Cystic Hygroma Research Articles

Vascular Anomalies Review of the Head and Neck for Physicians in Training

A basic understanding of vascular anomalies will aid physicians-in-training as they seek to properly diagnose and determine interventions for these patient presentations. The aim of this review is to create a resource for physicians in training that encompasses the most important clinical aspects of vascular anomalies. Vascular anomalies of the head and neck are divided into two categories: vascular tumors and vascular malformations. This review will first describe vascular tumors followed by vascular malformations. This review discusses major pathology found in both categories of vascular anomaly. Vascular anomalies are frequently found in pediatric populations and can persist into adulthood, making it important for trainees to identify them on physical exam. This developing field seeks to improve form, function, and quality of life for patients with vascular anomalies and often requires a multidisciplinary approach (i.e., otolaryngology, dermatology, genetics, plastic surgery, interventional radiology). Various medical and surgical treatment options are available. A basic knowledge of these anomalies will allow for accurate, early diagnosis and appropriate intervention which can ultimately improve patient outcomes. Search Strategy and Selection Criteria: The MEDLINE/PubMed database was searched for primary research and reviews discussing various vascular anomalies which include infantile hemangioma, congenital hemangioma, pyogenic granuloma, tufted angioma, kaposiform hemangioendothelioma, capillary malformations, lymphatic malformations, venous malformations, and arteriovenous malformations. This search was conducted from 7/5/2023 to 3/21/2024.

LOOKING BACKWARD AND LOOKING FORWARD: REVISITING "CLINICAL USEFULNESS OF THORACIC DUCT CANNULATION"

Over the past decade, there has been a resurgence of interest in the thoracic duct and central lymphatic system and its disorders, stimulated by advances in interventional magnetic resonance imaging techniques and urgent challenges in the clinical management of lymphatic malformations and lymphatic complications from congenital heart disease. The following chapter reprinted here written shortly after the formal founding of the discipline of lymphology and the International Society of Lymphology, describes early efforts, and also suggests future directions now being revisited and others yet to be explored (1).

Gastric cyst of the posterior mediastinum in a child: An unusual presentation

Gastric cyst of the posterior Mediastinum is a rare congenital anomaly of the gastrointestinal tract. They are classified according to their embryological origin, epithelial lining and location, as thymic cyst, cystic hygroma, mesothelial cysts, thoracic duct cyst and cystic malformation of the primitive foregut. They usually present in neonates or in infancy and are discovered incidentally on radiological examination or gastric endoscopy. Accurate diagnosis of these cysts before resection is difficult and differential diagnosis are varied. This case report presents a 6-year-old boy who complained of fever for 3 weeks. Chest X-ray revealed right para median oval shaped opacity. HRCT showed a well-defined cystic lesion measuring 9x4.4x3.3 cm in the right side of the posterior mediastinum in the perihilar location. There was also noted vertebral segmentation anomaly in the cervicothoracic spine. Cystectomy was and Gastric cyst was diagnosed through histopathological examination. This case report is presented for its rarity and an unusual delayed clinical presentation.

Exome sequencing for nonimmune hydrops fetalis and clinical utility of data reanalysis.

Nonimmune hydrops fetalis (NIHF) presents as life-threatening fluid collections in multiple fetal compartments and may be led by numerous etiologies. To establish the diagnostic yield of exome sequencing for single-gene disorders in unexplained NIHF and to evaluate the clinical utility of data reanalysis. A series of 53 unexplained cases of NIHF were enrolled, including 39 cases met a strict definition of NIHF, and 14 cases with increased nuchal translucency (NT) and/or cystic hygroma in combination with other fluid collections. Trio ES from fetal samples and parental blood was performed, and clinical reports were returned by geneticists and genetic counselors. Multidisciplinary team forums were conducted for accurate diagnoses and improved patient management. The clinical follow-up assessments were conducted, and the reanalysis was performed for cases with a non-positive result. Diagnostic variants were identified in 22.6% (12/53) of the cases, and variants of potential clinical significance were detected in an additional 13.2% (7/53) of the cases. Of them, 3 possible diagnoses (3/41, 7.3%) were obtained during reanalysis. Notably, half of the diagnosed cases were from the group exhibiting only skin edema and increased nuchal translucency and/or cystic hygroma. The diagnostic rate in this group was 42.8% (6/14), while in the classically defined NIHF group, the rate was 15.4% (6/39). The pregnancy termination and live birth rates of the cases with positive genetic testing results were found to be statistically significantly different from those with negative results (91.7% vs 53.6% and 8.3% vs 36.6%, P < 0.05 for both). ES provides high incremental diagnostic yield for NIHF after standard-of-care testing, and reevaluating non-diagnostic exomes in light of updated knowledge can maximize diagnostic yield. Identifying the etiology of NIHF facilitates prenatal diagnosis, improves the management of NIHF cases, and predicts recurrence risk in future pregnancies.

