Celso Tomás Corcuera Delgado

Background: MicroRNAs (miRNAs) function as post-transcriptional gene expression regulators and influence the development and progression of several cancers, yet their roles in pediatric sarcomas remain poorly defined. Methods: RNA extracted from formalin-fixed paraffin-embedded tumor tissue scrolls of 108 pediatric tumors, including 32 osteosarcoma (OS), 26 Ewing’s sarcoma (EWS), and 50 rhabdomyosarcoma (RMS) cases, were analyzed for microRNA expression using the NanoString multiplex nCounter platform that yielded information on 827 human miRNAs. The expression of candidate miRNAs was validated with in situ hybridization (miRNA-ISH) and QuPath quantification on tissue microarray slides comprising an independent set of 48 OS, 17 EWS, and 104 RMS adult and pediatric cases collectively. Results: The differential expression analysis of nCounter data identified 23 miRNAs enriched in RMS, 33 in EWS, and 45 in OS (>3 fold change and p < 0.01). miR-206 was most strongly associated (>55 fold change, p < 1 × 10⁻⁹) with RMS and demonstrated the highest sensitivity and specificity in distinguishing RMS from EWS and OS; this finding was also confirmed by miRNA-ISH. A combined signature of differentially expressed miRNAs reliably separated alveolar from embryonal RMS. The expression of miR-9-5p in EWS and miR-140-5p in OS discriminated among the different tumors and correlated with adverse patient outcome. The nCounter assay exhibited greater sensitivity than miRNA-ISH in detecting miR-206 and miR-140-5p expression. Conclusions: Collectively, these findings demonstrate that distinct miRNA profiles can differentiate pediatric sarcoma types and subtypes and offer clinically relevant insights into tumor biology, prognosis, and potential diagnostic application.

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.

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 (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.

Lactante de 6 meses de edad, enviada para valoración al servicio de Trasplante de células progenitoras hematopoyéticas del Instituto Nacional de Pediatría. Entre sus antecedentes personales: la madre de 24 años, primer embarazo, evolución normal, parto eutócico, peso al nacimiento 3 kg, talla 48 cm y Apgar 8/9. Desde el nacimiento se identificó dermatosis maculopapular generalizada, con nódulos subcutáneos infiltrativos violáceos en todo el cuerpo. (Figura 1) Se estableció el diagnóstico presuntivo de síndrome de neonato blueberry-muffin; además, se encontró hepatomegalia y esplenomegalia. La biometría hemática reportó hiperleucocitosis (215,900 leucocitos/mm3), a expensas de 75% de blastos, con inmunofenotipo de expresión: CD45+, MPO+, CD33+, CD13+ y CD14+, compatible con leucemia mieloblástica aguda.

Niño con antecedente de ictericia desde el nacimiento, que al alta hospitalaria le indicaron baños de sol sin mostrar mejoría; los padres negaron acolia y refirieron coluria ocasional. Las pruebas de sangre reportaron elevada concentración de bilirrubinas. Con estos datos lo transfirieron al Instituto Nacional de Pediatría, a la edad de 1 mes y 23 días (primer ingreso). Durante el examen físico se comprobó la ictericia de piel, mucosas y conjuntivas; el hígado se percibía blando, con percusión total de 7 cm. Las pruebas de función hepática resultaron con: bilirrubina total 21.04 mg/dL, bilirrubina directa 13.49 mg/ dL, bilirrubina indirecta 7.55 mg/dL (proteínas totales 5.63 mg/dL, albúmina 3.06 mg/dL, globulinas 2.57 mg/dL, AST 271 U/L, ALT 195 U/L, GGT 208 U/L, fosfatasa alcalina 546 U/L, DHL 295 U/L, proteína C reactiva 0.3 mg/dL).

Se presenta el caso de un niño con histiocitosis de células de Langerhans que inicialmente se diagnosticó erróneamente y se le trató quirúrgicamente sin la evaluación integra del paciente.