Infantile hemangioma (IH), the most common vascular tumor of infancy, is characterized by a paradoxical natural history of rapid proliferation followed by spontaneous but often incomplete involution. Although dysregulated angiogenic signaling has long been considered central to IH pathobiology, an angiogenesis-only model is insufficient to explain its phase-dependent behavior, marked clinical heterogeneity, syndromic associations, or variable response to therapy. Emerging evidence instead supports the view of IH as a dynamically remodeled immune–vascular lesion driven by signaling crosstalk among endothelial cells, stem/progenitor cells, stromal elements, extracellular matrix, and immune populations. In this narrative review, we summarize the current knowledge of the immune microenvironment of IH across the proliferative and involution phases, focusing on macrophage polarization, mast cell maturation, dendritic and dendritic-like stromal populations, neutrophil-associated inflammatory signaling, adaptive immune constraints, lymphatic endothelial networks and extracellular matrix remodeling. We further discuss the molecular networks that shape this landscape, including VEGF- and HIF-1α-driven angiogenic programs, metabolic immunosuppression linked to glycolysis and lactate accumulation, and hormonal and immune checkpoint pathways that may contribute to immune tolerance and vascular persistence. Accordingly, we examine the immunological mechanisms of current therapies, particularly propranolol, corticosteroids, and mTOR inhibitiors, and highlight how refractory, segmental, syndromic, or ulcerated IH may reflect distinct immune states. Finally, we outline future directions for mechanism-based treatment, including immune microenvironment reprogramming, metabolic targeting, lesion-confined drug delivery, and biomarker-guided precision stratification. Together, these advances support a transition from empiric vascular suppression toward lesion-targeted immunomodulatory therapy in IH.

Background PHACE syndrome is a neurocutaneous disorder characterized by large segmental infantile haemangiomas (IHs) on the head, face and neck with associated multisystem abnormalities. The reported prevalence of PHACE syndrome and its systemic manifestations and epidemiology vary substantially across studies. Procedure This meta‐analysis followed the PRISMA guidelines, and systematic searches of PubMed, Embase, Web of Science and the Cochrane Library (1996–2025) were performed. Random‐effects models were used to pool prevalence estimates with 95% confidence intervals. Results Eighteen studies were included; however, the available epidemiological evidence remains limited, as most studies were retrospective and conducted predominantly at research centres in North America and Europe. Among 709 infants with segmental IHs, the pooled prevalence of PHACE syndrome was 42.4%. PHACE syndrome showed a marked female predominance across studies. In patients with PHACE syndrome, cerebral vascular abnormalities were the most common (69.8%), followed by structural brain (46.8%), cardiovascular (44.6%), midline/ventral (28.6%) and ocular (26.5%) abnormalities. Conclusions This meta‐analysis revealed that 42.4% of infants with segmental IHs on the head, face and neck have PHACE syndrome. However, the prevalence of PHACE syndrome depends on the study design and diagnostic methods, which underscores the importance of systematic multisystem evaluation to facilitate timely diagnosis and risk‐stratified management.

Kaposiform hemangioendothelioma (KHE) is an aggressive vascular tumor often complicated by Kasabach-Merritt phenomenon (KMP), typically requiring aggressive treatment. This study reports four infants with pathologically confirmed KHE without KMP who underwent spontaneous regression under conservative management. Serial MRI showed objective tumor involution over 22-28 months. No KMP or complications occurred. These findings challenge universal aggressive intervention, supporting observation for selected non-coagulopathic cases.

BACKGROUND:Some patients with infantile hemangioma (IH) still develop ulcerations during oral propranolol, but these IH ulcerations have not been systematically studied. OBJECTIVE:To analyze the incidence, clinical features and risk factors associated with IH ulceration after oral propranolol initiation. METHODS:Retrospective study at one tertiary referral center. RESULTS:We evaluated 470 patients with IH who received oral propranolol and 51 patients with nonintervention IH ulceration; 24 (5.1%) developed IH ulceration during oral propranolol. The median age at the discovery of IH ulceration was 3.9 months in the IH ulceration group after oral propranolol initiation, which was significantly later than the 2.0 months in the nonintervention IH ulceration group (P = .013). Multivariate analysis revealed that mixed IH (odds ratio [OR] = 5.620; 95% confidence interval [CI]: 1.419-22.265), indeterminate IH (OR = 8.219; 95% CI: 1.560-43.305), and segmental IH (OR = 22.806; 95% CI: 2.157-241.028) were independent risk factors for IH ulceration after oral propranolol initiation. Conversely, IH on the trunk (OR = 0.063, 95% CI: 0.007-0.580) and extremity (OR = 0.016, 95% CI: 0.001-0.289) were protective factors. LIMITATIONS:This was a single-center retrospective study. CONCLUSIONS:This study reports the incidence of IH ulceration in patients who received oral propranolol and identifies risk factors associated with IH ulceration after oral propranolol initiation.