When Giant Lymphangioma Meets Hydrops Fetalis: An Uncommon Case Report of Lower Extremity Involvement

Abstract Approximately 75% of lymphangiomas manifest in the head and neck region, with limb and bone involvement observed in only 2% of cases. This case report presents a rare instance of fetal lymphangioma associated with hydrops fetalis, affecting the left lower extremity and abdomen. A 22-year-old secundigravida woman was referred to the gynecology department at 31.2 weeks of gestation. Initial fetal ultrasound revealed a live fetus with a large lymphangioma involving the left lower extremity, gluteal region, and abdomen. Additional ultrasound findings included subcutaneous edema, pericardial effusion, ascites, placentomegaly, and tricuspid regurgitation. Postnatal clinical examination confirmed the diagnosis of lymphatic malformation. Notably, only one other similar case has been reported in the English-language PubMed database. This report adds to the medical literature as a rare instance of prenatally diagnosed lymphangioma-associated hydrops fetalis.

Regimens and Response Assessment in Minimally Invasive Image-Guided Therapies for Vascular Malformations: Insights from a Large Cohort Study at a Tertiary-Care Hospital

This retrospective study was aimed at characterizing vascular malformations (VMFs) presenting for minimally invasive image-guided therapies (MIT) at a tertiary-care center and evaluating treatment regimens and image-based outcomes using MRI. We analyzed demographic, disease-related, and radiologic features of VMFs presenting to interventional radiology between May 2008 and August 2020 using compendium vascular anomaly (Compva) criteria. MIT and specific agents were evaluated, and treatment effects were assessed through volumetry and mean signal intensity (MSI) on multiparametric longitudinal MRI. The statistics included the paired t-test, ANOVA, and Fisher’s exact test. The cohort included 217 patients (mean age 30 ± 18.4 years; 134 female). Venous malformations were most common (47%). VMFs were frequently located in the head-neck region (23.5%), legs (23.04%), and arms (13.8%). Among 112 treatments, sclerotherapy was performed most frequently (63.9%), followed by embolization (19.3%). MRI showed a significant reduction in T2 MSI for venous (1107.95 vs. 465.26; p = 0.028) and decreased contrast media uptake for lymphatic malformations (557.33 vs. 285.33; p = 0.029) after sclerotherapy, while the lesion volumes did not change significantly (p = 0.8). These findings propose MRI-derived MSI as a potential non-invasive biomarker for assessing the response of VMF to MIT. By leveraging MRI, this study addresses challenges in managing rare diseases like VMFs, while advocating for standardized approaches and prospective studies to better link imaging findings with clinical outcomes.

Intramuscular vascular malformations in pediatric patients: a retrospective study in a vascular anomalies clinic.

Intramuscular vascular malformations (IVMs) are rare developmental congenital structural abnormalities. Their clinical diagnosis is difficult, and imaging studies are essential to determine the type and extent of vessels involved. Treatment can be challenging and must be managed by a multidisciplinary team. A descriptive, observational, retrospective, longitudinal study of clinical records of patients diagnosed with IVMs who were evaluated at the vascular anomalies clinic from January 2011 to December 2021 was performed. Demographic, clinical, imaging, diagnosis, treatment, and response data were collected. Seven patients (five females and two males) with a mean age of 13.66 years (standard deviation 5.82 years) were included in the study. In all cases, the clinical diagnosis was venous and lymphatic malformation. The radiological findings were dilated and tortuous vascular structures or multilobulated lesions with septa inside, with or without vascular flow; these findings allowed diagnosis in all cases. Treatment modalities included sclerotherapy in five patients, surgical resection in two, medical treatment with sirolimus in three, and surveillance in one. Subsequent clinical evolution was favorable in all patients, with decreased pain in six (partial in four and total in two) and size reduction in one patient. IVMs in our pediatric population most frequently affect the lower extremities. The main symptoms and signs were pain on exertion and volume increase. Treatment can be challenging given the extension and depth of the malformations, so a combination of therapeutic modalities may be necessary to obtain the best outcome.

