Cystic Hygroma Research Articles

Multimodal treatment of cystic lymphangioma – A challenge

Congenital cystic lymphangiomas or lymphatic malformations are benign malformations due to a developmental disorder of lymphatic vessels. The most frequent localization of lymphangiomas is the neck and head region. The fact that the lesions usually have no spontaneous regression, tend to augment in size and may cause life-threatening complications such as occlusion or infiltration of neighbouring organs and structures, underlines the need of an early adequate therapy. Surgical excision used to be the first-line treatment of lymphangiomas. However, complete excision often is not possible. Besides surgical excision, sclerosant therapy of these lesions by intracavitary injection of OK-432 (Picibanil®), a lyophilized mixture of group A Streptococcus pyogenes, is a common therapeutical option. We present two cases of lymphangioma which were challenging to manage, yet the results were good in one case and excellent in the other case (according to the Acevedo classification). Sclerotherapy with Ok-432 is recommended primary for macrocystic lymphangiomas. The application is safe and without serious side effects. It can be used alone or in combination with other treatment modalities.

Abdominal cystic lymphangiomas in pediatric cases

Mesenteric cystic lymphangiomas are benign but rare neoplasms, primarily seen in children. Among internal organs, these masses are commonly found in the ileal mesentery. In this case series, we presented nine pediatric patients with abdominal lymphangiomas admitted to the surgery ward during 2010 and 2020, of which 6 were boys and three girls. Symptoms varied from abdominal distention to chronic and acute abdominal pain, anorexia and vomiting, and a scrotal mass in our patients. Considering various presentations of these patients and possible critical complications, surgeons need to have lymphatic malformations in mind as a differential diagnosis in such cases to improve the outcome.

Giant Cystic Hygroma Encapsulating the Internal Jugular Vein and Causing Severe Airway Obstruction: A Rare Presentation and Review of Literatures

Giant Cystic Hygroma Encapsulating the Internal Jugular Vein and Causing Severe Airway Obstruction: A Rare Presentation and Review of Literatures

Expanding the phenotype of ATP6AP1 deficiency.

Vacuolar ATPases (V-ATPases) are large multisubunit proton pumps conserved among all eukaryotic cells that are involved in diverse functions including acidification of membrane-bound intracellular compartments. The ATP6AP1 gene encodes an accessory subunit of the vacuolar (V)-ATPase protein pump. Pathogenic variants in ATP6AP1 have been described in association with a congenital disorder of glycosylation (CDG), which are highly variable, but often characterized by immunodeficiency, hepatopathy, and neurologic manifestations. Although the most striking and common clinical feature is hepatopathy, the phenotypic and genotypic spectrum of ATP6AP1-CDG continues to expand. Here, we report identical twins who presented with acute liver failure and jaundice. Prenatal features included cystic hygroma, atrial septal defect, and ventriculomegaly. Postnatal features included pectus carinatum, connective tissue abnormalities, and hypospadias. Whole-exome sequencing (WES) revealed a novel de novo in-frame deletion in the ATP6AP1 gene (c.230_232delACT;p.Tyr77del). Although both twins have the commonly reported clinical feature of hepatopathy seen in other individuals with ATP6AP1-CDG-related disorder, they do not have neurological sequelae. This report expands the phenotypic spectrum of ATP6AP1-CDG-related disorder with both probands exhibiting unique prenatal and postnatal features, including fetal ventriculomegaly, umbilical hernia, pectus carinatum, micropenis, and hypospadias. Furthermore, this case affirms that neurological features described in the initial case series on ATP6AP1-CDG do not appear to be central, whereas the prenatal and connective tissue manifestations may be more common than previously thought. This emphasizes the importance of long-term clinical follow-up and variant interpretation using current updated recommendations.

