RESUMEN
mTOR inhibitors such as sirolimus are increasingly used in the management of multilineage immune cytopenia (m-IC) in children. Although sirolimus is effective in improving IC, it is unclear how sirolimus affects the broader immune dysregulation associated with m-IC. We profiled T- and B-cell subsets longitudinally and measured cytokines and chemokines before and after sirolimus treatment. Eleven of the 12 patients with m-IC who tolerated sirolimus were followed for a median duration of 17 months. All patients had an improvement in IC, and sirolimus therapy did not result in significant decreases in T-, B- and NK-cell numbers. However, the expansion and activation of circulating T follicular helper and the Th1 bias noted before the initiation of sirolimus were significantly decreased. Features of chronic T-cell activation and exhaustion within effector memory compartments of CD4+ and CD8+ T cells decreased with sirolimus therapy. Corresponding to these changes, plasma levels of CXCL9 and CXCL10 also decreased. Interestingly, no significant improvement in the proportion of class-switched memory B cells or frequencies of CD4+ naive T cells were noted. Longer follow-up and additional studies are needed to validate these findings and evaluate the effect of sirolimus on B-cell maturation.
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Subgrupos de Linfocitos B , Linfocitos T CD4-Positivos , Niño , Humanos , Sirolimus/farmacología , Sirolimus/uso terapéutico , Serina-Treonina Quinasas TOR , Linfocitos T CD8-positivosRESUMEN
Hemophagocytic lymphohistiocytosis (HLH) is characterized by hyperinflammation and multiorgan dysfunction. Infections, including the reactivation of viruses, contribute to significant disease mortality in HLH. Although T-cell and natural killer cell-driven immune activation and dysregulation are well described, limited data exist on the status of B-cell compartment and humoral immune function in HLH. We noted marked suppression of early B-cell development in patients with active HLH. In vitro B-cell differentiation studies after exposure to HLH-defining cytokines, such as interferon gamma (IFN-γ) and tumor necrosis factor, recapitulated B-cell development arrest. Messenger RNA sequencing of human CD34+ cells exposed to IFN-γ demonstrated changes in genes and pathways affecting B-cell development and maturation. In addition, patients with active HLH exhibited a marked decrease in class-switched memory B (CSMB) cells and a decrease in bone marrow plasmablast/plasma cell compartments. The decrease in CSMB cells was associated with a decrease in circulating T follicular helper (cTfh) cells. Finally, lymph node and spleen evaluation in a patient with HLH revealed absent germinal center formation and hemophagocytosis with associated lymphopenia. Reassuringly, the frequency of CSMB and cTfh improved with the control of T-cell activation. Taken together, in patients with active HLH, these changes in B cells may affect the humoral immune response; however, further immune studies are needed to determine its clinical significance.
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Linfohistiocitosis Hemofagocítica , Humanos , Linfohistiocitosis Hemofagocítica/patología , Citocinas/metabolismo , Interferón gamma/genética , Linfocitos T , Células Asesinas NaturalesRESUMEN
Pediatric Evans syndrome (pES) is increasingly identified as the presenting manifestation of several inborn errors of immunity. Despite an improved understanding of genetic defects in pES, the underlying immunobiology of pES is poorly defined, and characteristic diagnostic immune parameters are lacking. We describe the immune characteristics of 24 patients with pES and compared them with 22 patients with chronic immune thrombocytopenia (cITP) and 24 healthy controls (HCs). Compared with patients with cITP and HC, patients with pES had increased circulating T-follicular helper cells (cTfh), increased T-cell activation, and decreased naïve CD4+ T cells for age. Despite normal or high immunoglobulin G (IgG) in most pES at presentation, class-switched memory B cells were decreased. Within the cTfh subset, we noted features of postactivation exhaustion with upregulation of several canonical checkpoint inhibitors. T-cell receptor ß chain (TCR-ß) repertoire analysis of cTfh cells revealed increased oligoclonality in patients with pES compared with HCs. Among patients with pES, those without a known gene defect had a similar characteristic immune abnormality as patients with defined genetic defects. Similarly, patients with pES with normal IgG had similar T-cell abnormalities as patients with low IgG. Because genetic defects have been identified in less than half of patients with pES, our findings of similar immune abnormalities across all patients with pES help establish a common characteristic immunopathology in pES, irrespective of the underlying genetic etiology.