Introduction:Infantile hemangiomas, the commonest benign vascular tumors of infancy, often cluster on the head and neck where early treatment can avert permanent disfigurement, prompting us to evaluate 0.5% timolol maleate wet compresses as a non-invasive alternative to oral propranolol. Methods:We conducted a study of 359 consecutive infants treated at Sichuan Provincial People's Hospital between December 2018 and January 2024. Baseline demographics, lesion site and size, age at initial treatment, treatment duration, and follow-up period were recorded. Treatment outcomes were graded as excellent (complete regression), good (≥50% shrinkage), fair (<50% shrinkage), or poor (no change/growth). Eexcellent/good outcomes were defined as a positive therapeutic effect, while fair/poor outcomes were classified as negative therapeutic effect. Results:267 infants (74.37%) achieved positive therapeutic effect, with 117 excellent and 150 good, whereas 92 infants (25.63%) achieved negative therapeutic effect including 53 were fair and 39 poor. Treatment outcomes were significantly better when therapy began before 3 months (early age) (U = 9954, Z = - 3.256, P = 0.001) and for lesions ≤3 cm diameter (small size) (U = 2,869.5, Z = - 13.952, P < 0.001), and multivariate analysis confirmed early age (OR = 0.784, P = 0.024) and small size (OR = 0.113, P < 0.001) as independent predictors of positive therapeutic effect. Adverse events were mild: 24 (6.69%) local irritation, 41 (11.42%) transient systemic symptoms. Skin sequelae were observed in 12 (3.34%) cases. Discussion:Topical timolol compresses offer a safe, effective first-line option for superficial head-and-neck infantile hemangiomas, especially when started early and directed at smaller lesions.

Oral propranolol, with or without corticosteroids, has been shown to benefit diffuse infantile hepatic haemangioma (IHH); randomized trial evidence is lacking. We aimed to evaluate the efficacy and safety of propranolol monotherapy versus propranolol plus prednisone for the treatment of problematic IHHs to determine whether oral prednisone provided an added benefit to propranolol. We conducted an open-label, multicenter, randomized controlled trial across six referral centers in China from July 2019 to November 2023 (clinicaltrials.gov registration: NCT03331744). Infants with problematic diffuse IHH were assigned (1:1) to oral propranolol alone or propranolol plus a short course of prednisone. The primary endpoint was the proportion of patients who achieved a lesion response at week 4 on serial ultrasound. Analyses followed the intention-to-treat principle. Forty-five patients were included in this study (propranolol, n = 22; propranolol plus prednisone, n = 23). Four weeks following treatment, lesion response rates were higher with propranolol plus prednisone than with propranolol alone [21/23 (91.3

BackgroundPulmonary thromboembolism is rare in children, but can be life-threatening. Timely diagnosis and treatment of pulmonary thromboembolism are crucial for reducing mortality associated with pulmonary thromboembolism in children. While guidelines for pulmonary thromboembolism in adults are available, guidelines for standardized diagnosis and management of pulmonary thromboembolism in children are not. This expert consensus aims to provide recommendations for the management of pulmonary thromboembolism in children based on the current best available evidence.Data sourcesFollowing the World Health Organization Handbook for Guideline Development, the expert panel consisted of 30 members from different clinical areas. The panel identified clinical questions through systematic reviews and expert discussions, systematically reviewed evidence on pulmonary thromboembolism in children, and evaluated the quality of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Using the GRADE Evidence to Decision Framework, the panel made recommendations, considering the effects of interventions, resource use, values and preferences, equity, acceptability, and feasibility.ResultsThe epidemiology, classification, and pathophysiology characteristics are summarized. The expert panel developed 33 recommendations addressing 20 questions related to diagnosis steps, treatment approaches such as anticoagulant therapy, thrombolysis therapy, catheter-based interventional therapy, surgical embolectomy, multidisciplinary team, and treatment of patients with comorbidities, prognosis, education, as well as follow-up. Among these, 18 are weak recommendations based on very low quality evidence, and 15 are good practice statements.ConclusionsThe expert panel provided recommendations for pulmonary thromboembolism in children based on available evidence, which was generally low in quality and volume. The panel urges further research on early identification and diagnosis strategies, preventive and therapeutic regimens, and long-term management for pulmonary thromboembolism.

