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BACKGROUND: Pediatric Mycosis Fungoides (MF) management extrapolates from adult guidelines, despite differing clinical aspects. Recommendations are essential to address unique challenges in this distinct patient group. OBJECTIVE: This project aims to derive consensus recommendations for pediatric MF management. METHODS: Experts from pediatric dermatology, general dermatology, dermato-pathology, and pediatric hematology-oncology (N=83) were invited to contribute to consensus recommendations. The process involved three eDelphi rounds, concluding with a final consensus meeting using a modified Nominal Group Technique for unresolved items. RESULTS: Consensus included more clinical severity measures than TNMB staging: pruritus, functional or esthetic impairment (e.g., palms, soles, genitalia), quality of life impact, and psychological aspects (e.g., embarrassment, anxiety, depression), plus parental anxiety. Ten recommendations were made for managing early and advanced pediatric MF. Disagreement emerged in choosing therapies beyond stage I of the disease. DISCUSSION: This multinational initiative aimed to standardize optimal pediatric MF management and successfully generated consensus recommendations. Additional work is needed for structured, prospective protocols in advanced-stage pediatric MF. LIMITATIONS: Lack of pediatric hematologists-oncologists and patients' representatives. CONCLUSION: Documentation of extended clinical severity and outcome measures is recommended. Addressing the need for structured protocols in advanced-stage pediatric MF and implementing systematic, prospective data collection is crucial..
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T-lymphoblastic lymphoma (T-LLy) is the most common lymphoblastic lymphoma in children and often presents with a mediastinal mass. Lymphomatous suprarenal masses are possible but rare. Here, we discuss the case of a previously healthy 3-yr-old male who presented with mediastinal T-LLy with bilateral suprarenal masses. Following initial treatment, surgical biopsy of persisting adrenal masses revealed bilateral neuroblastoma (NBL). A clinical genetics panel for germline cancer predisposition did not identify any pathogenic variants. Combination large panel (864 genes) profiling analysis in the context of a precision oncology study revealed two novel likely pathogenic heterozygous variants: SMARCA4 c.1420-1G > T p.? and EZH2 c.1943G > C p.(Ile631Phefs*44). Somatic analysis revealed potential second hits/somatic variants in EZH2 (in the T-LLy) and a segmental loss in Chromosome 19p encompassing SMARCA4 (in the NBL). Synchronous cancers, especially at a young age, warrant genetic evaluation for cancer predisposition; enrollment in a precision oncology program assessing germline and tumor DNA can fulfill that purpose, particularly when standard first-line genetic testing is negative and in the setting of tumors that are not classic for common cancer predisposition syndromes.
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Neuroblastoma , Leucemia-Linfoma Linfoblástico de Células Precursoras , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Criança , Humanos , Masculino , Medicina de Precisão , Testes Genéticos , Neuroblastoma/genética , Predisposição Genética para Doença , DNA Helicases/genética , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genéticaRESUMO
BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) develop as a consequence of immune suppression. Programmed death protein 1 (PD-1), a regulator of host immune activation, binds to programmed death-ligand 1 (PD-L1) to suppress the T-cell immune response. PD-1/PD-L1 pathway may play a role in PTLD. The objective was to describe intratumoral expression of PD-L1 and PD-1 in pediatric monomorphic PTLD, and assess if density of these cells is associated with progression-free survival (PFS) and overall survival (OS). PROCEDURE: Clinical variables and outcome data were collected on B-cell monomorphic PTLD treated in Toronto, Canada between 2000 and 2017. Diagnostic area from tumor tissue was identified to count CD3-positive or PD-1-positive cells and CD3-negative lymphoma B cells or PD-L1-positive cells. CD3+ , PD-1+ , and PD-L1+ cell densities were compared between cases of PTLD. OS and PFS were analyzed. RESULTS: We identified 25 cases of B-cell monomorphic PTLD; majority Burkitt lymphoma (32%) and diffuse large B-cell lymphoma (56%). All cases had CD3+ cells infiltrating the tumor, and median percentage of CD3+ cells was 14% (interquartile range: 6.2%-25%). Twelve cases (48%) had PD-1+ cell infiltrating (range: 1%-83%) and 13 cases (52%) had no PD-1+ cells infiltrating. Sixteen cases (64%) had PD-L1+ cells present; however, there was no PD-L1 expression on any Burkitt lymphoma tissue. When comparing PD-1 and PD-L1 expression, there was no difference in OS or PFS. CONCLUSION: Intratumoral presence of PD-1+ and PD-L1+ cells varied in pediatric patients with monomorphic PTLD; however, no relationship to OS and PFS was identified.