Management for lymphatic malformations of head and neck.

To explore the management of lymphatic malformation in head and neck. This is a retrospective study at a single center. Data on demographic, surgery, sclerotherapy and follow-up information were collected from our Vascular Anomalies Center database. Patients with lymphatic malformation of head and neck who had undergone surgery and sclerotherapy between March 2020 and March 2024 were included. There were 94 patients in this study, the lesion sites included head (n = 60), tongue (n = 7), neck (n = 41), pharynx (n = 7), and head and neck (n = 7). Symptoms included bleeding (n = 6), infection (n = 2), dyspnea (n = 2), dysphonia (n = 4), and dysphagia (n = 4). Lymphatic malformation included macrocystic (n = 61), microcystic (n = 12) and mixed (n = 21). Surgeries for LM included radical resection, subtotal or partial resection and staged surgeries. Sclerotherapies included bleomycin monotherapy and combined sclerotherapy with ethanol and bleomycin, under ultrasound or fluoroscopy guidance. The follow-up period was from 3 months to 1 year. The therapeutic effect was evaluated according to the size of the treatment area. 55 patients, 21 patients, 11 patients and 7 patients were evaluated with excellent, good, moderate and no response, respectively. Surgical resection, sclerotherapy and the combination of the two are efficacious treatment modalities for head and neck LM. Combined with oral drugs and other new therapies may be warranted in future for challenging conditions.

Abdominal lymphatic malformations: a novel approach in management

Aim of the study:Abdominal lymphatic malformations (LM) are a challenging clinical entity. Complete excision can be impossible due to the infiltrative nature of some lesions and high rate of complications. Sclerotherapy may require multiple episodes of general anaesthesia and an inability to be definitive in terms of diagnosis and treatment. Subsequently we have adopted a newer algorithm of treatment involving a joint procedure with interventional radiology to enable an intra-operative treatment plan based on the findings. We present our early results. Method:A retrospective observational study in a single tertiary paediatric centre from January 2019 to December 2023. The details of each patient were recorded along with their treatment pathway and outcome. Results:12 children underwent treatment for abdominal LM. Under GA and laparoscopic vision, pigtail catheters were inserted into the lesion to effect maximal drainage and assessment of surgical anatomy. If resection was feasible this was undertaken through a laparotomy and if not, the drains were retained and sclerotherapy was started.Three underwent drainage with sclerotherapy without resection and 9 underwent drainage with resection. Of the 3 who underwent sclerotherapy 2 have had further treatment and remain under review at a mean follow up of 7.6 months. Of the other 9 there were no signs of recurrence of the LM at a mean follow up of 29 (range 6-56) months. Conclusion:We have found a combined procedure involving IR-guided drainage under laparoscopic vision enabling curative surgical resection to be undertaken, where feasible, with currently no significant morbidity. For those in whom this is not possible then direct intralesional sclerotherapy is the next most useful treatment modality for longer term control of symptoms. Level of evidence:II

Complications of pediatric macrocystic lymphatic malformations of the head and neck: a survival analysis of treated and untreated patients.

To compare events of recurrent swelling between treated and untreated patients with macrocystic lymphatic malformations of the head and neck not involving the airway. The frequency and timing of emergency department (ED) visits related to the event were analysed to provide data on efficacy and ideal timing of treatment. A 5-year retrospective review of a hospital database was conducted reviewing 35 patients (15 female, 20 male; mean age 3.9 years) with macrocystic lymphatic malformations of the head and neck not involving the airway. Patients treated with oral medications were excluded. A survival analysis was performed comparing the incidence of recurrent swelling of the malformation. A Cox regression analysis was conducted using age, gender, diameter of lymphatic malformation at presentation, and echogenicity on US as covariates. Fisher's test and mean comparisons were performed to correlate the populations baselines and the number and frequency of ED visits between the 2 groups. Thirteen patients underwent sclerotherapy soon after initial presentation and 22 elected for observation. The two baseline populations differed at presentation with the treatment group being younger (1.4 ± 2.4 vs. 5.4 ± 6.3 years, p = 0.03) and with larger lesions (5.7 ± 2.7 vs. 4.0 ± 1.7cm p = 0.03). Mean follow-up time was 2.7 years. Survival analysis showed 1 or multiple recurrences affected 16 patients in the untreated group and 3 patients in the treated group. (p = 0.04). Age, gender, diameter of the lesion at presentation and increased echogenicity on US were not predictive factors of recurrence. Although the probability of visiting the ED at least once did not differ between the two groups (p = 0.42), patients from the non-treatment group were more likely to visit the ED more than once (p = 0.03). Sclerotherapy treatment may reduce the chance of recurrent swelling or an event after initial presentation to the ED.

