International Society For The Study Of Vascular Anomalies Classification Research Articles

Discussion on pathological diagnosis of vascular diseases based on ISSVA classification

The diagnosis of vascular diseases is not only about distinguishing neoplastic or non-neoplastic lesions, but also focusing more on emphasizing the essence of the disease, namely the presence or absence of endothelial cell proliferation, and further to distinguishing true hemangioma tumors or vascular malformation. This article is based on the International Society for the Study of Vascular Anomalies (ISSVA) classification, which is widely used in clinical practice, and discusses the related pathological diagnosis issues of vascular diseases.

Vascular Malformations and Tumors: A Review of Classification and Imaging Features for Cardiothoracic Radiologists.

The International Society for the Study of Vascular Anomalies (ISSVA) classification is a comprehensive histology-based scheme that was updated in 2018. It is important for cardiothoracic imagers to understand this classification to ensure that accurate terminology is used and that archaic terms are avoided when vascular lesions are described. Knowledge of the various malformations (including common conditions, such as venous malformation, arteriovenous fistula, and arteriovenous malformation) and vascular tumors allows for timely diagnosis and appropriate management. This review describes various vascular anomalies, in accordance with ISSVA classification and terminology; highlights key imaging features associated with each; and discusses the role of different imaging modalities. Keywords: Pulmonary, Soft Tissues/Skin, Vascular, Arteriovenous Malformation © RSNA, 2023.

Clinical phenotype of adolescent and adult patients with extracranial vascular malformation

ObjectiveIn recent years, genotypic characterization of congenital vascular malformations (CVMs) has gained attention; however, the spectrum of clinical phenotype remains difficult to attribute to a genetic cause and is rarely described in the adult population. The aim of this study is to describe a consecutive series of adolescent and adult patients in a tertiary center, where a multimodal phenotypic approach was used for diagnosis. MethodsWe analyzed clinical findings, imaging, and laboratory results at initial presentation, and set a diagnosis according to the International Society for the Study of Vascular Anomalies (ISSVA) classification for all consecutively registered patients older than 14 years of age who were referred to the Center for Vascular Malformations at the University Hospital of Bern between 2008 and 2021. ResultsA total of 457 patients were included for analysis (mean age, 35 years; females, 56%). Simple CVMs were the most common (n = 361; 79%), followed by CVMs associated with other anomalies (n = 70; 15%), and combined CVMs (n = 26; 6%). Venous malformations (n = 238) were the most common CVMs overall (52%), and the most common simple CVMs (66%). Pain was the most frequently reported symptom in all patients (simple, combined, and vascular malformation with other anomalies). Pain intensity was more pronounced in simple venous and arteriovenous malformations. Clinical problems were related to the type of CVM diagnosed, with bleeding and skin ulceration in arteriovenous malformations, localized intravascular coagulopathy in venous malformations, and infectious complications in lymphatic malformations. Limb length difference occurred more often in patients with CVMs associated with other anomalies as compared with simple or combined CVM (22.9 vs 2.3%; P < .001). Soft tissue overgrowth was seen in one-quarter of all patients independent of the ISSVA group. ConclusionsIn our adult and adolescent population with peripheral vascular malformations, simple venous malformations predominated, with pain as the most common clinical symptom. In one-quarter of cases, patients with vascular malformations presented with associated anomalies on tissue growth. The differentiation of clinical presentation with or without accompanying growth abnormalities need to be added to the ISSVA classification. Phenotypic characterization considering vascular and non-vascular features remains the cornerstone of diagnosis in adult as well as pediatric patients.

Vascular Anomaly Syndromes in the ISSVA Classification System: Imaging Findings and Role of Interventional Radiology in Management.

