Introduction:The International Society for the Study of Vascular Anomalies developed in 1996 a Classification of Vascular Anomalies that became internationally accepted. The main feature was the division of vascular anomalies in 2 categories, vascular tumors and malformations. Major revisions occurred in 2014 and 2018, for updates and inclusion of newly described lesions. Major advances occurred in recent years, with improved understanding of genetic basis of vascular anomalies and its relevance in therapeutics. It created a demand for a new revision of ISSVA Classification, and the process is presented in this study. Methods:A group was created in 2019, joining experts from different specialties and coordinated by ISSVA Scientific Committee, to reevaluate the 2018 Classification on each subtype of vascular anomaly, considering the clinical presentation, histological subtypes, flow velocity and genetic aspects. After several multidisciplinary online discussions and in person meetings at ISSVA Congresses (2022, 2023 and 2024) the proposal for the new classification was presented for ISSVA Members ratification, after an opening window for comments and suggestions. A new tool was created, named "Glossary of Vascular Anomalies", along the contours of a medical dictionary. Results:A new layout of the classification was designed. The visualization begins with a general "Landing Page" where the basic division into vascular tumors and malformations are specified. For vascular tumors, the subdivision was kept between Benign, Borderline and Malignant tumors. For vascular malformations, the divisions were presented as Fast-flow lesions, Slow-flow lesions, and Developmental Anomalies of Named Vessels. A Full Classification Table page with all updated modifications followed the Landing Page. All changes and new terms are described in detail and summarized in a table. The glossary lists and explains, in alphabetic order, all technical terms, abbreviations, acronyms, eponyms, genes and syndromes related to vascular anomalies. Conclusions:The presented updated ISSVA classification of vascular anomalies reflects our evolving understanding of vascular anomalies which will be continuously updated by a dedicated Committee of ISSVA.

Objective: To report our institutional experience in diagnosing and surveilling patients with infantile subglottic hemangioma (SGH) using in-office flexible fiberoptic laryngoscopy (FFL) with video technology, without requiring operative endoscopy in the era of propranolol use. Methods: A retrospective case series was conducted on 4 children diagnosed with SGH between 2016 and 2022 at our institution. Results: Awake FFL with video technology provided adequate visualization of SGH lesions for diagnosis, without any complications. Serial examinations of the airway were performed in the outpatient setting and each SGH gradually regressed, with marked improvement in respiratory symptoms within 48 hours of oral propranolol initiation. Conclusion: Our findings showed that in select patients, FFL with video technology can successfully identify SGH lesions without general anesthesia exposure. FFL may be used as a low-risk screening tool for propranolol therapy initiation in some patients, but operative endoscopy should remain the gold standard procedure for others. By utilizing FFL in this manner, it is possible to diagnose SGH lesions and start propranolol therapy without exposing all patients to the risks of operative endoscopy.

OBJECTIVE:Infantile subglottic hemangioma (SGH) poses a risk of airway compromise if untreated. Traditionally, operative endoscopy (OH) diagnoses SGH, but since the discovery of beta-blockers' efficacy in treating infantile hemangiomas (IHs) in 2008, and advances in endoscopic technology, nonoperative methods have emerged. This review identifies endoscopic practices for diagnosing and monitoring infantile SGH during the oral beta-blocker treatment era. DATA SOURCES:A comprehensive literature search in October 2022 and August 2023 covered PubMed, Embase, Cochrane Library, SCOPUS, and Web of Science. REVIEW METHODS:The search was limited to English-language studies published since 2008, considering this when propranolol was demonstrated as an effective treatment option for IH. The articles were screened for relevance based on predefined inclusion and exclusion criteria. RESULTS:After inclusion and exclusion criteria, sixty final studies were identified, describing 240 cases of infantile SGH. Most children were diagnosed using OE alone (73.3%; n = 176/240), 23.3% (n = 56/240) using office-based laryngoscopy procedures (OBPs) followed by OE, 3.3% using OBP alone (n = 8/240). There were no reported diagnostic endoscopy-related complications. Twenty-nine studies described using endoscopy plus diagnostic imaging to either confirm an SGH lesion, characterize the extent of disease spread, or rule out other causes of presenting symptoms. The proportion of infants diagnosed with OE alone decreased from 2008 to 2023. CONCLUSION:Operative endoscopy remains the SGH diagnostic standard, but OBP adoption is increasing. Further research is needed to determine the optimal SGH diagnosis and management approach. LEVEL OF EVIDENCE:NA Laryngoscope, 135:1287-1294, 2025.

