Vascular Anomalies: Nomenclature and Diagnosis.

Before the development of the International Society for the Study of Vascular Anomalies (ISSVA) classification system in 1996, nomenclature used to describe vascular lesions was inconsistent and imprecise. This since widely adopted system stratifies vascular anomalies into vascular malformations and tumors. Vascular tumors involve abnormal proliferation of vascular cells and are further classified as benign, locally aggressive/borderline, or malignant. Vascular malformations are lesions of defective vascular morphogenesis with quiescent endothelium and are named according to their vessel composition, and subdivided into simple; combined, of major named vessels; and syndrome-associated malformations. The updated 2018 ISSVA criteria are referenced in this review.

ISSVA Classification of Vascular Anomalies and Molecular Biology.

Vascular anomalies include various diseases, which are classified into two types according to the International Society for the Study of Vascular Anomalies (ISSVA) classification: vascular tumors with proliferative changes of endothelial cells, and vascular malformations primarily consisting of structural vascular abnormalities. The most recent ISSVA classifications, published in 2018, detail the causative genes involved in many lesions. Here, we summarize the latest findings on genetic abnormalities, with the presentation of the molecular pathology of vascular anomalies.

Genes and phenotypes in vascular malformations.

Vascular malformations (VMs) are caused by localized defects of vascular development. Most VMs are due to sporadic, postzygotic mutations, while some are the result of autosomal dominant germline mutations. Genotype-phenotype correlation is influenced by many factors. Individual genes can induce different phenotypes (pleiotropy), and similar phenotypes can be due to different genes/mutations (redundancy). The phenotypic spectrum of somatic mutations is wide, and depends on variant allele frequency, timing during embryogenesis, cell type(s) involved and type of mutation. The phenotype of germline mutations is determined by penetrance and expressivity, and is influenced by epigenetic factors (DNA methylation, histone modification) or 'second-hit' somatic mutations. Except for disorders with pathognomonic phenotypes such as Proteus syndrome or a characteristic constellation of symptoms such as CLOVES [congenital lipomatous (fatty) overgrowth, vascular malformations, epidermal naevi and scoliosis/skeletal/spinal anomalies] or PIK3CA-related overgrowth spectrum syndrome, differential diagnosis of VM is therefore difficult. It will be greatly facilitated with increasing analytic sensitivity of sequencing techniques such as next-generation sequencing. High-sensitivity molecular techniques are a prerequisite for targeted pharmacotherapy, i.e. selective therapeutic inhibition of activating mutations underlying VM, which has shown promising results in preliminary studies.

Quadrifurcation Variants of the Celiac Trunk.

BACKGROUND: The celiac trunk (CT) commonly trifurcates into the left gastric artery, common hepatic artery (CHA), and splenic artery (SA). The CHA then sends off the proper hepatic artery and gastroduodenal artery (GDA). The arcades of the head of the pancreas are celiacomesenteric anastomoses between branches of the GDA and the superior mesenteric artery. A quadrifurcation of the CT commonly occurs when a different branch is added to the 3 normal ones. An uncommon quadrifurcation of the CT occurs when only one or 2 of the normal branches of the CT participate. METHODS: The CT quadrifurcations were documented on 112 computed tomography angiograms. RESULTS: Five different types of CT quadrifurcation-3 uncommon (types 1-3) and 2 common (types 4-5)-were found in 15/112 cases (13.39%). A marginal significant association was found between the presence of quadrifurcations and male gender (P = 0.05; Fisher's exact test). Type 1 showed a hepatogastric trunk+SA + right hepatic artery+GDA pattern, type 2 had an HGT + right inferior phrenic artery + CHA + SA pattern, type 3 had a gastrophrenic trunk + left inferior phrenic artery+CHA + SA pattern, type 4 showed an left gastric artery + CHA + SA + left inferior phrenic artery combination, and type 5 had an additional common inferior phrenic trunk. One of the type 4 cases showed a buildup of a mesentericomesenteric anastomotic pancreatic arcade between the inferior pancreaticoduodenal arteries, rather than a celiacomesenteric one. CONCLUSIONS: Anatomic variation of the celiacomesenteric axis is important during hepatobiliary and duodenopancreatic approaches. Therefore, preoperative evaluation is essential because theoretical anatomic possibilities could be real arterial variants.