Vascular anomalies encompass a spectrum of tumors and malformations that can cause significant morbidity and mortality in children and adults. Use of the International Society for the Study of Vascular Anomalies (ISSVA) classification system is strongly recommended for consistency. Vascular anomalies can occur in isolation or in association with clinical syndromes that involve complex multifocal lesions affecting different organ systems. Thus, it is critical to be familiar with the differences and similarities among vascular anomalies to guide selection of the appropriate imaging studies and possible interventions. Syndromes associated with simple vascular malformations include hereditary hemorrhagic telangiectasia, blue rubber bleb nevus syndrome, Gorham-Stout disease, and primary lymphedema. Syndromes categorized as vascular malformations associated with other anomalies include Klippel-Trenaunay-Weber syndrome, Parkes Weber syndrome, Servelle-Martorell syndrome, Maffucci syndrome, macrocephaly-capillary malformation, CLOVES (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and scoliosis, skeletal, and spinal anomalies) syndrome, Proteus syndrome, Bannayan-Riley-Ruvalcaba syndrome, and CLAPO (capillary malformations of the lower lip, lymphatic malformations of the face and neck, asymmetry of the face and limbs, and partial or generalized overgrowth) syndrome. With PHACES (posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects and/or coarctation of the aorta, eye abnormalities, and sternal clefting or supraumbilical raphe) syndrome, infantile hemangiomas associated with other lesions occur. Diagnostic and interventional radiologists have important roles in diagnosing these conditions and administering image-guided therapies-embolization and sclerotherapy, and different ablation procedures in particular. The key imaging features of vascular anomaly syndromes based on the 2018 ISSVA classification system and the role of interventional radiology in the management of these syndromes are reviewed. Online supplemental material is available for this article. ©RSNA, 2022.

The International Society for the Study of Vascular Anomalies (ISSVA) ontology

The International Society for the Study of Vascular Anomalies (ISSVA) provides a classification for vascular anomalies that enables specialists to unambiguously classify diagnoses. This classification is only available in PDF format and is not machine-readable, nor does it provide unique identifiers that allow for structured registration. In this paper, we describe the process of transforming the ISSVA classification into an ontology. We also describe the structure of this ontology, as well as two applications of the ontology using examples from the domain of rare disease research. We used the expertise of an ontology expert and clinician during the development process. We semi-automatically added mappings to relevant external ontologies using automated ontology matching systems and manual assessment by experts. The ISSVA ontology should contribute to making data for vascular anomaly research more Findable, Accessible, Interoperable, and Reusable (FAIR). The ontology is available at https://bioportal.bioontology.org/ontologies/ISSVA.

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.

A Large Fetal Venous Malformation

A 28-year-old woman was referred to our institution at 35 weeks after an ultrasound diagnosis of an oral fetal lesion. Magnetic resonance showed a mass originating from the anterior part of the tongue with some areas of internal heterogeneity, possibly representing vascular structures. The multidisciplinary team decided to perform a cesarean delivery at 38 weeks. A large, well-defined bluish/purple exophytic mass arising from the apex of the tongue was confirmed right after birth, and a vascular anomaly was suspected. Precocious complete surgical excision and oral motor rehabilitation and feeding were performed. According to the 2018 International Society for the Study of Vascular Anomalies Classification (ISSVA), histological analysis confirmed a venous vascular malformation. Although rare, venous malformations represent the most common type of congenital vascular malformation. They are considered simple and slow-flow vascular malformations. Airway compromise may be a major concern when aerodigestive system involvement is present. Anatomic deformities and their functional and psychosocial impact are also important concerns. Herein, prompt recognition of an oral fetal mass allowed cautious delivery and postnatal management. It highlights the importance of careful prenatal diagnosis in managing potentially life-threatening congenital malformations.

Orbital Vascular Anomalies: A Nomenclatorial, Etiological, and Nosologic Conundrum.

Vascular anomalies are a heterogeneous group of disorders that frequently present in the periorbital region. They encompass 2 broad entities: vascular tumors, which possess a proliferative endothelium, and vascular malformations, which are basically localized defects of vascular morphogenesis. The primary goal of this review was to address inaccurate or controversial terminology in the oculoplastic literature concerning orbital and periorbital vascular anomalies and to categorize these lesions in an abridged and simplified hierarchical list that adheres as much as possible to the most recent (2018) iteration for the classification of vascular lesions proposed by the International Society for the Study of Vascular Anomalies (ISSVA). The secondary goal of this review was to review and update information regarding the genetic underpinnings of vascular anomalies and the downstream signaling pathways that are subsequently affected as a result of these genetic errors. A literature review was conducted in PubMed, MEDLINE, PubMed Central, National Center for Biotechnology Information Bookshelf, and Embase for several related keywords including "vascular anomalies, vascular malformations, vascular tumors, and cavernous venous malformation," both with and without adding the keywords "eyelid," "orbital," and "periorbital." In addition, a detailed search was conducted for controversial or obsolete keywords like "cavernous hemangioma," "lymphangioma," and "varices," again in their systemic and orbital/periorbital context. Crucial issues in the 2018 ISSVA classification regarding the proper categorization of orbital vascular anomalies, particularly venous lesions, were critically evaluated and revised, and a regional, simplified, and abridged modification of the ISSVA 2018 classification was proposed. Interdisciplinary and intradisciplinary dialogue concerning orbital vascular anomalies is seriously compromised due to the lack of a unanimous agreement on terminology and the absence of a unified classification concept system. The authors recommend that oculoplastic surgeons adopt ISSVA terminology whenever technically possible and scientifically sound. However, they also propose modifying the ISSVA 2018 classification specifically to adapt to the peculiarities of vascular anomalies in the periorbital region. At present, the simplified classification proposed here is a preliminary first step towards managing patients with orbital vascular anomalies with greater diagnostic and therapeutic precision, until such time in the future when the entire genetic makeup of orbital vascular anomalies is more completely elucidated. Optimistically, this could pave the way for a more robust classification and the ultimate therapeutic cure.

