Update and audit of the St George's classification algorithm of primary lymphatic anomalies: a clinical and molecular approach to diagnosis.

Primary lymphatic anomalies may present in a myriad of ways and are highly heterogenous. Careful consideration of the presentation can lead to an accurate clinical and/or molecular diagnosis which will assist with management. The most common presentation is lymphoedema, swelling resulting from failure of the peripheral lymphatic system. However, there may be internal lymphatic dysfunction, for example, chylous reflux, or lymphatic malformations, including the thorax or abdomen. A number of causal germline or postzygotic gene mutations have been discovered. Some through careful phenotyping and categorisation of the patients based on the St George's classification pathway/algorithm. The St George's classification algorithm is aimed at providing an accurate diagnosis for patients with lymphoedema based on age of onset, areas affected by swelling and associated clinical features. This has enabled the identification of new causative genes. This update brings the classification of primary lymphatic disorders in line with the International Society for the Study of Vascular Anomalies 2018 classification for vascular anomalies. The St George's algorithm considers combined vascular malformations and primary lymphatic anomalies. It divides the types of primary lymphatic anomalies into lymphatic malformations and primary lymphoedema. It further divides the primary lymphoedema into syndromic, generalised lymphatic dysplasia with internal/systemic involvement, congenital-onset lymphoedema and late-onset lymphoedema. An audit and update of the algorithm has revealed where new genes have been discovered and that a molecular diagnosis was possible in 26% of all patients overall and 41% of those tested.

Guidelines (short version) of the French Society of Otorhinolaryngology (SFORL) on cervical lymphatic malformation in adults and children: Diagnosis.

OBJECTIVES: The authors present the guidelines of the French Society of Otorhinolaryngology (SFORL) for the diagnosis of cervical lymphatic malformation in adults and children. METHODS: A multidisciplinary work group was entrusted with a review of the scientific literature on the above topic. Guidelines were drawn up, based on the articles retrieved and the group members' individual experience. They were then read over by an editorial group independent of the work group, and finalized in a coordination meeting. Guidelines were graded A, B, C or expert opinion, by decreasing level of evidence. RESULTS: The SFORL recommends that complete ENT examination should be performed to identify lesions at high risk of complication or associated with poor prognosis. In case of diagnostic doubt, especially in latero-cervical or oral floor lesions, fine-needle aspiration cytology should be performed before therapeutic decision-making. One or more validated classifications should be used to assess treatment efficacy and monitor progression. The reliability of antenatal diagnosis should be ensured by associating MRI to ultrasound. In antenatal diagnosis, the locoregional extension of the cervical lymphatic malformation should be evaluated accurately for prognosis, and associated malformations should be screened for, to guide treatment options.

Vascular Anomalies (Part I): Classification and Diagnostics of Vascular Anomalies.

BACKGROUND: Vascular anomalies are a diagnostic and therapeutic challenge. They require dedicated interdisciplinary management. Optimal patient care relies on integral medical evaluation and a classification system established by experts in the field, to provide a better understanding of these complex vascular entities. METHOD: A dedicated classification system according to the International Society for the Study of Vascular Anomalies (ISSVA) and the German Interdisciplinary Society of Vascular Anomalies (DiGGefA) is presented. The vast spectrum of diagnostic modalities, ranging from ultrasound with color Doppler, conventional X-ray, CT with 4 D imaging and MRI as well as catheter angiography for appropriate assessment is discussed. RESULTS: Congenital vascular anomalies are comprised of vascular tumors, based on endothelial cell proliferation and vascular malformations with underlying mesenchymal and angiogenetic disorder. Vascular tumors tend to regress with patient's age, vascular malformations increase in size and are subdivided into capillary, venous, lymphatic, arterio-venous and combined malformations, depending on their dominant vasculature. According to their appearance, venous malformations are the most common representative of vascular anomalies (70 %), followed by lymphatic malformations (12 %), arterio-venous malformations (8 %), combined malformation syndromes (6 %) and capillary malformations (4 %). CONCLUSION: The aim is to provide an overview of the current classification system and diagnostic characterization of vascular anomalies in order to facilitate interdisciplinary management of vascular anomalies. KEY POINTS: · Vascular anomalies are comprised of vascular tumors and vascular malformations, both considered to be rare diseases.. · Appropriate treatment depends on correct classification and diagnosis of vascular anomalies, which is based on established national and international classification systems, recommendations and guidelines.. · In the classification, diagnosis and treatment of congenital vascular anomalies, radiology plays an integral part in patient management.. CITATION FORMAT: · Sadick M, Müller-Wille R, Wildgruber M et al. Vascular Anomalies (Part I): Classification and Diagnostics of Vascular Anomalies. Fortschr Röntgenstr 2018; 190: 825 - 835.

