Manejo de Linfangioma en la edad pediátrica: presentación de caso / Management of Lymphangioma in pediatric age: case presentation / Manejo do Linfangioma em idade pediátrica: apresentação de caso

Las malformaciones vasculares congénitas afectan con mayor frecuencia al sistema tegumentario y se hacen evidentes al nacer o en las primeras semanas de vida con una prevalencia estimada del 4,5%. Las anomalías linfáticas, suelen tener una presentación variable, y en la mayoría de ocasiones su manejo se convierte en un desafío. Se estima que su incidencia global oscila entre 1 en 2.000 y 1 en 16.0004,5 casos. Objetivo: Determinar la importancia de un adecuado manejo por cirugía vascular en el contexto de un paciente pediátrico con Linfangioma en miembro inferior tomando como metodología la presentación de un caso clínico. Descripción del caso: Paciente de 7 meses de edad sin antecedentes clínicos o quirúrgicos de interés, quien es traído por su madre a consulta de cirugía vascular por presencia de masa en miembro inferior derecho que progresivamente ha mostrado crecimiento, cuadro que se acompaña de tumefacción en partes blandas y roce o dolor a la distensión en la zona de la malformación, de acuerdo a la clasificación de Mulliken y Glowacki se concluye que se trata de un Linfangioma, diagnóstico que se corroboró por ultrasonografía Doppler, Angiotac y flebografía ascendente. Para su manejo se realizó drenaje percutáneo ecoguiado y escleroterapia mediante espuma de polidocanol al 1% para sellar la malformación vascular, obteniendo mejoría clínica con resultados estéticos y funcionales satisfactorios. Conclusión: El Linfangioma es una malformación vascular poco frecuente que no se ha documentado localmente, por lo tanto, la presentación de este caso pretendió proporcionar información científica actualizada sobre el tratamiento de la patología vascular y abogar por un manejo basado en la evidencia médica existente, que contribuya a resultados favorables para los pacientes pediátricos

Congenital vascular malformations most frequently affect the integumentary system and become evident at birth or in the first weeks of life with an estimated prevalence of 4.5%. Lymphatic anomalies usually have a variable presentation, and in most cases their management becomes a challenge. Its global incidence is estimated to range between 1 in 2,000 and 1 in 16,0004.5 cases. Objective: Determine the importance of adequate management by vascular surgery in the context of a pediatric patient with Lymphangioma in the lower limb using the presentation of a clinical case as a methodology. Description of the case: A 7-monthold patient with no clinical or surgical history of interest, who was brought by his mother to a vascular surgery consultation due to the presence of a mass in the right lower limb that has progressively shown growth, a condition that is accompanied by swelling in the soft tissues and friction or pain upon distension in the area of the malformation, according to the classification of Mulliken and Glowacki, it is concluded that it is a Lymphangioma, a diagnosis that was confirmed by Doppler ultrasonography, Angiotac and ascending phlebography. For its management, ultrasound-guided percutaneous drainage and sclerotherapy using 1% polidocanol foam was performed to seal the vascular malformation, obtaining clinical improvement with satisfactory aesthetic and functional results. Conclusion: Lymphangioma is a rare vascular malformation that has not been documented locally, therefore, the presentation of this case aimed to provide updated scientific information on the treatment of vascular pathology and advocate management based on existing medical evidence. that contributes to favorable outcomes for pediatric patients

As malformações vasculares congênitas afetam mais frequentemente o sistema tegumentar e tornam-se evidentes ao nascimento ou nas primeiras semanas de vida, com prevalência estimada em 4,5%. As anomalias linfáticas costumam ter apresentação variável e na maioria dos casos seu manejo torna-se um desafio. Estima-se que sua incidência global varie entre 1 em 2.000 e 1 em 16.0004,5 casos. Objetivo: Determinar a importância do manejo adequado por cirurgia vascular no contexto de um paciente pediátrico com Linfangioma em membro inferior utilizando como metodologia a apresentação de um caso clínico. Descrição do caso: Paciente de 7 meses, sem antecedentes clínicos ou cirúrgicos de interesse, que foi trazido pela mãe à consulta de cirurgia vascular devido à presença de uma massa no membro inferior direito que apresentava crescimento progressivo, quadro que vem acompanhado de inchaço nos tecidos moles e fricção ou dor à distensão na área da malformação, segundo a classificação de Mulliken e Glowacki, conclui-se que se trata de um Linfangioma, diagnóstico que foi confirmado por Ultrassonografia Doppler, Angiotac e flebografia ascendente. Para seu manejo foi realizada drenagem percutânea guiada por ultrassom e escleroterapia com espuma de polidocanol a 1% para selar a malformação vascular, obtendo melhora clínica com resultados estéticos e funcionais satisfatórios. Conclusão: O linfangioma é uma malformação vascular rara e não documentada localmente, portanto, a apresentação deste caso teve como objetivo fornecer informação científica atualizada sobre o tratamento da patologia vascular e defender uma gestão baseada na evidência médica existente que contribua para resultados favoráveis para a pediatria. pacientes