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Anemia Hemolítica Autoinmune/inmunología , Activación de Linfocitos , Linfocitos T Colaboradores-Inductores/inmunología , Trombocitopenia/inmunología , Adolescente , Adulto , Anemia Hemolítica Autoinmune/patología , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Púrpura Trombocitopénica Idiopática/inmunología , Púrpura Trombocitopénica Idiopática/patología , Linfocitos T Colaboradores-Inductores/patología , Trombocitopenia/patología , Adulto JovenRESUMEN
Neutropenia is a condition comprising an abnormally low number of neutrophils, a type of white blood cell, which puts patients at an increased risk of severe infections. Neutropenia is especially common among cancer patients and can disrupt their treatment or even be life-threatening in severe cases. Therefore, routine monitoring of neutrophil counts is crucial. However, the current standard of care to assess neutropenia, the complete blood count (CBC), is resource-intensive, time-consuming, and expensive, thereby limiting easy or timely access to critical hematological information such as neutrophil counts. Here, we present a simple technique for fast, label-free neutropenia detection and grading via deep-ultraviolet (deep-UV) microscopy of blood cells in polydimethylsiloxane (PDMS)-based passive microfluidic devices. The devices can potentially be manufactured in large quantities at a low cost, requiring only 1 µL of whole blood for operation. We show that the absolute neutrophil counts (ANC) obtained from our proposed microfluidic device-enabled deep-UV microscopy system are highly correlated with those from CBCs using commercial hematology analyzers in patients with moderate and severe neutropenia, as well as healthy donors. This work lays the foundation for the development of a compact, easy-to-use UV microscope system to track neutrophil counts that is suitable for low-resource, at-home, or point-of-care settings.
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Neoplasias , Neutropenia , Humanos , Microscopía , Neutropenia/diagnóstico , Recuento de Leucocitos , NeutrófilosRESUMEN
PURPOSE: T cell-Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (T cell-EBV-HLH) is prevalent in East Asia and has poor prognosis. Understanding of this disease is limited, and literature regarding prevalence in North America is scarce. Herein, we summarize our experience. METHODS: A retrospective analysis of T cell-EBV-HLH patients admitted to Children's Healthcare of Atlanta (GA, USA) from 2010 to 2020 was conducted. Additional immune studies were completed in a subset of patients. RESULTS: We report 15 patients (10 months-19 years of age) diagnosed with T cell-EBV-HLH. Nine patients were Hispanic, and the majority did not have primary HLH (p-HLH) gene defects. Soluble interleukin-2 receptor levels in T cell-EBV-HLH were significantly higher than other forms of secondary-HLH but comparable to p-HLH, and it correlated with disease severity at presentation. Natural killer cell function was decreased in most patients despite a negative workup for p-HLH. Depending on disease severity, initial therapy included dexamethasone or dexamethasone and etoposide. Refractory patients were managed with blended regimens that included one or more of the following therapies: combination chemotherapy, alemtuzumab, emapalumab, and nivolumab. Rituximab did not appreciably decrease EBV viremia in most patients. Non-critically ill patients responded well to immunosuppressive therapy and are long-term survivors without undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Alemtuzumab resulted in inflammation flare in two of the three patients. Three patients underwent allogeneic HSCT, with disease relapse noted in one. At a median follow-up of 3 years, 10 of the 15 patients are alive. CONCLUSION: T cell-EBV-HLH occurs in the USA among the non-Asian populations, especially in those who are Hispanic.
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Infecciones por Virus de Epstein-Barr/inmunología , Herpesvirus Humano 4 , Linfohistiocitosis Hemofagocítica/inmunología , Linfocitos T/inmunología , Adolescente , Adulto , Niño , Preescolar , Infecciones por Virus de Epstein-Barr/etnología , Infecciones por Virus de Epstein-Barr/genética , Infecciones por Virus de Epstein-Barr/terapia , Etnicidad , Femenino , Humanos , Lactante , Linfohistiocitosis Hemofagocítica/etnología , Linfohistiocitosis Hemofagocítica/genética , Linfohistiocitosis Hemofagocítica/terapia , Masculino , Persona de Mediana Edad , Grupos Raciales , Adulto JovenRESUMEN
We report a 1-year-old female child presenting with hypereosinophilia who was found to have concurrent myeloid sarcoma and a central nervous system (CNS) atypical teratoid/rhabdoid tumor (AT/RT). She was later found to have a germline mutation in SMARCB1. Concurrent hematologic malignancy and CNS AT/RT have not previously been described in the context of a SMARCB1 loss-of-function germline mutation.