Horner syndrome secondary to rapid enlargement of a mediastinal lymphatic malformation

Horner syndrome is a clinical triad of ptosis, miosis, and anhidrosis which commonly prompts urgent neuroimaging. The differential diagnosis of new onset Horner syndrome in children includes neurologic emergencies. We report here a case of a 13-month-old male infant with acute onset Horner syndrome, subsequently found to have a large mediastinal lymphatic malformation compressing the trachea and neck vasculature.

Pediatric mediastinal lymphatic malformation: misdiagnosis analysis and literature review

ObjectivesMediastinal cystic lymphatic malformation (MCLM) in children is prone to misdiagnosis as cystic teratoma. We compared the clinical and radiologic features between the two diseases and performed a cross-comparison with previous research on adult cases. This study aims to identify characteristic pediatric manifestations to improve diagnostic accuracy.MethodsA retrospective study of clinical and radiologic data was conducted on 12 MCLM and 20 cases of cystic teratomas confirmed by pathology or intervention biopsy. Clinical characters and radiology features (mass location and morphology, density, component, secondary complication) were recorded and compared. We reviewed clinical studies on MCLM published in the past decades, analyzing radiological differences and comparing pediatric MCLM cases at our hospital with those in the literature.ResultsGroup comparison in pediatrics between MCLM and cystic teratomas: There were significant age differences (p = 0.036), shape (p = 0.003), CT difference value (p < 0.001), CT difference ratio (p < 0.001), calcification (p < 0.001), fat (p < 0.001), and typing (p < 0.001) between the two diseases. An analysis of literature data on MCLM cases involved 16 studies.ConclusionThe absence of internal fat or irregular morphology, along with a minimal CT difference value, may suggest the diagnosis of MCLM. In pediatric cases, anterior mediastinal diseases tend to extend toward the neck, and the presence of the thymus can complicate the component analysis, thereby increasing the risk of misdiagnosis. Clinical diagnosis and differential diagnosis of pediatric MCLM rely heavily on imaging evaluation.

Cystic lymphangiomas of the cecal cause intussusception in adults

Lymphangiomas are rare benign lymphatic malformations. Even though these neoplasms can arise from any location and age, most of them are dominant in the head and neck of children. On the other hand, lymphangiomas are exceedingly rare in adults, especially in the gastrointestinal tract. Gastrointestinal tract lymphangiomas account for only about 1% of lymphatic malformations. Although there have been increasing cases of gastrointestinal lymphangiomas reported in recent years, cecal lymphangiomas causing intussusception in adults are rarely mentioned. In this article, we report a 27-year-old female patient with cecal lymphangiomas detected by imaging modalities and confirmed via postoperative histopathological examination.

Fetal Cystic Lymphatic Malformations: Systematic Review on Pregnancy and Neonatal Outcomes.

Evaluate pregnancy and neonatal outcomes with fetal cystic lymphatic malformations (LMs), excluding those arising from the posterior neck, to facilitate patient counseling. A systematic review was performed in accordance with PRISMA guidance. Case series and case reports published between 2000 and 2022 were included. Sixty-five studies (96 fetuses) met the inclusion criteria. The average gestational age at diagnosis was 25.5 weeks with the commonest location being the anterior neck (28%). All patients were diagnosed with LM using two-dimensional (2D) ultrasound. Prenatal progression in LM size, presence of intralesional bleeding, or fetal hydrops occurred in 70% (41/59), 9% (5/59), and 3% (2/59), respectively. Chromosomal and structural abnormalities were reported in 4% (2/52) and 2% (2/96), respectively. Overall livebirth rate was 94% (79/84); 12/96 resulted in termination and 5/84 in in utero demise. The average gestational age of delivery was 37.7 weeks. Exactly 19% (15/79) had a vaginal birth, of which shoulder dystocia occurred in one infant. Ex utero intrapartum treatment (EXIT) procedure was performed in 13% (10/79). Postnatal treatment commonly involved surgical excision 38% (30/79), sclerotherapy in 21.5% (17/79), or combination of both in 11.4% (9/79). Of those with reported follow-up, 4 died within 1 year, 1 developed heart failure at 2 years of life, and the remaining 44 had normal developmental outcomes. Fetal cystic LMs, excluding those in the posterior neck, are not commonly associated with chromosomal, or additional structural abnormalities. They usually increase in size before delivery with only a minority developing complications. The good developmental outcome was reported in all survivors.