Contemporary Management of Vascular Anomalies of the Head and Neck-Part 1: Vascular Malformations: A Review.

Importance: Vascular anomalies of the head and neck are relatively rare lesions. Management is challenging because of the high likelihood of involvement of functionally critical structures. Multiple modalities of treatment exist for vascular anomalies of the head and neck, including medical therapies, sclerotherapy and embolization procedures, and surgery. This review focuses on the accurate diagnosis and the relative roles of the various therapeutic options. Observations: Vascular anomalies are classified by the International Society for the Study of Vascular Anomalies into 2 major groups: vascular tumors and vascular malformations. Vascular tumors encompass proliferative lesions ranging from infantile and congenital hemangiomas to kaposiform hemangioendothelioma. Alternatively, vascular malformations are embryologic errors in vasculogenesis. This article focuses on the management of vascular malformations. The 3 primary vascular malformation subclassifications are lymphatic, venous, and arteriovenous. The burden of disease, diagnosis, and current management options are discussed in detail for each subtype. Conclusions and Relevance: Most vascular malformations of the head and neck require a multidisciplinary approach. Available medical, interventional radiologic, and surgical interventions are constantly evolving. Optimization of function and cosmesis must be balanced with minimization of treatment-associated morbidity. Otolaryngologists-head and neck surgeons must remain up to date regarding options for diagnosis and management of these lesions.

Thermography for the differential diagnosis of vascular malformations.

Vascular malformations classification may pose a diagnostic challenge for physicians. In the early stages, they are diagnosed clinically mainly by visual inspection. For a deeper analysis, Doppler ultrasonography is the preferred technique to determine the haemodynamic behaviour of the anomaly. However, this imaging method is not always available and it requires trained operators to acquire and interpret the images. There is a lack of portable and user-friendly systems that may help physicians in the assessment of vascular malformations. We propose a new diagnostic procedure, more affordable and easier to use, based on a portable thermal camera. This technique provides information about temperature, which has been found to be correlated with the flow rate of the lesion. In our study, > 60 vascular malformations of previously diagnosed patients were analysed with a thermal camera to classify them into low-flow and high-flow malformations. The value was 1 for both sensitivity and specificity of this technique.

Newcomers in Vascular Anomalies.

Vascular anomalies are composed of tumors and malformations and with overlapping histologies, thus are often misdiagnosed or labeled with imprecise terminology. Lesions are common and usually diagnosed during infancy or childhood; the estimated prevalence is 4.5%. Vascular tumors rapidly enlarge postnatally and demonstrate endothelial proliferation. Malformations are errors in vascular development with stable endothelial turnover; they are typically named based on the primary vessel that is malformed (capillary, arterial, venous, lymphatic). This article reviews the pathologic and molecular genetic characteristics for select recently described vascular anomalies.

Emerging importance of molecular pathogenesis of vascular malformations in clinical practice and classifications.

Vascular malformations occur during early vascular development resulting in abnormally formed vessels that can manifest as arterial, venous, capillary or lymphatic lesions, or in combination, and include local tissue overdevelopment. Vascular malformations are largely caused by sporadic somatic gene mutations. This article aims to review and discuss current molecular signaling pathways and therapeutic targets for vascular malformations and to classify vascular malformations according to the molecular pathways involved. A literature review was performed using Embase and Medline. Different MeSH terms were combined for the search strategy, with the aim of encompassing all studies describing the classification, pathogenesis, and treatment of vascular malformations. Major pathways involved in the pathogenesis of vascular malformations are vascular endothelial growth factor (VEGF), Ras/Raf/MEK/ERK, angiopoietin-TIE2, transforming growth factor beta (TGF-ß), and PI3K/AKT/mTOR. These pathways are involved in controlling cellular growth, apoptosis, differentiation, and proliferation, and play a central role in endothelial cell signaling and angiogenesis. Many vascular malformations share similar aberrant molecular signaling pathways with cancers and inflammatory disorders. Therefore, selective anticancer agents and immunosuppressants may be beneficial in treating vascular malformations of specific mutations. The current classification systems of vascular malformations, including the International Society of the Study of Vascular Anomalies (ISSVA) classification, are primarily observational and clinical, and are not based on the molecular pathways involved in the pathogenesis of the condition. Several molecular pathways with potential therapeutic targets have been demonstrated to contribute to the development of various vascular anomalies. Classifying vascular malformations based on their molecular pathogenesis may improve treatment by determining the underlying nature of the condition and their potential therapeutic target.

