RESUMO
Isolated optic nerve (ON) relapse is a rare occurrence in lymphoblastic leukemia (LBL). A 10-year-old boy with T-LBL presented 8 months after diagnosis with blurred vision and thickening of right ON on magnetic resonance imaging consistent with relapse. Cerebrospinal fluid and bone marrow were negative for leukemia. He received reinduction chemotherapy (including nelarabine and craniospinal radiation) followed by a myeloablative matched sibling donor bone marrow transplant. He remains in remission 2 years post-transplant with normal vision. We also review the literature for reports of isolated ON relapse in patients with LBL. Our patient's clinical course demonstrates that disease control can be achieved with early detection of ON relapse before disease progression.
Assuntos
Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Masculino , Criança , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Transplante de Medula Óssea , Nervo Óptico/patologia , Nervo Óptico/diagnóstico por imagem , Recidiva , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/diagnósticoRESUMO
A wide range of masses develop in the nose, nasal cavity, and nasopharynx in children. These lesions may arise from the nasal ala or other structures of the nose, including the mucosa covering any surface of the nasal cavity, the cartilaginous or osseous portion of the nasal septum, the nasal turbinates, and the nasal bones. Lesions may also arise from the nasopharynx or adjacent structures and involve the nose by way of direct extension. The causes of nasal masses in children include congenital and developmental disorders such as congenital nasolacrimal duct mucocele, dermoid cyst, cephalocele, and nasal neuroglial heterotopia; inflammatory and infectious processes such as mucocele, polyp, and pyogenic granuloma; benign neoplasms such as infantile hemangioma and juvenile nasopharyngeal angiofibroma; malignant lesions such as rhabdomyosarcoma and nasopharyngeal carcinoma; and masses related to prior trauma such as septal hematoma. Although direct visualization, without imaging, is frequently sufficient to diagnose pediatric nasal conditions, in many cases imaging has a key role in the treatment of the affected child. Some of these lesions have characteristic computed tomography and/or magnetic resonance imaging findings, some of them are diagnosed on the basis of the location and imaging findings combined, and others demonstrate nonspecific imaging findings. However, imaging is important for better defining the total extent of the lesion and guiding the clinician in determining whether medical and/or surgical intervention is required. In this article, the authors review the imaging findings of the most common causes-and many of the not-so-common causes-of nasal masses encountered in the pediatric population. ©RSNA, 2017.
Assuntos
Cavidade Nasal/diagnóstico por imagem , Doenças Nasofaríngeas/diagnóstico por imagem , Neuroimagem/métodos , Doenças Nasais/diagnóstico por imagem , Criança , Diagnóstico Diferencial , Humanos , Cavidade Nasal/patologia , Doenças Nasofaríngeas/patologia , Nariz/embriologia , Doenças Nasais/patologiaRESUMO
Aicardi-Goutières syndrome (AGS) is a progressive multisystem disorder including encephalopathy with significant impacts on intellectual and physical abilities. An early diagnosis is becoming ever more crucial, as targeted therapies are emerging. A deep understanding of the molecular heterogeneity of AGS can help guide the early diagnosis and clinical management of patients, and inform recurrence risks. Here, we detail the diagnostic odyssey of a patient with an early presentation of AGS. Exome and genome sequencing detected an intronic RNASEH2B variant missed in a conventional leukodystrophy NGS gene panel. RNA studies demonstrated that a c.322-17 A > G variant affected splicing and caused 16-nucleotide intronic retention in the RNASEH2B transcript, introducing an out-of-frame early termination codon. RNASEH2B expression in the patient's blood was reduced when compared to controls. Our study highlights the pathogenicity of this intronic variant and the importance of its inclusion in variant assessment.