Manejo de Linfangioma en la edad pediátrica: presentación de caso

Las malformaciones vasculares congénitas afectan con mayor frecuencia al sistema tegumentario y se hacen evidentes al nacer o en las primeras semanas de vida con una prevalencia estimada del 4,5%. Las anomalías linfáticas, suelen tener una presentación variable, y en la mayoría de ocasiones su manejo se convierte en un desafío. Se estima que su incidencia global oscila entre 1 en 2.000 y 1 en 16.0004,5 casos. Objetivo: Determinar la importancia de un adecuado manejo por cirugía vascular en el contexto de un paciente pediátrico con Linfangioma en miembro inferior tomando como metodología la presentación de un caso clínico. Descripción del caso: Paciente de 7 meses de edad sin antecedentes clínicos o quirúrgicos de interés, quien es traído por su madre a consulta de cirugía vascular por presencia de masa en miembro inferior derecho que progresivamente ha mostrado crecimiento, cuadro que se acompaña de tumefacción en partes blandas y roce o dolor a la distensión en la zona de la malformación, de acuerdo a la clasificación de Mulliken y Glowacki se concluye que se trata de un Linfangioma, diagnóstico que se corroboró por ultrasonografía Doppler, Angiotac y flebografía ascendente. Para su manejo se realizó drenaje percutáneo ecoguiado y escleroterapia mediante espuma de polidocanol al 1% para sellar la malformación vascular, obteniendo mejoría clínica con resultados estéticos y funcionales satisfactorios. Conclusión: El Linfangioma es una malformación vascular poco frecuente que no se ha documentado localmente, por lo tanto, la presentación de este caso pretendió proporcionar información científica actualizada sobre el tratamiento de la patología vascular y abogar por un manejo basado en la evidencia médica existente, que contribuya a resultados favorables para los pacientes pediátricos.

Congenital vascular malformations most frequently affect the integumentary system and become evident at birth or in the first weeks of life with an estimated prevalence of 4.5%. Lymphatic anomalies usually have a variable presentation, and in most cases their management becomes a challenge. Its global incidence is estimated to range between 1 in 2,000 and 1 in 16,0004.5 cases. Objective: Determine the importance of adequate management by vascular surgery in the context of a pediatric patient with Lymphangioma in the lower limb using the presentation of a clinical case as a methodology. Description of the case: A 7-month-old patient with no clinical or surgical history of interest, who was brought by his mother to a vascular surgery consultation due to the presence of a mass in the right lower limb that has progressively shown growth, a condition that is accompanied by swelling in the soft tissues and friction or pain upon distension in the area of the malformation, according to the classification of Mulliken and Glowacki, it is concluded that it is a Lymphangioma, a diagnosis that was confirmed by Doppler ultrasonography, Angiotac and ascending phlebography. For its management, ultrasound-guided percutaneous drainage and sclerotherapy using 1% polidocanol foam was performed to seal the vascular malformation, obtaining clinical improvement with satisfactory aesthetic and functional results. Conclusion: Lymphangioma is a rare vascular malformation that has not been documented locally, therefore, the presentation of this case aimed to provide updated scientific information on the treatment of vascular pathology and advocate management based on existing medical evidence. that contributes to favorable outcomes for pediatric patients.

