GNA14 and GNAQ somatic mutations cause spinal and intracranial extra-axial cavernous hemangiomas.

Extra-axial cavernous hemangiomas (ECHs) are complex vascular lesions mainly found in the spine and cavernous sinus. Their removal poses significant risk due to their vascularity and diffuse nature, and their genetic underpinnings remain incompletely understood. Our approach involved genetic analyses on 31 tissue samples of ECHs employing whole-exome sequencing and targeted deep sequencing. We explored downstream signaling pathways, gene expression changes, and resultant phenotypic shifts induced by these mutations, both in vitro and in vivo. In our cohort, 77.4% of samples had somatic missense variants in GNA14, GNAQ, or GJA4. Transcriptomic analysis highlighted significant pathway upregulation, with the GNAQ c.626A>G (p.Gln209Arg) mutation elevating PI3K-AKT-mTOR and angiogenesis-related pathways, while GNA14 c.614A>T (p.Gln205Leu) mutation led to MAPK and angiogenesis-related pathway upregulation. Using a mouse xenograft model, we observed enlarged vessels from these mutations. Additionally, we initiated rapamycin treatment in a 14-year-old individual harboring the GNAQ c.626A>G (p.Gln209Arg) variant, resulting in gradual regression of cutaneous cavernous hemangiomas and improved motor strength, with minimal side effects. Understanding these mutations and their pathways provides a foundation for developing therapies for ECHs resistant to current therapies. Indeed, the administration of rapamycin in an individual within this study highlights the promise of targeted treatments in treating these complex lesions.

A Novel Zn(II) Coordination Polymer: Fluorescence Performances, Molecular Docking and Loaded with Bleomycin-Hydrogels on Hemangiomas.

In this study, we successfully synthesized an innovative 1D-Zn(II) coordination polymer, denoted as [Zn(L)(H2O)2]n, employing the Schiff base {4-[(2-hydroxy-3-methoxy-benzylidene)-amino]-benzoic acid} (H2L). The Schiff base was obtained through the reaction of 4-aminobenzoic acid and o-vanillin under slow volatilization conditions. The resulting compound exhibits remarkable green fluorescence emission properties, indicating its potential as a novel fluorescent and sensing material. Hydrogels based on hyaluronic acid (HA) and carboxymethyl chitosan (CMCS), denoted as HA/CMCS hydrogels, were synthesized using a chemical method. Additionally, we utilized bleomycin as a model drug to synthesize a novel bleomycin metal gel and assessed its anti-hemangioma activity. Molecular docking simulations revealed that the Zn complex can form stable bonds with the key target, involving the methoxy and carboxyl groups on the Zn complex.

How many is too many? A review of the significant numbers in pediatric skin lesions and their recommended evaluation.

Pediatric dermatologists are frequently consulted to evaluate children for cutaneous signs of systemic disorders. Numerical thresholds of significance have been described in the dermatologic literature for various skin findings where the likelihood of an associated extracutaneous abnormality or known genetic syndrome increases significantly. Knowledge of these numerical thresholds facilitates diagnosis and management, which improves clinical outcomes and avoids severe complications. This review highlights the clinical presentation, complications, evaluation, and numerical significance, when applicable, for the following skin findings: infantile hemangiomas, capillary malformations, café-au-lait macules, hypopigmented macules, juvenile xanthogranulomas, pilomatricomas, and angiofibromas.

Neonatal nasal necrosis: Case series and brief review.

There is limited information available on pressure-related neonatal nasal injuries. We present three neonates born with erythema and purpura of the nasal tip that subsequently ulcerated, then evolved into a thick eschar. Each healed well with conservative management but left behind significant scarring. The sharp demarcation and location of the lesions were suggestive of hypoxic tissue damage akin to halo scalp ring alopecia. Further investigation is necessary to elucidate the etiology and optimal management of this condition.

Hemangioma of the Urinary Bladder: A Brief Narrative Review of Their Diagnosis, Histology, and Treatment Options.