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Eosinofilia/etiología , Mutación de Línea Germinal , Neoplasias Primarias Múltiples/genética , Tumor Rabdoide/genética , Proteína SMARCB1/genética , Sarcoma Mieloide/genética , Teratoma/genética , Femenino , Humanos , Lactante , Neoplasias Primarias Múltiples/complicaciones , Neoplasias Primarias Múltiples/patología , Tumor Rabdoide/complicaciones , Tumor Rabdoide/patología , Sarcoma Mieloide/complicaciones , Sarcoma Mieloide/patología , Teratoma/complicaciones , Teratoma/patologíaRESUMEN
BACKGROUND: Childhood acute leukemia is traditionally diagnosed from a bone marrow aspirate (BMA). New-onset acute leukemia patients do not always have visible circulating blasts in the peripheral blood (PB) at diagnosis. While the role of bone marrow flow cytometry for the diagnosis of acute leukemia is well established, the utility of PB flow cytometry (PBFC) is unknown. We performed a single-institution retrospective analysis to compare PBFC versus BMA in establishing or excluding a diagnosis of childhood acute leukemia. PROCEDURE: We retrospectively identified 485 PBFC samples with concurrent BMA from 2008 to 2013. Results of four-color flow cytometry for immunophenotypic characterization of leukemic versus nonclonal disease were characterized. Sensitivity and specificity were calculated among patients without a known diagnosis or prior therapy. RESULTS: Among 485 samples eligible for analysis, 120 had negative PBFC and BMA, 359 had positive PBFC and BMA, 3 had negative PBFC and positive BMA, and 3 had positive PBFC and negative BMA. There were small but significant differences in sensitivity (100 vs. 93.8%; P = 0.002) and positive predictive value (100 vs. 93.8%; P = 0.002) favoring BMA over PBFC among those demonstrating absence of circulating morphologic blasts. CONCLUSION: PBFC has high sensitivity and specificity for the diagnosis of childhood acute leukemia. The predictive value of PBFC remains high for patients without visible circulating blasts and may enhance the diagnostic process for determining the indications for marrow testing.
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Citometría de Flujo/métodos , Inmunofenotipificación/métodos , Leucemia/sangre , Leucemia/diagnóstico , Enfermedad Aguda , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas , Estudios RetrospectivosAsunto(s)
Prueba de COVID-19 , COVID-19/diagnóstico , Accesibilidad a los Servicios de Salud , Pandemias , SARS-CoV-2/aislamiento & purificación , Antígenos Virales/análisis , Antígenos Virales/inmunología , COVID-19/epidemiología , Prueba de Ácido Nucleico para COVID-19 , Prueba de COVID-19/economía , Prueba de COVID-19/métodos , Prueba de COVID-19/estadística & datos numéricos , Proteínas de la Nucleocápside de Coronavirus/análisis , Proteínas de la Nucleocápside de Coronavirus/inmunología , Análisis Costo-Beneficio , Estudios de Evaluación como Asunto , Financiación Gubernamental , Humanos , Invenciones , National Institutes of Health (U.S.) , Pruebas en el Punto de Atención , Asociación entre el Sector Público-Privado/organización & administración , ARN Viral/análisis , Juego de Reactivos para Diagnóstico/provisión & distribución , SARS-CoV-2/inmunología , Sensibilidad y Especificidad , Glicoproteína de la Espiga del Coronavirus/análisis , Glicoproteína de la Espiga del Coronavirus/inmunología , Estados Unidos/epidemiologíaRESUMEN
Monomorphic plasmacytoma-type posttransplant lymphoproliferative disorder (PTLD) has not been reported after pediatric hematopoietic stem cell transplantation. We present a child with hepatitis-associated severe aplastic anemia who underwent an unrelated allogeneic hematopoietic stem cell transplantation and subsequently developed graft failure and an Epstein-Barr virus-positive monomorphic plasmacytoma-type PTLD of recipient origin. Despite broad-spectrum antimicrobials, weaning immunosuppression, rituximab administration, and a stem cell boost she died from complications of PTLD and a fungal pulmonary infection on day +78.