Update on classification and diagnosis of vascular malformations.

PURPOSE OF REVIEW: This review provides an update of the classification in the classification of vascular anomalies since April 2014 at the International Society for the Study of Vascular Anomalies meeting in Melbourne, Australia. RECENT FINDINGS: The reader will become familiar with how to diagnose the major vascular malformations, including capillary, venous, arteriovenous, and lymphatic and combinations thereof. In addition, vascular malformation syndromes, including those with overgrowth, will be clarified. SUMMARY: Vascular malformations are common. Capillary malformations are now better understood through an updated classification. Verrucous hemangioma is truly a venulocapillary malformation that extends into the subcutis. PIK3Ca-Related Overgrowth Syndromes encompass Klippel-Trenaunay, Congenital Lipomatous Asymmetric Overgrowth of the Trunk with Lymphatic, Capillary, Venous, and Combined-Type Vascular Malformations, Epidermal Nevi, Scoliosis/Skeletal and Spinal Anomalies, Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome (M-CAP), fibroadipose hyperplasia, and macrodactyly. Yet another syndrome should be highlighted: Capillary Malformation of the Lower Lip, Lymphatic Malformation of the Face and Neck, Asymmetry and Partial/Generalized Overgrowth. Knowledge of the genetic basis of vascular malformations will lead to future treatments.

Considerations for Management of Head and Neck Lymphatic Malformations in Children.

OBJECTIVE: There exist inherent problems with previously described classification schemes for head and neck lymphatic malformations in children and lack of guidance for management. An organization scheme and management recommendations are proposed to improve communication between health care providers. STUDY DESIGN: Consecutive patient series with a chart review of children with head and neck lymphatic malformations. SETTING: Tertiary-care, academic children's hospital. METHODS: Children with lymphatic malformations of the head and neck were included. A proposed organization system for head and neck lymphatic malformations in children was developed and compared to 2 others currently predominantly used, de Serres and Cologne Disease Score. RESULTS: Seventeen patients were identified, 7 boys and 10 girls. The mean age was 64.4 months (range 0.89-185.5). Nine patients (52.9%) were managed expectantly, 5 (29.4%) with sclerotherapy with 1 awaiting treatment (5.9%), and 2 (11.8%) with surgical excision. All children who underwent active treatment with surgery or sclerotherapy were managed successfully. No treatment-related complications were encountered, and no children managed with watchful waiting/expectant management experienced failure. The proposed staging system differed from the de Serres stage in 11 children (64.7%), with 9 (81.8%) being down staged and 2 (18.2%) up staged. Cologne Disease Score ranged from 2 to 10, with only 1 (5.9%) patient with a score of 3 or less (severe disease). CONCLUSIONS: Treatment recommendations in children with head and neck lymphatic malformations should be individualized. Weaknesses of currently used staging systems are discussed as well as considerations for management decisions.

Pediatric lymphatic malformations: evolving understanding and therapeutic options.