Intrathyroid Thyroglossal Duct Cyst Extending into the Mediastinum: A Case Report and Review of Literature

Thyroglossal duct cyst (TGDC) is the most common congenital cyst in the neck and usually presents in children. It is most commonly located at the infrahyoid level. However, intrathyroid TGDC in the adult is extremely rare and its pathogenesis remains unclear. Curiously, an intrathyroid TGDC was found on the lateral aspect of the inferior pole of the thyroid gland. Given the unique position of this lesion, and its capacity to stimulate other nodules in the thyroid, it should be differentiated from other lateral neck masses, such as: thymic cysts, branchial cleft cysts, cystic hygroma, lipomas, lymphadenopathies, cervical teratomas, and lymphomas. In this case, a separate cystic mass was found in the right inferior pole of the thyroid gland and extended to the mediastinum. We confirmed it as TGDC by pathology and histological examination.

Abstract No. 389 Management of tongue venous and lymphatic malformations

To determine the efficacy of ethanol embolization in management of tongue venous and lymphatic malformations.

Abstract No. 39 Assessing safety and clinical outcomes of patients receiving serial doxycycline exchange sclerotherapy for lymphatic malformations

Abstract No. 39 Assessing safety and clinical outcomes of patients receiving serial doxycycline exchange sclerotherapy for lymphatic malformations

Adaptive Proton Therapy of Pediatric Head and Neck Cases Using MRI-Based Synthetic CTs: Initial Experience of the Prospective KiAPT Study.

Simple SummaryRadiation therapy with protons facilitates highly conformal dose distributions. Thus, normal tissue can be spared effectively, which is a benefit, especially for children. Magnetic resonance imaging (MRI) is ideally suited to assess anatomical changes during the radiation course due to its superior soft tissue contrast and non-existent X-ray exposure. The MRI data have to be transformed to X-ray computed tomography (CT) images, which form the basis of treatment planning. This is conducted by capturing anatomical deformations between MRIs acquired at different times and by warping the planning CT according to these deformations. This procedure was applied in a prospective study enrolling pediatric head and neck cases. The preliminary evaluation of eleven patients with mainly rhabdomyosarcoma diagnosis and at craniofacial and base of skull tumor sites show that neither the deterioration of the target volume coverage nor an increased dose to organs-at-risk over the treatment course is a concern.Background and Purpose: Interfractional anatomical changes might affect the outcome of proton therapy (PT). We aimed to prospectively evaluate the role of Magnetic Resonance Imaging (MRI) based adaptive PT for children with tumors of the head and neck and base of skull. Methods: MRI verification images were acquired at half of the treatment course. A synthetic computed tomography (CT) image was created using this MRI and a deformable image registration (DIR) to the reference MRI. The methodology was verified with in-silico phantoms and validated using a clinical case with a shrinking cystic hygroma on the basis of dosimetric quantities of contoured structures. The dose distributions on the verification X-ray CT and on the synthetic CT were compared with a gamma-index test using global 2 mm/2% criteria. Results: Regarding the clinical validation case, the gamma-index pass rate was 98.3%. Eleven patients were included in the clinical study. The most common diagnosis was rhabdomyosarcoma (73%). Craniofacial tumor site was predominant in 64% of patients, followed by base of skull (18%). For one individual case the synthetic CT showed an increase in the median and dose on the spinal cord from 20.5 GyRBE to 24.8 GyRBE and 14.7 GyRBE to 25.1 GyRBE, respectively. Otherwise, doses received by OARs remained relatively stable. Similarly, the target volume coverage seen by and remained unchanged. Conclusions: The method of transferring anatomical changes from MRIs to a synthetic CTs was successfully implemented and validated with simple, commonly available tools. In the frame of our early results on a small cohort, no clinical relevant deterioration for neither PTV coverage nor an increased dose burden to OARs occurred. However, the study will be continued to identify a pediatric patient cohort, which benefits from adaptive treatment planning.