Assuntos
Doenças Autoimunes do Sistema Nervoso , Malformações do Sistema Nervoso , Humanos , Mutação , Doenças Autoimunes do Sistema Nervoso/genética , Malformações do Sistema Nervoso/genética , ExomaRESUMO
In this follow-up report, we present updated information regarding a previously reported pediatric patient with a World Health Organization grade I ganglioglioma harboring a BRAF p.T599dup mutation (Cold Spring Harb Mol Case Stud 4: a002618). This patient, based on our initial finding, is receiving combination targeted therapy with a selective BRAF inhibitor (dabrafenib) plus MEK inhibitor (trametinib). The combination therapy was started after the patient experienced progressive tumor growth and worsening neurological symptoms, including visual changes, headaches, and peripheral neuropathy, despite 9 months of treatment with adjuvant chemotherapy (vinblastine). The patient has been receiving dabrafenib plus trametinib for 15 months and continues to have stable disease as well as improved neurological symptoms. Although combinatorial therapy targeting BRAF and MEK using dabrafenib and trametinib, respectively, is indicated for tumors harboring a BRAF p.V600E/K mutation, our report demonstrates efficacy of this combination in a non-V600E BRAF-mutated tumor. The identification of BRAF alterations may assist clinicians in determining alternative targeted treatment strategies, especially considering the paucity of effective treatments for primary brain tumors and the poor prognosis associated with many central nervous system (CNS) diagnoses. Additional case studies or larger cohort reports will continue to clarify the efficacy of BRAF and/or MEK inhibitors in patients whose tumors harbor a BRAF alteration.
Assuntos
Ganglioglioma/tratamento farmacológico , Ganglioglioma/genética , Imidazóis/uso terapêutico , Mutação , Oximas/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Piridonas/uso terapêutico , Pirimidinonas/uso terapêutico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Estudos de Coortes , Feminino , Ganglioglioma/diagnóstico por imagem , Ganglioglioma/patologia , Humanos , Inibidores de Proteínas Quinases/uso terapêutico , Resultado do TratamentoRESUMO
Primary spinal cord tumors contribute to ≤ 10% of central nervous system tumors in individuals of pediatric or adolescent age. Among intramedullary tumors, spinal ependymomas make up ~ 30% of this rare tumor population. A twelve-year-old male presented with an intradural, extramedullary mass occupying the dorsal spinal canal from C6 through T2. Gross total resection and histopathology revealed a World Health Organization (WHO) grade 2 ependymoma. He recurred eleven months later with extension from C2 through T1-T2. Subtotal resection was achieved followed by focal proton beam irradiation and chemotherapy. Histopathology was consistent with WHO grade 3 ependymoma. Molecular profiling of the primary and recurrent tumors revealed a novel amplification of the MYC (8q24) gene, which was confirmed by fluorescence in situ hybridization studies. Although MYC amplification in spinal ependymoma is exceedingly rare, a newly described classification of spinal ependymoma harboring MYCN (2p24) amplification (SP-MYCN) has been defined by DNA methylation-array based profiling. These individuals typically present with a malignant progression and dismal outcomes, contrary to the universally excellent survival outcomes seen in other spinal ependymomas. DNA methylation array-based classification confidently classified this tumor as SP-MYCN ependymoma. Notably, among the cohort of 52 tumors comprising the SP-MYCN methylation class, none harbor MYC amplification, highlighting the rarity of this genomic amplification in spinal ependymoma. A literature review comparing our individual to reported SP-MYCN tumors (n = 26) revealed similarities in clinical, histopathologic, and molecular features. Thus, we provide evidence from a single case to support the inclusion of MYC amplified spinal ependymoma within the molecular subgroup of SP-MYCN.
Assuntos
Ependimoma/diagnóstico , Proteína Proto-Oncogênica N-Myc , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Coluna Vertebral/diagnóstico , Criança , Ependimoma/genética , Ependimoma/patologia , Humanos , Masculino , Neoplasias da Medula Espinal/genética , Neoplasias da Medula Espinal/patologia , Neoplasias da Coluna Vertebral/genética , Neoplasias da Coluna Vertebral/patologiaRESUMO
Retinoblastoma is a childhood cancer of the retina involving germline or somatic alterations of the RB Transcriptional Corepressor 1 gene, RB1. Rare cases of sellar-suprasellar region retinoblastoma without evidence of ocular or pineal tumors have been described. A nine-month-old male presented with a sellar-suprasellar region mass. Histopathology showed an embryonal tumor with focal Flexner-Wintersteiner-like rosettes and loss of retinoblastoma protein (RB1) expression by immunohistochemistry. DNA array-based methylation profiling confidently classified the tumor as pineoblastoma group A/intracranial retinoblastoma. The patient was subsequently enrolled on an institutional translational cancer research protocol and underwent comprehensive molecular profiling, including paired tumor/normal exome and genome sequencing and RNA-sequencing of the tumor. Additionally, Pacific Biosciences (PacBio) Single Molecule Real Time (SMRT) sequencing was performed from comparator normal and disease-involved tissue to resolve complex structural variations. RNA-sequencing revealed multiple fusions clustered within 13q14.1-q21.3, including a novel in-frame fusion of RB1-SIAH3 predicted to prematurely truncate the RB1 protein. SMRT sequencing revealed a complex structural rearrangement spanning 13q14.11-q31.3, including two somatic structural variants within intron 17 of RB1. These events corresponded to the RB1-SIAH3 fusion and a novel RB1 rearrangement expected to correlate with the complete absence of RB1 protein expression. Comprehensive molecular analysis, including DNA array-based methylation profiling and sequencing-based methodologies, were critical for classification and understanding the complex mechanism of RB1 inactivation in this diagnostically challenging tumor.
Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Proteínas de Ligação a Retinoblastoma/genética , Retinoblastoma/genética , Retinoblastoma/patologia , Ubiquitina-Proteína Ligases/genética , Rearranjo Gênico , Genes do Retinoblastoma/genética , Humanos , Lactente , Masculino , Proteínas de Fusão OncogênicaRESUMO
Clinical observation suggests that the number of serious epidural catheter-associated infections have increased recently in children. This increase is likely attributed to an increase in reporting and in frequency of epidural analgesia usage. Estimates of infection rates are difficult to determine primarily because of insufficient study of large pediatric populations. In this retrospective study, the authors investigated the incidence of epidural catheter-associated soft tissue and epidural infections after use of continuous epidural analgesia spanning 17 yr. A total of 10,653 epidural catheters were used in 7,792 children. The majority of catheters, 10,437 (98%), were placed for the management of postoperative pain, and 216 (2%) were placed for the management of chronic pain. The authors identified 13 cases of infections (nine cellulitis, two paravertebral musculature infections, one epidural inflammation, and one epidural abscess) between 3 and 11 days after catheter insertion. The incidence of infection was significantly higher in patients treated for chronic pain (7 of 216 = 3.2%) compared with postoperative pain (6 of 10,437 = 0.06%; P < 0.0001). Surgical drainage of subcutaneous pus was performed in three patients, and medical therapy was administered in the remainder of patients; all patients recovered without sequelae. Although rare, epidural catheter-associated infections remain a serious concern in high-risk children who may benefit the most from epidural analgesia. The findings of the authors support the low rate of epidural infection previously reported despite growing concerns of serious infections in children. These findings highlight the importance of vigilance to early diagnostic indicators of infection and provide practitioners and families with incidence data to guide informed medical decision-making.
Assuntos
Analgesia Epidural/efeitos adversos , Analgesia Epidural/estatística & dados numéricos , Infecções Relacionadas a Cateter/epidemiologia , Infecção Hospitalar/epidemiologia , Adolescente , Boston/epidemiologia , Infecções Relacionadas a Cateter/etiologia , Criança , Pré-Escolar , Infecção Hospitalar/etiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Estudos RetrospectivosRESUMO
INTRODUCTION: Avascular necrosis (AVN) of the femoral head remains a major complication in the treatment of developmental dysplasia of the hip (DDH) in infants. We performed a retrospective analysis to look at the predictive ability of postclosed reduction contrast-enhanced magnetic resonance imaging (MRI) for AVN after closed reduction in DDH. METHODS: Twenty-eight hips in 27 infants (aged 1-11 months) with idiopathic hip dislocations who had failed brace treatment underwent closed reduction +/- adductor tenotomy and spica cast application under general anesthesia. Magnetic resonance imaging of the hips after intravenous gadolinium contrast injection for evaluation of epiphyseal perfusion was obtained immediately after cast application. Patients were followed with serial radiographs for a minimum of 1 year after closed reduction. Presence of AVN was determined by the presence of any one of the 5 Salter criteria by 2 readers. Magnetic resonance imaging was graded as normal, asymmetric enhancement, focal decreased enhancement, or global decreased enhancement by 2 radiologists. RESULTS: Six (21%) of 28 hips showed evidence of clinically significant AVN on follow-up radiographs. Fifty percent of the hips with AVN, but only 2 of 22 hips without AVN, showed a global decreased MRI enhancement (P < 0.05, Fisher exact test). Multivariate logistic regression indicated that a global decreased enhancement was associated with a significantly higher risk of developing AVN (P < 0.01), independently of age at reduction (P = 0.02) and abduction angle. CONCLUSIONS: In addition to accurate anatomical assessment of a closed reduction in DDH, gadolinium-enhanced MRI provides information about femoral head perfusion that may be predictive for future AVN. At present, it is premature to use the perfusion information for routine clinical use. However, it opens the door to studies looking at repositioning or alternative reduction methods that may reduce the risk of AVN in this higher risk group.
