RESUMO
Turner syndrome (45,X) is caused by a complete or partial absence of a single X chromosome. Vascular malformations occur due to abnormal development of blood and/or lymphatic vessels. They arise from either somatic or germline pathogenic variants in the genes regulating growth and apoptosis of vascular channels. Aortic abnormalities are a common, known vascular anomaly of Turner syndrome. However, previous studies have described other vascular malformations as a rare feature of Turner syndrome and suggested that vascular abnormalities in individuals with Turner syndrome may be more generalized. In this study, we describe two individuals with co-occurrence of Turner syndrome and vascular malformations with a lymphatic component. In these individuals, genetic testing of the lesional tissue revealed a somatic pathogenic variant in PIK3CA-a known and common cause of lymphatic malformations. Based on this finding, we conclude that the vascular malformations presented here and likely those previously in the literature are not a rare part of the clinical spectrum of Turner syndrome, but rather a separate clinical entity that may or may not co-occur in individuals with Turner syndrome.
Assuntos
Anormalidades Cardiovasculares , Anormalidades Linfáticas , Síndrome de Turner , Malformações Vasculares , Humanos , Síndrome de Turner/complicações , Síndrome de Turner/genética , Mosaicismo , Anormalidades Linfáticas/genética , Malformações Vasculares/complicações , Malformações Vasculares/genética , Classe I de Fosfatidilinositol 3-Quinases/genéticaRESUMO
Complex lymphatic anomalies are debilitating conditions characterized by aberrant development of the lymphatic vasculature (lymphangiogenesis). Diagnosis is typically made by history, examination, radiology, and histologic findings. However, there is significant overlap between conditions, making accurate diagnosis difficult. Recently, genetic analysis has been offered as an additional diagnostic modality. Here, we describe four cases of complex lymphatic anomalies, all with PIK3CA variants but with varying clinical phenotypes. Identification of PIK3CA resulted in transition to a targeted inhibitor, alpelisib. These cases highlight the genetic overlap between phenotypically diverse lymphatic anomalies.
RESUMO
Mesenteric lymphatic malformations result from abnormal proliferation of disorganized mesenteric lymphatic channels. Sclerotherapy is often preferred over surgery as it is less invasive and has lower post-procedure morbidity. Sclerotherapy has been described as durable and effective with a low complication rate. We describe a serious complication from sclerotherapy of a lymphatic malformation extending from the mesentery through the bowel wall, highlighting the spectrum of this pathology and the need for multidisciplinary management of complex cases.
Assuntos
Cavidade Abdominal , Perfuração Intestinal , Anormalidades Linfáticas , Humanos , Perfuração Intestinal/diagnóstico por imagem , Perfuração Intestinal/etiologia , Perfuração Intestinal/terapia , Anormalidades Linfáticas/diagnóstico por imagem , Anormalidades Linfáticas/terapia , Estudos Retrospectivos , Soluções Esclerosantes/efeitos adversos , Escleroterapia/efeitos adversos , Escleroterapia/métodos , Resultado do TratamentoRESUMO
BACKGROUND: While overall survival for children is greater than that for adults, synovial sarcoma remains an aggressive neoplasm with a potentially poor prognosis, and its magnetic resonance imaging (MRI) findings in children are not well described. OBJECTIVE: We aimed to characterize the spectrum of MRI findings of synovial sarcoma in children with respect to anatomical location and outcome. MATERIALS AND METHODS: Children with histologically confirmed synovial sarcoma and preoperative MRI performed within the past 11 years (2009-2020) were included. Two radiologists retrospectively reviewed each MRI to categorize location, signal characteristics and associated findings. Chi-square and Fisher exact tests were used to assess associations with locations and outcomes. RESULTS: This study included 23 children (13 girls, 10 boys; mean age: 12.7±4.2 years) with 7 axial, 8 proximal and 8 distal appendicular lesions. Kappa ranged from 0.53 to 1. MRI findings differed significantly between locations with axial lesions measuring larger (P=0.01) and more likely to contain fluid levels (P=0.02), triple sign (P=0.02), inhomogeneous signal (T1-weighted images, P=0.003; T2-weighted images, P=0.02, contrast-enhanced images, P=0.03) with all lesions containing partially solid composition (P=0.03). At a median follow-up of 14 months (interquartile range: 7-33 months), 39% relapsed. Predictors of relapse (P<0.05) included metastasis at presentation, larger lesions, axial lesions and MRI findings of fluid level, T1-weighted hyperintensity, inhomogeneous signal (T1- and T2-weighted images) and poorly circumscribed margins. CONCLUSION: A significant association was found between location and MRI findings in our cohort of children with synovial sarcoma. Axial lesions were more likely to be larger, appear heterogeneous and be associated with a worse outcome.
