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The classification and understanding of vascular anomalies have significantly evolved since the initial framework by Mulliken and Glowacki, distinguishing between vascular tumours and malformations. Recent advancements in molecular diagnostics have enhanced the accuracy of identifying and managing these complex lesions. This review provides an updated analysis of select vascular anomalies, focusing on Kaposiform hemangioendothelioma (KHE), Kaposiform lymphangiomatosis (KLA), and intramuscular fast‐flow vascular anomalies. It highlights the similarities and differences between these lesions, their histopathological features, and molecular underpinnings, including key genetic mutations in the RAS/PI3K/mTOR signalling pathways. Moreover, the role of PIK3CA mutations in vascular overgrowth syndromes is explored, alongside emerging targeted therapies, such as PI3K and MEK inhibitors, that promise improved outcomes for patients with these challenging conditions. The integration of histology, molecular diagnostics, and multidisciplinary care remains critical for the accurate diagnosis and optimal treatment of vascular anomalies in the era of precision medicine. [ABSTRACT FROM AUTHOR]

Sirolimus is being increasingly employed to manage specific vascular anomalies. We performed an exploratory cost‐utility analysis to evaluate sirolimus as a treatment for vascular malformations from the Australian healthcare system perspective. Over a one‐year time horizon, sirolimus treatment was associated with an increased expenditure of AU$2832.80 and a gain of 0.08 quality‐adjusted life years (QALYs) when compared to supportive care, resulting in an incremental cost‐effectiveness ratio of AU$35,410/QALY. By most metrics, sirolimus would be considered a cost‐effective treatment for vascular malformations. [ABSTRACT FROM AUTHOR]

Venous malformations (VM) are slow-flow vascular lesions that result from morphogenesis errors. Composed of dysfunctional veins lacking smooth muscle cells, VMs grow slowly and may initially be managed by observation. Treatment is indicated for lesions that cause functional impairment. One treatment option is laser therapy, which is very effective due to its tissue penetration and relative selectivity. The Nd:YAG laser has been shown to treat small and moderately sized mucosal vascular lesions; in this case, it was applied in a staged approach for treatment of a massive venous malformation of the tongue. A 66-year-old male presented with a venous malformation involving the tongue and lower lip, the lesion estimated to be 10 x 14 x 15 cm in size. The Nd:YAG laser was used in three separate stages to photocoagulate the venous lesion. Follow-up for recurrence is ongoing, but currently shows complete malformation ablation with a 36.2% volume reduction after treatment. The Nd:YAG laser is an effective tool in the treatment of large vascular lesions. Successful laser application in a staged approach for the treatment of a venous malformation of this size and complexity further supports its clinical value. Monitoring for possible recurrence of the venous malformation should be ongoing. [ABSTRACT FROM AUTHOR]

The pathological evaluation of hepatic vascular lesions in children requires special consideration. Inconsistent terminology, rarity of pathology specimens and overlapping pathological features between various lesions may pose a serious diagnostic challenge. In this review, we highlight the importance of using the International Society for the Study of Vascular Anomalies (ISSVA) classification scheme to characterise these lesions. Selected entities are discussed, including hepatic vascular tumours exclusively seen in the paediatric age group, hepatic infantile haemangioma and hepatic congenital haemangioma. Vascular malformations, with emphasis on their syndromic associations (venous malformation in blue rubber bleb naevus syndrome) and complications (hepatocellular nodules in Abernethy malformation) are also covered. [ABSTRACT FROM AUTHOR]

Background: The main challenges faced when using sirolimus in children with vascular anomalies (VAs) still include significant pharmacokinetic (PK) variability, uncertainty in the target concentration range, as well as inconsistencies in initial dosing and dosing frequency. The aim of this study is to establish a new population pharmacokinetic (PPK) model for children with VAs to guide the individualized use of sirolimus. Methods: A PPK study was performed using data from children with VAs who received sirolimus between July 2017 and April 2022. A nonlinear mixed-effect modeling with a one-compartment model structure was applied. Monte Carlo simulation was employed to propose specific dosing recommendations to achieve the target trough concentrations (C trough) of 5–15 ng/mL. Results: In total, 134 blood concentrations from 49 pediatric patients were used to characterize the sirolimus pharmacokinetics. Covariate analysis identified body weight (BW) as a significant factor affecting clearance (CL) in the final PPK model. The typical clearance rate and distribution volume, standardized to a BW of 16 kg, were 4.06 L/h (4% relative standard error, RSE) and 155 L (26% RSE), respectively. Optimal dosing regimens were simulated for different BWs. For a twice-daily regimen, the recommended doses were 0.05, 0.06, 0.07, and 0.08 mg/kg/day for BW of <10, 10–20, 20–40, and ≥40 kg, respectively; for a once-daily regimen, the recommended doses were 0.06, 0.07, 0.08, and 0.09 mg/kg/day for BW of <10, 10–30, 30–50, and ≥50 kg, respectively. Notably, sirolimus C trough could be maintained between 5–15 ng/mL across various dosing frequencies based on the recommended dosing regimen. Conclusion: We established a PPK model of sirolimus for children with VAs and proposed an initial dosing strategy. Integrating initial dose and medication frequency recommendations into sirolimus' guidelines will broaden its clinical options and simplify the clinical management for childhood VAs. [ABSTRACT FROM AUTHOR]

A series of randomized controlled trials (RCTs) have advanced the therapeutic approaches for vascular anomalies (VA). However, a notable obstacle in applying the findings of these trials to real-world patient care is trial waste (TW). To date, the extent of TW in RCTs for VA is not clear. In June 2024, we searched the ClinicalTrials database using the entity names defined by ISSVA classification as search terms. We documented the data available and then explored PubMed and Scopus for the publication status. Reporting adequacy was evaluated using the CONSORT checklist. Design limitations were analyzed based on bias risk and whether the article referenced a relevant systematic review. One hundred fifty-nine RCTs met the inclusion criteria. The majority of RCTs focused on benign VA (81.1%) and utilized pharmacotherapy (79.9%). Over 90% of these trials were conducted in North America, Europe, and Asia as single-center studies (68.6%), with funding primarily from official institutions (83.7%). The analysis of TW excluded 61 RCTs completed after June 2020 that remained unpublished. Among the remaining 98 RCTs, 53 were published, 41 had adequate reporting, and 16 had design limitations. In total, 67 RCTs exhibited at least one characteristic of TW. The 31 RCTs without waste tended to enroll more participants (P = 0.014) and conduct studies across multiple centers (P < 0.001) and countries (P = 0.022). Multicenter participation (P = 0.028) emerged as an independent protective factor against TW. Conclusion: We delineated the features of 159 VA RCTs and revealed that 68.4% of them exhibited TW. The diverse traits of the different TW indicators identified could serve as valuable insights for conducting future VA RCTs more rationally and efficiently. What is Known: • Currently, a number of RCTs have been conducted on vascular anomalies (VA). However, there has been no study analyzing the situation of trial waste in VA-related RCTs. What is New: • This study is the first to describe the characteristics of VA-related RCTs globally over the past 20 years and has identified a high burden of trial waste in this field. Multicenter participation was an independent protective factor against trial waste. [ABSTRACT FROM AUTHOR]