Assuntos
Necrose da Cabeça do Fêmur/diagnóstico , Luxação Congênita de Quadril/cirurgia , Imageamento por Ressonância Magnética/métodos , Complicações Pós-Operatórias/diagnóstico , Fatores Etários , Feminino , Necrose da Cabeça do Fêmur/etiologia , Seguimentos , Gadolínio , Humanos , Lactente , Modelos Logísticos , Masculino , Análise Multivariada , Complicações Pós-Operatórias/etiologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de RiscoRESUMO
Developmental delay (DD) affects approximately 1% to 3% of all children in the United States. This diagnosis significantly impedes quality of life and full participation in the life of the family, school, and community. In this setting, the clinician's ability to detect, diagnose, and possibly treat the cause for DD in a timely manner depends on a multimodality approach to neuroimaging and a robust understanding of the various imaging algorithms aimed at determining the etiology of disease, structural and/or anatomic defects, functional activity, metabolic profiles, and genetic characteristics. Taken separately and in combination, these features are effectively depicted and analyzed using an array of brain imaging modalities: ultrasound, computed tomography, nuclear medicine, magnetic resonance (MR) spectroscopy, and a growing mix of sophisticated MR imaging (MRI) techniques, including diffusion-weighted imaging, diffusion tensor imaging, perfusion MRI, and functional MRI. Thus, equipped with these advanced imaging capabilities, pediatric neurologists and neuroradiologists are now positioned to diagnose with greater accuracy and speed; this, in turn, results in more effective treatment plans and improved patient outcomes as measured by progress in reaching developmental milestones and in ameliorating secondary conditions such as seizures, poor motor control, incontinence, and impulsivity. The purpose of this article is to present the numerous causes of pediatric DD, describe their respective neuroimaging findings, discuss various neuroimaging approaches for elucidating etiology, and offer specific guidelines for optimizing imaging results in the setting of multimodality imaging capabilities.
Assuntos
Encefalopatias/diagnóstico , Deficiências do Desenvolvimento/diagnóstico , Diagnóstico por Imagem , Algoritmos , Encefalopatias/fisiopatologia , Criança , Meios de Contraste , Deficiências do Desenvolvimento/fisiopatologia , Humanos , Imageamento por Ressonância Magnética/métodosRESUMO
Phenotypic analysis of mutant mice is limited by lack of accurate, simple, and nondestructive in utero imaging techniques. This study evaluated the usefulness of ultrasound imaging (US) to stage fetal mouse gestational age (GA) and depict morphologic development. We imaged 16 pregnant CD-1 mice and a total of 92 fetuses with a 15-MHz US transducer from 9.5 d postcoitus (DPC) until 20.5 DPC or delivery. Parameters recorded included gestational sac dimensions, crown-rump length (CRL), biparietal diameter (BPD), thoracoabdominal diameter (TAD), onset of cardiac activity, and morphologic development. At 9.5 d DPC, all gestations appeared as rounded sacs, with a diameter (mean +/- standard error) of 4.4 +/- 1 mm. BPD, CRL, and GA were highly correlated. The following structures were first identifiable at the following GA: cardiac activity, 10.5 DPC; major cardiovascular structures, 11.5 DPC; limb buds, 10.5 DPC; spine, 12.5 DPC; face and skull ossification, 13.5 DPC; rib ossification, 15.5 DPC; hind- and forelimb digits, 15.5 DPC; stomach and urinary bladder, 17.5 DPC; visualization of the rhombencephalic vesicle, 13.5 DPC; and visualization of the lateral ventricles, 14.5 DPC. The echogenic lungs were distinct from the liver as early as 12.5 DPC. The circle of Willis was detectable with color Doppler as early as 13.5 DPC and was easily visualized at 15.5 DPC. We found that US provides accurate, simple staging criteria for fetal mouse gestational development after 9.5 DPC and may be a nondestructive means of documenting phenotypic alterations in mutant mice in utero.