Lymphatic Research and BiologyVol. 22, No. 1 Literature WatchUpdate February 2024Francine BleiFrancine BleiHassenfeld Children's Hospital at NYU Langone, The Laurence D. And Lori Weider Fink Children's Ambulatory Care Center, New York, New York, USA.Search for more papers by this authorPublished Online:21 Feb 2024https://doi.org/10.1089/lrb.2024.29157.fbAboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookXLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 22Issue 1Feb 2024 InformationCopyright 2024, Mary Ann Liebert, Inc., publishersTo cite this article:Francine Blei.Update February 2024.Lymphatic Research and Biology.Feb 2024.66-88.http://doi.org/10.1089/lrb.2024.29157.fbPublished in Volume: 22 Issue 1: February 21, 2024 TopicsBiotechnology laws and regulatory affairs PDF download

Background/Objectives: Ulceration is a common complication of infantile hemangioma (IH). Severe, persistent ulceration occurs in a minority of patients. This study aims to characterize the clinical features of IH with aggressive ulceration (AU).Methods: Multicenter retrospective study of clinical features of IH with AU.Results: Thirty-five patients with AU were identified and included in the study. The majority of AU occurred in segmental IH (23/35, 65%). Segmental IH with AU were large (>= 10 cm(2); 16/23, 69%, p < .001) with a thin (<3 mm) superficial component (16/23, 69%, p < .001). Localized IH with AU had a thick (>3 mm) superficial component (11/12, 92%, p < .001).All diaper area IH with AU (9/35) were segmental with thin superficial component (100%, p = .02). IH with AU in the head/neck (10/35) were more commonly localized (67%) and mixed (62.5%), while segmental, thick superficial morphology was more common on trunk (9/35) and upper extremities (7/35).Conclusions: IH resulting in AU differ in clinical features by anatomic site. Those in the diaper area are nearly always segmental with thin superficial component, whereas other sites tend to be localized, mixed, with thick superficial component. These distinct phenotypes may prove useful in the clinical setting for physicians to identify patterns of IH ulceration with increased risk of aggressive, persistent ulceration.

Objective:. The literature on surgical management of vascular anomalies has primarily focused on the head and neck area, while studies of anomalies on the extremities have typically included larger and more dramatic clinical presentations. In this article, we aim to present our experience with surgical management of smaller symptomatic anomalies of the extremities. Methods:. We performed a retrospective review of a single surgeon’s experience at a large academic center on patients from January 2013 to March 2022. We collected data on patient demographics, past medical and surgical history, operative dictations, clinic notes, and postoperative follow-up. Included patients were required to have confirmed vascular anomalies based on final pathology reports. Results:. A total of 47 patients underwent a total of 50 procedures, with 2 patients experiencing recurrence requiring repeat operative management. Our cohort had average age (standard deviation) of 27.16 (18.67). Sixteen patients had prior history of vascular anomalies upon presentation to our institution. The majority of lesions were located in a digit of the hand, the arm, or the foot. On surgical excision, the average size (range) of the excised lesions was 3.54 cm (0.5–15.0 cm) by 2.22 cm (0.3–8.0 cm). Four required coverage with local flaps, 3 with full-thickness skin graft (FTSG) and 2 with microvascular free flap. The 2 most common pathologic diagnoses were arteriovenous malformation and hemangioma, each with 14 patients. Overall complication rate was 2%, with 1 patient experiencing wound dehiscence requiring FTSG. Follow-up ranged from 0.1 months to 46.9 months with an average of 3.86 months. Conclusions:. In the appropriately selected patient, surgical excision of symptomatic vascular anomalies of the extremities can be successfully performed with a low complication rate. Most lesions can be appropriately treated with direct excision and direct closure, although some may require FTSG, local flap, or microvascular free flap.

