The dural angioleiomyoma harbors frequent GJA4 mutation and a distinct DNA methylation profile

The clinical relevance of any scheme for classification of vascular malformations of the brain remains controversial. Widely accepted pathologic classifications include discrete venous, arteriovenous, capillary, and cavernous malformations. Of 280 cases of possible vascular malformations evaluated by a single cerebrovascular service during a 5-year period, 14 were instances of mixed vascular malformations including definite features of more than one pathologically discrete type of malformation within the same lesion. There were six instances of mixed cavernous and venous malformations in the same lesion; in all instances, the cavernous malformation accounted for the clinical presentation. There were three cases of mixed venous and arteriovenous malformations (arterialized venous malformations), presenting with the typical histoarchitectural appearance of a venous malformation, but with arteriovenous shunting; all cases were symptomatic, two with hemorrhage and one with focal neurological symptoms. There were five cases of predominantly cavernous malformations with features of arteriovenous malformation or capillary telangiectasia in the same lesion. These five cases presented clinically as angiographically occult lesions indistinguishable from a cavernous malformation. Lesions including a venous malformation were recognizable preoperatively because of characteristic imaging features of the venous malformation. Other mixed vascular malformations were indistinguishable on diagnostic studies from pure cavernous malformations. Of the 14 mixed vascular malformations, 11 included a cavernous malformation that was usually responsible for the symptomatic presentation. In the other three cases, manifestations of clinical lesions were due to arteriovenous shunting within a venous malformation. We conclude that mixed vascular malformations of the brain are rare entities with distinct clinical, radiological, and pathological profiles. Their identification generates several hypotheses about common pathogenesis or causation-evolution among different types of lesions.

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.

A clinicopathological reappraisal of orbital vascular malformations and distinctive GJA4 mutation in cavernous venous malformations

Vascular Anomalies of the Mediastinum

Cavernous malformations (CMs), also known as cavernous angiomas or cavernomas, are low-flow vascular malformations of the brain and spinal cord that consist of clusters of dilated sinusoidal channels lined with endothelial cells that do not exhibit intervening tight junctions. The involved blood vessels lack muscular and elastic layers, and blood at various stages of thrombosis and organization often fills the thin-walled vascular caverns. CMs are grossly distinct from adjacent brain and have a lobulated appearance sometimes likened to a mulberry, with a characteristic dark red or purple color. Hemosiderin and gliosis often surround CMs of the brain and spinal cord; no neural tissue is present inside the lesion. Except for developmental venous anomalies (DVAs) present in ≈33% of CMs,1 no abnormal vascularity is typically seen on digital subtraction angiography, leading CMs to be termed cryptic or occult vascular malformations (Figure 1). Multiple small hemorrhage events lead to a pathognomonic popcorn appearance on magnetic resonance (MR) imaging because of hemosiderin staining from blood products of various ages. Calcifications may be present on computed tomographic imaging (Figure 2). Figure 1. A 48-year-old woman presented with headaches. A , Magnetic resonance imaging of the brain with T2-weighted imaging demonstrated a 1.1-cm lesion in the cerebellar vermis with mixed signal intensity. B – D , Susceptibility-weighted imaging demonstrated hemosiderin within the lesion’s core and a developmental venous anomaly associated with the cavernous malformation (arrowheads). Figure 2. A 28-year-old woman presented with partial seizures without secondary generalization. A , Noncontrast computed tomography of the head demonstrated a 1.4-cm right posterior cingulate hyperdensity, with evidence of mild hemorrhage and calcification. Magnetic resonance imaging of the brain demonstrated the cavernous malformation to have a core of mixed signal intensity, heterogeneous enhancement, and a rim of hemosiderin consistent with a cavernous malformation, as evidenced on ( B ) susceptibility-weighted imaging, ( C ) T2-weighted …

Cutaneous and hepatic vascular lesions due to a recurrent somatic GJA4 mutation reveal a pathway for vascular malformation.

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

A patient with short term memory problems and ataxia

Intracerebral capillary telangiectasia and venous malformation: A rare association

Venous malformation serving as the draining vein of an adjoining arteriovenous malformation: Case report and review of the literature

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.

Objective To preliminarily discuss the operation strategy in patients with intracranial cavernous hemangioma complicated with venous malformation. Methods The clinical data and postoperative follow-up results of 13 patients with intracranial cavernous hemangioma complicated with venous malformation operated at the Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University from January 2007 to December 2014 were analyzed retrospectively. Results In the 13 patients, intracranial cavernous malformation complicated with venous malformation achieved total resection in 7 patients. They all developed severe cerebral edema after procedure. Four of them were in the supratentorial region, their prognoses were good after strengthening dehydration treatment, and 1 in the supratentorial region died, and 2 left sequelae. The postoperative condition was stable and the prognosis was good in 4 patients whose abnormal expansion of medullary veins were resected, the main drainage veins were retained and in 2 patients whose venous vascular malformations were retained. Conclusion In the operation of resection of intracranial cavernous malformation complicated with venous malformation, the resection of abnormally dilated medullary veins and retaining main draining veins at the same time of the total resection of cavernous malformation are more conducive to the rehabilitation of patients. Key words: Hemangioma, cavernous, central nervous system; Venous malformation; Microsurgery

