The perinucleolar compartment (PNC) is a small nuclear body that plays important role in tumorigenesis. PNC prevalence correlates with poor prognosis and cancer metastasis. Its expression in pediatric Ewing sarcoma (EWS) has not previously been documented. In this study, we analyzed 40 EWS tumor cases from Caucasian and Hispanic patients for PNC prevalence by immunohistochemical detection of polypyrimidine tract binding protein and correlated the prevalence with dysregulated microRNA profiles. EWS cases showed staining ranging from 0 to 100%, which were categorized as diffuse (≥77%, n = 9, high PNC) or not diffuse (<77%, n = 31) for low PNC. High PNC prevalence was significantly higher in Hispanic patients from the US (n = 6, p = 0.017) and in patients who relapsed with metastatic disease (n = 4; p = 0.011). High PNC was associated with significantly shorter disease-free survival and early recurrence compared to those with low PNC. Using NanoString digital profiling, high PNC tumors revealed upregulation of eight and downregulation of 18 microRNAs. Of these, miR-320d and miR-29c-3p had the most significant differential expression in tumors with high PNC. In conclusion, this is the first study that demonstrates the presence of PNC in EWS, reflecting its utility as a predictive biomarker associated with tumor metastasis, specific microRNA profile, Hispanic ethnic origin, and poor prognosis.

We present the case of a 3-year-old female with cyclic neutropenia and history of febrile seizures who died acutely from coronavirus disease 2019 (COVID-19). While most children with COVID-19 infection are asymptomatic or have mild symptoms, there may be increased risk of severe disease in immunocompromised children. To the best of our knowledge, this is the first reported case of a COVID-19-related death in a pediatric patient with cyclic neutropenia.

AIMS:Historically, there has been no consensus on the diagnostic classification of high-grade B-cell lymphoma (HGBCL) with morphological features of Burkitt lymphoma (BL) but no MYC gene rearrangement (MYC-negative). The 2016 WHO classification of tumours of haematopoietic and lymphoid tissues has shed some light on this field with the modification of the grey-zone lymphoma with features intermediate between BL and diffuse large B-cell lymphoma, and the creation of several new entities. The aim of this study was to investigate how the revised WHO classification affects our practice in diagnosing these lymphomas in children.METHODS:We retrospectively reviewed cases of mature HGBCL diagnosed at our hospital between 2015 and 2018.RESULTS:Among 14 mature HGBCL cases with BL morphological features, 11 showed MYC rearrangement consistent with BL and 3 were MYC-negative. Two MYC-negative cases showed regions of 11q gain and loss by microarray consistent with Burkitt-like lymphoma with 11q aberration (BLL-11q). The third MYC-negative case showed diffuse and strong MUM1 expression, translocation involving 6p25 by chromosome analysis and IRF4 rearrangement by fluorescence in situ hybridisation analysis consistent with large B-cell lymphoma with IRF4 rearrangement (LBL-IRF4). All patients were treated according to applicable chemotherapeutic protocols and achieved remission.CONCLUSIONS:BLL-11q and LBL-IRF4, two newly defined entities, should be considered in paediatric MYC-negative mature HGBCL cases. Accurate diagnosis needs careful histopathological examination and proper cytogenetic testing. Since they have unique cytogenetic features, specific treatments for them may emerge in the future. Therefore, accurate diagnosis based on the 2016 WHO classification is clinically significant.

Neuroblastoma (NB) in children older than 10 years is rare. We reviewed our archives for patients with NB aged 10 to 18 years and summarized their clinicopathologic/genetic records. Of 96 patients, 4 patients were identified in this age group. Four tumors were abdominal; 1 patient had 2 tumors at diagnosis, one of which was presacral. Tumor sizes ranged from 3 to 20 cm. All tumors were high risk at clinical stages 3 and 4, with metastasis to bone marrow and other areas. Four tumors were poorly differentiated with unfavorable histology and one patient with bilateral adrenal disease had an intermixed ganglioneuroblastoma on one side. Another tumor exhibited pheochromocytoma-like morphology. MYCN amplification was present in bone marrow metastasis in one case. Complex chromosomal gains and 19p deletions were common. Exome sequencing revealed ALK variants in 2 cases and previously unreported MAGI2, RUNX1, and MLL mutations. All patients received standard chemotherapy and 2 patients received ALK-targeted trial therapy. Three patients died of disease, ranging 18 to 23 months after diagnosis. One patient has active disease and is receiving trial therapy. In conclusion, NB in children older than 10 years may exhibit unusual clinicopathologic and genetic features with large tumors, bilateral adrenal disease, rare morphologic features, complex DNA microarray findings and novel mutations. Patients often have grim prognoses despite genomic profiling-guided targeted therapy.