Contrast enhanced ultrasound for characterization of suspected soft tissue vascular anomalies

BackgroundEvaluation of perfusion characteristics is the key to characterize vascular anomalies. Contrast-enhanced ultrasound (CEUS) is a radiation-free modality to evaluate this in real-time and can be coupled along with Doppler-ultrasound (US). ObjectiveTo evaluate the utility of CEUS in characterization of suspected soft-tissue vascular anomalies and compare its diagnostic accuracy with Doppler-US. Materials and methodsThis was an ethically-approved cross-sectional study, done from November 2017- November 2019, involving 93 patients (55 M/38F; mean age 23.6 ± 11.9 years) in development cohort and 128 (66 M/62F; mean age 21.4 ± 11.1 years) in validation cohort. Patients suspected to have soft-tissue vascular anomalies on clinical evaluation and US were included. Clinical features, US, Doppler, subjective and quantitative CEUS features (from time-intensity curves) were evaluated. Composite gold standard employing MRI, phlebogram, DSA or biopsy was used to make the final diagnosis. The CEUS features found to be significantly different in the development cohort were prospectively validated in the validation cohort. P-value < 0.05 was considered significant, ROC curves were drawn and threshold values obtained for the various quantitative parameters. A prospective diagnosis was suggested in the validation group along with a degree of diagnostic confidence and accuracy was calculated. ResultsThe spectrum of lesions included 77 venous malformations, 46 fibro-adipose vascular anomalies, 32 vascular tumors, 20 arteriovenous malformations and 20 lymphatic malformations. All lesions were found to have distinctive temporal and morphological subjective enhancement patterns. Quantitative parameters like rise-time, mean-transit-time, time-to-peak, peak-enhancement showed significant differences between the various groups (P value < 0.05). Addition of CEUS not only increased the diagnostic accuracy of Doppler-US from 76.5% (91/119) to 88.2% (105/119), but also the degree of diagnostic confidence in characterization of soft-tissue vascular anomalies. None of the patients showed any contrast-related adverse effects. ConclusionContrast-enhanced ultrasound is useful to characterize different types of soft-tissue vascular anomalies and increases the diagnostic accuracy and confidence over Doppler-ultrasound.

Annual prevalence estimation of lymphatic malformation with a cutaneous component: observational study of a national representative sample of physicians

BackgroundLymphatic malformations (LMs) represent a potentially life-threatening, rare disease of the lymphatic system characterized by development of abnormal vessels, outpouchings, or cysts filled with lymphatic fluid. There are three morphologic types of LMs based on the size of the individual cysts: macrocystic (typically > 2 cm), microcystic (generally < 2 cm), and mixed (includes aspects of both). Macrocystic LMs typically exist beneath the skin and often can involve vascular components and/or organs. Microcystic LMs often have a cutaneous component and clinically present with lymphorrhea, bleeding, pain, itching, malodor, and functional deficits. There are no treatments approved by the US Food and Drug Administration (FDA) for either macrocystic or microcystic lymphatic malformations. The totality of the epidemiologic literature for LM is limited to the incidence of the disease among various birth cohorts. This is the first nationally representative study to estimate the national managed prevalence for patients with microcystic LM or combined LM with a cutaneous component annually across physician specialties likely to manage this condition. We conducted a retrospective observational survey of a nationally representative sample of patient-care physicians in the United States most likely to manage lymphatic malformations with a cutaneous component (LMC). Once recruited, target physicians participated via an electronic questionnaire. We weighted study physician self-estimates of the number of LMC patients treated in the past 12 months to reflect the specialists’ corresponding proportion in the national universe. All patient information was anonymous; no personally identifiable information was collected.ResultsOf the 420 physicians who visited the study website, 316 agreed to be screened and to participate (75.2% participation rate). Our survey results indicated the estimated number of unique annually managed LMC patients by target specialists is 79,920 (CI 66,600–93,250). This number corresponds to managed prevalence of 24.1 LMC patients per 100,000 population (CI 19.6/100,000–28.4/100,000).ConclusionsThe study indicates that while rare, LMC affects a substantial number of people in the US (79,920) who are being managed by one or more specialists. By better understanding the prevalence of people living with LMC who require treatment, efforts to both increase disease awareness and to identify underserved populations in need of potential new treatments can be better focused.