Multimodal treatment of lymphatic malformations continues to expand as new information about the biology and genetics of these lesions is discovered, along with knowledge gained from clinical practice. A patient-centered approach, ideally provided by a multidisciplinary medical and surgical team, should guide timing and modality of treatment. Current treatment options include observation, surgery, sclerotherapy, radiofrequency ablation, and laser therapy. New medical and surgical therapies are emerging, and include sildenafil, propranolol, sirolimus, and vascularized lymph node transfer. The primary focus of management is to support and optimize these patients' quality of life. Researchers continue to study lymphatic malformations with the goal of increasing therapeutic options and developing effective clinical pathways for these complicated lesions.

Lymphatic malformations: diagnosis and management.

Lymphatic malformations are benign vascular lesions that arise from embryological disturbances in the development of the lymphatic system. They encompass a wide spectrum of related abnormalities, including cystic lymphatic lesions, angiokeratoma, lymphatic malformations that occur in bones (Gorham-Stout Syndrome), lymphatic and chylous leak conditions, and lymphedema. This article will focus only on lymphatic malformation mass lesions, whereas other related disease entities will be covered elsewhere in this journal issue. Lymphatic malformations occur frequently in lymphatic-rich areas such as the head and neck region, but they can also be found on any anatomical site in the body. In general, lymphatic malformations are categorized into macrocystic, microcystic, or combined depending on the size of the cysts contained within the lesion. Lymphatic malformations can cause both deformation of the anatomical site involved and functional deficits. The goal of this article is to discuss the etiology, epidemiology, treatment modalities, and comorbidities associated with lymphatic malformations.

Histopathology of vascular anomalies.

Vascular anomalies may be appropriately classified into two broad categories, vascular tumors and vascular malformations, which are distinguished by the presence of cellular proliferation in contrast to aberrations in morphogenesis, respectively. This system of classification is based upon histological features that may in large part be differentiating, but nevertheless, may show morphological overlap. Advances in immunophenotyping allow for more precise diagnoses as well as further delineation of cell origins. In the discussion, we present the clinical, histological, and, when applicable, the immunophenotypic presentation of vascular anomalies commonly seen in infancy and early childhood.

Classification of lymphatic-system malformations in primary lymphoedema based on MR lymphangiography.

OBJECTIVES: The study aims to investigate lymphatic-system malformations and proposes a classification of primary lymphoedema based on comprehensive imaging data of both lymph vessel- and lymph-node abnormalities. MATERIALS AND METHODS: A total of 378 patients with primary lymphoedema of the lower extremity were examined with magnetic resonance lymphangiography (MRL) using gadobenate dimeglumine as contrast agent. Lymph vessels and drainage lymph nodes were evaluated, leading to the proposal of the classification of primary lymphoedema and the relative proportions. RESULTS: A total of 63 (17%) patients exhibited defects of the inguinal lymph nodes with mild or moderate dilatation of afferent lymph vessels. A total of 123 (32%) patients exhibited lymphatic anomalies as lymphatic aplasia, hypoplasia or hyperplasia with no obvious defect of the drainage lymph nodes. The involvement of both lymph vessel- and lymph-node abnormalities in the affected limb was found in 192 (51%) patients. The primary lymphoedema was classified as three major types as: (1) lymph nodes affected only; (2) lymph vessel affected only with three subtypes and (3) both lymph vessel and lymph node affected with subgroups. CONCLUSIONS: A comprehensive classification of lymphatic-system malformation in primary lymphoedema is proposed, which clearly defines the location and pathologic characteristics of both lymphatics and lymph node and may lead to further study of the aetiology as well as rational treatment of the disease.

Lymphatic malformation: risk of progression during childhood and adolescence.