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Anemia Aplásica/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trastornos Linfoproliferativos/etiología , Plasmacitoma/etiología , Anemia Aplásica/complicaciones , Niño , Infecciones por Virus de Epstein-Barr , Resultado Fatal , Femenino , Rechazo de Injerto , Humanos , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/microbiología , Trastornos Linfoproliferativos/virología , Plasmacitoma/virología , Trasplante HomólogoAsunto(s)
Leucemia Bifenotípica Aguda/genética , Leucemia Bifenotípica Aguda/mortalidad , Peroxidasa/genética , Enfermedad Aguda , Adolescente , Linfocitos B/patología , Niño , Preescolar , Femenino , Regulación Leucémica de la Expresión Génica , Humanos , Lactante , Recién Nacido , Leucemia Bifenotípica Aguda/patología , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/patología , Masculino , Fenotipo , Estudios RetrospectivosRESUMEN
AIMS: To report a series of acute lymphoblastic leukemia (ALL) cases with spontaneous remission and provide presenting clinical and pathologic information and details of clinical course to raise awareness among oncologists and patients. METHODS: We identified and analyzed nine patients with ALL and spontaneous remission. Review of literature reveals an additional nine previously reported cases with similar clinical course. RESULTS: All of these patients, ranging in age from 2 to 12 years of age, presented with inciting signs and symptoms of viral or bacterial infection. All of the patients showed varying percentages of lymphoblasts (.2% to 90%) in diagnostic bone marrow biopsy. All B-ALL cases shared a similar blast phenotype on flow cytometry with coexpression of CD19, CD10 and TdT and variable CD20 expression. All nine patients achieved spontaneous remission of their leukemia as confirmed by flow cytometry and/or bone marrow biopsy without chemotherapeutic intervention. Time to remission from presentation ranged from 1 to 8 weeks. After remission, all patients redeveloped ALL, and time from remission to reemergence ranged from 2 to 24 weeks. CONCLUSION: Our series of cases and cases identified in literature show that ALL diagnosed with modern methods of flow cytometry and molecular analysis will recur within weeks to months from disappearance, usually with cytopenias, which provides a template for oncologic follow-up and testing in these patients.
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Linfoma de Células B , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Remisión Espontánea , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Médula Ósea/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patología , Linfoma de Células B/patología , Citometría de Flujo , InmunofenotipificaciónRESUMEN
Different driver mutations and/or chromosomal aberrations and dysregulated signaling interactions between leukemia cells and the immune microenvironment have been implicated in the development of T-cell acute lymphoblastic leukemia (T-ALL). To better understand changes in the bone marrow microenvironment and signaling pathways in pediatric T-ALL, bone marrows collected at diagnosis (Dx) and end of induction therapy (EOI) from 11 patients at a single center were profiled by single cell transcriptomics (10 Dx, 5 paired EOI, 1 relapse). T-ALL blasts were identified by comparison with healthy bone marrow cells. T-ALL blast-associated gene signature included SOX4, STMN1, JUN, HES4, CDK6, ARMH1 among the most significantly overexpressed genes, some of which are associated with poor prognosis in children with T-ALL. Transcriptome profiles of the blast cells exhibited significant inter-patient heterogeneity. Post induction therapy expression profiles of the immune cells revealed significant changes. Residual blast cells in MRD+ EOI samples exhibited significant upregulation (P < 0.01) of PD-1 and RhoGDI signaling pathways. Differences in cellular communication were noted in the presence of residual disease in T cell and hematopoietic stem cell compartments in the bone marrow. Together, these studies generate new insights and expand our understanding of the bone marrow landscape in pediatric T-ALL.