Klippel-Trenaunay Syndrome: Case series from a university hospital of Nepal

IntroductionKlippel Trenaunay Syndrome (KTS) is a rare congenital malformation with capillary and venous malformations and soft tissue/bony overgrowth with or without lymphatic malformation. Cutaneous vascular stain, varicosities and tissue hypertrophy represent its main clinical features. Besides, the patient can develop thromboembolic pathologies, recurrent bouts of infection, stasis eczema, limb length discrepancy and intolerable pain typical of intraosseous involvement. MethodsHere, we report a case series of seven patients aged 10–45 who presented to our centre with clinical features suggestive of KTS. Out of them, six patients had involvement of unilateral lower limb, while only one had involvement of bilateral lower limb. They all had typical cutaneous vascular stains and underlying venous malformation, while one patient had developed complications with multiple ulcer formation. OutcomesAn interdisciplinary team of vascular surgeons, dermatologists, interventional radiologists, orthopaedics, and physiotherapists managed the cases. We performed an individualized treatment as per the patient's presentation, which included a combination of supportive, medical, interventional radiologic, and surgical interventions. The follow-up outcomes of all the patients revealed significant resolution of symptoms. ConclusionPatients with KTS can have diverse presentations. Therefore, clinicians should ensure an individualized treatment with the involvement of a multidisciplinary team for proper management and prevention of complications.

Outcome of pregnancies with first-trimester increased nuchal translucency and cystic hygroma in a tertiary maternity hospital in United Arab Emirates.

To study the outcome of pregnancies with first-trimester increased nuchal translucency and cystic hygromas. Retrospective study of 132 pregnancies with first-trimester increased nuchal translucency and cystic hygromas, between January 2015 to December 2018 at Corniche Hospital, Abu Dhabi, UAE. Fetal karyotyping, detailed ultrasound at 18-22 weeks and fetal echocardiography were offered to all women. Adverse outcomes included miscarriage, intrauterine fetal death, termination of pregnancy, neonatal death and structural abnormalities. Of the 132 pregnancies, 13 had NT > 95th percentile, 89 had NT ≥3 mm and 30 had cystic hygroma. Among 13 pregnancies with NT > 95th centile, 7.6% had abnormal karyotype. Among 89 pregnancies with NT ≥3 mm, 29.2% had abnormal karyotype, 13.4% miscarriage, 7.8% underwent TOP, 5.6% intrauterine fetal death, 1.1% neonatal death and 14.6% had structural abnormalities. Among 30 pregnancies with cystic hygroma, 40% had abnormal karyotype, 20% miscarriage, 13.3% TOP, 13.3% intrauterine fetal death, 6.6% had neonatal death and 20% had structural abnormalities. In our study, karyotype abnormalities increased with increasing nuchal translucency with highest risk in fetuses with cystic hygromas. Increased nuchal translucency was associated with adverse pregnancy outcome, which was higher in the group with NT≥6 mm and cystic hygromas.