Pediatric Blood & CancerVolume 62, Issue 10 p. 1868-1869 Letter to the Editor Intraperitoneal bleomycin for sarcomatosis-related malignant ascites: Prolonged symptom relief Karen S. Fernández MD, Corresponding Author Karen S. Fernández MD Correspondence to: Karen S. Fernández, Assistant Professor of Pediatrics, University of Illinois College of Medicine at Peoria, Children's Hospital of Illinois, 530 NE Glen Oak Ave, Peoria, IL 616137. E-mail: [email protected]Search for more papers by this authorLaura McCarthy DO, Laura McCarthy DOSearch for more papers by this authorReuben Antony MD, Reuben Antony MDSearch for more papers by this author Karen S. Fernández MD, Corresponding Author Karen S. Fernández MD Correspondence to: Karen S. Fernández, Assistant Professor of Pediatrics, University of Illinois College of Medicine at Peoria, Children's Hospital of Illinois, 530 NE Glen Oak Ave, Peoria, IL 616137. E-mail: [email protected]Search for more papers by this authorLaura McCarthy DO, Laura McCarthy DOSearch for more papers by this authorReuben Antony MD, Reuben Antony MDSearch for more papers by this author First published: 01 April 2015 https://doi.org/10.1002/pbc.25527 Conflict of interest: Nothing to declare. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. REFERENCES 1 Huh WW, Fitzgerald NE, Mahajan A, Hayes-Jordan A. Peritoneal sarcomatosis in pediatric malignancies. Pediatr Blood Cancer 2013; 60: 12–17. 2 Mercadante S, Intravaia G, Ferrera P, Villari P, David F. Peritoneal catheter for continuous drainage of ascites in advanced cancer patients. Suppor Care Cancer 2008; 16: 975–978. 3 Becker G, Galandi D, Blum HE. Malignant ascites: Systematic review and guideline for treatment. Eur J Cancer 2006; 42: 589–597. 4 Rafiei R, Yazdani B, Ranjbar SM, Torabi Z, Asgary S, Najafi S, Keshvari M. Long-term results of pleurodesis in malignant pleural effusions: Doxycycline vs Bleomycin. Adv Biomed Res 2014; 3: 149. 5 Chaudry G, Guevara CJ, Rialon KL, Kerr Mulliken CJB, Greene AK, Fishman SJ, Boyer D, Alomari AI. Safety and efficacy of bleomycin sclerotherapy for microcystic lymphatic malformation. Cardiovasc Intervent Radiolo 2014; 37: 1476–1481. 6 Saving KL, Kimler BF, Vats TS. Intraperitoneal bleomycin for ventriculoperitoneal spread of a hypothalamic astrocytoma. Cancer Drug Deliv 1986; 3: 205–210. Volume62, Issue10October 2015Pages 1868-1869 ReferencesRelatedInformation

Noninvasive measures of limb muscle strength are quite useful in preclinical translational studies that use mouse models of muscle disease, peripheral nerve disease, and movement disorders. The present study uses a simple protocol for assessing both inter-trial and inter-examiner reliability for two noninvasive methods of assessing limb strength in dystrophic (mdx) and wild type mice. One method, termed the whole body tension (WBT) method or escape test, measures the total phasic pulling tension exerted by the fore- and hindlimbs while a mouse attempts to escape into a darkened tube. Another procedure, termed the four limb wire grid holding test, measures the minimal amount of sustained tension (physical impulse) exerted by the fore- and hindlimbs while the mouse hangs suspended in an upside-down position. A comparison of the two methods revealed significant inter-trial and inter-examiner correlations in each procedure, although the WBT procedure consistently produced higher correlations than the four limb wire grid holding test. Inter-trial reliability for each test was higher than inter-examiner reliability, indicating that each longitudinal series of tests is best performed by a single investigator. The holding test also did not consistently detect differences between wild type and mdx populations at ages greater than 4 months. These results demonstrate the utility of a simple protocol for assessing the reliability of noninvasive tests that measure limb strength, and should be useful in comparing different functional measures in a broad range of translational studies.

We describe the late Cenozoic structure and evolution of the Jid right-lateral strike-slip fault in the northern Mongolian Altay mountain chain. Parts of the Jid fault have a vertical component of motion, introduced by bending along the fault. Some locations show additional structural complexity at the Earth's surface, with parallel strands having strike-slip, normal and reverse faulting, probably indicating a spatial separation of dip-slip and strike-slip components of motion in cross-section. The Jid fault shows indications of recent movements at scales ranging from drainage re-organisation at the kilometre scale, to ground deformations likely to result from movements during the last earthquake, which occurred ∼870–980 years ago based on OSL dating of deposits exposed in trenching. From the scale of the ruptures the earthquake would have had a magnitude of ∼7.5 with an estimated right-lateral slip of ∼5 m. Numerous horizontal offsets of about 10–15 m, and vertical scarps of ∼5 m in the youngest alluvial deposits show the likely cumulative movement over the last ∼15,000 years, and suggest a maximum slip-rate of roughly 1 mm/yr. The minimum cumulative right-lateral slip on the Jid fault is 1 km, which would accumulate in ∼1 Ma at present-day rates of slip. The relatively small vertical component of motion on the Jid fault is not sufficient to generate topography in the adjacent Kharkhiraa and Türgen Uul mountains, with relief of over 2000 m. The high mountains may therefore result from localised uplift on thrust faults rather than by oblique slip on the Jid fault.