Lymphatic malformations (LMs) in soft tissues tend to enlarge over time, causing distortion, obstruction, and functional problems. The purpose of this study was to determine the natural progression of LMs to facilitate patient counseling, gain insight into pathophysiology, and guide therapy. Our Vascular Anomalies Center database was reviewed for patients with cutaneous and soft tissue LMs; combined or visceral lesions were excluded. Predictive variables were age, channel type (macrocystic, microcystic, combined), sex, lesion size (localized, diffuse), and location (head/neck, extremities, trunk). The outcome variable was natural progression of the malformation defined by expansion or the onset/worsening of signs and symptoms. The study included 441 patients: 234 females (53.1%) and 207 males (46.9%). Lymphatic malformations were located in the head/neck (61.2%), extremities (17.5%), trunk (16.1%), or multiple sites (5.2%). Children had a 42.2% risk of progression before adolescence, 84.7% before adulthood, and 95.3% during their lifetime. Progression was more likely in adolescence (63.8%) than in childhood (40.8%); the odds ratio was 2.6 (P=0.003). Diffuse LMs worsened more often than localized lesions (P=0.001), whereas channel type (P=0.63), sex (P=0.42), and location (P=0.28) did not influence progression.Lymphatic malformations have a greater risk of progression in adolescence than in childhood; pubertal hormones may contribute to expansion. Because of this high rate of progression, early treatment of asymptomatic LMs should be considered.

[Hereditary vascular malformations: classification, symptoms, diagnostics and prognosis]. / Angeborene Gefäßmalformationen: Klassifikation, Symptome, Diagnostik und Prognose.

The understanding of hereditary vascular anomalies was hampered for a long time by unclear und unspecific terminology. Today, the classification of the International Society for the Study of Vascular Anomalies (ISSVA) differentiates between vascular tumours (mostly infantile haemangioma) with active endothelial proliferation and regression and vascular malformations (VM), which are defects of the vascular morphogenesis and are distinguished in predominantly venous, arterial, capillary, lymphatic, arteriovenous or combined VM. Symptoms are pain, swelling and restricted movement, accompanied by skin signs like dys-plastic veins and capillary VM (naevus flammeus). Thrombophlebitis and chronic venous insufficiency are related to venous VM. Arteriovenous VM are progressive and can cause ischaemic necroses, in rare cases even a high-output cardiac fail-ure. Lymphatic VM lead to localised swelling, in the long run often to recurrent erysipelas and lymphorroea. Primary imaging is provided by -ul-trasound including flow measurements. Mor-phol-ogy and organ involvement is best delineated by magnetic resonance imaging. Phlebography is used to image deep venous system anomalies and is always accompanied by varicography of the dysplastic parts of the venous VM. Digital subtraction angiography is performed to demon-strate the flow pattern in feeding arteries, the nidus and the drainage veins of arteriovenous VM. Besides size and localisation the prognosis of the patients is determined by the pressure (the high-er the pressure, the poorer the prognosis) and the flow rate (the higher the flow rate, the poorer the prognosis) in the VM. Diagnosis and treatment of these rare diseases are best performed in special-ised, interdisciplinary centres.

Hobnail hemangioma reclassified as superficial lymphatic malformation: a study of 52 cases.

BACKGROUND: Hobnail hemangioma (HH) is currently classified as a benign vascular tumor, although it is not well understood whether this lesion differentiates toward blood or lymphatic endothelial cells. Immunostaining with the endothelial marker Wilms tumor 1 (WT1) helps distinguish between vascular neoplasms and malformations, being positive in the former and negative in the latter. OBJECTIVE: We sought to investigate WT1, human herpesvirus 8 latent nuclear antigen, D2-40, and Ki-67 immunoprofile in HH, to gain further insight into its histogenesis. METHODS: We evaluated 52 HHs collected in Dermatohistopathologische Gemeinschaftslabor, Friedrichshafen, Germany. Immunohistochemical expression of WT1 was performed in all cases. Ten of 52 lesions were also studied for D2-40 and Ki-67 staining and 12 lesions were stained for human herpesvirus 8 latent nuclear antigen. RESULTS: All 52 HHs were completely negative for WT1 immunostaining. Immunohistochemistry performed in 10 HHs showed diffuse and strong positive staining for D2-40 in 8 lesions and focal positivity in two. All cases tested showed negative staining for Ki-67 and human herpesvirus 8 latent nuclear antigen. LIMITATIONS: There are no limitations. CONCLUSIONS: Although the exact histogenesis of HH is unknown, most of the performed immunohistochemical studies support a lymphatic line of differentiation. However, on the basis of the WT1 negativity, we believe that HH is better considered as a lymphatic malformation rather than a lymphatic neoplasm.