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Background And Objectives: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm with a wide spectrum of clinical presentations. Programmed Cell Death-1 (PD-1) receptor and its ligand (PD-L1) are overexpressed in LCH, but their clinical significance is unknown. We performed a clinical correlation study of PD-1/PD-L1 and VE1(BRAFp.V600E) expression in 131 children with LCH. Methods: A total of 111 samples were tested for PD-1/PD-L1 and 109 for VE1(BRAFp.V600E) mutant protein by immunohistochemistry. Results: PD-1, PD-L1 and VE1(BRAFp.V600E) positivity was observed in 40.5%, 31.53% and 55%, respectively. PD-1/ PD-L1 expression showed no significant effect on the rate of disease reactivations, early response to therapy or late sequelae. The 5-year EFS was not statistically different between patients with PD-1 positive compared to those with PD-1 negative tumours (47.7% vs.58.8%, p=0.17). Similar 5-year EFS rates were also seen in those who were PD-L1 positive compared to PD-L1 negative cases (50.5% vs.55.5%, p=0.61). VE1(BRAFp.V600E) positivity was associated with a significantly higher frequency of risk-organ involvement (p=0.0053), but no significant effect on early response to therapy or rates of reactivations or late sequelae. Conclusions: Our study showed no significant correlation between VE1(BRAFp.V600E) expression, PD-1 and PD-L1 and clinical outcome in pediatric LCH.
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Differentiating hepatoblastomas from other congenital benign hepatic tumors is key to surgical management. We, herein, present an unusual case of an antenatally diagnosed liver lesion assessed in the neonatal period. Because of its predominantly cystic ultrasound/MRI appearance and borderline alpha-fetoprotein serum levels the diagnosis of mesenchymal hamartoma was favored and protocol-based tumor resection was performed. Due to the intraoperative diagnosis of a fetal subtype of hepatoblastoma with positive resection margins the child had to undergo a second laparotomy. This report raises awareness to an unusual appearance of hepatoblastoma and discusses noninvasive imaging clues to consider atypical appearances of hepatoblastoma preoperatively as they can have profound implications in patient management.
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Hamartoma , Hepatoblastoma , Neoplasias Hepáticas , Recém-Nascido , Criança , Humanos , Hepatoblastoma/diagnóstico , Hepatoblastoma/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética , Hamartoma/diagnóstico por imagem , Hamartoma/cirurgiaRESUMO
BACKGROUND: Genetic aberrations in the NFκB pathway lead to primary immunodeficiencies with various degrees of severity. We previously demonstrated that complete ablation of the RelB transcription factor, a key component of the alternative pathway, results in an early manifested combined immunodeficiency requiring stem cell transplantation. OBJECTIVE: To study the molecular basis of a progressive severe autoimmunity and immunodeficiency in three patients. METHODS: Whole exome sequencing was performed to identify the genetic defect. Molecular and cellular techniques were utilized to assess the variant impact on NFκB signaling, canonical and alternative pathway crosstalk, as well as the resultant effects on immune function. RESULTS: Patients presented with multiple autoimmune progressive severe manifestations encompassing the liver, gut, lung, and skin, becoming debilitating in the second decade of life. This was accompanied by a deterioration of the immune system, demonstrating an age-related decline in naïve T cells and responses to mitogens, accompanied by a gradual loss of all circulating CD19+ cells. Whole exome sequencing identified a novel homozygous c. C1091T (P364L) transition in RELB. The P364L RelB protein was unstable, with extremely low expression, but retained some function and could be transiently and partially upregulated following Toll-like receptor stimulation. Stimulation of P364L patient fibroblasts resulted in a marked rise in a cluster of pro-inflammatory hyper-expressed transcripts consistent with the removal of RelB inhibitory effect on RelA function. This is likely the main driver of autoimmune manifestations in these patients. CONCLUSION: Incomplete loss of RelB provided a unique opportunity to gain insights into NFκB's pathway interactions as well as the pathogenesis of autoimmunity. The P364L RelB mutation leads to gradual decline in immune function with progression of severe debilitating autoimmunity.