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.

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.

How is the term haemangioma used in the literature? An evaluation against the revised ISSVA classification.

The International Society for the Study of Vascular Anomalies (ISSVA) classification separates vascular anomalies into vascular malformations and vascular tumors. However, misdiagnoses and misperceptions still persist around the use of the term "hemangioma." We assessed whether the term "haemangioma" (British spelling) was used as part of ISSVA terminology in the literature. We searched PubMed for all English-language publications containing the British spelling "haemangioma" in the title or abstract from January 1, 2015 to December 31, 2016. Each paper was judged by two independent reviewers, with conflicts resolved by senior review. By the standard of the 2014 ISSVA classification, 126/195 (64.6%) publications used incorrect terminology for vascular anomalies. This was reduced to 118/195 (60.5%) when using the 2018 ISSVA classification. The most commonly misused terms were cavernous haemangioma (27.1%), haemangioma without further specification (26.3%), and hepatic/liver haemangioma (12.7%). Age was a significant predictor of accuracy of terminology (P=0.01), with a higher accuracy in children. Correct usage also varied by the site of the vascular anomaly, being highest for lesions of the skin (76.5%) followed by muscle (58.3%), soft tissue (23.5%), bone (21.4%), viscera (7.7%), and eye (0.0%) (P=0.02). The term "haemangioma" is frequently used incorrectly by the standards of the 2014 and 2018 ISSVA classifications. Correct terminology is important as the natural history and treatment options vary depending on the type of vascular anomaly.

International Society for the Study of Vascular Anomalies Classification of Soft Tissue Vascular Anomalies: Survey-Based Assessment of Musculoskeletal Radiologists’ Use in Clinical Practice

There is controversy regarding the diagnosis and classification of vascular anomalies (VA). As torso and extremities are the second most common body part for presentation of VAs, musculoskeletal (MSK) radiologists play a central role in VA classification. The purpose of this study was to evaluate the awareness and clinical use of the International Society for the Study of Vascular Anomalies (ISSVA) classification by MSK radiologists. A Web-based survey was designed and electronically sent to Society of Skeletal Radiology (SSR) members, with 3 questions on demographics and 7 questions on ISSVA classification use and knowledge. The Z-test for binomial proportions is used to assess for statistical significance between subgroups. The response rate was 12% (130 of 1091), comprised of 64% (83 of 130) academic and 36% (47 of 130) nonacademic MSK radiologists. VAs accounted for only a small (0%-5%) proportion of clinical practice in the majority 92% (119 of 130). Only 17% (22 of 130) of MSK radiologists used the ISSVA classification in practice. Of all respondents, 74% (94 of 127) considered hemangioma a type of vascular malformation (VM). There was no significant difference in the response characteristics between academic and nonacademic radiologists. A greater proportion of MSK radiologists with >5 years' experience provided responses that were discordant with the ISSVA classification compared with less experienced radiologists (0-5 years) in diagnosing hemangiomas in adult patients (P = 0.02), and using the presence of phleboliths to diagnose hemangiomas (P = 0.004). Our survey results indicate a lack of familiarity with the ISSVA classification by the MSK radiology community.