Arteriovenous malformations (AVM) are benign vascular anomalies prone to pain, bleeding, and progressive growth. AVM are mainly caused by mosaic pathogenic variants of the RAS-MAPK pathway. However, a causative variant is not identified in all patients. Using ultra-deep sequencing, we identified novel somatic RIT1 delins variants in lesional tissue of three AVM patients. RIT1 encodes a RAS-like protein that can modulate RAS-MAPK signaling. We expressed RIT1 variants in HEK293T cells, which led to a strong increase in ERK1/2 phosphorylation. Endothelial-specific mosaic overexpression of RIT1 delins in zebrafish embryos induced AVM formation, highlighting their functional importance in vascular development. Both ERK1/2 hyperactivation in vitro and AVM formation in vivo could be suppressed by pharmacological MEK inhibition. Treatment with the MEK inhibitor trametinib led to a significant decrease in bleeding episodes and AVM size in one patient. Our findings implicate RIT1 in AVM formation and provide a rationale for clinical trials with targeted treatments. [ABSTRACT FROM AUTHOR]

Background: The main challenges faced when using sirolimus in children with vascular anomalies (VAs) still include significant pharmacokinetic (PK) variability, uncertainty in the target concentration range, as well as inconsistencies in initial dosing and dosing frequency. The aim of this study is to establish a new population pharmacokinetic (PPK) model for children with VAs to guide the individualized use of sirolimus. Methods: A PPK study was performed using data from children with VAs who received sirolimus between July 2017 and April 2022. A nonlinear mixed-effect modeling with a one-compartment model structure was applied. Monte Carlo simulation was employed to propose specific dosing recommendations to achieve the target trough concentrations (Ctrough) of 5-15 ng/mL. Results: In total, 134 blood concentrations from 49 pediatric patients were used to characterize the sirolimus pharmacokinetics. Covariate analysis identified body weight (BW) as a significant factor affecting clearance (CL) in the final PPK model. The typical clearance rate and distribution volume, standardized to a BWof 16 kg, were 4.06 L/h (4% relative standard error, RSE) and 155 L (26% RSE), respectively. Optimal dosing regimens were simulated for different BWs. For a twice-daily regimen, the recommended doses were 0.05, 0.06, 0.07, and 0.08 mg/kg/day for BW of <10, 10-20, 20-40, and =40 kg, respectively; for a once-daily regimen, the recommended doses were 0.06, 0.07, 0.08, and 0.09 mg/kg/day for BW of <10, 10-30, 30-50, and =50 kg, respectively. Notably, sirolimus Ctrough could be maintained between 5-15 ng/mL across various dosing frequencies based on the recommended dosing regimen. Conclusion: We established a PPK model of sirolimus for children with VAs and proposed an initial dosing strategy. Integrating initial dose and medication frequency recommendations into sirolimus' guidelines will broaden its clinical options and simplify the clinical management for childhood VAs. [ABSTRACT FROM AUTHOR]

Objectives: Sirolimus (SRL), a mammalian target of rapamycin inhibitor, has been widely used to treat patients with vascular anomalies (VAs). The objectives of this study were to summarize the routine blood SRL monitoring data for VAs children, to investigate the factors contributing to the variable blood SRL concentrations and to evaluate the efficacy and safety of SRL therapy. Methods: VAs patients with routine blood SRL monitoring from July 2017 to April 2022 at the Department of Burns and Plastic Surgery, Children's Hospital of Nanjing Medical University were retrospectively collected. Clinical data were obtained from the hospital information system. Results: In total, 67 children (35 females) were enrolled. The therapeutic drug monitoring data showed that the range of measured blood trough concentrations (Ctrough) was 3.6–46.8 ng/mL. At the initial measurements, only 33% of patients were in the target concentration range (10–15 ng/mL). But this proportion became 54% at the last measurements. The whole blood-Ctrough-to-daily dose (Ctrough/Dose) ratio was significantly associated with age and body weight (BW). The patients' laboratory results did not change significantly after SRL treatment. Although the incidence of adverse events was relatively high (44.8%), most of them were mild and tolerable. 70.3% patients had total responses to SRL, whereas 29.7% children exhibited stable disease or progressive disease. No significant differences were found in Ctrough between the total response group and non-response group. Conclusions: This retrospective study revealed a high variability in SRL blood concentrations in Chinese children with VAs. Of note, pediatric patients with older age and a higher BW had a lower Ctrough/Dose ratio. It is a concern whether the range of 10–15 ng/mL is feasible for Chinese children based only on our study. Further studies recruiting more patients are required to redefine the target reference range for children with VAs. [ABSTRACT FROM AUTHOR]