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Doenças Autoimunes , Fator de Transcrição RelB , Humanos , Fator de Transcrição RelB/genética , Fator de Transcrição RelB/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Regulação da Expressão Gênica , Doenças Autoimunes/genéticaRESUMO
Congenital pseudodiverticula of the esophagus are very rare. This case report describes the presentation, management and histopathology of a peudodiverticulum of the cervical esophagus in a neonate. The infant presented with respiratory distress and a right neck mass that required surgical excision. Pathology revealed a pseudodiverticulum that contained ectopic thymic, thyroid, and parathyroid tissue within the wall of the lesion. The presence of ectopic tissues of branchial origin and an aberrant right subclavian artery suggest an error in branchial development and neural crest cell migration.
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Coristoma , Pescoço , Coristoma/diagnóstico , Coristoma/cirurgia , Esôfago , Humanos , Lactente , Recém-Nascido , Artéria SubcláviaRESUMO
Rationale: Mucin homeostasis is fundamental to airway health. Upregulation of airway mucus glycoprotein MUC5B is observed in diverse common lung diseases and represents a potential therapeutic target. In mice, Muc5b is required for mucociliary clearance and for controlling inflammation after microbial exposure. The consequences of its loss in humans are unclear. Objectives: The goal of this study was to identify and characterize a family with congenital absence of MUC5B protein. Methods: We performed whole-genome sequencing in an adult proband with unexplained bronchiectasis, impaired pulmonary function, and repeated Staphylococcus aureus infection. Deep phenotyping over a 12-year period included assessments of pulmonary radioaerosol mucociliary clearance. Genotyping with reverse phenotyping was organized for eight family members. Extensive experiments, including immunofluorescence staining and mass spectrometry for mucins, were performed across accessible sample types. Measurements and Main Results: The proband, and her symptomatic sibling who also had extensive sinus disease with nasal polyps, were homozygous for a novel splicing variant in the MUC5B gene (NM_002458.2: c.1938 + 1G>A). MUC5B was absent from saliva, sputum, and nasal samples. Mucociliary clearance was impaired in the proband, and large numbers of apoptotic macrophages were present in sputum. Three siblings heterozygous for the familial MUC5B variant were asymptomatic but had a shared pattern of mild lung function impairments. Conclusions: Congenital absence of MUC5B defines a new category of genetic respiratory disease. The human phenotype is highly concordant with that of the Muc5b-/- murine model. Further study of individuals with decreased MUC5B production could provide unique mechanistic insights into airway mucus biology.
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Pneumopatias , Mucinas , Adulto , Animais , Feminino , Humanos , Pulmão/metabolismo , Pneumopatias/metabolismo , Camundongos , Mucina-5AC/genética , Mucina-5B/genética , Mucinas/metabolismo , Depuração Mucociliar/genética , Muco/metabolismoRESUMO
BACKGROUND/PURPOSE: The objectives of this study were: (1) to determine the incidence of lymphoproliferative disorders in a cohort of patients requiring a biopsy at a tertiary pediatric center; and (2) to elucidate the demographic, clinical, laboratory and diagnostic imaging characteristics associated with a malignant diagnosis. METHODS: A retrospective review of pediatric cervical lymph node biopsies performed between 2012 and 2019 at a tertiary center was undertaken. Demographic data, clinical presentations, laboratory results, diagnostic imaging findings, and pathology results were compiled and analyzed to identify characteristics associated with a malignant diagnosis. RESULTS: Malignancy was identified in 49.5% of patients (55/111) subjected to a cervical lymph node biopsy. The median age of patients with a benign diagnosis was lower than malignant diagnosis (11.0 vs. 14.0 years, p < 0.01). Mediastinal lymphadenopathy based on chest radiography and/or computed tomography scan was identified in 37/49 malignant cases (75.5%) CONCLUSION: In this retrospective study, 49.5% of biopsies performed at a tertiary pediatric setting yielded a malignant diagnosis. Traditional clinical characteristics such as weight loss, night sweats and nodal texture were not informative when derived retrospectively. The most valuable features identified were increased age, increased long and short axis measurements of the involved node(s), and the presence of mediastinal lymphadenopathy. LEVEL OF EVIDENCE: Level III.