As malformações vasculares congênitas afetam mais frequentemente o sistema tegumentar e tornam-se evidentes ao nascimento ou nas primeiras semanas de vida, com prevalência estimada em 4,5%. As anomalias linfáticas costumam ter apresentação variável e na maioria dos casos seu manejo torna-se um desafio. Estima-se que sua incidência global varie entre 1 em 2.000 e 1 em 16.0004,5 casos. Objetivo: Determinar a importância do manejo adequado por cirurgia vascular no contexto de um paciente pediátrico com Linfangioma em membro inferior utilizando como metodologia a apresentação de um caso clínico. Descrição do caso: Paciente de 7 meses, sem antecedentes clínicos ou cirúrgicos de interesse, que foi trazido pela mãe à consulta de cirurgia vascular devido à presença de uma massa no membro inferior direito que apresentava crescimento progressivo, quadro que vem acompanhado de inchaço nos tecidos moles e fricção ou dor à distensão na área da malformação, segundo a classificação de Mulliken e Glowacki, conclui-se que se trata de um Linfangioma, diagnóstico que foi confirmado por Ultrassonografia Doppler, Angiotac e flebografia ascendente. Para seu manejo foi realizada drenagem percutânea guiada por ultrassom e escleroterapia com espuma de polidocanol a 1% para selar a malformação vascular, obtendo melhora clínica com resultados estéticos e funcionais satisfatórios. Conclusão: O linfangioma é uma malformação vascular rara e não documentada localmente, portanto, a apresentação deste caso teve como objetivo fornecer informação científica atualizada sobre o tratamento da patologia vascular e defender uma gestão baseada na evidência médica existente que contribua para resultados favoráveis para a pediatria. pacientes.

Differential Diagnosis of Generalized Cystic Lymphangiomatosis: A Literature Review.

BACKGROUND: Generalized cystic lymphangiomatosis (GCL) is a rare disease characterized by the widespread proliferation of lymphatic vessels, often seen in the pediatric patient group. Imaging techniques are instrumental in revealing the extent and morphological features of the disease. OBJECTIVE: The objective of this study is to interpret the radiological findings of GCL and address the differential diagnosis between GCL and other lymphatic malformations in light of the relevant literature data. METHODS: The sample of this retrospective study consisted of six pediatric patients, four males and two females, diagnosed with GCL based on clinical, radiological, and histopathological findings between 2015 and 2022. The age of the patients at the time of diagnosis and their symptoms at admission were obtained from the hospital database. Radiological imaging findings were evaluated in detail based on the involved systems (thorax, abdomen, and musculoskeletal). RESULTS: The median age of the sample, 4/6 were male, was 9 years at admission (min. 3, max. 12). The most common symptom at admission was dyspnea, often accompanied by pleural effusion. Bone involvement was the most common extrathoracic finding. Abdominal involvement was primarily asymptomatic, and the spleen was the most frequently involved organ in the abdomen. CONCLUSION: The diagnosis of GCL is challenging because of its rarity and overlapping diseases. Whole-body magnetic resonance imaging is a valuable tool as it reveals the typical radiological features of GCL and how far it has spread throughout the body.

Sirolimus treatment for intractable lymphatic anomalies: an open-label, single-arm, multicenter, prospective trial.

Introduction: Intractable lymphatic anomalies (LAs) include cystic lymphatic malformation (LM; macrocystic, microcystic, or mixed), generalized lymphatic anomaly, and Gorham-Stout disease. LAs can present with severe symptoms and poor prognosis. Thus, prospective studies for treatments are warranted. We conducted a prospective clinical trial of sirolimus for intractable LAs. Methods: This was an open-label, single-arm, multicenter, prospective trial involving five institutions in Japan. All patients with LAs received oral sirolimus once daily, and the dose was adjusted to ensure that the trough concentration remained within 5-15 ng/mL. We prospectively assessed the drug response (response rate for radiological volumetric change in target lesion), performance state, change in respiratory function, visceral impairment (pleural effusion, ascites, bleeding, pain), laboratory examination data, quality of life (QOL), and safety at 12, 24, and 52 weeks of administration. Results: Eleven patients with LAs (9 generalized lymphatic anomaly, 1 cystic LM, 1 Gorham-Stout disease) were treated with sirolimus, of whom 6 (54.5%; 95% confidence interval: 23.4-83.3%) demonstrated a partial response on radiological examination at 52 weeks of administration. No patients achieved a complete response. At 12 and 24 weeks of administration, 8 patients (72.7%) already showed a partial response. However, patients with stable disease showed minor or no reduction after 12 weeks. Adverse events, such as stomatitis, acneiform dermatitis, diarrhea, and fever, were common with sirolimus. Sirolimus was safe and tolerable. Conclusion: Sirolimus can reduce the lymphatic tissue volume in LAs and may lead to improvements in clinical symptoms and QOL.