Background: Endoscopic resection has been reported for vascular anomalies (VA) previously. However, there is no study comparing endoscopic resection surgery (ERS) with open resection surgery (ORS) in children. We aimed to compare clinical and cosmetic outcomes between two approaches in pediatric VA. Methods: Between June 2018 and June 2023, 138 pediatric VA patients undergoing ERS or ORS were retrospectively reviewed. Propensity score matching (PSM) was performed to minimize selection bias. The Scar Cosmesis Assessment and Rating (SCAR) Scale and numerical rating scale (NRS) based on patient satisfaction were used for cosmetic assessment. Results: After PSM for age, depth of lesion, size of lesion, and site of surgery, 72 patients (ERS = 24, ORS = 48) were analyzed. Patients undergoing ERS had longer operative time (164.25 ± 18.46 vs. 112.85 ± 14.26 min; P < 0.001), less estimated blood loss (5.42 ± 2.15 vs. 18.04 ± 1.62 ml; P < 0.001), and shorter median hospital stay (4.50 [3.00–5.00] vs. 6.00 [5.00–6.00] days; P < 0.001). The follow-up time was 8.04 ± 1.23 month for ERS group and 8.56 ± 1.57 month for ORS group. For aesthetic results, the median overall SCAR score in ERS was lower than that in ORS (2 [1–3] vs. 5 [4–5]; P < 0.001), and the subscales of "scar spread," "dyspigmentation," "track marks or suture marks," and "overall impression" were better. The median NRS score was higher (8 [7–8] vs. 6 [5–6]; P < 0.001) and length of scars was shorter (2.18 ± 0.30 vs. 8.75 ± 1.98 cm; P < 0.001) in ERS group than those in ORS group. The incidences of total complications and recurrence showed no significant difference between two groups. Conclusions: Endoscopic surgery can be a safe and effective option for pediatric VA in the limbs and trunk. It offers the advantages of improving aesthetic outcomes and reducing postoperative wound healing time. [ABSTRACT FROM AUTHOR]

Vascular anomalies affecting the head and neck region pose significant diagnostic and therapeutic challenges due to their varied presentations and potential involvement of critical anatomical structures. This case series presents five cases of vascular malformations encountered at our tertiary care hospital, including capillary malformations, lymphatic malformations, venous malformations, and arteriovenous malformations, each with distinct clinical presentations and management considerations. The importance of a multidisciplinary approach involving specialists from various fields is underscored to ensure optimal patient outcomes. [ABSTRACT FROM AUTHOR]

Ureteropelvic junction obstruction (UPJO) is a pathological condition characterized by obstruction of the junction between the renal pelvis and ureter, often resulting in dilatation of the renal collecting system. Aberrant accessory vessels or early branching of the inferior pole vessels are the most common causes of extrinsic UPJO. The inferior mesenteric artery has not been reported as a common cause of UPJO. Here, we report the case of a 7-year-old patient with UPJO and an anomalous inferior mesenteric artery. The patient was initially diagnosed with congenital uropathy during the evaluation for primary enuresis.

Background Arteriovenous malformations (AVMs) within the mediastinum are rare vascular anomalies. With the increasing number of coronary angiographies being performed, the number of incidentally found cases is rising. This presents challenges in terms of determining the appropriate treatment strategy. Case summary We present the case of a 79-year-old man with aortic stenosis, experiencing functional dyspnoea and fatigue. Echocardiography showed a bicuspid aortic valve, and while left heart catheterization confirmed no significant coronary stenosis, it revealed a tortuous vessel originating from the circumflex artery (Cx), assumed to be heading toward the pulmonary circulation. The patient was scheduled for a surgical replacement of the aortic valve (SAVR). During the SAVR, the tortuous vessel was revealed to be a large, complex AVM located in the mediastinum. This increased both the duration of the surgery and the use of cardioplegia. Further, bleeding occurred per-operatively. Post-operatively, the patient developed tachy-brady syndrome and was treated with a pacemaker before discharge. Discussion Due to the rarity of incidental AVMs in the middle/posterior mediastinum, no standard treatment protocol is available. This leaves clinicians and surgeons to manage the disease on a case-by-case basis, often with limited experience to guide their decisions. This patient case underscores the challenge of determining whether patients should be offered transcatheter aortic valve implantation (TAVI) or surgery. Furthermore, it highlights the intricate challenges that can arise when dealing with thoracic AVMs during cardiac procedures, emphasizing the importance of pre-operative awareness and tailored surgical approaches based on multidisciplinary discussions. [ABSTRACT FROM AUTHOR]

Historically, the care for patients with vascular anomalies has been challenging due to the complex nature and diversity of these anomalies with a wide array of symptomatology. In the recent past, most therapies for vascular anomalies focused on surgical, procedural, and supportive care measures to treat local symptoms, but many patients still experienced significant disease with excess morbidity and mortality. Today, the pharmacotherapeutic options available for treating vascular anomalies have greatly expanded due to the increased understanding of the genetic and molecular pathways causing these anomalies, with the subsequent development of more targeted pharmacotherapies. In addition to the growth in targeted medications available to treat patients with vascular anomalies, there has been an improved understanding of the hematologic abnormalities related to these diseases and how to manage them. While interventional radiologists do not typically primarily manage systemic medications to treat vascular anomalies, a baseline understanding of the medical management of these diseases is essential to ensuring that a contemporary, multidisciplinary, multimodal approach to treatment is pursued when appropriate. Ultimately, patients are now benefitting from having multiple modalities of treatments available to them and are experiencing improved quality of life and less morbidity. [ABSTRACT FROM AUTHOR]

Vascular malformations (VMs) are a heterogeneous group of arterial, venous, capillary, and/or lymphatic networks that typically are present at birth and grow with the patient. Signs and symptoms associated with VM range from absent to severe, with a broad spectrum of pain, cosmetic disfigurement, and local tissue destruction. Treatment options for these malformations extend from observation to surgical reconstruction. Each treatment modality has a role in the management of vascular anomalies, but also has specific challenges. Observation is not always sufficient, medical therapies may only be available for a subset of patients and are ultimately not curative, and surgical excision may itself be disfiguring or incomplete/not definitive. Sclerotherapy and/or embolotherapy have become a cornerstone of treatment for many types of VMs. These techniques are applicable to a wide range of VMs, are less invasive, have a shorter recovery period, and are repeatable. Although some VMs may not be amenable to percutaneous or endovascular treatment given their location, and multiple sessions may be required for select large and complex VMs, these minimally invasive treatments are often first line and may be definitive in treating VMs. Various agents may be used in sclerotherapy and embolotherapy, each with their own risks and benefits. Although there is a paucity of Level 1 evidence supporting the superiority of one agent over another, longstanding case series and expert experience exist, informing our knowledge of the safety and efficacy of sclerotherapy and embolotherapy. A brief overview of the most used sclerotherapy and embolotherapy agents and their uses is provided. [ABSTRACT FROM AUTHOR]

Vascular anomalies (VAs) are a heterogeneous group of vascular malformations and tumors that are frequently encountered in daily practice. While most are benign, malignant vascular tumors exist, as do other nonvascular soft-tissue malignancies that may masquerade as a benign VA. The subtleties of arriving at an accurate diagnosis can be intimidating, as new entities are described and names of conditions have been modified. Therefore, the goal of this article is to describe the classic imaging findings of VAs so that the interventional radiologist can confidently and competently contribute to management decisions, with special attention to ominous imaging features that should prompt biopsy or further imaging workup. [ABSTRACT FROM AUTHOR]