Autophagy plays a critical role in dynamic cell growth under different environmental conditions and maintains cellular homeostasis and cell viability in response to different cellular injuries, especially in tumor angiogenesis, where there is a controversial dual role. Angiogenesis plays a key role in facilitating tumor development. Therefore, investigating the mechanism of action of autophagy in the flexible shift of tumor angiogenesis is essential for antiangiogenic clinical therapy, and modulating the autophagy process is expected to constitute a new strategy to inhibit tumor angiogenesis and stop tumor growth and spread. This review highlights the close connection between autophagy and tumor angiogenesis. We also attempt to explain the seemingly contradictory promotion or inhibition of angiogenesis in tumor development reported in past studies. We focus on the potential clinical value of autophagy agonists and inhibitors in antiangiogenic therapy, which will provide new theoretical bases for antitumor therapy and may lead to innovative therapeutics.

Background:Pediatric hepatic angiosarcoma (HAS) is poorly understood. The lack of effective therapies for unresectable pediatric liver tumors creates a clinical imperative, positioning liver transplantation (LT) as a pivotal modality for exploring the roadmap to prolonged survival. Case Description:We report the first Chinese pediatric case of HAS treated with LT. A 2-year-old boy was admitted to hospital due to abdominal pain and distension. Imaging findings were suggestive of possible malignancy, but initial biopsy yielded a diagnosed infantile hepatic hemangioma (IHH). Following living-donor LT for unresectable disease, explant pathology revealed an angiosarcoma arising within a hemangioma. The patient ultimately died from metastasis 21 months after LT. Our review of pediatric LT for liver tumors over 15 years identified nine pediatric HAS cases, only one of whom was correctly diagnosed pre-LT, with survival ranging from 3 to 66 months. Regarding other tumors, six cases of IHH were reported prior to 2010, without survival data. Recent studies on hepatoblastoma (HB) report a 5-year overall survival (OS) of 80-90%, and the prognosis for hepatocellular carcinoma (HCC) has markedly improved, with a combined 5-year OS of 74%. In the largest reported study, the 5-year OS rates for hepatic epithelioid hemangioendothelioma (HEH) and hepatic undifferentiated embryonal sarcoma (HUES) were 60.6% and 90.0%, respectively. Evidence for biliary tract rhabdomyosarcoma (BT-RMS) and malignant rhabdoid tumor (MRT) of the liver are anecdotal, and no pediatric cases of primary hepatic kaposiform hemangioendothelioma (KHE) treated with LT have been reported. Conclusions:Pediatric HAS is rare and difficult to distinguish from IHH; contrast-enhanced computed tomography/magnetic resonance imaging (CT/MRI) aids differentiation. For suspected malignant transformation, contrast-enhanced ultrasound (CEUS) and ultrasound-guided multi-site biopsy are recommended. No standardized treatment exists for pediatric HAS. Given the poor long-term survival, LT or combined chemotherapy remains exploratory but is the only option for unresectable tumors. The high survival rates of LT for HB and HCC offer a promising blueprint. With advances in surgical techniques and increased living donor availability, pediatric LT deserves more attention.

Infantile hemangioma (IH) is the most common benign soft tissue tumor in children. While most exhibit a tendency for spontaneous regression, a minority can lead to severe, life-threatening complications, necessitating active intervention. Treatment modalities vary depending on the lesion's location, size, and depth. In recent years, topical β-blockers have increasingly become a preferred treatment option for many parents and clinicians. This review aims to systematically summarize the pharmacological mechanisms, clinical efficacy, safety profile, and formulation innovations of topical propranolol in the treatment of IH by synthesizing domestic and international literature, thereby providing a valuable reference for clinical practice and future research.