Challenging diagnosis of Kaposiform lymphangiomatosis: Unveiling a rare primary lymphatic disorder.

Kaposiform lymphangiomatosis (KLA) is a rare and complex lymphatic anomaly associated with substantial morbidity and mortality. It features diffuse and multifocal malformed lymphatic channels, often leading to diagnostic difficulties due to its uncommon occurrence and non-specific clinical presentation. This case report emphasizes the crucial role of expert radiologists in accurately diagnosing a challenging KLA case initially mistaken for a neoplasm.

Generalized lymphatic anomaly in adult patients: An eminently radiological diagnosis.

Generalized lymphatic anomaly (GLA) is an uncommon congenital disease secondary to the proliferation of lymphatic vessels in any organ except the central nervous system. GLA has a wide spectrum of clinical and radiological presentations, among which osteolytic lesions are the most widespread, being the ribs the most commonly affected bone. GLA is diagnosed mainly in children and young adults; nevertheless, on rare occasions it can remain asymptomatic and be detected incidentally in older patients. We present an unusual case of GLA in an asymptomatic 54-year-old man who had atypically distributed, purely cystic bone lesions on CT; measuring the Hounsfield (HU) of these lesions enabled us to suspect GLA. This suspicion was confirmed with MRI, PET/CT, CT-guided fine-needle aspiration biopsy, and fluoroscopy-guided percutaneous vertebral biopsy. After surgical resection of one of the lesions, histologic study provided the definitive diagnosis.

Pathogenic variants in PIK3CA are associated with clinical phenotypes of kaposiform lymphangiomatosis, generalized lymphatic anomaly, and central conducting lymphatic anomaly.

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.

Kaposiform lymphangiomatosis: Diagnosis, pathogenesis, and treatment.

Kaposiform lymphangiomatosis (KLA) is a life-threatening rare disease that can cause substantial morbidity, mortality, and social burdens for patients and their families. Diagnosis often occurs long after initial symptoms, and there are few centers in the world with the expertise to diagnose and care for patients with the disease. KLA is a lymphatic anomaly and significant advancements have been made in understanding its pathogenesis and etiology since its first description in 2014. This review provides multidisciplinary, comprehensive, and state-of-the-art information on KLA patient presentation, diagnostic imaging, pathology, organ involvement, genetics, and pathogenesis. Finally, we describe current therapeutic approaches, important areas for research, and challenges faced by patients and their families. Further insights into the pathogenesis of KLA may advance our understanding of other vascular anomalies given that similar signaling pathways may be involved.

Multicompartment Dynamic Contrast Magnetic Resonance Lymphangiography in Diagnosis of Complicated Lymphatic Anomaly.

Background: To describe the dynamic contrast magnetic resonance lymphangiography (DCMRL) findings of three patients with complicated lymphatic anomaly (CLA) and protein losing enteropathy. We further discuss the importance of a multicompartment (intrahepatic [IH], intramesenteric [IM], and intranodal [IN]) DCMRL in delineating central lymphatic flow pathologies. Methods and Results: This is a retrospective study of three patients-one adult and two children who individually underwent the three-compartment DCMRL, namely IN-DCMRL, IH-DCMRL, and IM-DCMCRL. Findings from the results of the DCMRL for these three patients were obtained from the medical records and compared. Using the multicompartment imaging modalities, chylous fluid leakage into the peritoneum was observed using IM-DCMRL and IH-DCMRL but not IN-DCMRL for one of the patients in the case series. In contrast, leakage of chyle into the mediastinum was noted using IN-DCMRL but not IH-DCMRL and IM-DCMRL on another patient in this case series. Conclusion: Owing to the variability in outlining lymphatic flow pathologies, multicompartment imaging gives a more global picture of individual conduction disorders, has the potential to improve clinical assessment, and in some cases leads to a diagnosis of the abnormality and thus provides a better understanding of lymphatic flow anomalies in patients with CLAs.

Genetic Variants in Genes Correlated to the PI3K/AKT Pathway: The Role of ARAP3, CDH5, KIF11 and RELN in Primary Lymphedema.