Assuntos
Sarcoma Sinovial , Adolescente , Adulto , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Recidiva Local de Neoplasia , Estudos Retrospectivos , Sarcoma Sinovial/diagnóstico por imagemRESUMO
The addition of contrast US to an existing pediatric US service requires several preparatory steps. This overview provides a guide to simplify the process. Initially, it is important to communicate to all stakeholders the justifications for pediatric contrast US, including (1) its comparable or better diagnostic results relative to other modalities; (2) its reduction in procedural sedation or anesthesia by avoiding MRI or CT; (3) its reduction or elimination of radiation exposure by not having to perform fluoroscopy or CT; (4) the higher safety profile of US contrast agents (UCA) compared to other contrast agents; (5) the improved exam comfort and ease inherent to US, leading to better patient and family experience, including bedside US exams for children who cannot be transported; (6) the need for another diagnostic option in light of increasing demand by parents and providers; and (7) its status as an approved and reimbursable exam. It is necessary to have an UCA incorporated into the pharmacy formulary noting that only SonoVue/Lumason is currently approved for pediatric use. In the United States this UCA is approved for intravenous administration for cardiac and liver imaging and for vesicoureteric reflux detection with intravesical application. In Europe and China it is only approved for the intravesical use in children. All other applications are off-label. The US scanner needs to be equipped with contrast-specific software. The UCA has to be prepared just before the exam and it is important to strictly follow the steps as outlined in the packaging inserts in order to prevent premature destruction of the microbubbles. The initial training in contrast US is best focused on the frontline staff actually performing the US studies; these might be sonographers, pediatric or interventional radiologists, or trainees. It is important from the outset to educate the referring physicians about contrast US. It is helpful to participate in existing contrast US courses, particularly those with hands-on components.
Assuntos
Meios de Contraste , Refluxo Vesicoureteral , Criança , Fluoroscopia , Humanos , Microbolhas , UltrassonografiaRESUMO
Effective surveillance is necessary for early detection of tumors in children with cancer predisposition syndromes. Instituting a surveillance regimen in children comes with practical challenges that include determining imaging modality and timing, and considering cost efficiency, accessibility, and the significant consequences of false-positive and false-negative results. To address these challenges, the American Association for Cancer Research has recently published consensus recommendations that focus on surveillance of cancer predisposition syndromes in children. This review condenses the imaging surveillance recommendations for syndromes that carry a predisposition to renal tumors in childhood, and includes summaries of the predisposition syndromes and discussion of considerations of available imaging modalities.
Assuntos
Predisposição Genética para Doença , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/genética , Criança , Diagnóstico Precoce , Humanos , Vigilância da População , Medição de Risco , Fatores de RiscoRESUMO
Cancer predisposition syndromes increase the incidence of tumors during childhood and are associated with significant morbidity and mortality. Imaging is paramount for ensuring early detection of neoplasms, impacting therapeutic interventions and potentially improving outcome. While conventional imaging techniques involve considerable exposure to ionizing radiation, whole-body MRI is a radiation-free modality that allows continuous imaging of the entire body and has increasingly gained relevance in the surveillance, diagnosis, staging and monitoring of pediatric patients with cancer predisposition syndromes. Nevertheless, widespread implementation of whole-body MRI faces several challenges as a screening tool. Some of these challenges include developing clinical indications, variability in protocol specifications, image interpretation as well as coding and billing practices. These factors impact disease management, patient and family experience and research collaborations. In this discussion we review the aforementioned special considerations and the potential direction that might help overcome these challenges and promote more widespread use of whole-body MRI in children with cancer predisposition syndromes.
