Perinucleolar Compartment (PNC) Prevalence as an Independent Prognostic Factor in Pediatric Ewing Sarcoma: A Multi-Institutional Study.

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.

Macrophage Activation Syndrome as a Complication of Chronic Granulomatous Disease: A Case Report.

Chronic granulomatous disease (CGD) presents with granuloma formation and lethal infections. It is inherited in an autosomal or X-linked recessive pattern. We describe a 10-month-old patient with a fatal secondary HLH as a CGD primary manifestation. We carried out an autopsy and found noncaseating granulomas, an aspergilloma in the lung, and hemophagocytosis. We performed a DHR assay on the patient's mother and grandmother, showing a bimodal pattern conclusive of X-linked CGD. Thus, our definitive diagnosis was CGD complicated by macrophage activation syndrome. CGD is caused by phagocytes' inability to control pathogens, resulting in granulomas. Secondary HLH is a severe complication and could be characterized by the proliferation of macrophages and T lymphocytes and the production of proinflammatory cytokines. The early suspicion of this presentation helps establish a specific treatment, and the study of the carriers helps determine the etiology.

Not enough by half: NFAT5 haploinsufficiency in two patients with Epstein-Barr virus susceptibility.

Introduction: The transcription factor Nuclear factor of activated T cells 5 (NFAT5), pivotal in immune regulation and function, can be induced by osmotic stress and tonicity-independent signals. Objective: We aimed to investigate and characterize two unrelated patients with Epstein-Barr virus susceptibility and no known genetic etiology. Methods: After informed consent, we reviewed the electronic charts, extracted genomic DNA, performed whole-exome sequencing, filtered, and prioritized their variants, and confirmed through Sanger sequencing, family segregation analysis, and some functional assays, including lymphoproliferation, cytotoxicity, and characterization of natural killer cells. Results: We describe two cases of pediatric Mexican patients with rare heterozygous missense variants in NFAT5 and EBV susceptibility, a school-age girl with chronic-active infection of the liver and bowel, and a teenage boy who died of hemophagocytic lymphohistiocytosis. Discussion: NFAT5 is an important regulator of the immune response. NFAT5 haploinsufficiency has been described as an immunodeficiency syndrome affecting both innate and adaptive immunity. EBV susceptibility might be another manifestation in the spectrum of this disease.

Validez del hallazgo de nódulos en la colonoscopia para el diagnóstico de hiperplasia nodular linfoide en niños / Validity of nodules detected at colonoscopy for the diagnosis of nodular lymphoid hyperplasia in children

Resumen Introducción: la hiperplasia nodular linfoide del colon se define como > 10 nódulos linfoides visibles en colonoscopia. No existen estudios de su validez al compararlo con la histopatología. Objetivos: determinar la validez del hallazgo de nódulos en colonoscopia para el diagnóstico de hiperplasia nodular linfoide. Material y métodos: estudio prospectivo de prueba diagnóstica. Se incluyeron colonoscopias realizadas consecutivamente de 2014 al 2018 con equipos Olympus PCFQ150AI y GIFXP150N con obtención de biopsias. El criterio endoscópico fue la presencia de > 10 nódulos de 2 a 10 mm y el criterio histológico fue hiperplasia de folículos linfoides y mantos de linfocitos en lámina propia o submucosa. Los datos se analizaron en Epidat3.1. Se obtuvo la sensibilidad (S), especificidad (E), valor predictivo positivo (VPP) y negativo (VPN), y coeficientes de probabilidad positivo (LR+) y negativo (LR-) con sus intervalos de confianza. Resultados: se incluyeron 327 colonoscopias, la mediana de edad fue de 84 meses. La principal indicación para la colonoscopia fue sangrado digestivo bajo (38,8%). El hallazgo de nódulos se encontró en el 21% y el sitio de mayor frecuencia fue el colon total (46%), mientras que por histopatología se encontró hiperplasia nodular linfoide en el 38%. El hallazgo de nódulos obtuvo una S de 32% (intervalo de confianza [IC] del 95%: 24-140), E de 84% (IC 95%: 79-89), VPP de 56% (IC 95%: 44-68), VPN de 67% (IC 95%: 61-72), LR+ de 2,04 (IC 95%: 1,4-3) y LR- de 0,8 (IC 95%: 0,8-0,9). Conclusiones: la validez diagnóstica del hallazgo de nódulos en colonoscopia para hiperplasia nodular linfoide es pobre, por lo que la toma de biopsia debe recomendarse siempre.

Abstract Introduction: Nodular lymphoid hyperplasia of the colon is characterized by the presence of >10 lymphoid nodules visible in colonoscopy. There are no studies that confirm their validity when compared with histopathology. Objective: To determine the validity of nodules detected at colonoscopy for the diagnosis of nodular lymphoid hyperplasia in children. Materials and methods: Prospective study of diagnostic test accuracy. Colonoscopies performed consecutively from 2014 to 2018 using Olympus PCFQ150AI and GIFXP150N biopsy machines were included. The endoscopic criterion was the presence of >10 nodules from 2 to 10mm of diameter, while the histological criterion was presence of follicular lymphoid hyperplasia and lymphocyte mantles in lamina propia or submucosa. Data were analyzed in Epidat3.1. Sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+) and negative likelihood ratio (LR-) were obtained with their corresponding confidence intervals. Results: 327 colonoscopies were included; the median age was 84 months. The main indication for colonoscopy was lower gastrointestinal bleeding (38.8%). Nodules were found in 21% of the patients, predominantly throughout the whole colon (46%), whereas histopathology found nodular lymphoid hyperplasia in 38%. SE for the finding of nodules was 32% (95% confidence interval [CI]: 24-140), SP was 84% (95% CI: 79-89), PPV was 56% (95% CI: 44-68), NPV was 67% (95% CI: 61-72), LR+ was 2.04 (95% CI: 1.4-3) and LR- was 0.8 (95% CI: 0.8-0.9). Conclusions: The validity of the presence of nodules on colonoscopy for the diagnosis of nodular lymphoid hyperplasia is poor, so biopsy should always be performed.