Lymphatic malformations involving the parotid gland.

INTRODUCTION: Cases of salivary gland involvement of lymphatic malformations have been occasionally reported in the literature. Of all the lymphatic malformations in the salivary glands, the parotid is the most common site. The present study aimed to analyze a series of lymphatic malformations of the parotid gland. MATERIALS AND METHODS: A retrospective analysis of the localization, symptoms, management and outcome was performed. RESULTS: Out of a total of 20 patients with lymphatic malformations of the parotid gland, 4 patients suffered from lymphatic malformations limited to the parotid gland (type I) and 16 patients from extensive cervicofacial lymphatic malformations involving the parotid gland (typeII). In 2 cases with type I disease and 4 cases with type II disease the malformations could be completely resected. In 3 patients with type II lymphatic malformations a partial resection was performed. The other patients were closely observed. 8 of them had already been treated elsewhere with surgery, sclerotherapy or laser therapy. One patient suffered from facial paralysis and 1 from transient facial nerve weakness immediately after surgery. In all, 11 patients suffered from persistent lymphatic malformations despite several attempts to reduce or resect the lymphatic malformation. CONCLUSION: The treatment of lymphatic malformations of the parotid gland remains challenging and persistent disease after therapy is common. Care should be taken to excise the entire malformation during initial surgery in order to avoid recurrence.

Vascular malformations.

Vascular malformations are rare but important skin disorders in children, which often require multidisciplinary care. The goal of this article is to orient pediatricians to the various types of vascular malformations. We discuss the clinical characteristics, diagnostic criteria, and management of capillary, venous, arteriovenous, and lymphatic malformations. Associated findings and syndromes are also discussed briefly.

Primary lymphoedema and lymphatic malformation: are they the two sides of the same coin?

OBJECTIVES: To clear the confusion regarding the relationship between the 'primary lymphoedema' and (truncular) lymphatic malformation (LM); the latter is one of congenital vascular malformations. MATERIALS & METHODS: A literature review was carried out on the primary lymphoedema either existing as an independent LM lesion or as a component of the Klippel-Trenaunay syndrome. RESULTS: The review was able to provide a contemporary guide/conclusion on the definition and classification, clinical evaluation and clinical management regarding conservative (physical) therapy, reconstructive surgical therapy and ablative/excisional surgical therapy, for the primary lymphoedema as an LM. CONCLUSIONS: Primary lymphoedema can be considered as 'congenital' since its majority represents a clinical manifestation of the truncular type of LM arising during the later stages of lymphangiogenesis. Such embryological staging information of the LM is critical for proper management of the primary lymphoedema when it exists with other congenital vascular malformations (Klippel-Trenaunay syndrome). 2. Basic non-invasive to minimally invasive tests will provide an adequate diagnosis and lead to the correct multidisciplinary, specifically targeted and sequenced treatment strategy. 3. The mainstay of current management of the primary lymphoedema/truncular LM is complex decongestive therapy; and the reconstructive as well as ablative surgical therapy remain adjunctive therapies at best.

Vascular birthmarks.

Vascular birthmarks can be classified into hemangioma and vascular malformations. Hemangioma are frequent tumours of early infancy demonstrating endothelial hyperplasia, a history of rapid neonatal growth and slow involution during later childhood. Treatment of hemangioma is dependent of stage and type of the lesion. Given the current availability of drugs, lasers, and other techniques to treat hemangioma safely, philosophy of "benign neglect" should not be considered anymore. Vascular malformations show a normal endothelial turnover, being present at birth and growing commensurately with the child. Exact diagnosis by employing modern diagnostic means,which are able to differentiate low-flow from high flow lesions is important for further therapeutic management. Beside conservative treatment strategies, use of laser, sclerotherapy, interventional embolization and surgical treatment are possible management options. Patients should receive multidisciplinary care in qualified vascular centres.