OBJECTIVE:Sirolimus is the cornerstone therapy for Kaposiform hemangioendothelioma (KHE). The purpose of this study was to evaluate whether anatomical location independently predicts radiologic response to sirolimus monotherapy in KHE without Kasabach-Merritt phenomenon (KMP). PATIENTS AND METHODS:We included 21 patients with head and neck KHE without KMP and 50 matched patients with non-head and neck KHE without KMP, all treated with sirolimus monotherapy in five tertiary referral centers in China. The primary outcome was the 12-month radiologic response rate (defined as ≥ 20% tumor volume reduction on MRI). The Cochran-Mantel-Haenszel test was used to adjust for matching factors, and multivariate logistic regression was performed to identify independent predictors of treatment response. RESULTS:The head and neck group achieved a 100% 12-month radiologic response rate versus 76% in the non-head and neck group (adjusted p = 0.012). A near-complete involution rate was 81% versus 44% (adjusted p = 0.003). Multivariate analysis confirmed that head and neck location was the only independent predictor of both radiologic response (OR = 12.34, 95% CI: 1.45-105.21, p = 0.021) and near-complete involution (OR = 5.87, 95% CI: 1.89-18.23, p = 0.002). No disease progression occurred in head and neck cases, while 4% of non-head and neck lesions progressed. Safety and quality-of-life outcomes were comparable between groups. CONCLUSION:Anatomical location is a significant independent predictor of sirolimus monotherapy efficacy in KHE without KMP. The exceptional radiologic response rate and favorable safety profile support sirolimus monotherapy as a sufficient first-line therapy for head and neck KHE, providing evidence for location-based precision treatment strategies. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT04775173. SUMMARY:What is known about this subject: Kaposiform hemangioendothelioma (KHE) without Kasabach-Merritt phenomenon (KMP) can cause functional impairments, but sirolimus is used as therapy. Efficacy of sirolimus monotherapy may vary by anatomical location, though evidence is limited. This study aimed to evaluate location-specific responses to address this gap. WHAT THIS STUDY ADDS:Head and neck KHE lesions exhibit a prominent response to sirolimus monotherapy, with 100% radiologic response at 12 months, which is an independent predictor of treatment efficacy. Near-complete involution was higher in head and neck cases (81% vs. 44%), with no disease progression. Sirolimus monotherapy is recommended for head and neck KHE without KMP, while non-head and neck lesions may need aggressive approaches.

Case Presentation A 2-month-old male infant with symptoms of dyspnea and progressive thrombocytopenia was referred to our tertiary care center. Physical examination at the referring hospital revealed tachypnea, head-nodding respiration, and poor appetite. Laboratory tests revealed severe thrombocytopenia (platelet count, 11 × 109/L), anemia (hemoglobin, 73 g/L), and coagulopathy (thrombin time, 33.9 s; fibrinogen: 0.25 g/L; D-dimer: 55.13 mg/L). Echocardiography revealed pericardial effusion and decreased ventricular function. He was initially diagnosed at the referring hospital with “severe pneumonia and thrombocytopenia” and received empirical treatment with antibiotics and platelet and red cell transfusions but showed limited clinical improvement.

Early oral propranolol for infantile hemangioma (IH) can improve the success rate. However, few studies have been conducted on the specific age threshold for initiating treatment with propranolol. This study aimed to determine the cutoff value of treatment success for IH with oral propranolol. This was a retrospective study involving 207 patients with IH and clinical data.The primary outcome measure was treatment success with oral propranolol at months 6 to 12. Multivariate analysis showed that age at treatment initiation (P < 0.001), high-risk IH (P = 0.002), and segmental IH (P = 0.012) were independent risk factors for treatment unsuccess with oral propranolol at months 6 to 12. Receiver operating characteristic (ROC) curve analysis indicated that the cutoff value for age at treatment initiation was 69.5 days for all patients, 65.5 days for patients with segmental IH or high-risk IH, and 93.5 days for patients with non-high-risk and nonsegmental IH. Patients who started treatment before 69.5 days had a success rate of 73.8

BackgroundPrimary lymphedema (PLE) and kaposiform hemangioendothelioma-related lymphedema (KLE) are rare vascular anomalies (VAs). This study aimed to examine the clinical features, management, and prognosis of PLE and KLE.MethodThe clinical features, imaging, treatments, and outcomes of 12 patients with PLE and 12 patients with KLE were retrospectively reviewed.ResultsThe mean age at which signs/symptoms were diagnosed was 68.2 months for PLE patients and 25 months for KLE patients. In PLE, the involvement of multiple sites is common, whereas in KLE, it typically affects a single site. Morbid obesity, which is common in adult patients, is rare in pediatric PLE and KLE patients. Imaging agent accumulation was observed in KLE but not in PLE via lymphoscintigraphy. In contrast, complications of PLE primarily involve skin and soft tissue, whereas musculoskeletal system complications are more common in KLE. Regarding prognosis, most patients stabilize or even experience lesion regression after standard treatment.ConclusionPLE and KLE share clinical symptoms. PLE often involves multiple sites, whereas KLE typically presents unilaterally with local lymphatic stasis. Standardized treatment enables the majority of children with lymphedema to control the disease without progression, with KLE showing potential reversibility. Given their rarity, a multidisciplinary approach is crucial for diagnosis and management.