Faculty Bibliography

BACKGROUND:The proliferative phase of infantile hemangiomas (IHs) is usually complete by 9 months of life. Late growth beyond age 3 years is rarely reported. OBJECTIVE:To describe the demographic and clinic characteristics of a cohort of patients with late growth of IH, defined as growth in a patient >3 years of age. METHODS:A multicenter, retrospective cohort study. RESULTS:In total, 59 patients, 85% of which were female, met the inclusion criteria. The mean first episode of late growth was 4.3 (range 3-8.5) years. Head and neck location (55/59; 93%) and presence of deep hemangioma (52/59; 88%) were common characteristics. Posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, eye abnormalities (PHACE) syndrome was noted in 20 of 38 (53%) children with segmental facial IH. Systemic therapy (corticosteroid or β-blocker) was given during infancy in 58 of 59 (98%) and 24 of 59 (41%) received systemic therapy (β-blockers) for late IH growth. LIMITATIONS/CONCLUSIONS:The retrospective nature and ascertainment by investigator recall are limitations of the study. CONCLUSION/CONCLUSIONS:Late IH growth can occur in children after 3 years of age. Risk factors include head and neck location, segmental morphology, and involvement of deep dermal/subcutaneous tissues.

Infantile hemangiomas (IHs) occur in as many as 5% of infants, making them the most common benign tumor of infancy. Most IHs are small, innocuous, self-resolving, and require no treatment. However, because of their size or location, a significant minority of IHs are potentially problematic. These include IHs that may cause permanent scarring and disfigurement (eg, facial IHs), hepatic or airway IHs, and IHs with the potential for functional impairment (eg, periorbital IHs), ulceration (that may cause pain or scarring), and associated underlying abnormalities (eg, intracranial and aortic arch vascular abnormalities accompanying a large facial IH). This clinical practice guideline for the management of IHs emphasizes several key concepts. It defines those IHs that are potentially higher risk and should prompt concern, and emphasizes increased vigilance, consideration of active treatment and, when appropriate, specialty consultation. It discusses the specific growth characteristics of IHs, that is, that the most rapid and significant growth occurs between 1 and 3 months of age and that growth is completed by 5 months of age in most cases. Because many IHs leave behind permanent skin changes, there is a window of opportunity to treat higher-risk IHs and optimize outcomes. Early intervention and/or referral (ideally by 1 month of age) is recommended for infants who have potentially problematic IHs. When systemic treatment is indicated, propranolol is the drug of choice at a dose of 2 to 3 mg/kg per day. Treatment typically is continued for at least 6 months and often is maintained until 12 months of age (occasionally longer). Topical timolol may be used to treat select small, thin, superficial IHs. Surgery and/or laser treatment are most useful for the treatment of residual skin changes after involution and, less commonly, may be considered earlier to treat some IHs.

OBJECTIVE:To define the types of hepatic hemangiomas using the updated International Society for the Study of Vascular Anomalies classification and to create a set of guidelines for their diagnostic evaluation and monitoring. STUDY DESIGN/METHODS:We used a rigorous, transparent consensus protocol defined by an approved methodology, with input from multiple pediatric experts in vascular anomalies from hematology-oncology, surgery, pathology, radiology, and gastroenterology. RESULTS:In the first section, we define the subtypes of hepatic hemangiomas based on the clinical course, histology, and radiologic characteristics. We recommend against using the term "hemangioma" for any vascular malformations affecting the liver or any hypervascular tumors that are not characterized by the approved definitions. We recommend against using the term "hemangioendothelioma" for infantile or congenital hemangioma. The following 2 sections dedicated to infantile hepatic hemangioma and to congenital hepatic hemangioma individually describe these subtypes in further detail, including complications to be considered during monitoring and respectively recommended screening evaluations. CONCLUSIONS:Although institutional variations may exist for specific clinical details, a clear understanding of the diagnosis of hepatic hemangiomas affecting children and the possible complications that require screening during the monitoring period should be standard. As children with hepatic hemangiomas are managed by different medical and surgical specialties, we offer an expert opinion multidisciplinary consensus based on current literature and on data extracted from the liver hemangioma registry.

RASA1-related disorders are vascular malformation syndromes characterized by hereditary capillary malformations (CM) with or without arteriovenous malformations (AVM), arteriovenous fistulas (AVF), or Parkes Weber syndrome. The number of cases reported is relatively small; and while the main clinical features are CMs and AVMs/AVFs, the broader phenotypic spectrum caused by variants in the RASA1 gene is still being defined. Here, we report the clinical and molecular findings in 69 unrelated cases with a RASA1 variant identified at ARUP Laboratories. Sanger sequencing and multiplex ligation-dependent probe amplification were primarily used to evaluate RASA1. Several atypical cases were evaluated using next-generation sequencing (NGS) and array-comparative genomic hybridization (aCGH). Sixty individuals had a deleterious RASA1 variant of which 29 were novel. Nine individuals had a variant of uncertain significance. Five large RASA1 deletions were detected, giving an overall deletion/duplication rate of 8.3% (5/60) among positive cases. Most (75.4%) individuals with a RASA1 variant had CMs, and 44.9% had an AVM/AVF. Clinical findings in several cases expand the RASA1 phenotype. Our data suggest that screening for large RASA1 deletions and duplications in this disorder is important and suggest that NGS multi-gene panel testing is beneficial for the molecular diagnosis of cases with complex vascular phenotypes.