone bone marrow transplantation and none had undergone lung transplantation. The mean time between chemotherapy, radiation therapy, and/or bone marrow transplantation and the presentation of PPFE was 8.4 years (range: 5.6-12.1 years). Most of the patients presented with dyspnea (63%), cough (50%) and/or pneumothorax (38%). The mean percentage of predicted FEV1 (forced expiratory volume in one second) was 14.1 (range: 7.7-27.5). All eight patients demonstrated platythorax, bronchiectasis, pleural and septal thickening (upper lobes in four, upper and lower lobes in four) and six had pneumothorax. Five underwent lung biopsies, four of whom developed pneumothoraces. CONCLUSION: Clinical and radiologic findings of pediatric PPFE are similar to those in adults, although a majority of the former have a history of treated cancer. Clinical presentation of restrictive lung disease, dyspnea, cough or spontaneous pneumothorax years after treatment for childhood cancer combined with platythorax, upper lobe pleural and septal thickening and traction bronchiectasis on chest CT establishes a presumptive diagnosis of PPFE.

Multiple DICER1-related tumors in a child with a large interstitial 14q32 deletion.

Germ-line interstitial deletions involving the 14q32 chromosomal region, resulting in 14q32 deletion syndrome, are rare. DICER1 is a recently described cancer-predisposition gene located at 14q32.13. We report the case of a male child with a ∼5.8 Mbp 14q32.13q32.2 germ-line deletion, which included the full DICER1 locus. We reviewed available clinical and pathological material, and conducted genetic analyses. In addition to having congenital dysmorphic features, the child developed multiple DICER1 syndrome-related tumors before age 5 y: a pediatric cystic nephroma (pCN), a ciliary body medulloepithelioma (CBME), and a small lung cyst (consistent with occult pleuropulmonary blastoma Type I/Ir cysts seen in DICER1 mutation carriers). He also developed a cerebral spindle-cell sarcoma with myogenous differentiation. Our investigations revealed that the deletion encompassed 31 protein-coding genes. In addition to the germ-line DICER1 deletion, somatic DICER1 RNase IIIb mutations were found in the CBME (c.5437G > A, p.E1813K), pCN (c.5425G > A, p.G1809R), and sarcoma (c.5125G > A, p.D1709N). The sarcoma also harbored a somatic TP53 mutation: c.844C > T, p.R282W. Additional copy number alterations were identified in the CBME and sarcoma using an OncoScan array. Among the 8 cases with molecularly-defined 14q32 deletions involving DICER1 and for whom phenotypic information is available, our patient and one other developed DICER1-related tumors. Biallelic DICER1 mutations have not previously been reported to cause cerebral sarcoma, which now may be considered a rare manifestation of the DICER1 syndrome. Our study shows that DICER1-related tumors can occur in children with 14q32 deletions and suggests surveillance for such tumors may be warranted.

The optimal timing of surgical resection in high-risk neuroblastoma.

BACKGROUND: While most high-risk neuroblastoma (HRNB) patients are enrolled in cooperative group or institutional protocols, variability exists within these protocols as to when surgical resection of the primary tumor should be performed after neoadjuvant induction chemotherapy. We sought to determine if the number of chemotherapy cycles prior to surgery affects surgical or survival outcomes in HRNB patients. METHODS: We performed a retrospective review of all HRNB patients <18years of age from 2000 to 2010, at Texas Children's Hospital. Patients were stratified based on the number of neoadjuvant induction chemotherapy cycles prior to surgical resection. Pre and post- chemotherapy tumor size, MYCN status, iodine-131-metaiodobenzylguanidine (MIBG) score at diagnosis, extent of surgical resection, estimated surgical blood loss, post-operative outcomes, and event free (EFS) and overall survival (OS) were evaluated. Data were analyzed using Wilcoxon rank-sum test, Kruskal-Wallis test, Fisher's exact test, Kaplan-Meier analyses, and Cox regression analyses. P-value <0.05 was considered significant. RESULTS: Data from 50 patients with HRNB were analyzed. Patients were stratified by the number of cycles of chemotherapy received prior to surgery. Six patients received 2cycles of chemotherapy (12%), 20 patients received 3cycles (40%), 13 patients received 4cycles (26%), and 11 patients received 5cycles (22%) prior to surgical resection of the primary tumor. The 5-year OS was 33%, 45%, 83% and 36% in patients who received 2, 3, 4 and 5cycles of chemotherapy prior to surgery, respectively (p=0.07). Multivariate analysis revealed that patients who received 4cycles of chemotherapy had a significantly lower mortality (HR: 0.11, 95% CI: 0.01-0.87, p=0.04) compared to those with 2cycles of chemotherapy. Among the different cohorts, there were no differences with respect to MYCN status, MIBG score at diagnosis, incidence of bone marrow metastasis, extent of surgical resection, estimated blood loss, incidence of post-operative complications, or length of stay. CONCLUSION: HRNB patients who receive 4cycles of chemotherapy prior to surgical resection have a superior OS than patients who receive 2. Based on the superior survival of patients who received 4cycles of chemotherapy prior to surgery, further studies are warranted to elucidate these differences.