Radiological classification of azygos anterior cerebral artery and evaluation of the accompanying vascular anomalies.

PURPOSE: There is not a classification of azygos anterior cerebral artery (ACA) based on anatomical branching levels in the literature. In the present study, a classification of azygos ACA was made based on radiological imaging for a common terminology, and frequency, accompanying vascular anomalies and malformations were investigated. METHODS: A total of 4913 cases who had brain CTA, MRA, contrast-enhanced MRI and DSA in January 2010-January 2020 period were screened for the study. Based on anatomical branching level, azygos ACAs were classified into four groups. Aneurysms, anomalies and malformations accompanying azygos ACA were identified. The associations of azygos ACA types with the presence of aneurysm or ACA A1 segment anomalies were investigated. RESULTS: Azygos ACA was observed in 57 cases (29 male and 28 female) and frequency of azygos ACA was 1.16%. Average age of the cases with ACA was 56.19 ± 19.65 years. Forty-eight of the cases had type C azygos ACA, four cases type B, four cases type D and one case type A azygos ACA. A total of nine intracranial aneurysms were identified in seven of the cases (12.28%). Five of the aneurysms were located in MCA and four in distal ACA. Most common vascular anomalies accompanying azygos ACA were unilateral vertebral artery hypoplasia and ACA A1 segment hypoplasia. Azygos types did not have significant correlations with the presence of aneurysms or ACA A1 segmental anomalies (p = 0.683 and p = 0.949, respectively). CONCLUSION: Azygos ACA is a rare variation, but it could be accompanied by aneurysms or other vascular anomalies.

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.

Japanese clinical practice guidelines for vascular anomalies 2017.

The objective was to prepare guidelines to perform the current optimum treatment by organizing effective and efficient treatments of hemangiomas and vascular malformations, confirming the safety, and systematizing treatment, employing evidence-based medicine (EBM) techniques and aimed at improvement of the outcomes. Clinical questions (CQs) were decided based on the important clinical issues. For document retrieval, key words for literature searches were set for each CQ and literature published from 1980 to the end of September 2014 was searched in Pubmed, Cochrane Library, and Japana Centra Revuo Medicina (JCRM). The strengths of evidence and recommendations acquired by systematic reviews were determined following the Medical Information Network Distribution System (MINDS) technique. A total of 33 CQs were used to compile recommendations and the subjects included efficacy of resection, sclerotherapy/embolization, drug therapy, laser therapy, radiotherapy, and other conservative treatment, differences in appropriate treatment due to the location of lesions and among symptoms, appropriate timing of treatment and tests, and pathological diagnosis deciding the diagnosis. Thus, the Japanese Clinical Practice Guidelines for Vascular Anomalies 2017 have been prepared as the evidence-based guidelines for the management of vascular anomalies.

Benign vascular anomalies: A transition from morphological to etiological classification.

The International Society for the Study of Vascular Anomalies (ISSVA) devised a multidisciplinary etiopathogenesis based approach to classify benign vascular anomalies into tumors and malformations. This classification scheme has major therapeutic and prognostic implications as treatment modalities differ for both the categories. Inappropriate usage of the term "hemangioma" for etiopathogenetically distinct entities is commonly seen in clinical practice leading to delivery of incorrect treatment to the patients. We aimed to study the histomorphological and immunohistochemical features of benign vascular anomalies for their precise histopathological classification. A total of 48 cases diagnosed over a period of 3.5 years were reviewed and reclassified into vascular tumors and malformations based on ISSVA classification and prototypical histopathological features. Biopsies were reviewed based on 5 histopathological criteria viz. endothelial morphology, mitotic activity, intralesional nerve bundles, intralesional inflammation, and prominent vessel type. A panel of GLUT-1, WT-1, and Ki-67 was performed in each case. Seven cases of infantile hemangioma, 4 cases each of non-involuting congenital hemangioma and pyogenic granuloma, and 33 cases of vascular malformations were diagnosed. Endothelial cell morphology (p < 0.001), mitotic activity (p < 0.001), and intralesional nerve bundles (p < 0.001) were found to be statistically significant in differentiating hemangioma from malformations. GLUT-1 (p < 0.001) and Ki-67 labeling index (p < 0.001) were useful to distinguish infantile hemangioma from vascular malformations. To conclude, the ISSVA classification of benign vascular anomalies can be reliably done on histopathology. However, every case must be interpreted in the light of clinical and radiological features.

