Injectable chitosan hydrogel effectively controls lesion growth in a venous malformation murine model.

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of intralesional injection of chitosan hydrogel (CH) combined with sodium tetradecyl sulfate (STS) to sclerose and embolize venous malformations (VMs) by comparison with 3% STS foam and placebo in a mouse model. MATERIALS AND METHODS: Subcutaneous VMs were created by injecting HUVEC_TIE2-L914F cells, mixed with matrigel, into the back of athymic mice (Day [D] 0). After VM-like lesions were established at D10, 70 lesions were randomly assigned to one of six treatment groups (untreated, saline, 3% STS-foam, CH, 1% STS-CH, 3% STS-CH). For 3% STS-foam, the standard Tessari technique was performed. VMs were regularly evaluated every 2-3 days to measure lesion size until the time of collection at D30 (primary endpoint). At D30, VM lesions including the matrigel plugs were culled and evaluated by histological analysis to assess vessel size, chitosan distribution and endothelial expression. One-way analysis of variance (ANOVA) test was performed to compare quantitative variables with normal distribution, otherwise Kruskal-Wallis test followed by pairwise comparisons by a Wilcoxon rank sum test was performed. RESULTS: All VMs were successfully punctured and injected. Six VMs injected with 3% STS-CH showed early skin ulceration with an extrusion of the matrigel plug and were excluded from final analysis. In the remaining 64 VMs, skin ulceration occurred on 26 plugs, resulting in the loss of three 3% STS-foam and one 1% STS-CH plugs. Both chitosan formulations effectively controlled growth of VMs by the end of follow-up compared to untreated or 3% STS-foam groups (P < 0.05). Vessel sizes were smaller with both CH formulations compared to untreated and saline groups (P < 0.05). Additionally, there were smaller vascular channels within the 1% STS-CH group compared to the 3% STS-foam group (P < 0.05). CONCLUSION: Chitosan's ability to control the growth of VMs suggests a promising therapeutic effect that outperforms the gold standard (STS-foam) on several variables.

Segmental congenital vascular anomaly with atrophy, ulceration, and scarring (SeCVAUS): Case series and review of literature.

BACKGROUND: Next-generation sequencing has greatly increased our understanding of vascular birthmarks. Many port-wine birthmarks are due to somatic mutations in GNAQ/GNA11 exon 183, but other genomic causes have been identified. Most congenital hemangiomas are due to somatic mutations in GNAQ/GNA11 at exon 209. Although genomically distinct, clinical overlap of congenital hemangiomas and port-wine birthmarks has occasionally been described. OBJECTIVE: We report a case series of a unique segmentally distributed vascular anomaly with overlapping characteristics of port-wine birthmarks and congenital hemangiomas with other distinctive features including ulceration, atrophy, and scarring. METHODS: This was a multicenter study with retrospective identification of patients via a detailed review of medical records. We also reviewed previously published cases. RESULTS: The clinical, histological, radiological, and genomic characteristics of 19 new and 13 previously reported cases characterized by segmental distribution, sharply demarcated borders, with variable thickening are presented. All cases had central atrophy with or without episodic ulceration. Those with genomic studies (13 out of 32) had somatic activating missense mutations in GNA11 or GNAQ codon 209. CONCLUSIONS: We describe the features and propose a descriptive name segmental congenital vascular anomaly with atrophy, ulceration, and scarring (SeCVAUS) for this condition.

Primary intracranial sarcoma, DICER-1 mutant, with hemorrhagic presentation: A case report.

Background: Primary intracranial sarcomas (PIS) are rare tumors with mesenchymal origins. These tumors have a heterogeneous clinical presentation and are associated with a poor prognosis. Case Description: This report highlights the complexities associated with PIS by focusing on a 26-year-old male with recurrent tumor growth facing unique challenges regarding diagnosis and treatment options . A high-grade spindle-celled neoplasm with sarcomatous features characterized the patient's tumor. There were additional morphologic changes, including multinucleated giant cells and rare foci with eosinophilic spheroids. Genomic analysis revealed a DICER1-associated PIS. Treatment involved endovascular embolization, multiple surgical interventions, intrathecal etoposide injections, and oral pazopanib with adjuvant radiation therapy. Conclusion: This case additionally highlights an unusual association between PIS and anomalous hypervascularity, refractory hemorrhage, and subdural effusions, a presentation that is increasingly being reported in this type of tumor.

Intramuscular hemangioma of the infraspinatus muscle: a rare presentation.

Intramuscular hemangiomas (IMH) are extremely rare, accounting for 0.8% of all hemangiomas. IMH must be included in the differential diagnosis of soft tissue masses, and unexplained muscular pain. We herein describe the case of a patient who presented with an atypical localization of IMH in the infraspinatus muscle.