"Letter to editor regarding “Clinical practice guidelines on management of infantile hemangioma: a systematic quality appraisal using the AGREE II instrument”." Pediatric Hematology and Oncology, ahead-of-print(ahead-of-print), pp. 1–2

Background In the last few decades there has been development of innovative therapies for the treatment of craniofacial lymphatic malformations. Percutaneous sclerotherapy has demonstrated efficacy in the management of macrocystic lymphatic lesions, but it is less suitable for microcystic lesions given their size. The gravity-dependent technique is a novel augmentation of standard percutaneous sclerotherapy: the technique enables a sclerosing agent to permeate the small microchannels seen in microcystic lesions that would otherwise be difficult to treat. Methods Between 2005 and 2021, 124 patients with microcystic or mixed lymphatic malformations were treated using a novel gravity-dependent sclerotherapy technique. Bleomycin at a maximum dose of 15 IU per session was used as the main sclerosing agent. Fluoroscopy and ultrasound were used to ensure proper positioning of the catheter prior to injecting the sclerosing agent. The response to treatment was assessed clinically and with cross-sectional imaging. Results Nearly all cases showed significant improvement after the gravity-dependent technique. There have been no permanent complications from sclerotherapy treatment. There was a mild transient adverse effect from bleomycin in one case of erythema and tenderness that lasted several weeks then ameliorated. Conclusions The gravity-dependent sclerotherapy technique is a suitable treatment option for microcystic lymphatic malformations.

Lymphatic Research and BiologyVol. 21, No. 4 Literature WatchUpdate August 2023Francine BleiFrancine BleiHassenfeld Children's Hospital at NYU Langone, The Laurence D. And Lori Weider Fink Children's Ambulatory Care Center, New York, New York, USA.Search for more papers by this authorPublished Online:22 Aug 2023https://doi.org/10.1089/lrb.2023.29146.fbAboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 21Issue 4Aug 2023 InformationCopyright 2023, Mary Ann Liebert, Inc., publishersTo cite this article:Francine Blei.Update August 2023.Lymphatic Research and Biology.Aug 2023.410-429.http://doi.org/10.1089/lrb.2023.29146.fbPublished in Volume: 21 Issue 4: August 22, 2023PDF download

Lymphatic Research and BiologyVol. 21, No. 5 Literature WatchUpdate October 2023Francine BleiFrancine BleiHassenfeld Children's Hospital at NYU Langone, The Laurence D. And Lori Weider Fink Children's Ambulatory Care Center, New York, New York, USA.Search for more papers by this authorPublished Online:17 Oct 2023https://doi.org/10.1089/lrb.2023.29150.fbAboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 21Issue 5Oct 2023 InformationCopyright 2023, Mary Ann Liebert, Inc., publishersTo cite this article:Francine Blei.Update October 2023.Lymphatic Research and Biology.Oct 2023.504-533.http://doi.org/10.1089/lrb.2023.29150.fbPublished in Volume: 21 Issue 5: October 17, 2023PDF download

Lymphatic Research and BiologyVol. 20, No. 2 Literature WatchUpdate April 2022Francine BleiFrancine BleiLenox Hill Hospital, New York, New York, USA.Search for more papers by this authorPublished Online:20 Apr 2022https://doi.org/10.1089/lrb.2022.29121.fbAboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 20Issue 2Apr 2022 InformationCopyright 2022, Mary Ann Liebert, Inc., publishersTo cite this article:Francine Blei.Update April 2022.Lymphatic Research and Biology.Apr 2022.228-244.http://doi.org/10.1089/lrb.2022.29121.fbPublished in Volume: 20 Issue 2: April 20, 2022PDF download