Persistent sciatic artery (PSA) is a rare congenital vascular anomaly resulting from embryologic axial artery malformation in the lower limb. This case report presents three patients aged 45–60, each with bilateral PSA presenting with symptoms indicative of PSA complications, including aneurysmal degeneration, limb ischemia, thromboembolism, or neuralgia from nerve compression. It highlights the diagnostic process, management strategies, and clinical outcomes observed at a tertiary referral hospital. Treatment involved a collaborative, multidisciplinary approach with vascular surgeons, internists, and radiologists tailoring interventions to individual patient findings and disease progression. This report aims to provide insights into the diverse presentations and management of PSA in a resource limited setting, encouraging further reporting and case studies to enhance understanding of therapeutic outcomes. [ABSTRACT FROM AUTHOR]

We described an unusual combination of fibroblastic connective nevus (FCTN) already present at birth with underlying vascular anomalies. Overall, the lesion appeared as a large purplish‐brown mass in the groin region up to the third of the right thigh, with partial spontaneous regression during the first three months of life. The FCTN observed exhibited several unusual characteristics: it was congenital, large in size, and located in the lower limbs. Finally, it represented the first case described in which an FCTN arose in association with vascular anomalies. [ABSTRACT FROM AUTHOR]

PIK3CA‐related overgrowth spectrum (PROS) encompasses different clinical entities caused by somatic activating mutations in PIK3CA. Among PROS, CLOVES syndrome represents a severe phenotype with poor survival rate. We present the case of a 4‐month‐old girl with CLOVES syndrome successfully treated with alpelisib, a PIKC3A inhibitor. [ABSTRACT FROM AUTHOR]

BackgroundArteriovenous malformations (AVMs) account for

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

Kommerell's diverticulum is a rare congenital anomaly of the aortic arch system in which there is a left- or right-sided aortic arch with an aberrant subclavian artery on the contralateral side. Patients with this anomaly can be asymptomatic or have features of tracheal or oesophageal compression. However, there is a rising suspicion that it may be a rare cause of unilateral vocal cord palsy through its compression of the recurrent laryngeal nerve. We describe a patient who had a long history of hoarse voice and left vocal cord palsy with no other obvious cause, who was found to have a Kommerell's diverticulum on a contrast-enhanced computed tomography scan. [ABSTRACT FROM AUTHOR]

Background: Patients with complex rare disorders often require the care of multiple specialists. Effective coordination between primary and specialty care is needed to ensure patients receive high-quality care. Previous research has documented the importance of primary care clinicians providing referrals to specialty care and the importance of specialists in helping patients reach a diagnosis. However, little is known about primary care clinicians’ roles in the ongoing care of patients with rare disorders. In the current study, we explored the role of primary care clinicians in the care of rare and complex vascular anomalies. Materials and Methods: Data were collected using semi-structured qualitative interviews with 34 parents and 25 adult patients recruited from advocacy groups for patients with complex vascular anomalies participated. We asked participants about their diagnosis, care experiences, and communication with clinicians. We used thematic analysis to identify themes illustrating the roles of primary care clinicians. Results: PCC roles were characterized by four behaviors. Supporting behaviors included learning more about vascular anomalies and asking participants about the care they received from specialists. Facilitating included providing referrals, ordering tests, and engaging in problem-solving. Interfering included failing to provide referrals or help participants coordinate care, ordering incorrect tests, or making inappropriate recommendations. Disregarding included focusing narrowly on primary care needs and not showing concern about the vascular anomaly. Conclusions: The results reveal opportunities to improve primary care for patients with vascular anomalies. Disregarding and interfering behaviors furthered the division between primary and specialty care for patients with vascular anomalies and prevented patients from receiving comprehensive primary care. Supporting and facilitating behaviors convey genuine interest in the care of the vascular anomaly and a commitment to helping the patient and parent.

Shina Song,1,2 Xiaofeng Li,1 Xuting Xue,3 Wenping Dong,2 Changxin Li1 1Department of Neurology, The First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Geriatrics, General Hospital of TISCO, Taiyuan, People’s Republic of China; 3Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, The First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Wenping Dong, Department of Geriatrics, General Hospital of TISCO, North Street, Xinhualing District, Taiyuan, Shanxi Province, 030009, People’s Republic of China, Tel +86 13703581782, Email tgzyydwp@163.com Changxin Li, Department of Neurology, The First Hospital of Shanxi Medical University, Jiefangnan Road 85, Taiyuan, Shanxi Province, 030001, People’s Republic of China, Tel +86 13834635428, Email dslcxyx@126.comAbstract: High temperature requirement A1 (HTRA1) is a member of the serine protease family, comprising four structural domains: IGFBP domain, Kazal domain, protease domain and PDZ domain. HTRA1 encodes a serine protease, a secreted protein that is widely expressed in the vasculature. HTRA1 regulates a wide range of physiological processes through its proteolytic activity, and is also involved in a variety of vascular abnormalities-related diseases. This article reviews the role of HTRA1 in the development of vascular abnormalities-related hereditary cerebral small vessel disease (CSVD), age-related macular degeneration (AMD), tumors and other diseases. Through relevant research advances to understand the role of HTRA1 in regulating signaling pathways or refolding, translocation, degradation of extracellular matrix (ECM) proteins, thus directly or indirectly regulating angiogenesis, vascular remodeling, and playing an important role in vascular homeostasis, further understanding the mechanism of HTRA1’s role in vascular abnormality-related diseases is important for HTRA1 to be used as a therapeutic target in related diseases.Keywords: HTRA1, vascular anomalies, cerebral small vessel disease, AMD, tumor

This narrative review aims to summarise the classification of vascular anomalies, their clinical presentation, and their radiological features to propose a diagnostic algorithm to approach patients with suspected soft tissue vascular anomalies of the extremities. The management of vascular anomalies necessitates a multidisciplinary approach. Clinical presentation and physical examination are sufficient in most cases to achieve a correct diagnosis. This is especially true for small congenital lesions of the skin and subcutaneous tissue. Imaging is used for accurate characterization of these lesions, especially in cases of atypical or vague clinical presentation, and to assess extension in cases of lesions that are larger and localized in deeper tissues. [ABSTRACT FROM AUTHOR]