Targeting Neuropilin‐2 in Lymphatic Malformation

Lymphatic malformations (LM) are sporadic, non‐familial congenital lesions consisting of dilated, abnormal lymphatic vessels that can cause severe lymphedema, disfigurement, organ dysfunction, and in some cases morbidity. These vascular anomalies grow slowly but progress over time and recur after surgery; no effective drugs or preventions currently exist for LM. Genome sequencing identified that approximately 80% of LM patients have somatic activating mutations in the PIK3CA gene. Lymphatic endothelial cells (LEC) expressing mutant PIK3CAH1047Rinduce both macrocystic and microcystic LM in mouse models. Our goal is to understand the cellular and molecular processes that regulate LM growth in order to develop novel therapeutic strategies for patients with LM. Neuropilin‐2 (NRP2) is an essential co‐receptor for VEGFC/VEGFR3 signaling through the PI3K/AKT pathway which is crucial for LEC viability and motility, yet NRP2 also mediates inhibitory signals from its Semaphorin‐3F (SEMA3F) ligand to attenuate activation of AKT and induce cytostasis. Our results using immunohistochemistry to detect NRP2 protein in paraffin‐embedded human samples indicate that NRP2 is highly upregulated in LM lesions compared to normal lymphatic vessels. LM‐LEC primary cell lines, derived separately from several patients, show increased NRP2 levels and hyper‐activated AKT compared to primary LEC derived from healthy human dermis. Additionally, LEC isolated from the skin of transgenic mice (prox1‐creERT2;Nrp2 f/f) specifically lacking Nrp2 in lymphatic vessels following tamoxifen induction (LEC‐Nrp2‐KO) show suppressed proliferation and migration following VEGF‐C stimulation compared to normal LEC isolated from wildtype mice. Importantly, SEMA3F exogenous protein, in a dose‐dependent manner, inhibits the proliferation of normal LEC and LM‐LEC and attenuates the phosphorylation of AKT. Taken together, our study suggests that NRP2 may be an important target for therapy in LM patients. Future studies using SEMA3F protein or specific antibodies targeting the VEGF‐binding domain of NRP2 will be tested in preclinical trials.

Lymphoscintigraphic Findings of Scrotal Lymphangioma.

As congenital lymphatic malformations, lymphangiomas commonly occur in the neck, tongue, and extremities, whereas scrotum is one of the least frequent sites. For this lymphatic flow disease, lymphoscintigraphy is regarded as a useful imaging method. Herein, in a child with scrotal cysts, scrotal region activity was detected in lymphoscintigraphy, consistent with likely lymphatic disorder. The postsurgical pathology confirmed the diagnosis of lymphangioma.

Cystic malformation (lymphangioma) of the thoracic lymphatic duct (peculiarities of clinical and radiological diagnosis, a brief review)

Introduction. The thoracic lymphatic duct in the upper half of the body collects lymph from the left lung, the left half of the heart, the walls of the left half of the chest, from the left upper limb and the left half of the neck and head. Therefore, the left-sided localization of the revealed pathological changes, with the involvement of the mediastinum and neck in the process at the same time, can be a sign of damage to the thoracic lymphatic duct (at the location), and therefore the key to a successful diagnosis of the disease. Aim. Demonstration of modern possibilities of clinical and radiological diagnosis of cystic malformation of the thoracic lymphatic duct (CMTLD). Results. In the literature, the pathology of the thoracic lymphatic duct is designated by two terms: “lymphangioma” and “cystic malformation of the thoracic lymphatic duct”. According to the generally accepted classification of vascular formations ISSVA (adopted at the 20th ISSVA conference in Melbourne in April 2014, last revised in May 2018), the term “lymphangioma” with regard to lymphatic malformations is considered obsolete, its use is recommended for true benign tumors of the lymphatic vessels. CMTLD – benign, extremely rare lymphovascular lesions resulting from embryological disorders (weakness of the duct wall and valve mechanism) in the development of the lymphatic system. The median prevalence is less than 1 % among all mediastinal cystic formations. Effective non-invasive diagnostics at the initial visit of the patient already at the outpatient stage deserves professional evaluation. We present the own clinical and radiological observation of a 26-year-old patient without any special clinical manifestations, in whom volumetric changes in the mediastinum on the left were detected during routine fluorography. The nature (X-ray semiotics) of preoperative imaging using computed tomography has been clarified. The revealed X-ray and pathoanatomical changes were compared. Conclusion. CMTLD – congenital lymphatic anomalies, more frequent and symptomatic in children. In older patients, acquired and asymptomatic CMTLD are most often diagnosed. The logistics of modern imaging technologies makes it possible to successfully diagnose such a rare disease as CMTLD already at the stage of the patient’s initial visit to the doctor.