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Linfadenopatia , Transtornos Linfoproliferativos , Doenças do Mediastino , Biópsia , Criança , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfadenopatia/diagnóstico por imagem , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Central nervous system (CNS) relapse is rare in childhood anaplastic large cell lymphoma (ALCL) and is associated with a poor prognosis. CASE: We describe an 8-year-old boy with ALCL who developed an early CNS relapse without initial CNS disease. Despite aggressive medical management, the patient's neurological status deteriorated rapidly and he died shortly after. CONCLUSION: Optimal treatment for children with relapsed ALCL involving the CNS remains unclear. Novel agents, including ALK inhibitors, that have CNS-penetration might be helpful and pediatric studies are warranted.
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Doenças do Sistema Nervoso Central/patologia , Linfoma Anaplásico de Células Grandes/patologia , Recidiva Local de Neoplasia/patologia , Doenças do Sistema Nervoso Central/terapia , Criança , Humanos , Linfoma Anaplásico de Células Grandes/terapia , Masculino , Recidiva Local de Neoplasia/terapia , Prognóstico , Fatores de RiscoRESUMO
Post-hematopoietic stem cell transplant secondary solid neoplasms are uncommon and usually host-derived. We describe a 6-year-old female who developed a mixed donor-recipient origin mesenchymal stromal tumor-like lesion in the liver following an unrelated hematopoietic stem cell transplant complicated by severe graft-versus-host disease. This lesion arose early post-transplant in association with hepatic graft-versus-host disease. At 12 years post-transplant, the neoplasm has progressively shrunken in size and the patient remains well with no neoplasm-associated sequelae. This report characterizes a novel lesion of mixed origin post-transplant and offers unique insights into the contribution of bone marrow-derived cells to extra-medullary tissues.
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Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neoplasias Hepáticas/etiologia , Fígado/patologia , Células-Tronco Mesenquimais/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Proliferação de Células , Criança , Feminino , Doença Enxerto-Hospedeiro/complicações , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/complicações , Transplante HomólogoRESUMO
OBJECTIVE: Evaluate patterns and predictors of spread to the neck in pediatric metastatic differentiated thyroid carcinoma (DTC). METHODS: Patients <18 years old undergoing thyroidectomy by a single surgeon from January 2015 to December 2019 were included. Neck sublevels were removed separately according to AJCC boundaries. Clinical outcomes included nerve injury, hypocalcemia, hematoma, and residual tumor. RESULTS: Forty-eight children underwent thyroid surgery. Thirty (63%) were for malignancy, 27 (90%) of which were DTC. Nineteen (70%) patients with DTC underwent 24 neck dissections; 19 central plus lateral and 5 central alone. The female to male ratio increased from 1:1 to 3:1 with age. Two children with lateral neck involvement had sub-centimeter primaries. Patients requiring neck dissection were more likely to have 1) diffuse sclerosing or tall cell variant, 2) T3 or T4 disease, 3) genetic mutation, 4) lymphatic invasion, 5) extracapsular extension, 6) positive resection margin. Levels IIA (79%), III (89%), IV (84%), VI (100%) were most commonly involved. Levels IB (16%), IIB (16%), VB (16%) were also involved, often without involvement of adjacent levels. Permanent injuries included one unilateral recurrent laryngeal nerve, one mild marginal mandibular nerve and one mild accessory nerve. Hypocalcemia was highest following neck dissection for malignant disease. One patient was re-operated for a mediastinal node. Most patients with N1 disease received radioactive iodine. Most patients have no evidence or indeterminate disease on long-term follow-up. CONCLUSION: Children with lateral nodal spread from DTC should be considered for neck dissection including Levels IB, IIA, IIB, III, IV, VB, bilateral VI. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1002-E1009, 2021.