Genomic technologies are now utilized for the genetic diagnosis of vascular anomalies. This provides the opportunity for genetic counselors to make a significant contribution to patient care for this complex disease. The aim of this study was to explore Australian healthcare professionals' perspectives on the relatively recent integration of molecular diagnostic testing for vascular anomalies, with or without genetic counseling support. Nine semi‐structured interviews were conducted with Australian healthcare professionals involved in the provision of care for individuals with vascular anomalies. Thematic analysis identified six themes: (1) Molecular diagnosis is beneficial; (2) psychosocial needs can motivate families to pursue a molecular diagnosis; (3) molecular genetic testing for vascular anomalies is complex; (4) genetic service provision is not a one size fits all; (5) a client‐centered approach for genetic service provision can go a long way; and (6) the value of genetic counselors. Based on our findings, implementation of a vascular anomalies genetic diagnostic program inclusive of genetic counseling may be challenging, yet such programs are likely to benefit both patients and their families, as well as healthcare professionals. As this paradigm shift unfolds, genetic counselors have an opportunity to contribute to the vascular anomaly field by educating healthcare professionals and patients, by participating in multidisciplinary clinics to support complex cases and by raising awareness regarding their practice and potential contributions. [ABSTRACT FROM AUTHOR]

The effects of anomalous vasculature impeding optimal exposure to an anterior lumbar interbody fusion approach are limited in literature. We present five individual, unique cases of vascular anomalies in patients undergoing two-stage anterior-posterior lumbar interbody fusion. Cases 1, 2, 4, and 5 have yet to be described in literature in context of anterior lumbar interbody fusions. Case 3 presents anomalous vasculature that has only been described in two other case reports. Case 1 presents the right internal iliac vein originating from the left common iliac vein which was transected for L4-L5 vertebral disc exposure. Case 2 presents the left internal iliac vein originating from the right common iliac vein which required an oblique approach. Case 3 presents a duplicated inferior vena cava that was taken into account but did not interfere with the anterior retroperitoneal approach. Case 4 presents large osteophytes adhering to the left common iliac vein which limited safe dissection and mobilization. Case 5 presents the left internal iliac vein with a high takeoff spanning across the L5-S1 vertebral disc space and requiring transection. This case series highlights the need for preoperative imaging and a working detailed knowledge of anatomy to avoid damaging vasculature that can potentially lead to fatal consequences. The information given in this case series should inform both spine and vascular surgeons on proper preoperative planning. To maximize operative efficiency and safety, spine surgeons and vascular surgeons should collaborate to minimize surgical complications. [ABSTRACT FROM AUTHOR]

Background: Patients with complex rare disorders often require the care of multiple specialists. Effective coordination between primary and specialty care is needed to ensure patients receive high‑quality care. Previous research has documented the importance of primary care clinicians providing referrals to specialty care and the importance of specialists in helping patients reach a diagnosis. However, little is known about primary care clinicians’ roles in the ongoing care of patients with rare disorders. In the current study, we explored the role of primary care clinicians in the care of rare and complex vascular anomalies. Materials and Methods: Data were collected using semi‑structured qualitative interviews with 34 parents and 25 adult patients recruited from advocacy groups for patients with complex vascular anomalies participated. We asked participants about their diagnosis, care experiences, and communication with clinicians. We used thematic analysis to identify themes illustrating the roles of primary care clinicians. Results: PCC roles were characterized by four behaviors. Supporting behaviors included learning more about vascular anomalies and asking participants about the care they received from specialists. Facilitating included providing referrals, ordering tests, and engaging in problem‑solving. Interfering included failing to provide referrals or help participants coordinate care, ordering incorrect tests, or making inappropriate recommendations. Disregarding included focusing narrowly on primary care needs and not showing concern about the vascular anomaly. Conclusions: The results reveal opportunities to improve primary care for patients with vascular anomalies. Disregarding and interfering behaviors furthered the division between primary and specialty care for patients with vascular anomalies and prevented patients from receiving comprehensive primary care. Supporting and facilitating behaviors convey genuine interest in the care of the vascular anomaly and a commitment to helping the patient and parent. [ABSTRACT FROM AUTHOR]

Vascular anomalies are vascular lesions that are present from childhood. They are classified into tumours or malformations based on clinical and histological features. Benign infantile haemangiomas are the most common vascular tumour and have a predictable self-limiting course. Rarer vascular tumours exist, and some may cause platelet consumption. Management is usually conservative, with active treatment reserved for functional or cosmetic complications (ulceration, or obstruction and distortion of vital structures). Oral propranolol is useful for troublesome lesions. Vascular malformations are structural anomalies of vascular morphogenesis present at birth without cellular proliferation that, in general, grow with the patient. They are sub-classified by vessel type as 'low flow' (capillary, lymphatic and venous) and 'high flow' (arteriovenous) or lesions with a combination of vessel type. They become problematic under certain circumstances, usually puberty and also pregnancy. The most troublesome are extensive lesions, especially venous and arteriovenous. Their effects may be cosmetic, those of a space-occupying lesion, infection, bleeding, pain or coagulopathy. Venous lesions cause consumptive coagulopathy, sometimes with life-threatening risks. Treatment options include medication and symptom control with antibiotics, analgesia, control of menses, compression garments and intervention with laser (capillary type), sclerotherapy, embolization and/or surgical excision. Patients with complex lesions are best managed by a multidisciplinary team and all surgical sub-specialties may be involved. [ABSTRACT FROM AUTHOR]

This observational retrospective study conducted at Hasan Sadikin General Hospital (RSHS) in Bandung from January 2019 to February 2023 aimed to characterise oral hemangiomas and vascular malformations. Out of 52 medical records analysed, infantile hemangioma was the most common type (17%), typically presenting between ages 13 to 24 years. Predominantly located around the lip, tongue, and buccal mucosa, it seldom caused bleeding or pain, with women being more affected. Treatment often involved sclerotic agent injections. Venous malformations accounted for 58% of vascular malformations, showing similar age of presentation and distribution as hemangiomas, and were also treated with sclerotic agents. Accurate diagnosis and tailored treatment are crucial due to the diverse nature of these anomalies. Early detection using imaging techniques like ultrasound and CT angiography is imperative, given the potential impact on patients, including pain, swelling, and cosmetic concerns, particularly in the head and neck area. However, treatment approaches vary based on factors such as type and size, necessitating further research to refine diagnostic and therapeutic strategies and optimise patient outcomes. [ABSTRACT FROM AUTHOR]

Abernethy malformation also known as congenital extrahepatic portosystemic shunt (CEPS) are rare (1 in 50,000 people) vascular anomalies of the splanchnic venous system and results from persistence of embryonic vessels. We present a rare case of abernethy malformation in a 4-year-old girl. First case was reported by John Abernethy in 1793 and till now 83 cases have been reported till now.