[Diagnostic capabilities of spinal MR-angiography and spinal MR-tractography in Foix-Alajouanine syndrome]. / Diagnosticheskie vozmozhnosti spinal'noi MR-angiografii i spinal'noi MR-traktografii pri sindrome Fua­Alazhuanina.

The Foix-Alajouanine syndrome was originally reported by these authors in 1926, as rapidly progressive vasculitis on the background of a viral infection. The pathology was represented by the huge, more than 10 times, dilation either of the lumen, or the walls of the spinal vessels, either of the arteries, or the veins. There were no signs of thrombosis, no malformations. Massive necrosis was observed in the spinal cord. Though plenty of observations of the syndrome were reported over the past 100 years, most of them deal with arteriovenous malformations and/or thrombosis, which had not been revealed originally. We present the case of spinal viral vasculitis detected by means of spinal MR-angiography. The undoubted viral etiology of vasculitis allows us to attribute this observation to Foix-Alajouanine syndrome.

Fibroadipose Vascular Anomaly: Diagnosis and Treatment.

Fibro-Adipose Vascular Anomaly (FAVA) is a recently identified type of vascular malformation predominantly affecting adolescent females. Comprising abnormal adipose and vascular components, FAVA is frequently misdiagnosed as other vascular anomalies. It primarily manifests with pain, functional impairment, and musculoskeletal symptoms, particularly in the lower extremities. Accurate diagnosis requires a combination of clinical, radiologic, and histopathologic evaluation, with MRI and ultrasound being the primary imaging tools. Management of FAVA is multidisciplinary and tailored to individual patients. Interventional radiology procedures, such as percutaneous cryoablation, sclerotherapy, and embolization, are effective in long term control of symptoms. Cryoablation is particularly successful in alleviating pain and improving function. Surgical resection is reserved for specific cases with extensive lesions involving joints or when there is severe muscle or joint dysfunction. Additionally, sirolimus, an mTOR inhibitor, has shown promise in symptom relief, although further research is needed to confirm its long-term efficacy. Early diagnosis and treatment are essential for improving the quality of life in FAVA patients. Advances in imaging and treatment strategies have enhanced the ability to manage this complex and rare condition effectively.

Complex Arterio-Portal-Venous Malformation of the Liver.

A neonatal female patient exhibited a congenital intricate vascular malformation affecting the liver, encompassing anomalies in the arterial, venous, and portal venous systems and notably including an aneurysm within the portal vein. The management strategy involved a staged endovascular approach, initially using retrograde embolization via the venous outflow tract. Subsequently, transarterial embolization was performed to address complications associated with pulmonary and portal hypertension.

A Microphysiological HHT-on-a-Chip Platform Recapitulates Patient Vascular Lesions.

Hereditary Hemorrhagic Telangiectasia (HHT) is a rare congenital disease in which fragile vascular malformations (VM) - including small telangiectasias and large arteriovenous malformations (AVMs) - focally develop in multiple organs. There are few treatment options and no cure for HHT. Most HHT patients are heterozygous for loss-of-function mutations affecting Endoglin (ENG) or Alk1 (ACVRL1); however, why loss of these genes manifests as VMs remains poorly understood. To complement ongoing work in animal models, we have developed a fully human, cell-based microphysiological model based on our Vascularized Micro-organ (VMO) platform (the HHT-VMO) that recapitulates HHT patient VMs. Using inducible ACVRL1 -knockdown, we control timing and extent of endogenous Alk1 expression in primary human endothelial cells (EC). Resulting HHT-VMO VMs develop over several days. Interestingly, in chimera experiments AVM-like lesions can be comprised of both Alk1-intact and Alk1-deficient EC, suggesting possible cell non-autonomous effects. Single cell RNA sequencing data are consistent with microvessel pruning/regression as contributing to AVM formation, while loss of PDGFB implicates mural cell recruitment. Finally, lesion formation is blocked by the VEGFR inhibitor pazopanib, mirroring positive effects of this drug in patients. In summary, we have developed a novel HHT-on-a-chip model that faithfully reproduces HHT patient lesions and that can be used to better understand HHT disease biology and identify potential new HHT drugs.

Congenital right subclavian artery aneurysm resection in a 30-year-old woman.

Right-sided subclavian artery aneurysms (SAAs) are exceedingly rare. The most common cause of intrathoracic SAAs is atherosclerosis; however, causes can also include infection, trauma, cystic medial degeneration, Marfan syndrome, and Takayasu arteritis. Symptoms present most commonly with compression of surrounding structures, although adverse events, including rupture, thrombosis, and embolization, can also occur. We present a case of a 30-year-old woman with an asymptomatic, 15-mm, right-sided SAA, which was successfully resected with subsequent end-to-end primary anastomosis.