Genetic anomalies affecting lymphatic development and function can lead to lymphatic dysfunction, which could manifest as lymphedema. Understanding the signaling pathways governing lymphatics function is crucial for developing targeted diagnostic and therapeutic interventions. This study aims to characterize genetic variants in genes involved in the PI3K/AKT signaling pathway, which plays a critical role in lymphangiogenesis. 408 patients diagnosed with primary lymphedema were sequenced using a next-generation sequencing (NGS) gene panel composed of 28 diagnostic genes and 71 candidate genes. The analysis revealed six variants in genes RELN, ARAP3, CDH5, and KIF11. Five of these variants have never been reported in the literature. All these genes have been correlated to lymphatic activity and are involved in the PI3K/ AKT pathway. As the PI3K/AKT signaling pathway plays an essential role in lymphangiogenesis and lymphatic function, genetic variants in genes correlated to this pathway could lead to lymphedema. Our findings underscore the potential of the PI3K/AKT pathway in lymphedema pathogenesis, supporting the role of RELN, ARAP3, CDH5,, and KIF11 as diagnostic and therapeutic targets.

An Updated Classification of Primary Lymphedema Based on Age of Onset, Lymphatic Anomalies, and Genetics.

Primary lymphedema (PLE) is a chronic disease caused by lymphatic dysplasia and progresses to irreversible tissue edema and hypertrophy. Understanding of PLE has been hitherto limited. The aim of this study is to devise an updated classification system for PLE of 1013 patients with PLE of lower limb were enrolled. Sex, age of onset, location, family history and morbidity were documented. The lymphatic imaging findings of magnetic reso-nance lymphography (MRL), indocyanine green lymphography (ICGL) and lymphoscin-tigraphy (LSG), skin tissue immunohisto-chemical staining, whole exome sequencing and the correlation of genotype-phenotype were evaluated. Patients were divided into a congenital onset category and a late onset category. The late onset category was further divided according to developmental age. The ratio of congenital-onset to late-onset PLE was 1:4 and that the highest incidence was in adolescence. The sex ratio was 1.04:1 and 1.5:1 in congenital-onset and late-onset groups, respectively. Three major lymphatic anomalies were identified, in which segmental lymphatic dysfunction, characterized by delayed or partial demonstration of lymph vessels, is the most common and associated with FLT4, GJC2, CELSR1, and PTPN14 mutations. The next most common type is lymphatic hyperplasia, which is associated with FOXC2 and GATA2 variants, followed by initial lymphatic aplasia or dysfunction, which is more common in pa-tients with congenital PLE and associated with FLT4 mutation. A functional and structural combined classification of lymphatic anomalies is proposed, which includes segmental lymphatic dysfunction, lymphatic hyperplasia and initial lymphatic aplasia or dysfunction.

Lymphatic anomalies during lifetime in patients with Noonan syndrome: Retrospective cohort study.

Noonan syndrome (NS) has been associated with an increased risk of lymphatic anomalies, with an estimated prevalence of 20%. The prevalence of lymphatic anomalies seems to differ between pathogenic variants. Therefore, this study aims to describe the clinical presentation, prevalence and genotype-phenotype correlations of lymphatic anomalies during life in patients with NS. This retrospective cohort study included patients (n = 115) who were clinically and genetically diagnosed with NS and visited the Noonan expertise Center of the Radboud University Medical Center between January 2015 and March 2021. Data on lymphatic anomalies during lifetime were obtained from medical records. Lymphatic anomalies most often presented as an increased nuchal translucency, chylothorax and/or lymphedema. Prenatal lymphatic anomalies increased the risk of lymphatic anomalies during infancy (OR 4.9, 95% CI 1.7-14.6). The lifetime prevalence of lymphatic anomalies was 37%. Genotype-phenotype correlations showed an especially high prevalence of lymphatic anomalies during infancy and childhood in patients with a pathogenic SOS2 variant (p = 0.03 and p < 0.01, respectively). This study shows that patients with NS have a high predisposition for developing lymphatic anomalies during life. Especially patients with prenatal lymphatic anomalies have an increased risk of lymphatic anomalies during infancy. Genotype-phenotype correlations were found in pathogenic variants in SOS2.

Cellular variant of kaposiform lymphangiomatosis: a report of three cases, expanding the morphologic and molecular genetic spectrum of this rare entity.