IntroductionVascular anomalies (VAs) constitute a heterogeneous group of tumors and malformations capable of inducing significant clinical events in specific patients, such as the compression of vital organs, pain, functional impairment, or acquired coagulopathy. Molecular investigations into the underlying mechanisms of VAs have unveiled the frequent involvement of the PI3 K/AKT/mTOR pathway. Sirolimus, a specific mTOR inhibitor, has emerged as a potential therapeutic agent; however, its routine clinical application in complex VAs is currently restricted by a lack of extensive clinical experience.MethodsBetween 2015 and 2024, we administered sirolimus to 14 pediatric patients with various types of vascular anomalies in two Italian centers, subjecting them to clinical and instrumental follow-up to investigate its efficacy and the possible occurrence of adverse events.ResultsAn overall improvement in or stability of their vascular anomalies was reported by 86% of patients. We also assessed toxicity, noting a low prevalence of life-threatening adverse events: only one case of sepsis was reported in a patient with a severe clinical condition, and four cases of recurrent aphthosis (28%) were reported. The most common side effect was dyslipidemia, with 43% of patients developing hypercholesterolemia (21%) or hypertriglyceridemia (21%), although these patients generally did not reach severe levels.DiscussionIn line with data in the literature, according to our experience, medical therapy with sirolimus should be considered in pediatric patients affected by vascular anomalies.

According to the International Society for the Study of Vascular Anomalies (ISSVA) classification, vascular anomalies include a diverse range of pathologies, classified as either vascular tumors or vascular malformations. This classification, last revised in 2018, aims to explain the biological basis of vascular lesions and help clinicians to manage the anomalies. In vascular tumors, there are proliferative changes of endothelial cells, while vascular malformations primarily consist of structural vascular abnormalities. Infantile hemangioma is the most common soft-tissue vascular tumor. Vascular malformations are an extensive group of malformations of the arterial, venous, and lymphatic systems, either in isolation or in combination. Radiological evaluation plays a key part in the management of pediatric patients with these entities. The understanding of sonography and magnetic resonance imaging findings entails its correlation with clinical findings at the time of scanning.

The burden of treatment (BOT) related to propranolol treatment for infantile hemangiomas (IH) has never previously been explored. A modified validated questionnaire, the Treatment Burden Questionnaire, and one‐on‐one semi‐structured interviews were used to assess the BOT for propranolol for IH. Out of 80 caregivers, the overall burden score was very low at 1.2 out of 10; thematic analysis of interviews grouped themes into administration, monitoring, financial, and associated anomalies. The BOT of propranolol for IH is very low but could be reduced further by offering age‐based risk stratification related to feeding frequency and risk of hypoglycemia, pragmatic advice around timing of doses before sleep, and reducing frequency of vital sign monitoring. [ABSTRACT FROM AUTHOR]

Vascular anomalies (VAs) are a group of rare diseases affecting 0.01 to 0.02% of the population. VA may be associated with complex disorders affecting multiple organ systems, requiring a multidisciplinary approach to treatment. Multidisciplinary clinics are most frequently affiliated with pediatric centers. Multidisciplinary clinics in the adult setting are rare. Many adult VA patients find it difficult to establish care with individual providers, let alone a multidisciplinary clinic, leading to barriers to lifelong comprehensive care. [ABSTRACT FROM AUTHOR]

Abernethy malformation also known as congenital extrahepatic portosystemic shunt(CEPS) are rare (1 in 50,000 people) vascular anomalies of the splanchnic venous system and results from persistence of embryonic vessels. We present a rare case of abernethy malformation in a 4 year old girl. First case was reported by John Abernethy in 1793 and till now 83 cases have been reported till now. [ABSTRACT FROM AUTHOR]

PHACE (posterior fossa malformations, hemangiomas, arterial anomalies, cardiac anomalies, eye anomalies) association has many recognized clinical features. A link between PHACE and non‐vascular intracranial lesions has not been well‐described. We report three pediatric patients with PHACE and non‐vascular intracranial lesions. [ABSTRACT FROM AUTHOR]

High‐flow vascular malformations have been associated with multiple syndromes including capillary malformation–arteriovenous malformation (CM–AVM) syndrome, hereditary hemorrhagic telangiectasia syndrome, and less commonly, phosphatase and tensin homolog hamartoma tumor syndrome (PHTS). We present a series of three patients with clinically challenging complex AVMs who were found to have underlying PHTS. In all patients, diagnosis was delayed, and the presence of the AVM prompted sampling and genetic testing for PHTS in the absence of other clinical features of the condition. This series highlights the importance of screening for PHTS in the setting of high‐flow vascular malformations. [ABSTRACT FROM AUTHOR]

Background and Aim: The approach to vascular malformations in the face is a challenging step for professionals involved in the treatment of these anomalies. The objective is to describe a rare case of extensive vascular malformation in the face in an adult patient who had previously undergone several unsuccessful treatments during childhood and adolescence. Materials and Methods: A 46‐year‐old female patient reported an aesthetic discomfort in her face due to an increase in the volume of the upper lip and recurrent spontaneous bleeding in the oral cavity. On oral clinical evaluation, a blue‐purple colour, firm consistency on palpation, extension into the oral cavity, and moderate mobility of the incisors in the right hemimaxilla were observed. Angiography, magnetic resonance imaging and cone beam computed tomography were performed to verify the lesion's anatomical limits and hemodynamic properties. Four injections of sclerotherapy with an injection of 5% monoethanolamine oleate foam were performed. Results: A significant reduction in the extent of vascular malformation was noted. At the moment, the patient had 3 years of follow‐up. She is extremely satisfied with the aesthetic result, and has had no episode of spontaneous bleeding or other complications. Conclusions: The request for new imaging exams allowed the characterization and precise delimitation of the vascular malformation, guiding the use of a minimally invasive technique using the injection of monoethanolamine oleate foam, providing an effective and satisfactory result for the patient. [ABSTRACT FROM AUTHOR]