BACKGROUND: Hemangioma of the urinary bladder is a rare benign tumor. Although benign, their presenting symptoms are alarming for both patients and doctors, and their rarity makes them challenging to correctly diagnosis and treat. This review paper summarizes current knowledge about hemangioma of the urinary bladder, treatment options, and follow-up modalities. SUMMARY: After the kidney, the bladder is the second most common location of hemangiomas in the urinary tract. There is painless gross hematuria on clinical presentation once the lesion has eroded the urothelium. Magnetic resonance imaging (MRI) has been reported to be valuable in diagnosing soft-tissue hemangiomas. Cystoscopic findings of a sessile, blue, multilocular mass suggest hemangioma. Most tumors are solitary, smaller than 3 cm, and have smooth or irregular surfaces. Histologically, lesions comprise numerous proliferative capillaries with thin-walled, dilated, blood-filled vessels lined with flattened endothelium. The treatment of patients with hemangioma has been controversial. It depends on the tumor size and the degree of penetration. The prognosis of these tumors is excellent. KEY MESSAGES: Despite the widespread use of MRI, CT, and endoscopy in evaluating hematuria, hemangioma remains one of the rarest bladder tumors. Moreover, only a histological examination can confirm the diagnosis. Transurethral resection, fulguration, and YAG laser ablation are standard treatments for small tumors. In terms of follow-up, cystoscopy after 6 months of treatment helps assess recurrence. In addition, MRI is a practical, noninvasive technique for follow-up of small hemangiomas.

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.

Synovial hemangioma presenting with chronic painful infrapatellar mass: a case report.

BACKGROUND: Synovial hemangiomas are rare benign vascular anomalies surrounded by a synovial lining and were first described by Bouchut in 1856. These neoplasms can develop in the intra-articular region, resulting in effusions and knee pain. However, their cause remains unknown. Prompt diagnosis and intervention are critical to prevent chondral damage. Histopathological examination is used to achieve the diagnosis, which is often delayed because of a lack of specific clinical signs. This report describes a unique case in which a painful infrapatellar mass was diagnosed as a synovial hemangioma. The absence of typical magnetic resonance imaging (MRI) findings highlights the importance of arthroscopic excision for diagnosis and symptom relief. CASE PRESENTATION: A 20-year-old woman presented with persistent anterior left knee pain that became exacerbated when she climbed stairs. Despite previous pain management and physical therapy, she developed a painful lump beneath her patella that worsened over time. She had also undergone arthrocentesis, but this did not relieve her pain. Physical examination revealed a palpable, immobile 5-cm mass along the patellar tendon with limited knee flexion and extension and normal ligament stability. T1-weighted fat-saturated MRI of the left knee with gadolinium-based contrast revealed a lobulated intra-articular mass in Hoffa's fat pad that resembled a soft tissue chondroma. A biopsy of the mass was performed to provide histopathological evidence, confirming the benign nature of the mass. The subsequent excisional arthroscopy, combined with incision enlargement for mass removal, confirmed the histopathologic diagnosis of synovial hemangioma based on the presence of numerous dilated blood vessels and venous proliferation within sections of the synovium. Recovery was complete, and no residual tumor was detected on follow-up MRI after 1 year. CONCLUSION: This case study emphasizes the importance of arthroscopic excision over open surgery for patients with synovial hemangioma. The minimally invasive nature of arthroscopy combined with the well-encapsulated nature and location of the mass facilitates complete resection.

Revealing the mechanism of 755-nm long-pulsed alexandrite laser in inhibiting infantile hemangioma endothelial cells through transcriptome sequencing.