Assuntos
Desenvolvimento Embrionário/fisiologia , Desenvolvimento Fetal/fisiologia , Idade Gestacional , Prenhez , Ultrassonografia Pré-Natal/veterinária , Animais , Feminino , Camundongos , Gravidez , Reprodutibilidade dos Testes , Ultrassonografia Pré-Natal/instrumentação , Ultrassonografia Pré-Natal/métodosRESUMO
OBJECT: Intrasacral meningoceles are rare cystic lesions that can cause focal compression within the bony sacral canal. Their mechanisms are poorly understood, but most intrasacral meningoceles appear to be intrasacral extradural cysts caused by arachnoid herniating through a small dural defect in the caudal end of the thecal sac. As opposed to perineural cysts, they are not associated with an exiting nerve root. When symptomatic, they can cause sacral pain or sacral nerve root dysfunction due to local compression. METHODS: This is a retrospective series from Boston Children's Hospital. All patients in whom symptomatic intrasacral meningocele that required surgical treatment was diagnosed between May 1994 and March 2011 were included in the study. Spine MRI was the diagnostic modality of choice. All patients underwent sacral exploration, with ligation and obliteration of the cyst. Resected cyst wall was subjected to pathological examination. RESULTS: There were 13 patients (11 boys and 2 girls) who underwent operation for intrasacral meningocele. The median age was 8 years (range 5 months-16 years). The most common presenting symptom was back pain (in 5) often described as deep tail bone pain, followed by urinary incontinence (3) and constipation (2). Three patients had evidence of associated tethered cord on MRI studies. Four patients were asymptomatic and their diagnosis was made following imaging for other reasons; they were surgically treated because of the increasing size of the lesion or association with other congenital lesions. Most patients had symptomatic improvement after surgery. CONCLUSIONS: Intrasacral meningoceles are rare lesions that may result from a congenital dural weakness and a resultant arachnoid diverticulum. They present in childhood either incidentally or with symptoms secondary to nerve root compression. Identification of the point of herniation through the dura mater and ligation of the lesion provides cyst cure and resolution of symptoms in most patients.
Assuntos
Aracnoide-Máter/anormalidades , Imageamento por Ressonância Magnética , Meningocele/diagnóstico , Meningocele/cirurgia , Sacro , Adolescente , Dor nas Costas/etiologia , Boston , Criança , Pré-Escolar , Constipação Intestinal/etiologia , Feminino , Humanos , Imageamento Tridimensional , Achados Incidentais , Lactente , Imageamento por Ressonância Magnética/métodos , Masculino , Meningocele/complicações , Meningocele/patologia , Mielografia , Defeitos do Tubo Neural/etiologia , Procedimentos Neurocirúrgicos/métodos , Estudos Retrospectivos , Espinha Bífida Oculta/complicações , Espinha Bífida Oculta/diagnóstico , Cistos de Tarlov/diagnóstico , Cistos de Tarlov/etiologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Incontinência Urinária/etiologiaRESUMO
OBJECTIVE: Our purpose was to evaluate the imaging characteristics and clinical outcomes of children less than 5 years old who underwent surgery for presumed appendicitis. CONCLUSION: Appendicitis is not rare in young children and imaging findings reflect the high frequency of perforation in this population.
Assuntos
Apendicite/diagnóstico por imagem , Adolescente , Fatores Etários , Apendicite/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , UltrassonografiaRESUMO
Appendicitis is the most common condition requiring intraabdominal surgery in infancy and childhood. Yet, despite its common occurrence, accurate diagnosis remains challenging. Acute appendicitis may be missed at initial clinical examination in 28%-57% of children aged 12 years and younger and in nearly 100% of children under the age of 2 years. Diagnostic imaging has an ever-increasing role in the prompt and accurate diagnosis of acute appendicitis in the pediatric population. At the authors' institution, helical computed tomography (CT) is the primary tool for diagnosing or excluding appendicitis in children. Since its inception in 1998, helical CT with rectally administered contrast material has been shown to reduce the total number of inpatient observation days, laparotomies with negative findings, and per-patient cost. Helical CT is a highly sensitive and specific tool for diagnosing pediatric appendicitis and has resulted in a beneficial change in patient care in 68.5% of all patients seen in the authors' emergency department for suspected appendicitis. This includes both those patients who receive an eventual diagnosis of appendicitis and those who do not have the disease. Major strengths of limited helical CT with rectal contrast material include producing uniformly high published sensitivity and specificity values for diagnosis of appendicitis and enabling diagnosis of alternative conditions of acute abdominal pain in children. In contrast, limitations of graded-compression ultrasonography in children include highly operator-dependent sensitivity and specificity values and relative infrequency with which the normal appendix can be visualized in this population. Although there have been many exciting diagnostic advancements for the diagnosis of acute appendicitis in the pediatric population, the role of helical CT is far from clear. The purpose of this article is to describe a helical CT approach to imaging in children suspected of having acute appendicitis at a large urban pediatric teaching hospital and its effects on patient outcomes and hospital costs.