Additional outlet occlusion as an important factor in avoiding retreatment after transvenous embolization for cavernous sinus dural arteriovenous fistulas.

BACKGROUND: Transvenous embolization (TVE), such as selective shunt occlusion, is the first line treatment for cavernous sinus dural arteriovenous fistula (CSDAVF). Despite the favorable outcomes of TVE, some cases necessitating retreatment due to recurrence or incomplete occlusion persist. Given the physical, psychological, and financial burden of multiple treatments, understanding the predictive factors for recurrence, spontaneous occlusion, or retreatment is important. However, few reports have addressed these factors, complicating decision making regarding the need for retreatment. This study analyzed predictive factors for retreatment and spontaneous occlusion to offer new insights into CSDAVF management. METHODS: This retrospective, observational study was conducted in two acute care hospitals. Patients aged 18-100 years undergoing endovascular treatment for CSDAVF from January 2011 to December 2022 were included. RESULTS: Of 65 patients treated with TVE, 29 experienced immediate complete occlusion. Meanwhile, 22 of 36 patients with incomplete occlusion had spontaneous occlusion, and retreatment was performed in 20% of patients. Additional outlet occlusion was negatively associated with retreatment (P=0.046), and it tended to promote spontaneous occlusion (P=0.056). Favorable functional outcomes were observed in all patients, and approximately 94% of patients showed complete occlusion at the latest follow-up. CONCLUSION: TVE is an effective treatment for CSDAVF. Outlet occlusion, when immediate complete occlusion is unattainable, is important to reduce retreatment and promote spontaneous occlusion. Substantially reducing shunt flow, carefully assessing dangerous drainage routes, and closely monitoring the residual shunt are crucial for preventing intracranial hemorrhage when outlet occlusion is performed.

Somatic RIT1 delins in arteriovenous malformations hyperactivate RAS-MAPK signaling amenable to MEK inhibition.

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.

Similarities and differences between brain and skin GNAQ p.R183Q driven capillary malformations.

Capillary malformations (CM) are congenital vascular irregularities of capillary and venous blood vessels that appear in the skin, leptomeninges of the brain, and the choroid of the eye in the disorder known as Sturge Weber Syndrome (SWS). More common are non-syndromic CM found only in the skin, without brain or ocular involvement. A somatic activating mutation in GNAQ (p.R183Q) is found in ~90% of syndromic and non-syndromic CM specimens and is present in CD31pos endothelial cells isolated from brain and skin CM specimens. Endothelial expression of the GNAQ p.R183Q variant is sufficient to form CM-like vessels in mice. Given the distinct features and functions of blood vessels in the brain versus the skin, we examined the features of CM vessels in both tissues to gain insights into the pathogenesis of CM. Herein, we present morphologic characteristics of CM observed in specimen from brain and skin. The GNAQ p.R183Q variant allelic frequency in each specimen was determined by droplet digital PCR. Sections were stained for endothelial cells, tight junctions, mural cells, and macrophages to assess the endothelium as well as perivascular constituents. CM blood vessels in brain and skin were enlarged, exhibited fibrin leakage and reduced zona occludin-1, and were surrounded by MRC1pos/LYVE1pos macrophages. In contrast, the CMs from brain and skin differ in endothelial sprouting activity and localization of mural cells. These characteristics might be helpful in the development of targeted and/or tissue specific therapies to prevent or reverse non-syndromic and syndromic CM.

Spinal dural arteriovenous fistula in a child: a rare presentation.

Spinal dural arteriovenous fistula (AVF) is an abnormal shunting between the segmental artery and radicular vein adjacent to the dural root sleeve in the spine. This is the most common vascular malformation of the spinal cord and is a rare but treatable cause of para or quadriplegia. It most commonly occurs in elderly men and often affects the thoracolumbar region. These patients clinically present with progressive myelopathies, and other autonomic symptoms (e.g., bladder and bowel dysfunction) subsequently in the later course of the disease. Computed tomography angiography and magnetic resonance imaging remain the modality for initial evaluation. Herein, we present a rare case of spinal dural AVF in a child along with a review of imaging modalities. To the best of our knowledge, there are few case reports of this condition in a paediatric age group.

Optical coherence tomography-measured blood vessel characteristics of port-wine birthmarks by depth: A cross-sectional study.