Laser therapy has shown promising outcomes in treating infantile hemangiomas. However, the molecular mechanisms underlying laser treatment for IH remain incompletely elucidated. This study aimed to unravel the molecular mechanisms of laser therapy in IH treatment. We evaluated the inhibitory effects of laser treatment on the proliferation and promotion of apoptosis in human hemangioma endothelial cells (HemECs) through cell counting kit-8 (CCK-8) assay, Hoechst 33342 staining, and flow cytometric analysis. Transcriptome sequencing analysis of HemECs following laser treatment revealed a significant decrease in the expression level of the GSTM5 gene. The qRT-PCR and western blot analysis also showed that GSTM5 expression in HemECs was downregulated compared to human umbilical vein endothelial cells (HUVECs), and concomitantly, the p62-Nrf2 pathway was suppressed. Using siRNA to downregulate GSTM5 expression, we observed that inhibiting GSTM5 expression could restrain cell proliferation, elevate intracellular ROS levels, and induce apoptosis in HemECs. Furthermore, upon inhibition of the p62-Nrf2 pathway using p62-specific siRNA, a significant decrease in GSTM5 expression and an elevation in intracellular ROS levels were noted in laser-treated HemECs. These findings suggested that laser treatment may operate by inhibiting the p62-Nrf2 pathway, thereby downregulating GSTM5 expression, elevating ROS levels, and consequently inducing apoptosis in HemECs.

Recent updates in laryngeal hemangioma management: a scoping review.

PURPOSE: To provide a comprehensive review of the current strategies in the management of laryngeal hemangiomas, with an aim to introduce a management algorithm that aligns with the variable clinical presentations and anatomical complexities of these lesions. METHODS: We conducted an extensive literature search across major databases using specific and general terms, combined with Boolean operators, to ensure comprehensiveness. Articles from January 2004 to August 2023 were included, with findings categorized by management approach. RESULTS: Laryngeal hemangiomas exhibit a spectrum of manifestations, ranging from asymptomatic lesions to those causing severe airway obstruction. Optimal management demands an individualized approach tailored to the patient's unique presentation and anatomical considerations. Diverse treatment modalities, each with distinct indications, advantages, and limitations, are explored. Notable highlights encompass the prominent role of Beta-blockers, notably Propranolol, in addressing problematic infantile hemangiomas, the nuanced efficacy of laser therapies contingent upon hemangioma type and depth, and the critical relevance of tracheotomy in emergencies. Novel approaches like transoral robotic surgery and transoral ultrasonic surgery, demonstrate promise in specific scenarios. We propose a management algorithm based on the complexity and presentation of laryngeal hemangiomas, emphasizing individualized treatment strategies, thereby addressing the unique challenges and nuances of each case. CONCLUSION: Laryngeal hemangioma management requires personalized approaches informed by diverse therapies, clinical expertise, and collaboration. The review introduces an algorithm spanning observation to advanced interventions, adapting to each case's complexity. Ongoing research promises innovative treatments.

Hepatic Hemangioma: Review of Imaging and Therapeutic Strategies.

Hepatic hemangiomas are the most common benign liver tumors. Typically, small- to medium-sized hemangiomas are asymptomatic and discovered incidentally through the widespread use of imaging techniques. Giant hemangiomas (>5 cm) have a higher risk of complications. A variety of imaging methods are used for diagnosis. Cavernous hemangioma is the most frequent type, but radiologists must be aware of other varieties. Conservative management is often adequate, but some cases necessitate targeted interventions. Although surgery was traditionally the main treatment, the evolution of minimally invasive procedures now often recommends transarterial chemoembolization as the treatment of choice.

Efficacy of 0.5% timolol maleate gel in the management of infantile hemangiomas.

Objective: This study aimed to evaluate the efficacy and safety of 0.5% timolol maleate gel, reported as an efficacious option for management of infantile hemangiomas (IH) in children. Methods: A retrospective study was conducted among patients diagnosed with IH from January 2019 to December 2021. All patients were treated 0.5% timolol gel. Data parameters, including photographs, at baseline and the final or most recent follow-up visit, were reviewed. Outcomes based on photographic assessment were categorized as excellent, good, fair or poor. Results: Sixty-four children with 76 lesions were enrolled. Median age was eight months (two months to 36 months) with most lesions (75.0%) presenting during the first year of life. Female preponderance (84.4%) was seen and the cervicofacial region was most commonly involved (52.6%). The majority of lesions (54, 84.4%) were solitary and most were treatment naïve (n=61, 80.3%). Excellent, good, fair, and poor responses were seen in 24 (31.5%), 39 (51.3%), 6 (7.9%), and 7 (9.2%) lesions. No complications were seen and no statistically significant difference was observed with respect to gender, age group, region involved and treatment naïve versus previously treated patients. Conclusion: Timolol maleate 0.5% gel is an effective and safe treatment option for IH irrespective of location of lesion, age and history of prior treatment.