Bowel perforation following percutaneous sclerotherapy of an intra-abdominal lymphatic malformation.

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.

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.

Role of ultrasound and colored Doppler examination in the diagnosis and the classification of the superficial soft tissue vascular anomalies

BackgroundVascular anomalies are congenital lesions of abnormal vascular development, and a primary distinction have to be made between a vascular tumor and a vascular malformation, hemangiomas are considered the commonest vascular tumor, correct diagnosis is imperative for appropriate treatment. In this report, we tried to verify the role of ultrasonography and Doppler examination in the initial diagnosis, the classification of vascular anomalies and in the post-treatment follow-up.Results (main findings)This report included cases of vascular anomalies who attended the interventional radiology department as well as the vascular anomaly clinic in Abo El-Rish hospitals during the period 2019 through 2021. Data of all patients attending the clinic were prospectively examined. Files of 60 cases with vascular anomalies were available for review. The diagnosis of vascular anomalies was done according to their history and characteristic findings at clinical examination as well as U/S and color Doppler examinations, MRI and angiographic studies were done as needed. A significant female predominance was noticed. A significant predominance in the head and neck region was noticed (60%). Treatment was individualized according to each case; propranolol was chosen as the first line of treatment in IH. Intra-lesional steroids injections were done in hemangiomas, and intra-lesional bleomycin was done in venous and lymphatic malformations, endovascular embolization was done in high flow vascular malformations.ConclusionUltrasound and color Doppler examination were effective and accurate methods in the diagnosis, the classification of superficial soft tissue vascular anomalies, the detection of early complications and in the follow-up after different treatment methods applied, it was also beneficial in the exclusion of non-vascular lesions.

Cystic Hygroma: 3 case reports of head and neck cystic hygroma in neonates

Objective: Congenital malformations of the lymphatic system, known as lymphatic lymphangiomas, are benign vascular tumors that are usually detected on prenatal ultrasound, and most commonly occur in the head and neck region. The aim of this paper it to report our experience with three cases of cystic hygromas along with a review of the literature. Materials and methods: Herein we present three cases of cystic hygroma detected within the neonatal period treated with ultrasound guided aspiration. Results: Following the procedure, two babies had recurrence of the lesion and then died secondary to cardiorespiratory failure. The third baby had many recurrences requiring repetitive aspiration, however, he was lost to follow up and no information is available on his current medical status. Conclusion: Different modalities of treatment have been used with variable results. However, surgical treatment remains the gold-standard of treatment.

SUCCESSFUL NON-OPERATIVE TREATMENT IN MICROCYSTIC LYMPHATIC MALFORMATION OF THE TONGUE: A CASE REPORT

Background: Microcystic lymphatic malformation (MLM) is an abnormal congenital growth of lymphatic vessels. It may occur in any part of the human body, with 75 % cases found in the head and neck, including in oral cavity. This case report aimed to describe a case of MLM in a child who was successfully treated non-operatively with antibiotics and corticosteroid. Case Report: A 4-year-old child came to Oral Medicine Clinic of Dr. Hasan Sadikin General Hospital, Bandung, with a chief complaint lesions of the tongue since a year ago, accompanied by bleeding in the affected areas but not pain. Patient gave history of recurrent episodes of the symptoms since 7 months old. Result : Ultrasonography was performed and diagnosis of microcystic lymphatic malformation was established. Systemic oral corticosteroid, antibiotics, and multivitamins were given and the lesions showed significant improvement after 2-weeks treatment. Conclusion: Therapy of MLM with antibiotics and systemic oral corticosteroid significantly improved patient’s condition, and ultrasonography may be used as a diagnostic modality in MLM diagnosis.