Kaposiform lymphangiomatosis (KLA) is a very rare form of generalized lymphatic anomaly, consisting of a diffuse proliferation of abnormal, dilated lymphatics, and small fascicles of hemosiderin-laden spindled lymphatic endothelial cells. KLA occurs in children and young adults and may present with multicentric disease, pleural and pericardial effusions, and life-threatening coagulopathy. Genetically, KLA most often harbors somatic activating mutations in NRAS. We recently encountered 3 cases of KLA with cellular features, resembling kaposiform hemangioendothelioma (KHE), and studied their clinicopathologic, radiologic, and molecular genetic features. The patients (1 male, 2 females; aged 2 years, 2 months, 4 years) presented with multicentric disease involving skin, soft tissue, bone, and spleen and thrombocytopenia/coagulopathy. Advanced imaging studies confirmed multicentric disease. Biopsies (skin, soft tissue, bone, and spleen) demonstrated both conventional KLA and much more cellular foci, consisting of sheets, nodules, glomeruloid structures, and sieve-like arrays of lymphatic endothelial cells (positive for CD31 and D2-40). Cellular areas superficially resembled KHE but displayed more epithelioid cytology and lacked surrounding hyaline fibrosis and minute platelet aggregates. Molecular genetic studies demonstrated NRAS c.181C > A p.Q61K (Gln61Lys) in 2 specimens from one patient and HRAS p.A59_Q61delinsGGSIL in another. Two patients were treated with sirolimus; all are currently alive with stable disease. We conclude that cellular morphology in KLA, a previously undescribed feature, does not appear to be associated with clinical features, site of disease, mutation type, response to sirolimus, or outcome. Although cellular KLA may mimic KHE, there are sufficient clinical, morphologic, and genetic differences such that these are likely unrelated diseases.

The VASCERN European Reference Network: An overview.

Established since 2017 and co-funded by the European commission, VASCERN is the European Reference Network aiming at improving and homogenizing care of patients with rare multisystemic vascular diseases throughout Europe. It gathers 31 expert teams from 26 highly specialized multidisciplinary HCPs, plus 7 Affiliated Partner centers, from 16 EU Member States, as well as more than 65 patient organisations (ePAG). It is structured around 5 main RDWGs, each specialized in a specific disease or group of diseases. It produces resources for doctors or patients in English, which are translated and used across Europe and the world. These resources include educational videos, guidelines, clinical outcome measures and expert consensus statements. Communication through VASCERN's social media channels and website ensure these valuable documents and media are shared across the EU and beyond. VASCERN's activities are enabled by the use of eHealth tools like the CPMS (Clinical Patient Management System), to discuss complex cases, and WebEx, for videoconferences. VASCERN also develops its own registry of rare vascular diseases, as well as a Mobile Application referencing all the expert centers and patient organisations in Europe to facilitate patient access to optimal care. Finally, VASCERN is coordinated at the Hopital Bichat-Claude Bernard in Paris by a team of 5, responsible for the organizational, technical, communication, administrative and budgetary tasks of the project. This review focuses on the notable achievements made in the first four years of the network and the challenges it still faces.

Lymphatic Anomalies in Children: Update on Imaging Diagnosis, Genetics, and Treatment.

Lymphatic anomalies comprise a spectrum of disorders ranging from common localized microcystic and macrocystic lymphatic malformations (LMs) to rare complex lymphatic anomalies, including generalized lymphatic anomaly, Kaposiform lymph-angiomatosis, central conducting lymphatic anomaly, and Gorham-Stout disease. Imaging diagnosis of cystic LMs is generally straightforward, but complex lymphatic anomalies, particularly those with multiorgan involvement or diffuse disease, may be more challenging to diagnose. Complex lymphatic anomalies are rare but associated with high morbidity. Imaging plays an important role in their diagnosis, and radiologists may be the first clinicians to suggest the diagnosis. Furthermore, radiologists are regularly involved in management given the frequent need for image-guided interventions. For these reasons, it is crucial for radiologists to be familiar with the spectrum of entities comprising complex lymphatic anomalies and their typical imaging findings. In this article, we review the imaging findings of lymphatic anomalies, including LMs and complex lymphatic anomalies. We discuss characteristic imaging findings, multimodality imaging techniques used for evaluation, pearls and pitfalls in diagnosis, and potential complications. We also review recently discovered genetic changes underlying lymphatic anomaly development and the advent of new molecularly targeted therapies.

Propranolol treatment for chylothorax after congenital cardiac surgery.