Vascular and Lymphatic Malformations: Perspectives From Human and Vertebrate Studies.

Vascular malformations, affecting ≈1% to 1.5% of the population, comprise a spectrum of developmental patterning defects of capillaries, arteries, veins, and/or lymphatics. The majority of vascular malformations occur sporadically; however, inherited malformations exist as a part of complex congenital diseases. The malformations, ranging from birthmarks to life-threatening conditions, are present at birth, but may reveal signs and symptoms-including pain, bleeding, disfigurement, and functional defects of vital organs-in infancy, childhood, or adulthood. Vascular malformations often exhibit recurrent patterns at affected sites due to the lack of curative treatments. This review series provides a state-of-the-art assessment of vascular malformation research at basic, clinical, genetic, and translational levels.

Characteristics and complications of anogenital infantile hemangiomas: A multicenter retrospective analysis.

BACKGROUND: Infantile hemangiomas (IHs) of the anogenital region remain poorly characterized. OBJECTIVE: To examine the distribution, ulceration rate, and associated congenital anomalies of anogenital IHs. METHODS: Retrospective study at 8 tertiary referral centers. RESULTS: A total of 435 infants with an IH of the anogenital region were enrolled (of which, 319 [73%] were girls). Congenital anomalies were present in 6.4% (n = 28) of infants with an anogenital IH. Segmental or partial segmental anogenital IHs ulcerated in 72% (n = 99 of 138) of infants, whereas 45% (n = 133 of 297) of focal anogenital IHs experienced ulceration (P < .001). In a multivariable logistic regression analysis, segmental or partial segmental morphology (adjusted odds ratio [aOR], 2.70; 95% CI, 1.60-4.64), mixed type (aOR, 3.44; 95% CI, 2.01-6.07), and perianal (aOR, 3.01; 95% CI, 1.53-6.12) and buttocks location (aOR, 2.08; 95% CI, 1.17-3.76) had increased odds of ulceration. Segmental or partial segmental IHs of the genitalia were confined to distinct anatomic territories and were predominantly distributed unilaterally, with a linear demarcation at the perineal raphe. LIMITATIONS: Possible selection bias, given recruitment at tertiary referral centers. CONCLUSION: This study improves our understanding of high-risk features of anogenital IHs and demonstrates that genital segmental or partial segmental IHs develop within distinct anatomic territories.

Our experience with propranolol for infantile hemangioma.

BACKGROUND/OBJECTIVES: The most frequent benign vascular tumor in children is infantile hemangioma (IH). For severe IHs, propranolol has become the first-line Treatment. Despite the fact that several studies have comprehensive therapy regimens, including the best time to start Treatment, dosage, visit frequency, and treatment duration, there is still controversy about the best time to start and stop propranolol medication. METHODS: Between January 2016 and February 2019, dermatologists experienced hemangioma treatment and recommended propranolol treatment for 232 IHs. A total of 90 patients completed the treatment process after undergoing a color Doppler ultrasound test. RESULTS: Propranolol uniquely affects each IH. Ninety patients were divided into two groups in this study: entire regression (n = 40) and partial regression (n = 50). The entire regression group's initial treatment period (4.3 ± 2.97 months) was substantially shorter than the partial regression group's (5.2 ± 4.57 months) (p < 0.05). Between the entire regression group (23.4 ± 12.8 months) and the partial regression group (24.5 ± 16.6 months), there was no significant difference in time to reduce propranolol. The partial regression group (32.9 ± 25.3month) had a lengthier treatment course than the entire regression group (23.4 ± 13.7 months) (p < 0.05). The partial regression group (22%), like the entire regression group, had a higher recurrence rate (5%). The overall proportion of hemangiomas on the face (particularly periocular hemangioma) in the regression group was greater than in the control group. CONCLUSION: The entire regression group's initial treatment time was significantly shorter than the partial regression group's. As a result, as soon as a hemangioma is discovered, it should be treated. To determine the appropriate time to reduce propranolol, we must evaluate the patient's age and the percentage of tumor regression. Periocular hemangioma may have a better prognosis than other types. Given the small number of patients in our study, we will need to do more research in the future to confirm our findings.