Anomalías Vasculares de la Cavidad Oral: Revisión de la Clasificación y Tratamiento Aplicado a dos Casos Clínicos / Vascular Anomalies of the Oral Cavity: Review of Classification and Treatment Applied to Two Clinical Cases

RESUMEN: Las anomalías vasculares de cabeza y cuello son un grupo de lesiones que afectan vasos sanguíneos y linfáticos donde el tratamiento sigue siendo un desafío. La clasificación actualizada de anomalías vasculares de cabeza y cuello es la clasificación de Mulliken modificada, que las subdivide en a) tumores vasculares y, b) malformaciones vasculares. En este reporte, presentamos dos casos clínicos de pacientes de sexo masculino, con diagnóstico de anomalías vasculares que afectan al labio y paladar duro, diagnosticados como malformación arteriovenosa y malformación venosa, respectivamente. Dichas lesiones remitieron completamente mediante tratamientos conservadores (agentes esclerosantes) y/o quirúrgicos (exéresis quirúrgica completa de la lesión) logrando una remisión completa. Consecutivamente, presentamos una revisión de la literatura enfocado a la clasificación actual, enfoques terapéuticos actuales y futuros.

ABSTRACT: Vascular anomalies of the head and neck are a group of lesions that affect blood and lymph vessels where treatment remains a challenge. The updated classification of head and neck vascular anomalies is the modified Mulliken classification, which subdivides them into a) vascular tumors and b) vascular malformations. In this report, we present two clinical cases of male patients, with diagnosis of vascular anomalies affecting the lip and hard palate, diagnosed as arteriovenous malformation and venous malformation, respectively. These lesions were completely treated with conservative (sclerosing agents) and/or surgical (complete surgical exeresis of the lesion) treatments, achieving a complete remission. Consequently, we present a review of the literature focused on the current classification, current and future therapeutic approaches.

Hepatic arterial system anomalies encountered during pancreaticoduodenectomy - our experience.

We present our experience of incidence and management of aberrant hepatic arterial anatomy encountered during pancreaticoduodenectomy (PD). Patients undergoing PD between December 2014 and November 2016 at the Shaukat Khanum Memorial Cancer Hospital, Lahore were included in this short report. Preoperative imaging and operative findings of these patients were reviewed to evaluate the hepatic arterial anatomy and classified according to Hiatt classification. Sixty-four PD were performed with aberrant arterial anatomy identified in 24 (37.5%) of the cases. Most common anomaly was replaced right hepatic artery (rRHA) arising from the superior mesenteric artery seen in seven (11%) of the patients. Aberrant vessels were recognised and preserved in 23 cases. In one patient, the rRHA was coursing through the pancreatic parenchyma needing resection and reconstruction with uneventful postoperative recovery. Hepatic arterial anomalies are common and it is possible to preserve these vessels with careful surgical dissection using artery first technique.

Tratamiento farmacológico de las anomalías vasculares / Drug treatment of vascular anomalies

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Brief Description of ISSVA Classification for Radiologists.

Ongoing discovery regarding the origin and treatment of vascular anomalies requires standardized nomenclature which itself must undergo iterative updating. This article introduces the 2018 International Society for the Study of Vascular Anomalies (ISSVA) classification, emphasizing the biologic basis of vascular anomalies, summarizing the key features of commonly encountered entities, and serving as a foundation for subsequent articles presented herein. Vascular tumors are discussed to highlight their distinction from vascular malformations which will receive greater attention with respect to management and technical considerations within the issue.

[Interventional therapies of vascular malformations]. / Interventionelle Behandlungsoptionen bei vaskulären Malformationen.

Vascular malformations can appear at any age and in every region of the body. Due to their rare appearance and differences in clinical manifestations the appropriate diagnosis and subsequent classification remains challenging. Once the diagnosis is established, various treatment options exist, requiring an interdisciplinary approach. This review provides an overview over state-of-the-art interventional therapies of vascular malformations.