Clinical characteristics and risk factors for acute abdomen in patients with abdominal lymphatic malformations

ObjectiveThe diagnosis of abdominal lymphatic malformations (ALMs) is often overlooked in clinical practice. However, reports in the literature about ALMs are limited to case reports/series with small sample sizes. This study aimed to review our currently available data to describe the clinical characteristics of ALMs and evaluate the risk factors for acute abdomen caused by ALMs. MethodsWe reviewed the records of patients with ALMs who were diagnosed between December 2008 and January 2023 in our institution. The associations between acute abdomen and ALMs were analyzed based on single-factor and multivariate logistic regression analyses. ResultsThis study included 345 patients with pathologically confirmed ALMs, with a slight female predominance of 1:1.4. Approximately 39.1% (135/345) of patients were asymptomatic, and 24.6% (85/345) presented with acute abdomen. Among the ALMs in the cohort, 42.6% (147/345) were retroperitoneal lymphatic malformations (LMs). The maximal lesion dimensions in patients with acute abdomen and nonacute abdomen were 10.0 cm and 7.8 cm, respectively, with no significant difference based on multivariate analyses. Children were more likely to develop acute abdomen than adults were (P=0.002; odds ratio [OR], 5.128; 95% confidence interval [CI], 1.835-14.326). ALMs accompanying acute abdomen were more common for lesions involving the small intestinal mesentery (P=0.023; OR, 2.926; 95% CI, 1.157-7.400). ConclusionALMs are rare with insidious onset, and retroperitoneal LMs are the most common ALMs, followed by jejunal MLMs. Our retrospective analysis suggested that young age and small intestinal mesenteric lymphatic malformation are independent risk factors for acute abdomen with ALMs.

Identifying Genetic Mutations in Vascular Anomalies Using a Sequencing Panel for Childhood Cancers: A Pilot Study

Introduction: Genetic mutations have been identified in the pathogenesis of vascular anomalies. Due to overlaps in genetic variants causing vascular anomalies and cancer, we used a next-generation sequencing panel for genomic profiling of childhood cancers to detect somatic mutations in children with vascular anomalies. We aim to review the utility of an oncology panel for the molecular diagnosis of vascular anomalies. Methods: Nine patients with histologically confirmed vascular anomalies were included. DNA was extracted from formalin-fixed paraffin-embedded tissue specimens obtained from affected tissue following diagnostic punch biopsies of the skin and core biopsies of the vascular malformation or tumor during sclerotherapy or surgical excision. Molecular analysis of the tissue samples was performed using AmpliSeq for Childhood Cancer DNA Assay Panel. Results: Two patients had antenatally detected vascular anomalies. The median age at diagnosis for the remaining patients was 7.0 years (IQR, 0.6–10.0 years). Seven were diagnosed with vascular malformations, while 2 had vascular tumors. Pathological somatic mutations were identified in 4 patients, leading to a diagnostic yield of 44.4%. Two different PIK3CA mutations were identified in 3 cases: 1 in a case of macrocystic lymphatic malformation, the other in a case of Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevus, Spinal/Skeletal anomalies syndrome and Klippel–Trenaunay syndrome. BRAF mutation was identified in a patient with a veno-lymphatic malformation. Conclusion: An oncology next-generation sequencing panel can be used for genetic profiling of vascular anomalies. However, a more customized and sensitive panel may be of better diagnostic yield, as detection of somatic mutations in vascular anomalies is challenging due to tissue mosaicism, low-abundant genetic variants, and specimen limitations.

Non-immune hydrops fetalis is associated with bi-allelic pathogenic variants in the MYB Binding Protein 1a (MYBBP1A) gene.