Hybrid lung lesions in children with segmental infantile hemangiomas, a new association?

Infantile hemangiomas (IHs) are the most common tumors of infancy and, in rare instances, can present in the setting of congenital structural anomalies or as part of syndromic disorders. In this study, we present three cases of children with segmental IHs born with concurrent pulmonary anomalies: congenital pulmonary airway malformations and bronchopulmonary sequestration. To date, no known association between these entities and hemangiomas has been described.

Spinal epidural capillary hemangioma: case report and review of the literature.

BACKGROUND: Almost all of the epidural hemangiomas reported are cavernous hemangiomas. Purely extradural spinal capillary hemangiomas are very rare. Capillary hemangiomas are hamartomatous malformations that result from proliferations of vascular endothelial cells. Only ten cases have been reported in the English literature, treated with surgical excision. CASE DESCRIPTION: A case of a dorsal extradural spinal capillary hemangioma is described. A total surgical removal has been performed after spinal angiography and embolization. Complete surgical removal should always be the goal in these lesions. Embolization did not show to reduce bleeding during the surgical procedure in this case.

Safety and Feasibility of Transarterial Bleomycin-Lipiodol Embolization in Patients with Giant Hepatic Hemangiomas.

Giant hepatic hemangiomas present a significant clinical challenge, and effective treatment options are warranted. This study aimed to assess the safety and feasibility of transarterial bleomycin-lipiodol embolization in patients with giant hepatic hemangiomas. A retrospective analysis was conducted on patients with giant hepatic hemangiomas (>5 cm). Transarterial chemoembolization (TACE) was performed using 7-20 cc of lipiodol mixed with 1500 IU of bleomycin. Safety outcomes, including post-embolization syndrome (PES), hepatic artery dissection, systemic complications, and access site complications, were evaluated. Radiation doses were also measured. Feasibility was assessed based on the achieved hemangioma coverage. Seventy-three patients (49 female, 24 male) with a mean age of 55.52 years were treated between December 2014 and April 2023. The average hospitalization duration was 3.82 days, and 97.3% of lesions were limited to one liver lobe. The average bleomycin dose per procedure was 1301.5625 IU, while the average lipiodol dose was 11.04 cc. The average radiation dose was 0.56 Gy. PES occurred after 45.7% of TACE procedures, with varying severity. Complications such as hepatic artery dissection (three cases), access site complications (two cases), and other complications (one case) were observed. No treatment-related mortality occurred. Hemangioma coverage exceeding 75% was achieved in 77.5% of cases. The study results suggest that transarterial bleomycin-lipiodol embolization is a safe and feasible treatment option for a heterogeneous group of patients with giant hepatic hemangiomas. This approach may hold promise in improving outcomes for patients with this challenging condition.

Importance of Determining Vascular Endothelial Growth Factor Serum Levels in Children with Infantile Hemangioma.