Background: Vascular anomalies often result in aesthetic flaws, pain, and impair the quality of life. They require challenging treatments that frequently do not provide the desired results. The mammalian target of rapamycin (mTOR) is directly involved in the development of these malformations. However, the exact mechanism behind mTOR dysregulation has not been unambiguously defined. The purpose of this study is to investigate the activation of selected substrates of mTOR to partially assess its involvement in the disease process. Methods: We analyzed tissue samples collected from patients with vascular anomalies treated in our department. We included patients with histopathological diagnoses of lymphatic, venous, capillary malformations, mixed lesions, and a control group of healthy skin samples. We stained the samples using H and E and immunohistochemistry. We used primary antibodies against p70 S6 Kinase, 4EBP1, and p-4EBP1. We graded their color reactions. The statistical analyses were performed using the FactoMineR and factoextra R v.4.1 packages. p-values < 0.05 were considered statistically significant. Results: The analysis of 82 patients showed that healthy tissue vessels expressed lower levels of tested mTOR pathway substrates compared to high activation in vascular malformations. Elevated substrate expression in a comparison between sexes revealed higher P-4EBP1 expression in the female malformation group. We observed a decrease in mTOR substrate expression with age. Conclusion: The higher expression of mTOR substrates in vascular malformations compared to healthy tissue confirms their involvement in abnormal vascular development. Age-related changes in mTOR substrate expression highlight the need for timely intervention. Our study contributes to the understanding of the mTOR signaling pathway in vascular malformations and highlights its potential as a therapeutic target, contributing to personalized medicine. [ABSTRACT FROM AUTHOR]

According to the International Society for the Study of Vascular Anomalies (ISSVA) classification, vascular anomalies include a diverse range of pathologies, classified as either vascular tumors or vascular malformations. This classification, last revised in 2018, aims to explain the biological basis of vascular lesions and help clinicians to manage the anomalies. In vascular tumors, there are proliferative changes of endothelial cells, while vascular malformations primarily consist of structural vascular abnormalities. Infantile hemangioma is the most common soft-tissue vascular tumor. Vascular malformations are an extensive group of malformations of the arterial, venous, and lymphatic systems, either in isolation or in combination. Radiological evaluation plays a key part in the management of pediatric patients with these entities. The understanding of sonography and magnetic resonance imaging findings entails its correlation with clinical findings at the time of scanning. [ABSTRACT FROM AUTHOR]

Introduction Vascular anomalies are a spectrum of disorders, including vascular tumors and malformations, that often require multispecialty care. The rarity and variety of these lesions make diagnosis, treatment, and management challenging. Despite the recognition of the medical complexity and morbidity associated with vascular anomalies, there is a general lack of education on the subject for pediatric primary care and subspecialty providers. A needs assessment and the lack of an available standardized teaching tool presented an opportunity to create an educational workshop for pediatric trainees using the POGIL (process-oriented guided inquiry learning) framework. Methods We developed a 2-hour workshop consisting of an introductory didactic followed by small- and large-group collaboration and case-based discussion. The resource included customizable content for learning assessment and evaluation. Residents completed pre- and posttest assessments of content and provided written evaluations of the teaching session. Results Thirty-four learners in pediatrics participated in the workshop. Session evaluations were positive, with Likert responses of 4.6-4.8 out of 5 on all items. Pre- and posttest comparisons of four content questions showed no overall statistically significant changes in correct response rates. Learners indicated plans to use the clinical content in their practice and particularly appreciated the interactive teaching forum and the comprehensive overview of vascular anomalies. Discussion Vascular anomalies are complex, potentially morbid, and often lifelong conditions; multispecialty collaboration is key to providing comprehensive care for affected patients. This customizable resource offers a framework for trainees in pediatrics to appropriately recognize, evaluate, and refer patients with vascular anomalies.

Background We aimed to correlate alterations in the rat sarcoma virus (RAS)/mitogen‐activated protein kinase pathway in vascular anomalies to the clinical phenotype for improved patient and treatment stratification. Methods and Results This retrospective multicenter cohort study included 29 patients with extracranial vascular anomalies containing mosaic pathogenic variants (PVs) in genes of the RAS/mitogen‐activated protein kinase pathway. Tissue samples were collected during invasive treatment or clinically indicated biopsies. PVs were detected by the targeted sequencing of panels of genes known to be associated with vascular anomalies, performed using DNA from affected tissue. Subgroup analyses were performed according to the affected genes with regard to phenotypic characteristics in a descriptive manner. Twenty‐five vascular malformations, 3 vascular tumors, and 1 patient with both a vascular malformation and vascular tumor presented the following distribution of PVs in genes: Kirsten rat sarcoma viral oncogene (n=10), neuroblastoma ras viral oncogene homolog (n=1), Harvey rat sarcoma viral oncogene homolog (n=5), V‐Raf murine sarcoma viral oncogene homolog B (n=8), and mitogen‐activated protein kinase kinase 1 (n=5). Patients with RAS PVs had advanced disease stages according to the Schobinger classification (stage 3–4: RAS, 9/13 versus non‐RAS, 3/11) and more frequent progression after treatment (RAS, 10/13 versus non‐RAS, 2/11). Lesions with Kirsten rat sarcoma viral oncogene PVs infiltrated more tissue layers compared with the other PVs including other RAS PVs (multiple tissue layers: Kirsten rat sarcoma viral oncogene, 8/10 versus other PVs, 6/19). Conclusions This comparison of patients with various PVs in genes of the RAS/MAPK pathway provides potential associations with certain morphological and clinical phenotypes. RAS variants were associated with more aggressive phenotypes, generating preliminary data and hypothesis for future larger studies.

Abstract Treatment of oral vascular anomalies (OVA) has focused on minimally invasive techniques rather than radical surgery. We investigated the efficacy and safety of diode laser using the photocoagulation technique in the management of OVA. Forty-seven subjects with OVA were treated with forced dehydration with induced photocoagulation (FDIP) using diode laser (808 nm/4.5 W). This series consisted mostly of male (63.8%) and non-white (63.8%) patients with a mean age of 57.4 years. Varices (91.5%), venous malformations (6.4%), and hemangiomas (2.1%) with a mean size of 7.1 (±4.9) mm were the conditions treated. OVA presented as a nodular lesion (63.8%) involving mainly the lower lip (46.8%). Pulsed laser mode was used as standard and the number of applications varied from one to four sessions, with the majority requiring only one (83%) FDIP session. Kaplan-Meier analysis revealed that complete clinical healing can occur on the 15th day (n=9/29.5%), followed by the 20th (n=6/45.5%), and 30th (n=7/70.5%) days. Postoperative edema was observed in 31 (66%) patients, and recurrence of the lesion occurred in two (4.2%). Based on the data on complete clinical healing, minimal patient discomfort, and satisfactory esthetic results, we can confirm that FDIP by diode laser is a promising candidate for the safe and efficacious treatment of OVA.