Dear Editor, We read the article “Pure spinal epidural cavernous hemangioma” by Zhong et al. [4] published recently in Acta Neurochirurgica with great interest and found that some discussion is pertinent. In 1982, Mulliken and Gloweki [3] classified vascular anomalies into two categories of hemangiomas (infantile hemangioma, congenital hemangioma, kaposiform hemangioendothelioma, and tufted angioma) and vascular malformation (arteriovenous, venous, lymphatic, and capillary malformations). In 1996, the International Society for the Study of Vascular Anomalies approved this classification system to establish a common language for the many different medical specialists who are involved in the management of these lesions. Previously, there was no precise classification and naming of hemangioma and vascular malformation. They were mostly referred to as hemangioma or lymphangioma together, and were primarily named according to the lesion’s morphology. For example, hemangioma included capillary hemangioma, cavernous hemangioma, racemose hemangioma; lymphangioma included capillary, cavernous and cystic. Since patients with hemangioma or vascular malformations can be treated in different clinical departments, even the same lesion can also get different names, as wine-color stains are referred as PWS in some departments. In 1982, Mulliken and Gloweki put forward that there should be a re-classification according to the cell biological and pathological characteristics, and made it clear that the two types of lesions as tumor and deformity should be distinguished. They were divided into two categories of hemangiomas and vascular malformations according to whether the proliferations of endothelial cells were found in the pathologic tissues. Hemangioma was the embryonic vascular endothelial cell proliferation characterized by benign tumor. This is quite different from the original traditional classification that was based on morphology and pathology. The occurance of hemangioma in neonates is about 3 %, which often occurs in the neonatal period and then enters the proliferative phase. Generally, it should get timely treatment once it is found. Ninety percent of vascular malformations are there at birth, but with no proliferation phase, they will grow proportionally with the increase in age [1]. Previous traditional classification rules defined wine-color stains, cavernous hemangioma, and racemose hemangioma as all belonging to vascular malformation, but they are now named as capillary malformations, venous malformation and arteriovenous malformations respectively. Due to errors in classification, many vascular malformations are mistaken as hemangioma, and many patients received false and ineffective treatment. The term “cavernous hemangioma” refers to a venous malformation. It consists of dilated sinusoidal channels lined by quiescent endothelium. The magnetic resonance imaging features of vascular malformations include: T2-weighted images that performed as high-intensity signal, T1-weighted images performed as the iso-intensity signal, just as that recorded in the article; magnetic resonance imaging can reveal the spinal epidural venous malformation, intra-lesion hemorrhage and thrombosis. Magnetic resonance imaging can demonstrate the breadth of lesions and the relationship between lesions and adjacent tissues; it can also help to provide the potential treatment plans. M. Zhu :Y. Luo : L. Qiu (*) Department of Diagnostic Ultrasound, West China Hospital of Sichuan University, No.37 Guo Xue Xiang, Chengdu 610041, Sichuan, China e-mail: vigour_sky@163.com

Venous malformations (VM) represent a localized error in the embryological development of the venous branch of the circulation. The management of VM is complex and challenging. The aim of this study was to assess the efficacy and safety of combined sequential pulsed dye laser (PDL)-Nd:YAG laser in patients with cutaneous or mucosal VM. Thirty patients (age from 8 to 65 years) with cutaneous or mucosal VM treated with dual wavelength PDL-Nd:YAG laser were retrospectively analyzed. Laser parameters were 10 mm spot size with 10 ms pulse and 8-10 J/cm(2) of PDL, followed with a second delay by Nd:YAG with 15 or 20 ms at 35-70 J/cm(2); or 7 mm spot size with 10 ms pulse and 5-10.5 J/cm(2) of PDL, followed with a second delay by Nd:YAG with 15 or 20 ms at 50-100 J/cm(2). Laser sessions were repeated approximately every 2-6 months. Air cooling was applied during treatment. Three dermatologists evaluated treatment effectiveness by means of photographs of the patients before and after laser treatment (scale from 0 to 4). Differences in the degree of clinical improvement between patients with cutaneous or mucosal VM were also assessed. Adverse events were registered. Patient satisfaction was also assessed in 19 cases (scale from 0 to 10). Mean global improvement was rated as 3.37. Mean improvement in patients with cutaneous VM was 3.35 and 3.38 in patients with mucosal VM. No significant difference between both groups was observed (P = 0.53). Long-lasting side effects included partial epilation of the eyelashes in one patient, ulceration in two patients and permanent scarring in three patients. Mean patient satisfaction was 8.55. Our study concludes that dual wavelength PDL-Nd:YAG laser was effective for treatment of the superficial component of cutaneous and mucosal VM.

Background: Bacillus Calmette-Guérin (BCG) immunotherapy, the standard adjuvant intravesical therapy for some intermediate and most high-risk non-muscle invasive bladder cancers (NMIBCs), suffers from a heterogenous response rate. Molecular markers to help guide responses are scarce and currently not used in the clinical setting. Methods: To identify novel biomarkers and pathways involved in response to BCG immunotherapy, we performed a genome-wide DNA methylation analysis of NMIBCs before BCG therapy. Genome-wide DNA methylation profiles of DNA isolated from tumors of 26 BCG responders and 27 failures were obtained using the Infinium MethylationEPIC BeadChip. Results: Distinct DNA methylation patterns were found by genome-wide analysis in the two groups. Differentially methylated CpG sites were predominantly located in gene promoters and gene bodies associated with bacterial invasion of epithelial cells, chemokine signaling, endocytosis, and focal adhesion. In total, 40 genomic regions with a significant difference in methylation between responders and failures were detected. The differential methylation state of six of these regions, localized in the promoters of the genes GPR158, KLF8, C12orf42, WDR44, FLT1, and CHST11, were internally validated by bisulfite-sequencing. GPR158 promoter hypermethylation was the best predictor of BCG failure with an AUC of 0.809 (p-value < 0.001). Conclusions: Tumors from BCG responders and BCG failures harbor distinct DNA methylation profiles. Differentially methylated DNA regions were detected in genes related to pathways involved in bacterial invasion of cells or focal adhesion. We identified candidate DNA methylation biomarkers that may help to predict patient prognosis after external validation in larger, well-designed cohorts.