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Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Niño , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Transcriptoma , Médula Ósea , Recurrencia , Células de la Médula Ósea , Pronóstico , Microambiente Tumoral/genética , Factores de Transcripción SOXCRESUMEN
Siglec-15 (Sig15) has been implicated as an immune checkpoint expressed in solid tumor-infiltrating macrophages and is being targeted in clinical trials with mAbs to normalize the tumor immune microenvironment and stimulate antitumor immunity. However, the role of Sig15 in hematologic malignancies remains undefined. Sig15 mRNA and protein expression levels in hematologic malignancies were determined from publicly available databases, cell lines, and primary patient samples. Human B-cell acute lymphoblastic leukemia (B-ALL) cell lines were used to identify signaling pathways involved in the regulation of Sig15 expression. Secreted/soluble Sig15 and cytokine levels were measured from the plasma of children with leukemia and healthy controls. Knockdown and knockout of Siglec15 in a murine model of B-ALL was used to evaluate the effect of leukemia-derived Sig15 on the immune response to leukemia. We observed pathologic overexpression of Sig15 in a variety of hematologic malignancies, including primary B-ALL samples. This overexpression was driven by NFκB activation, which also increased the surface localization of Sig15. Secreted/soluble Sig15 was found to circulate at elevated levels in the plasma of children with B-ALL and correlated with an immune-suppressive cytokine milieu. Genetic inhibition of Sig15 in murine B-ALL promoted clearance of the leukemia by the immune system and a marked reversal of the immune-privileged leukemia bone marrow niche, including expanded early effector CD8+ T cells and reduction of immunosuppressive cytokines. Thus, Sig15 is a novel, potent immunosuppressive molecule active in leukemia that may be targeted therapeutically to activate T lymphocytes against leukemia cells. Significance: We demonstrate that Sig15 is overexpressed in hematologic malignancies driven by NFκB, is required for immune evasion in a mouse model of leukemia, and, for the first time, that it circulates at high levels in the plasma of children with leukemia.
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Linfoma de Burkitt , Neoplasias Hematológicas , Leucemia , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Animales , Niño , Humanos , Ratones , Inmunidad Adaptativa , Linfocitos T CD8-positivos , Citocinas , Inmunoglobulinas , Proteínas de la Membrana , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Lectinas Similares a la Inmunoglobulina de Unión a Ácido Siálico , Microambiente Tumoral/genéticaRESUMEN
Acute myeloid leukemia (AML) microenvironment exhibits cellular and molecular differences among various subtypes. Here, we utilize single-cell RNA sequencing (scRNA-seq) to analyze pediatric AML bone marrow (BM) samples from diagnosis (Dx), end of induction (EOI), and relapse timepoints. Analysis of Dx, EOI scRNA-seq, and TARGET AML RNA-seq datasets reveals an AML blasts-associated 7-gene signature (CLEC11A, PRAME, AZU1, NREP, ARMH1, C1QBP, TRH), which we validate on independent datasets. The analysis reveals distinct clusters of Dx relapse- and continuous complete remission (CCR)-associated AML-blasts with differential expression of genes associated with survival. At Dx, relapse-associated samples have more exhausted T cells while CCR-associated samples have more inflammatory M1 macrophages. Post-therapy EOI residual blasts overexpress fatty acid oxidation, tumor growth, and stemness genes. Also, a post-therapy T-cell cluster associated with relapse samples exhibits downregulation of MHC Class I and T-cell regulatory genes. Altogether, this study deeply characterizes pediatric AML relapse- and CCR-associated samples to provide insights into the BM microenvironment landscape.
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Leucemia Mieloide Aguda , Microambiente Tumoral , Humanos , Niño , Leucemia Mieloide Aguda/patología , Inducción de Remisión , Recurrencia , Análisis de la Célula Individual , Antígenos de Neoplasias , Proteínas Portadoras , Proteínas Mitocondriales/metabolismoRESUMEN
The rarity of malignant Hodgkin and Reed Sternberg (HRS) cells in classic Hodgkin lymphoma (cHL) limits the ability to study the genomics of cHL. To circumvent this, our group has previously optimized fluorescence-activated cell sorting to purify HRS cells. Using this approach, we now report the whole-genome sequencing landscape of HRS cells and reconstruct the chronology and likely etiology of pathogenic events leading to cHL. We identified alterations in driver genes not previously described in cHL, APOBEC mutational activity, and the presence of complex structural variants including chromothripsis. We found that high ploidy in cHL is often acquired through multiple, independent chromosomal gains events including whole-genome duplication. Evolutionary timing analyses revealed that structural variants enriched for RAG motifs, driver mutations in B2M, BCL7A, GNA13, and PTPN1, and the onset of AID-driven mutagenesis usually preceded large chromosomal gains. This study provides a temporal reconstruction of cHL pathogenesis. SIGNIFICANCE: Previous studies in cHL were limited to coding sequences and therefore not able to comprehensively decipher the tumor complexity. Here, leveraging cHL whole-genome characterization, we identify driver events and reconstruct the tumor evolution, finding that structural variants, driver mutations, and AID mutagenesis precede chromosomal gains. This article is highlighted in the In This Issue feature, p. 171.