Discrepancy between the clinical and histopathologic diagnosis of soft tissue vascular malformations

Soft tissue vascular malformations are generally diagnosed clinically, according to the International Society for the Study of Vascular Anomalies (ISSVA) classification. Diagnostic histopathologic examination is rarely performed. We sought to evaluate the validity of the current diagnostic workup without routinely performed diagnostic histopathology. We retrospectively determined whether there were discrepancies between clinical and histopathologic diagnoses of patients with clinically diagnosed vascular malformations undergoing therapeutic surgical resections in our center (2000-2015). Beforehand, a pathologist revised the histopathologic diagnoses according to the ISSVA classification. Clinical and histopathologic diagnoses were discrepant in 57% of 142 cases. In these cases, the pathologist indicated the diagnosis was not at all a vascular malformation (n=24; 17%), a completely different type of vascular malformation (n=26; 18%), or a partially different type with regard to the combination of vessel-types involved (n=31; 22%). Possible factors associated with the discrepancies were both clinician-related (eg, diagnostic uncertainty) and pathology-related (eg, lack of immunostaining). Retrospective analysis of a subgroup of patients undergoing surgery. The large discrepancy between clinical and histopathologic diagnoses raises doubt about the validity of the current diagnostic workup for vascular malformations. Clear clinical and histopathologic diagnostic criteria might be essential for a uniform diagnosis.

Vascular lesions of the female genital tract: Clinicopathologic findings and application of the ISSVA classification

IntroductionVascular lesions of the female genital tract are extremely rare and their nomenclature does not widely follow the International Society for the Study of Vascular Anomalies (ISSVA) classification. Aim of the studyTo describe the clinicopathologic characteristics of vascular lesions of the female genital tract and to apply the ISSVA classification. Material and methods19 vascular lesions were diagnosed during a 20 year period. Their histological features including size, localization, type of vessels, endothelial atypia, mitotic activity, relation with surrounding tissues are described. Immunohistochemical analysis using CD31, CD34, D2-40, WT1, MiB1 and GLUT1 is performed. Results8 ovarian lesions were found including small cortical lymphatic malformations and medullary lesions resembling pyogenic granulomas, as well as two tubal lesions resembling true hemangiomas. They were all incidental findings. Cervical lesions (n=7) included endocervical polypoid venous malformations and paracervical combined malformations presenting clinically as leiomyomas; they probably represent static vessels. Vulvar lesions (n=4) consist of lymphatic and venous malformations and by angiokeratomas. No malignant lesions were found. WT1 is expressed by most of these lesions with the exception of the lymphatic malformations and the paracervical combined malformations. GLUT1 was consistently negative. MiB1 was only rarely positive. ConclusionVascular lesions of the female genital tract consist of lesions with different morphology by organ and of probably different pathogenesis. The ISSVA classification can be adopted for most of these lesions. WT1 should be best considered as a marker of endothelia with proliferative capacity rather than a marker of neoplastic endothelia.

Histopathology of vascular anomalies: update based on the revised 2014 ISSVA classification.

Precise diagnosis of childhood vascular anomalies is challenging, and requires careful correlation of clinical findings, diagnostic imaging, histopathology and genetic analysis. Skin and soft tissue biopsies remain an important element in the complete evaluation of many vascular anomalies included in the revised 2014 International Society for the Study of Vascular Anomalies (ISSVA) classification. Here we present an overview of the light microscopic and immunohistochemical features of the entities in this updated classification scheme, with emphasis on newly-included diagnoses such as PTEN hamartoma of soft tissue.

Vascular Anomalies Classification: Recommendations From the International Society for the Study of Vascular Anomalies.

Vascular anomalies represent a spectrum of disorders from a simple "birthmark" to life- threatening entities. Incorrect nomenclature and misdiagnoses are commonly experienced by patients with these anomalies. Accurate diagnosis is crucial for appropriate evaluation and management, often requiring multidisciplinary specialists. Classification schemes provide a consistent terminology and serve as a guide for pathologists, clinicians, and researchers. One of the goals of the International Society for the Study of Vascular Anomalies (ISSVA) is to achieve a uniform classification. The last classification (1997) stratified vascular lesions into vascular malformations and proliferative vascular lesions (tumors). However, additional disease entities have since been identified that are complex and less easily classified by generic headings, such as capillary malformation, venous malformation, lymphatic malformation, etc. We hereby present the updated official ISSVA classification of vascular anomalies. The general biological scheme of the classification is retained. The section on tumors has been expanded and lists the main recognized vascular tumors, classified as benign, locally aggressive or borderline, and malignant. A list of well-defined diseases is included under each generic heading in the "Simple Vascular Malformations" section. A short definition is added for eponyms. Two new sections were created: one dealing with the malformations of individually named vessels (previously referred to as "truncular" malformations); the second groups lesions of uncertain or debated nature (tumor versus malformation). The known genetic defects underlying vascular anomalies are included in an appendix. This classification is meant to be a framework, acknowledging that it will require modification as new scientific information becomes available.