Non-immune hydrops fetalis (NIHF) is a rare entity characterized by excessive accumulation of fluid within the fetal extravascular compartments and body cavities. Here we present two intrauterine fetal demises with NIHF presenting with oligohydramnios, cystic hygroma, pleural effusion, and generalized hydrops with predominance of subcutaneous edema. The fetuses also presented with ascites, severe and precocious IUGR and skeletal anomalies. Whole exome sequencing was applied in order to screen for a possible genetic cause. The results identified biallelic variants in MYBBP1A in both fetuses. A previous report described another case with a similar phenotype having compound heterozygous variants in the same gene. The protein encoded by MYBBP1A is involved in several cellular processes including the synthesis of ribosomal DNA, the response to nucleolar stress, and tumor suppression. Our functional protein analysis through immunohistochemistry indicates that MYBBP1A is a gene expressed during fetal stages. Altogether, we concluded that MYBBP1A is associated with the development of hydrops fetalis. More cases and further studies are necessary to understand the role of this gene and the mechanism associated with NIHF.

Dysfunctional mechanotransduction regulates the progression of PIK3CA-driven vascular malformations.

Somatic activating mutations in PIK3CA are common drivers of vascular and lymphatic malformations. Despite common biophysical signatures of tissues susceptible to lesion formation, including compliant extracellular matrix and low rates of perfusion, lesions vary in clinical presentation from localized cystic dilatation to diffuse and infiltrative vascular dysplasia. The mechanisms driving the differences in disease severity and variability in clinical presentation and the role of the biophysical microenvironment in potentiating progression are poorly understood. Here, we investigate the role of hemodynamic forces and the biophysical microenvironment in the pathophysiology of vascular malformations, and we identify hemodynamic shear stress and defective endothelial cell mechanotransduction as key regulators of lesion progression. We found that constitutive PI3K activation impaired flow-mediated endothelial cell alignment and barrier function. We show that defective shear stress sensing in PIK3CA E542K endothelial cells is associated with reduced myosin light chain phosphorylation, junctional instability, and defective recruitment of vinculin to cell-cell junctions. Using 3D microfluidic models of the vasculature, we demonstrate that PIK3CA E542K microvessels apply reduced traction forces and are unaffected by flow interruption. We further found that draining transmural flow resulted in increased sprouting and invasion responses in PIK3CA E542K microvessels. Mechanistically, constitutive PI3K activation decreased cellular and nuclear elasticity resulting in defective cellular tensional homeostasis in endothelial cells which may underlie vascular dilation, tissue hyperplasia, and hypersprouting in PIK3CA-driven venous and lymphatic malformations. Together, these results suggest that defective nuclear mechanics, impaired cellular mechanotransduction, and maladaptive hemodynamic responses contribute to the development and progression of PIK3CA-driven vascular malformations.

Turner Syndrome Associated with Cystic Hygroma in One Twin of a Dichorionic Diamniotic Pregnancy: A Unique Case Report

We present a rare case of dichorionic diamniotic twin pregnancy, in which one fetus had Turner syndrome associated with cystic hygroma while the other fetus was phenotypically normal. The pregnancy was terminated due to twin A being alive but with cystic hygroma and twin B having missed abortion. Because it was dichorionic diamniotic with discordant gender, karyotyping was done only on the affected fetus, revealing loss of chromosome X-Turner syndrome. This case highlights that in order to gain a better understanding of the underlying genetic pathways, it is important to send tissue samples for investigation, even for fetuses that appear structurally normal. Dichorionic may not be dizygotic.

Lymphatic System Development and Function.

This review delves into recent advancements in understanding generalized and organ-specific lymphatic development. It emphasizes the distinct characteristics and critical anomalies that can impair lymphatic function. By exploring developmental mechanisms, the review seeks to illuminate the profound impact of lymphatic malformations on overall health and disease progression. The introduction of genome sequencing, single-cell transcriptomic analysis, and advanced imaging technologies has significantly enhanced our ability to identify and characterize developmental defects within the lymphatic system. As a result, a wide range of lymphatic anomalies have been uncovered, spanning from congenital abnormalities present at birth to conditions that can become life-threatening in adulthood. Additionally, recent research highlights the heterogeneity of lymphatics, revealing organ-specific developmental pathways, unique molecular markers, and specialized physiological functions specific to each organ. A deeper understanding of the unique characteristics of lymphatic cell populations in an organ-specific context is essential for guiding future research into lymphatic disease processes. An integrated approach to translational research could revolutionize personalized medicine, where treatments are precisely tailored to individual lymphatic profiles, enhancing effectiveness and minimizing side effects.