BACKGROUND: Port-Wine Birthmarks (PWB) are congenital capillary malformations requiring multiple treatments. Optical coherence tomography (OCT), a noninvasive imaging technique, characterizes vessels in cutaneous vascular lesions, including PWBs. OBJECTIVE: To assess variability in blood vessel characteristics within and between individual PWBs. METHODS: OCT was used to measure blood vessel density (%) and modal vessel diameter (micrometers) at increments of 0.05 mm from the skin surface to a depth of 0.50 mm at several adjacent spots of single PWBs in this cross-sectional study. Average ratios of vessel density and diameter in affected to control skin were obtained for each PWB by averaging data for all spots within a lesion. Statistical analysis was performed with a linear mixed effects model using SPSS software (IBM Corporation). RESULTS: There was great variability in vessel density and diameter within and between PWBs. Depths where average ratios of vessel density were consistently greater in affected to control skin were shallow, between 0.15 mm and 0.2 mm deep from the skin surface. LIMITATIONS: Small sample size and device's inability to measure diameters smaller than 20 micrometers. CONCLUSION: There is variability in vessel density and diameter within and between PWBs. Individualized treatment planning guided by OCT mapping should be studied further.

ACR Appropriateness Criteria® Soft Tissue Vascular Anomalies: Vascular Malformations and Infantile Vascular Tumors (Non-CNS)-Child.

Soft tissue vascular anomalies may be composed of arterial, venous, and/or lymphatic elements, and diagnosed prenatally or later in childhood or adulthood. They are divided into categories of vascular malformations and vascular tumors. Vascular malformations are further divided into low-flow and fast-flow lesions. A low-flow lesion is most common, with a prevalence of 70%. Vascular tumors may behave in a benign, locally aggressive, borderline, or malignant manner. Infantile hemangioma is a vascular tumor that presents in the neonatal period and then regresses. The presence or multiple skin lesions in an infant can signal underlying visceral vascular anomalies, and complex anomalies may be associated with overgrowth syndromes. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

A Rare Case of Internal Jugular Venous Malformation Treated by Surgical Excision.

This paper reports a case of an internal jugular venous malformation (IJVM) and route of treatment in a patient with limited symptoms. After history and imaging studies, a determination of surgical excision was made to rule out possible malignancy and future problems such as thrombosis. The mass was resected, and part of the IJVM was ligated. The mass had no identifiable malignancy, and the patient recovered fully with no complications. The paper highlights the importance of identifying venous malformations and highlights the reasoning behind the course of action.

Soft tissue vascular tumor-like lesions in adults: imaging and pathological analysis pitfalls per ISSVA classification.

OBJECTIVES: To compare the magnetic resonance imaging (MRI) and Doppler ultrasound (DUS) findings with the pathological findings of soft tissue vascular tumors (STVTs) according to the 2018 ISSVA (International Society for the Study of Vascular Anomalies) classification to differentiate vascular tumors from vascular malformations. METHODS: This retrospective study included patients with STVTs who underwent contrast-enhanced MRI and pathological analysis at our hospital between 2010 and 2020. The presumptive diagnosis based on the on-site imaging and histological analysis was compared with imaging and histological analysis conducted off-site utilizing the ISSVA criteria. RESULTS: This study included 31 patients with 31 vascular tumors located in the head and neck (n = 3), trunk (n = 2), and extremities (n = 26). The off-site pathological analysis confirmed benign vascular tumors in 54.8% of cases (non-involuting congenital hemangioma: 35.5%; epithelioid hemangioma: 13%; pyogenic granuloma: 3%; and spindle cell hemangioma: 3%). Based on the off-site histological analysis, 25.8% were reclassified as having a vascular malformation whereas three had other benign lesions. Only phleboliths were associated with a vascular malformation (p = 0.03). The concordance between off-site MRI and pathological findings was fair (k = 0.3902 (0.0531-0.7274)), whereas that between on-site and off-site pathological analyses was poor (k = -0.0949 (-0.4661 to 0.2763)). CONCLUSION: Benign vascular tumors have non-specific imaging features on imaging with some overlap with atypical vascular malformations. Therefore, histological analysis is recommended. Imaging and pathological analyses should be performed in accordance with the ISSVA classification to minimize inter-observer discrepancies. CRITICAL RELEVANCE STATEMENT: Imaging features of benign vascular tumors on MRI are non-specific, leading to discrepancies with pathological findings and potential overlap with atypical vascular malformations. Imaging and histological analyses should be performed in accordance with ISSVA guidelines to improve patient management. KEY POINTS: The imaging features of benign vascular tumors are non-specific. Histological analysis is recommended for soft tissue vascular tumors in adults. Analyses of soft tissue vascular tumors should be performed in accordance with ISSVA guidelines.

Proteus Syndrome: A Rare Congenital Disorder.

An uncommon congenital hamartomatous disorder called Proteus syndrome is characterized by multifocal tissue expansion originating from all three germinal layers. Diagnosis mainly relies on clinical and radiological criteria. Here, we present a case of a 13-year-old female child exhibiting bony, soft tissue, and vascular abnormalities, along with developmental delay. We conclude by highlighting the importance of imaging studies in conjunction with physical examination, which are characterized by general and specific criteria to diagnose this rare condition until a specific gene test becomes available.