Background and Objectives: A potential role of vascular endothelial growth factor (VEGF) in the pathophysiology of infantile hemangiomas (IH) is thought to be plausible. The primary objective of this study was to investigate the importance of determining VEGF serum levels at various stages of IH growth in children. Materials and Methods: A nested case-control study was conducted. For the purposes of the researched target group, samples of fifty (N = 50) children with IH without associated diseases at different stages of hemangioma growth (proliferative and involutional stages) were used. The control group consisted of one hundred (N = 100) healthy children comparable in terms of age and sex, in whom the existence of IH and vascular malformations was ruled out via clinical examination. An immunoassay (ELISA) was used to determine VEGF serum levels in hemangioma growth's proliferation and involution phases. Results: A comparison of serum levels of VEGF in the phases of proliferation and involution in the group of patients with IH did not show a statistically significant difference (p = 0.171). The control group had significantly higher serum VEGF levels than the patient group in both the proliferation phase (p = 0.009) and the involution phase (p = 0.019). In the proliferation phase, a multivariate regression model explained 15% of the variance in the dependent variable, without significant predictor variables, while in the involution phase, it explained 21% of the variance in the dependent variable, and the history of invasive prenatal procedures stood out as a significant predictor variable positively associated with serum VEGF levels (beta coefficient = 0.33; p = 0.043). Conclusions: Although IH is thought to be the result of the dysregulation of angiogenesis and vasculogenesis under the influence of angiogenic factors, especially VEGF, this study did not demonstrate that VEGF serum levels in the proliferation phase of hemangioma growth were higher than those in the involution phase, or in relation to the control group.

Propranolol for Vascular Anomalies: Efficacy and Complications in Pediatric Patients.

Context: Congenital vascular anomalies are classically subdivided into vascular tumors and vascular malformations. The role of propranolol in the regression of infantile hemangioma (IH), a vascular tumor, is well establishe. Aims: This study aimed to analyze the therapeutic efficacy and complications associated with oral propranolol and adjuvant therapy in the treatment of vascular anomalies. Settings and Design: A prospective interventional study was undertaken over 10 years duration extending from 2012 to 2022 at a tertiary care teaching institute. Materials and Methods: All children with cutaneous hemangiomas and lymphatic and venous malformations under 12 years of age, except those with contraindications for administration of propranolol, were included in the study. Results: Out of 382 patients, there were 159 males and 223 females (male: female = 1:1.4). The majority (53.66%) were between ≥3 months and 1 year. There were 481 lesions in 382 patients. There were 348 patients with IH, and 11 were congenital hemangiomas (CHs). There were 23 patients with vascular malformations; lymphatic malformation (n = 19) and venous malformation (n = 4) were present. The size of the lesions ranged from 5 mm to 20 cm; 50.73% were 2-5 cm in size. Ulceration (>5 mm) was the most common complication present in 20/382 (5.24%) patients. Complications related to oral propranolol were seen in 23 (6.02%) patients. Drugs were given for a mean period of 10 months (range from 5 months to 2 years). At the end of the study, 282 (81.03%) out of 348 patients with IH showed an excellent response; 4 (36.36%) patients in the case of CH (n = 11) and 5 (21.74%) patients with vascular malformation (n = 23) showed excellent response. Conclusion: The study validates the use of propranolol hydrochloride as the first-line agent for the treatment of IHs and congenital hemangiomas. It may have an additive role in lymphatic malformations, and venous malformations, as a part of a multimodality treatment approach for vascular malformations.

Congenital and Infantile Hemangiomas: Epidemiological, Clinical, and Treatment Characteristics Based on 3 Years' Experience at a Tertiary Care Hospital - A Retrospective Case Comparison and Review of the Literature. / Características clínico-epidemiológicas y consideraciones terapéuticas de los hemangiomas congénitos e infantiles de un hospital de tercer nivel durante un periodo de 3 años: estudio comparativo y revisión de la literatura.

Distinguishing between congenital and infantile hemangiomas is challenging, but essential for appropriate treatment. The immunohistochemical marker glucose transporter type 1 is helpful, but biopsies are uncommon in this setting. The aim of this retrospective study was to describe and compare epidemiological, clinical, and treatment characteristics of congenital and infantile hemangiomas diagnosed at a tertiary care hospital over 3 years. We studied 107 hemangiomas: 34 congenital hemangiomas (rapidly involuting, partially involuting, and noninvoluting), 70 infantile hemangiomas, and 3 hemangiomas pending classification. Superficial infantile hemangiomas of the head and neck were the most prevalent tumors. Congenital hemangiomas were most often located on the trunk. Studied risk factors were more common in patients with infantile hemangiomas. In this group of patients, treatment response was independent of sex, in vitro fertilization, lesion depth and location, and type of treatment.