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Metástase Linfática/terapia , Esvaziamento Cervical/estatística & dados numéricos , Pescoço/patologia , Câncer Papilífero da Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/patologia , Adolescente , Criança , Feminino , Seguimentos , Humanos , Metástase Linfática/patologia , Masculino , Pescoço/cirurgia , Medição de Risco/estatística & dados numéricos , Câncer Papilífero da Tireoide/secundário , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Resultado do TratamentoRESUMO
BACKGROUND: No study has evaluated the diagnostic accuracy of sonography for the depiction of metastatic cervical adenopathy in children with differentiated thyroid carcinoma at presentation or determined which sonographic features are most useful. OBJECTIVE: To evaluate the diagnostic accuracy of sonography for identifying metastatic cervical adenopathy in children with differentiated thyroid carcinoma at presentation and to determine the most useful sonographic features. MATERIALS AND METHODS: We evaluated cervical lymph node sonography and histology in children with proven thyroid carcinoma in a 10-year period. We excluded children in whom a preoperative sonogram was not available and those who did not have surgical resection of lymph nodes. We used histology as the gold standard. On sonography, we analyzed the size, shape, echotexture and vascularity of the lymph nodes and correlated these findings with the histology. RESULTS: We reviewed sonograms and histology of resected lymph nodes in 52 children and adolescents with proven differentiated thyroid carcinoma (33 females; ages 5-18 years, mean 13.2 years). Metastatic cervical lymph node disease was proved on histology in 33/52 (64%) of our patients at presentation. Sonographic findings correctly predicted whether the nodes were histologically involved with metastatic disease in 42/52 (81%). Sensitivity of sonography was 79%, specificity 84%, positive predictive value (PPV) 90%, negative predictive value (NPV) 70% and accuracy 81%. A significant association was seen between round shape (P=0.0002), abnormal echotexture (P≤0.0001) and vascularity (P≤0.0001), and abnormal lymph node histology. Importantly, in 11/26 (47%) patients with sonographic and histologically proven abnormal nodes, the nodes were normal in size and shape and the presence of metastatic involvement was recognized sonographically only on the basis of abnormal echogenicity and vascularity. CONCLUSION: Sonography has a high accuracy, specificity and PPV for identifying metastatic cervical lymph node involvement in children with differentiated thyroid carcinoma at presentation. Most of the abnormal lymph nodes were round in shape and had abnormal echogenicity and vascularity. Importantly, this paper emphasizes that in children, nodes with histologically proven metastases from differentiated thyroid carcinoma can be normal in size and shape. In these patients the presence of metastatic involvement might be recognized sonographically only on the basis of abnormal echogenicity and vascularity.
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Carcinoma Papilar , Linfadenopatia , Neoplasias da Glândula Tireoide , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Pescoço/diagnóstico por imagem , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/diagnóstico por imagem , UltrassonografiaRESUMO
BACKGROUND: Genetic faults in several components of the nuclear factor-κB pathway cause immunodeficiency. Most defects lead to combined immunodeficiency with a range of severity. Heterozygous mutations in NFKB1 were associated with common variable immunodeficiency, however, homozygous mutations have not been described. OBJECTIVE: We studied the molecular basis of combined immunodeficiency in a patient who presented with failure to thrive, persistent EBV viremia and hepatitis, pneumocystis jirovecii pneumonitis, and generalized lymphadenopathy. METHODS: Whole genome and exome sequencing followed by Sanger confirmation were performed to identify the genetic defect. Molecular and cellular techniques were used to assess the variant impact on the nuclear factor-κB pathway and lymphocyte function. RESULTS: Genetic analysis revealed a novel homozygous mutation in NFKB1, c.2878G>A, p.Gly960Arg (G960R). This affected p105 phosphorylation and p50 formation on antigen and cytokine stimulation, as well as attenuating nuclear signal transmission. As a result, both T- and B-cell maturation and function were perturbed. The number of memory CD4+ T cells were reduced, while CD8+ T cells consisted predominately of expanded differentiated populations. The function of T cells were diminished as shown by reduced responses to mitogens as well as diminished cytokine secretion. B-cell maturation was also affected, with decreased IgD+CD27+ memory B cells while transitional B cells were increased, likely contributing to the reduced ability to produce specific antibodies. CONCLUSION: Homozygous G960R mutation in NFKB1 leads to a severe clinical presentation of combined immunodeficiency. This was associated with blockade of nuclear factor-κB pathway signaling, resulting in aberrations in T- and B-cell maturation and function.