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Enfermedad de Hodgkin , Células de Reed-Sternberg , Humanos , Células de Reed-Sternberg/patología , Enfermedad de Hodgkin/genética , Enfermedad de Hodgkin/patología , Citometría de Flujo , Evolución MolecularRESUMEN
The correlation between cardiovascular disease and iron deficiency anemia (IDA) is well documented but poorly understood. Using a multi-disciplinary approach, we explore the hypothesis that the biophysical alterations of red blood cells (RBCs) in IDA, such as variable degrees of microcytosis and decreased deformability may directly induce endothelial dysfunction via mechanobiological mechanisms. Using a combination of atomic force microscopy and microfluidics, we observed that subpopulations of IDA RBCs (idRBCs) are significantly stiffer and smaller than both healthy RBCs and the remaining idRBC population. Furthermore, computational simulations demonstrated that the smaller and stiffer idRBC subpopulations marginate toward the vessel wall causing aberrant shear stresses. This leads to increased vascular inflammation as confirmed with perfusion of idRBCs into our "endothelialized" microfluidic systems. Overall, our multifaceted approach demonstrates that the altered biophysical properties of idRBCs directly lead to vasculopathy, suggesting that the IDA and cardiovascular disease association extends beyond correlation and into causation.
RESUMEN
CONTEXT.: Diagnostic testing for SARS-CoV-2 in symptomatic and asymptomatic children remains integral to care, particularly for supporting return to and attendance in schools. The concordance of SARS-CoV-2 detection in children, using various specimen types, has not been widely studied. OBJECTIVE.: To compare 3 sample types for SARS-CoV-2 polymerase chain reaction (PCR) testing in children, collected and tested at a single facility. DESIGN.: We prospectively recruited 142 symptomatic and asymptomatic children/young adults into a sample comparison study performed in a single health care system. Each child provided self-collected saliva, and a trained health care provider collected a mid-turbinate nasal swab and nasopharyngeal (NP) swab. Specimens were assayed within 24 hours of collection by using reverse transcription-polymerase chain reaction (RT-PCR) to detect SARS-CoV-2 on a single testing platform. RESULTS.: Concurrently collected saliva and mid-turbinate swabs had greater than 95% positive agreement with NP swabs when obtained within 10 days of symptom onset. Positive agreement of saliva and mid-turbinate samples collected from children with symptom onset >10 days prior, or without symptoms, was 82% compared to NP swab samples. Cycle threshold (Ct) values for mid-turbinate nasal samples more closely correlated with Ct values from NP samples than from saliva samples. CONCLUSIONS.: These findings suggest that all 3 sample types from children are useful for SARS-CoV-2 diagnostic testing by RT-PCR, and that concordance is greatest when the child has had symptoms of COVID-19 within the past 10 days. This study provides scientific justification for using sample types other than the NP swab for SARS-CoV-2 testing in pediatric populations.
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COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , Prueba de COVID-19 , Niño , Humanos , Nasofaringe , Pacientes Ambulatorios , Reacción en Cadena de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transcripción Reversa , SARS-CoV-2/genética , Saliva , Manejo de Especímenes/métodos , Cornetes Nasales , Adulto JovenRESUMEN
Mediastinal masses commonly present in children and may pose diagnostic challenges, particularly with limited sampling. This article aids the pathologist by reviewing the hematologic differential diagnosis of a pediatric mediastinal mass, along with ancillary testing useful for rendering the correct diagnosis. A review of the more common lymphomas is presented, including classic Hodgkin lymphoma, T-lymphoblastic leukemia/lymphoma, and primary mediastinal (thymic) large B-cell lymphoma, along with brief mentions of less common entities such as gray zone lymphoma and thymoma as well as non-neoplastic conditions such as benign cysts and infections.