Intraosseous haemangioma: semantic and medical confusion

The literature is rich in case reports of intraosseous haemangioma, although most of these are actually cases of venous or capillary malformations. To illustrate this confusion in terminology, we present three cases of slow-flow vascular malformations misnamed as intraosseous haemangioma. A retrospective study of children diagnosed with intraosseous haemangioma was conducted. Clinical and radiological data were evaluated. Histopathological examinations and immunohistochemical studies were redone by three independent pathologists to classify the lesions according to the International Society for the Study of Vascular Anomalies (ISSVA) and World Health Organization (WHO) classifications. Three children who had presented with jaw haemangiomas were identified. Computed tomography scan patterns were not specific. All tumours were GLUT-1-negative and D2-40-negative. The lesions were classified as central haemangiomas according to the WHO, and as slow-flow malformations according to the ISSVA. The classification of vascular anomalies is based on clinical, radiological, and histological differences between vascular tumours and malformations. Based on this classification, the evolution of the lesion can be predicted and adequate treatment applied. The binary ISSVA classification is widely accepted and should be applied for all vascular lesions.

Vascular Malformations of the Orbit

To describe the authors' experience with orbital vascular malformations using the International Society for the Study of Vascular Anomalies (ISSVA) classification and the preferred radiologic techniques. Review of clinical and radiologic experience from 1976 to 2012. This article presents the findings from several studies conducted on vascular malformations of the orbit, all of which received institutional review board approval when needed. The orbital vascular malformations can be evaluated, classified, and managed according to the ISSVA classification to provide a common language of communication between specialties, which takes into account flow dynamics. The ISSVA can be applied for vascular malformations of the orbit.

Imaging of vascular tumors with an emphasis on ISSVA classification

The International Society for the Study of Vascular Anomalies (ISSVA) classification is becoming the international standard classification system for vascular tumors and vascular malformations. The ISSVA classification strictly distinguishes vascular tumors (neoplastic lesions) from vascular malformations (non-neoplastic lesions) based on whether there is a proliferation of vascular endothelial cells present, and it is an extremely useful classification system for determining therapeutic measures. For vascular tumors, it is clinically significant in terms of discriminating infantile hemangioma and rapidly involuting congenital hemangioma, which are expected to spontaneously regress, from other vascular tumors requiring treatment. Needless to say, clinical courses are important for diagnosis, and it is also important for radiologists to understand imaging findings on vascular tumors because such tumors have unique findings on diagnostic images. In this paper, vascular tumors are classified based on the ISSVA classification, and clinical and imaging findings are reviewed.

Syndromes Associated with Vascular Tumors and Malformations: A Pictorial Review

Use of the International Society for the Study of Vascular Anomalies (ISSVA) classification system has been strongly recommended in recent years because of the need for separate therapeutic measures for patients with vascular tumors and malformations. In the ISSVA classification system, vascular tumors, which are neoplastic, are distinguished from vascular malformations, which are caused by vascular structural anomalies and are not neoplastic, on the basis of the presence or absence of neoplastic proliferation of vascular endothelial cells. It is important that radiologists be familiar with the development, diagnosis, and treatment of vascular tumors and malformations, especially the imaging features of low- and high-flow vascular malformations. Some vascular tumors and malformations develop in isolation, whereas others develop within the phenotype of a syndrome. Syndromes that are associated with vascular tumors include PHACE syndrome. Syndromes that are associated with vascular malformations include Sturge-Weber, Klippel-Trénaunay, Proteus, blue rubber bleb nevus, Maffucci, and Gorham-Stout syndromes, all of which demonstrate low flow, and Rendu-Osler-Weber, Cobb, Wyburn-Mason, and Parkes Weber syndromes, all of which demonstrate high flow. Because imaging findings may help identify such syndromes as systemic, it is important that radiologists familiarize themselves with these conditions.