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Subunidade p50 de NF-kappa B/genética , Imunodeficiência Combinada Severa/genética , Homozigoto , Humanos , Lactente , Masculino , Mutação , LinhagemRESUMO
Necrotizing enterocolitis (NEC) is a devastating neonatal disease characterized by acute intestinal injury. Intestinal stem cell (ISC) renewal is required for gut regeneration in response to acute injury. The Wnt/ß-catenin pathway is essential for intestinal renewal and ISC maintenance. We found that ISC expression, Wnt activity and intestinal regeneration were all decreased in both mice with experimental NEC and in infants with acute active NEC. Moreover, intestinal organoids derived from NEC-injured intestine of both mice and humans failed to maintain proliferation and presented more differentiation. Administration of Wnt7b reversed these changes and promoted growth of intestinal organoids. Additionally, administration of exogenous Wnt7b rescued intestinal injury, restored ISC, and reestablished intestinal epithelial homeostasis in mice with NEC. Our findings demonstrate that during NEC, Wnt/ß-catenin signaling is decreased, ISC activity is impaired, and intestinal regeneration is defective. Administration of Wnt resulted in the maintenance of intestinal epithelial homeostasis and avoidance of NEC intestinal injury.
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Enterocolite Necrosante/fisiopatologia , Intestinos/fisiopatologia , Regeneração/fisiologia , Via de Sinalização Wnt , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Enterocolite Necrosante/genética , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Intestinos/efeitos dos fármacos , Intestinos/patologia , Camundongos Endogâmicos C57BL , Modelos Biológicos , Organoides/efeitos dos fármacos , Organoides/metabolismo , Proteínas Proto-Oncogênicas/administração & dosagem , Proteínas Proto-Oncogênicas/farmacologia , Regeneração/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Análise de Sobrevida , Proteínas Wnt/administração & dosagem , Proteínas Wnt/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/genéticaRESUMO
BACKGROUND: Patients at greatest risk of posttransplant lymphoproliferative disorder (PTLD) are those who acquire primary Epstein-Barr virus (EBV) infection after solid organ transplantation. The incidence of PTLD among patients who are EBV-seropositive before transplant is lower, and little is known about the differences in presentation and outcome of this population. We describe the characteristics of EBV-seropositive transplant recipients (R+) who developed PTLD and compare survival outcomes with EBV-seronegative recipients (R-). METHODS: A hospital-based registry was used to identify all patients with biopsy-proven PTLD for the period 2000-2014. Characteristics and outcomes were compared between R+ and R- patients with PTLD. RESULTS: Sixty-nine patients were included, among which 20 (29.0%) were R+ and 49 (71.0%) were R-. Multiorgan transplant patients accounted for 25% of PTLD cases in R+ patients, while accounting for only 2.1% of all transplants during the study period. There was no difference in PTLD site between R+ and R- patients. PTLD among R+ individuals occurred during the second year after transplant (median: 1.92; range: 0.35-3.09 y) compared with during the first year for R- individuals (median: 0.95; range: 0.48-2.92 y; P = 0.380). There was a trend for a higher overall mortality among R+ individuals (log rank: 0.09). PTLD-related mortality did not differ between R+ and R- individuals (log rank: 0.17). CONCLUSIONS: PTLD among R+ individuals was more likely to occur among multiorgan recipients, and there was a tendency for poorer outcomes at 1 and 5 years after the diagnosis of PTLD.
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Infecções por Vírus Epstein-Barr/complicações , Transtornos Linfoproliferativos/diagnóstico , Transplante de Órgãos/efeitos adversos , Adolescente , Biópsia , Criança , Pré-Escolar , Infecções por Vírus Epstein-Barr/sangue , Feminino , Seguimentos , Herpesvirus Humano 4 , Humanos , Terapia de Imunossupressão , Lactente , Estimativa de Kaplan-Meier , Transtornos Linfoproliferativos/mortalidade , Transtornos Linfoproliferativos/virologia , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/virologia , Sistema de Registros , Transplantados , Resultado do TratamentoRESUMO
Juvenile Xanthograuloma (JXG) is part of a diverse set of rare histiocytic disorders marked by infiltration of tissues with neoplastic myelomonocytic-derived cells. Molecular analysis has yielded new insights into the classification and management of histiocytic diseases. A three-year-old presented with atypical croup due to a localized subglottic histiocytic lesion mimicking subglottic hemangioma. The lesion was removed via tracheofissure. Pathology revealed a JXG-like histopathology with a rare KIF5B-ALK fusion gene. This is the first isolated ALK-positive lesion to be reported in this location. The discovery of the new ALK-positive subclass of histiocytosis has opened the door for targeted monoclonal ALK inhibition.