Laser technology has significantly improved giving better results, which in turn has led to an increase in the indications for laser therapy. Vascular anomalies comprise vascular tumors and malformations. They are classified according to the type of vessels involved including arteries, capillaries, postcapillary venules, veins, lymphatic vessels, and a combination of two or more of these. Laser needs a chromophore to get absorbed and act. Hemoglobin, both oxy and deoxy, is one of the naturally occurring chromophore that is abundant in vascular lesions. Therefore, in most of the vascular lesions, lasers can bring improvement of a varying degree, while for superficial hemangiomas and port wine stain (PWS) laser treatment is now the standard of care. However, even though there is increase in the use of lasers in clinical practice, many surgeons are still unaware of its versatility and they are unsure about its safety. This article provides a brief overview of laser and intense pulsed light (IPL) technology, and describes the key principles in using these energy sources in vascular malformations. Readers are also familiarized with possible adverse effects and measures to prevent and treat them.

Objectives: Sirolimus (SRL), a mammalian target of rapamycin inhibitor, has been widely used to treat patients with vascular anomalies (VAs). The objectives of this study were to summarize the routine blood SRL monitoring data for VAs children, to investigate the factors contributing to the variable blood SRL concentrations and to evaluate the efficacy and safety of SRL therapy. Methods: VAs patients with routine blood SRL monitoring from July 2017 to April 2022 at the Department of Burns and Plastic Surgery, Children’s Hospital of Nanjing Medical University were retrospectively collected. Clinical data were obtained from the hospital information system. Results: In total, 67 children (35 females) were enrolled. The therapeutic drug monitoring data showed that the range of measured blood trough concentrations (Ctrough) was 3.6–46.8 ng/mL. At the initial measurements, only 33% of patients were in the target concentration range (10–15 ng/mL). But this proportion became 54% at the last measurements. The whole blood-Ctrough-to-daily dose (Ctrough/Dose) ratio was significantly associated with age and body weight (BW). The patients’ laboratory results did not change significantly after SRL treatment. Although the incidence of adverse events was relatively high (44.8%), most of them were mild and tolerable. 70.3% patients had total responses to SRL, whereas 29.7% children exhibited stable disease or progressive disease. No significant differences were found in Ctrough between the total response group and non-response group. Conclusions: This retrospective study revealed a high variability in SRL blood concentrations in Chinese children with VAs. Of note, pediatric patients with older age and a higher BW had a lower Ctrough/Dose ratio. It is a concern whether the range of 10–15 ng/mL is feasible for Chinese children based only on our study. Further studies recruiting more patients are required to redefine the target reference range for children with VAs.

Аim: to present two clinical cases of successful surgical treatment of patients with a combination of complete transposition of internal organs and cancer of the biliopancreatoduodenal zone.Key points. A 65-year-old man underwent gastropancreatoduodenal resection for cancer of the large duodenal papilla. In addition to the situs vicserum inversus, this patient revealed a special variant of vascular anatomy, namely: separate separation of the left and right hepatic arteries from the ventral trunk. A 70-year-old man, in addition to complete transposition of internal organs, had a combination of cancer of the terminal part of the common bile duct and heterotaxy syndrome in the form of polysplenia, aplasia of the hepatic segment of the inferior vena cava, agenesis of the dorsal pancreatic rudiment (“short” pancreas), intrapancreatic course of the right hepatic artery extending from the superior mesenteric arteries, rotational abnormalities of intestinal development. This patient underwent a total pancreatectomy. In both cases, the main difficulties in mobilizing the pancreatoduodenal complex arose due to anatomical disorientation and the absence of standard (familiar) topographic and anatomical landmarks for the surgeon.Conclusion. In all patients with tumors of the biliopancreatoduodenal zone, a detailed assessment of the vascular anatomy of this area is required before surgery, with the study of the course of the main visceral vessels and their large branches using multispiral computed tomography in vascular mode. If heterotaxy syndrome is suspected, additional examination is necessary to identify hidden developmental anomalies, which allows surgeons to be prepared for an unusual situation. Gastropancreatoduodenal resection or total pancreatectomy in situs viscerum inversus is a technically complex intervention and should be performed in large multidisciplinary medical institutions, and the operating team should have extensive experience in operations on the organs of the biliopancreatoduodenal zone.

Background: Discrepancies have been noted between the clinical and histologic diagnosis of vascular malformations. Objective: To evaluate the effectiveness of the International Society for Study of Vascular Anomalies (ISSVA) classification in diagnosing benign vascular anomalies based on clinical and (immuno) histologic parameters, focusing on lymphatic differentiation and vascular proliferation. Method: A retrospective study of 121 consecutive patients with benign skin and soft-tissue vascular anomalies located in the head and neck region (pyogenic granulomas and angioma senilis were excluded) by applying multiplex immunohistochemistry staining for lymph vessels (D2-40), endothelial blood vessels, and proliferating cells (Ki67). Clinical and histologic diagnosis was revised after the ISSVA classification. Results: Initially, 64 lesions were diagnosed as tumors and 57 as malformations. Revision diagnosis following the ISSVA classification revealed 27 tumors, 90 malformations (22.2% lymphatic), and 4 non-ISSVA. Immunostaining showed lymphatic differentiation in 24 (19.8%) of 121 cases, of which 20 were malformations. Proliferative activity (Ki67+) was found in 41 (33.8%) of 121 cases, of which 8 were arteriovenous malformations. Limitation: Quality and size of materials (biopsies vs resections) and clinical information. Conclusion: The diagnostic accuracy of combined histologic and clinical approaches for identifying vascular anomalies following the ISSVA classification can be substantially enhanced by incorporating additional immunostaining techniques to evaluate lymphatic differentiation and proliferative activity, particularly in identifying the occurrence of vascular malformations.