OBJECTIVE: Postoperative chylothorax causes significant morbidities in pediatric patients with cardiac disease. New treatment approaches based on evolving understanding of underlying lymphatic dysfunction are being developed. We hypothesized that propranolol reduces morbidities and duration of chest tube requirement in high-output chylous effusion. METHODS: The postoperative courses of 50 pediatric patients with cardiac disease and high-output chylous effusion (control, n = 25; propranolol-treated, n = 25) were reviewed, including morbidities, length of hospitalization, and duration of chest tube requirement. Statistical analysis was performed using Welch's t test, Kruskal-Wallis tests for continuous variables, and chi-square and Fisher exact tests for categorical variables. Univariable logistic regression was used to determine predictors of response. RESULTS: Propranolol response was defined as 80% or more drainage reduction in 9 days or less. Treated patients were grouped into responders (<9 days) and nonresponders (>10 days). Neither initial amount of drainage (P = .12) nor day of propranolol initiation (P = .17) correlated with response. When compared with controls and nonresponders, responders had significantly fewer days with chest tube requirement (P < .01), infection (P < .0002), and thrombus (P = .005), and shorter hospitalization (P < .05). All patients had low serum albumin, although nonresponders had significantly decreased serum albumin when compared with responders and control patients (P < .002), and were more likely to receive albumin replacement (P < .01). Malnutrition was prevalent in all patient groups. CONCLUSIONS: Responders to propranolol had significantly less morbidity and duration of chest tube requirement when compared with control patients and nonresponders. Nonresponders did not have worse outcomes than control patients. We conclude that propranolol may be an effective treatment of patients with refractory chylothorax.

Generalized lymphatic anomalies and review of the current management landscape: a case report and review of the literature.

BACKGROUND: Generalized lymphatic anomaly previously known as diffuse systemic lymphangiomatosis is a rare multisystem congenital disease arising from the lymphatic system, and it is characterized by abnormal proliferation of the lymphatic channels in osseous and extraosseous tissues. It typically affects children or young adults. Although it is benign, it can be misdiagnosed as malignancy because of its diffuse and debilitating nature depending on the site of involvement. Due to its rarity, diagnosis is often delayed, leading to potential significant morbidity or mortality if vital organs are involved. Furthermore, its potential for multiorgan involvement with no curative treatment makes its management challenging. CASE PRESENTATION: We describe a case of a 35-year-old Caucasian female, who presented with epigastric pain and was subsequently extensively investigated at multiple tertiary centers by numerous specialists for query malignancy and metabolic bone disorder following incidental computed tomography imaging findings of multiple osteolytic lesions in the axial skeleton, and low-attenuating lesions in the axilla, spleen, and mediastinum. The diagnosis was confirmed with an axillary excisional biopsy. She was clinically stable with no end organ damage. She was monitored conservatively. CONCLUSIONS: The case illustrates the importance of increased awareness among clinicians for this rare congenital disease to enable earlier diagnosis and to avoid unnecessary invasive investigations. Furthermore, this case highlights the potential need for multiple biopsies of affected sites to confirm diagnosis. We also discuss the emergence of interferon therapy, chemotherapy, immunosuppression, and immunotherapy as medical management for this condition.

Lymphatic Development and Implications for Diagnosis and Therapy.

The lymphatic system was first described in the 17th century independently by Olaus Rudbeck and Thomas Bartholin. Since then, there has been deep-seated fascination with its development, function, and dysfunction.

Development and physiological functions of the lymphatic system: insights from human genetic studies of primary lymphedema.

Primary lymphedema is a long-term (chronic) condition characterized by tissue lymph retention and swelling that can affect any part of the body, although it usually develops in the arms or legs. Due to the relevant contribution of the lymphatic system to human physiology, while this review mainly focuses on the clinical and physiological aspects related to the regulation of fluid homeostasis and edema, clinicians need to know that the impact of lymphatic dysfunction with a genetic origin can be wide ranging. Lymphatic dysfunction can affect immune function so leading to infection; it can influence cancer development and spread, and it can determine fat transport so impacting on nutrition and obesity. Genetic studies and the development of imaging techniques for the assessment of lymphatic function have enabled the recognition of primary lymphedema as a heterogenic condition in terms of genetic causes and disease mechanisms. In this review, the known biological functions of several genes crucial to the development and function of the lymphatic system are used as a basis for understanding normal lymphatic biology. The disease conditions originating from mutations in these genes are discussed together with a detailed clinical description of the phenotype and the up-to-date knowledge in terms of disease mechanisms acquired from in vitro and in vivo research models.