Assuntos
Predisposição Genética para Doença , Imageamento por Ressonância Magnética/métodos , Síndromes Neoplásicas Hereditárias/diagnóstico por imagem , Imagem Corporal Total , Criança , Detecção Precoce de Câncer , HumanosRESUMO
BACKGROUND: At fetal MR, congenital lung lesions are usually T2 hyperintense with respect to normal lung parenchyma. Some lesions, however, demonstrate unusual patterns of T2 hypointensity, sometimes in a rosette-like pattern. These lesions usually present a diagnostic conundrum. OBJECTIVE: To evaluate the imaging findings and pathological characterization of fetal solid lung lesions with elements showing T2-hypointense signal with respect to lung. MATERIALS AND METHODS: This is a retrospective study of lung lesions with elements showing T2 hypointensity treated prenatally and postnatally at our center and with available pathological evaluation. Prenatal imaging evaluation included US and MR; postnatal evaluation consisted of pathological examination of the lesion. We also performed prenatal and postnatal chart review. RESULTS: Six cases met study criteria. Areas of decreased echogenicity/T2-hypointense signal were more conspicuous at MR than US. At pathology, these areas correlated with immature parenchymal development and increased mesenchymal tissue. Five of these lesions were congenital pulmonary airway malformations (CPAM); one was a congenital peribronchial myofibroblastic tumor (CPMT). The lesions did not significantly change in size after steroid administration. They were all large in volume and were associated with increased amniotic fluid. All cases of CPAM underwent premature delivery (one of them weeks after fetal surgical resection of the lesion for worsening hydrops); the fetus with CPMT was delivered at term. The neonate with CPMT succumbed shortly after birth secondary to lung hypoplasia; the remaining five neonates survived. CONCLUSION: The differential diagnoses of prenatal lung lesions that contain unusual T2-hypointense elements include CPAM and CPMT. The T2-hypointense areas appear to correlate with increasing degree of immaturity at histology. None of the lesions significantly changed in size after prenatal administration of steroids. All cases with CPAM lesions did well despite persistent polyhydramnios and premature birth. The single case of CPMT, however, resulted in neonatal demise shortly after birth secondary to pulmonary hypoplasia. It is important that fetal radiologists, obstetricians and fetal surgeons alike are aware of these lesions so that appropriate diagnosing and parental counseling can be reached.
Assuntos
Pulmão/anormalidades , Imageamento por Ressonância Magnética/métodos , Anormalidades do Sistema Respiratório/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Diagnóstico Diferencial , Feminino , Humanos , Recém-Nascido , Gravidez , Diagnóstico Pré-Natal , Anormalidades do Sistema Respiratório/patologia , Anormalidades do Sistema Respiratório/cirurgiaRESUMO
Vascular anomalies are malformations or tumors of the blood or lymphatic vasculature and can be life-threatening. Although molecularly targeted therapies can be life-saving, identification of the molecular etiology is often impeded by lack of accessibility to affected tissue samples, mosaicism or insufficient sequencing depth. In a cohort of 356 participants with vascular anomalies, including 104 with primary complex lymphatic anomalies (pCLAs), DNA from CD31+ cells isolated from lymphatic fluid or cell-free DNA from lymphatic fluid or plasma underwent ultra-deep sequencing thereby uncovering pathogenic somatic variants down to a variant allele fraction of 0.15%. A molecular diagnosis, including previously undescribed genetic causes, was obtained in 41% of participants with pCLAs and 72% of participants with other vascular malformations, leading to a new medical therapy for 63% (43/69) of participants and resulting in improvement in 63% (35/55) of participants on therapy. Taken together, these data support the development of liquid biopsy-based diagnostic techniques to identify previously undescribed genotype-phenotype associations and guide medical therapy in individuals with vascular anomalies.
Assuntos
Anormalidades Linfáticas , Malformações Vasculares , Humanos , Mutação , Testes Genéticos/métodos , Malformações Vasculares/diagnóstico , Malformações Vasculares/genética , Malformações Vasculares/terapia , Alelos , Anormalidades Linfáticas/genética , GenômicaRESUMO
Lymphatic malformations are slow-flow vascular anomalies composed of dilated lymphatic channels and cysts of varying sizes. Percutaneous treatments, particularly sclerotherapy, play an important role in the treatment of these lesions, often obviating the need for surgical intervention. Owing to the complex nature of these lesions, a multidisciplinary approach should be used to guide diagnosis and management. This submission focuses on the workup and treatment of pediatric lymphatic malformations at our institution, with a focus on sclerotherapy. Therapeutic outcomes and the management of postprocedural complications are also discussed.