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Hemangioma/diagnóstico , Neoplasias Laríngeas/diagnóstico , Proteínas de Fusão Oncogênica/genética , Xantogranuloma Juvenil/diagnóstico , Pré-Escolar , Diagnóstico Diferencial , Marcadores Genéticos , Humanos , MasculinoRESUMO
Dieulafoy's lesion (DL) is a small gastrointestinal (GI) mucosal erosion due to an abnormally large caliber and persistent submucosal arteriole. Typically occurring in adults, they are an extremely rare cause of GI bleeding in pediatrics. We report a case of multiple jejunal DLs in a 9-year-old girl with posterior fossa brain malformations, hemangiomas, arterial lesions, cardiac abnormalities, eye abnormalities (PHACE) syndrome, and the first described use of rapamycin in the treatment of pediatric DLs.
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Coartação Aórtica/complicações , Malformações Arteriovenosas/etiologia , Anormalidades do Olho/complicações , Hemorragia Gastrointestinal/etiologia , Doenças do Jejuno/etiologia , Jejuno/irrigação sanguínea , Síndromes Neurocutâneas/complicações , Malformações Arteriovenosas/cirurgia , Criança , Endoscopia Gastrointestinal , Feminino , Hemorragia Gastrointestinal/cirurgia , Humanos , Doenças do Jejuno/cirurgiaRESUMO
BACKGROUND: Lymphoid malignancies other than acute lymphoblastic leukemia (ALL) are rare in children with Down syndrome (DS). Information about the toxicity of chemotherapy and prognosis is largely derived from the experience of children with DS and ALL or children without DS. PROCEDURE: We describe the treatment and outcome of two unusual lymphoid malignancies in children with DS. One patient was diagnosed with Burkitt lymphoma (BL) and the second, after treatment for B precursor ALL, with T-cell EBV-positive proliferative disorder (LPD). RESULTS: BL was treated with standard doses of LMB group B therapy subsequently intensified to group C therapy, including high-dose methotrexate (HD-MTX, 3-8 g/m2 ). The patient did not experience excessive toxicity and remains in complete remission 13 months later. Despite presentation with disseminated disease the patient with T-cell EBV-positive LPD after treatment for B precursor ALL responded to dexamethasone and rituximab and remains in complete remission two years later. CONCLUSIONS: Upfront reduction of the high treatment intensity, which is associated with excellent survival outcomes in BL, may not be warranted in all children with DS. Response to therapy and prognosis of T-cell EBV-positive LPD in a patient with DS was not predicted by reported experience in the absence of DS.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma de Burkitt , Síndrome de Down , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/virologia , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Herpesvirus Humano 4 , Humanos , Masculino , Metotrexato/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/virologia , Linfócitos T/virologiaRESUMO
Posttransplant lymphoproliferative disorder (PTLD) is a devastating complication of organ transplant. In a hospital-based registry, we identified biopsy-proven cases of PTLD among children during a 15-year period and reviewed trends in PTLD rates, the sites of involvement, and the associated survival rates. Cases that were included had at least 1 year of follow-up after the diagnosis of PTLD. We studied 82 patients with first-episode PTLD. Median age at diagnosis was 6.4 years (IQR 3.2-12.3 years). The most frequent PTLD sites were tonsillar/adenoidal (T/A [34%]) and gastrointestinal (32%), followed by miscellaneous (defined as less common sites including central nervous system, kidney, lung, and soft tissue [12%]), lymph node (11%), and multisite (11%). Kaplan-Meier survival curves showed that T/A PTLD was associated with decreased all-cause mortality compared with PTLD at other sites (log-rank 0.004), even after adjustment for histological subtype (P = .047). PTLD-related mortality was also decreased among T/A PTLD (log-rank 0.012) but showed a trend toward significance only after adjustment for histological subtype (P = .09). Among first episodes of PTLD, T/A PTLD was associated with a survival advantage compared with PTLD at other sites, even after adjustment for potential confounders. Based on our observations, we propose a clinical categorization of PTLD according to anatomical site of occurrence.