Patients with vascular anomalies can present in a variety of clinical scenarios. The astute physician must understand how to ascertain the correct diagnosis, often without histologic confirmation. In this chapter, we discuss common clinical presentations, suggest appropriate investigations to support the diagnoses, and recommend elements of management. We also identify scenarios where the vascular anomaly represents a clue to a known syndrome. As new targeted medical therapy has been developed for specific vascular conditions, more hematologist/oncologists became involved in the evaluation, diagnosis, and management of these cases. The chapter is organized into four sections: (1) the initial evaluation of patients: history, physical examination, and diagnostic investigations required to reach an accurate diagnosis; (2) vascular hepatic anomalies; (3) syndromic vascular anomalies; and (4) complex lymphatic anomalies.

Lymphatic Research and BiologyVol. 20, No. 4 Literature WatchUpdate August 2022Francine BleiFrancine BleiLenox Hill Hospital, New York, New York, USA.Search for more papers by this authorPublished Online:22 Aug 2022https://doi.org/10.1089/lrb.2022.29127.fbAboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 20Issue 4Aug 2022 InformationCopyright 2022, Mary Ann Liebert, Inc., publishersTo cite this article:Francine Blei.Update August 2022.Lymphatic Research and Biology.Aug 2022.443-464.http://doi.org/10.1089/lrb.2022.29127.fbPublished in Volume: 20 Issue 4: August 22, 2022PDF download

Background We report a 3-month-old female with cardiovascular anomalies and diffuse intestinal infantile hemangioma (IIH) of the small bowel suggesting possible diagnosis of PHACE syndrome (posterior fossa anomalies, hemangioma, arterial lesions, cardiac abnormalities/coarctation of the aorta, eye anomalies). The GI symptoms persisted under treatment with propranolol, whereas the addition of sirolimus led to regression of the IIH. Methods A systematic review was conducted using PubMed, EMBASE, and Ovid MEDLINE databases between 1982 and 2021. Results A total of 4933 articles were identified; 24 articles met inclusion criteria with 46 IIH cases. The most common GI presentations were unspecified GI bleed (40%) and anemia (38%). The most common treatments were corticosteroids (63%), surgical resection (32.6%), and propranolol (28%). Available outcomes were primarily bleeding arrest (84%). Nine cases (19.5%) were diagnosed with definite PHACE, 5 (11%) with possible PHACE, and 32 (69.5%) no PHACE. Our case presented with symptoms most consistent with those of possible PHACE and definite PHACE. No cases in this review underwent treatment with sirolimus. Conclusions This is the first reported case of successful treatment of IIH with sirolimus. Our case, along with other patients who present with IIH and PHACE features, suggests consideration of IIH as a diagnostic criterion for PHACE syndrome. Impact This is the first reported case in which sirolimus showed regression of an intestinal infantile hemangioma. This study serves to demonstrate the presentation, treatment, outcomes of intestinal infantile hemangioma, and correlation with PHACE. The potential correlation between intestinal infantile hemangioma and PHACE deserves more study in consideration of intestinal infantile hemangioma as a diagnostic criterion of PHACE.

The acronym PHACE (posterior fossa anomalies, infantile hemangiomas, arterial anomalies, cardiac defects and eye anomalies) was coined to describe the features of an uncommon sporadic condition with a vascular tumor (infantile hemangioma), developmental and progressive vascular abnormalities. Here, we report the findings of our analysis of whole genome sequencing of germline samples from 98 unrelated trios in which the probands had PHACE. Two coding variants, RASA3–p.Val85Met and THBS2–p.Asp859Asn, were predicted to be pathogenic by numerous algorithms. This analysis was negative for a shared gene across multiple probands; however, a g:Profiler pathway analysis of the genes with rare, de novo variants demonstrated combinatorial variants in the RAS/MAPK pathway. Coding and noncoding variants in six RAS pathway genes were prioritized based on the vascular abnormalities reported in knockout mouse models. To identify lineages in which the genes may be acting, we explored the expression of the prioritized candidate genes RASA3, AFF2, DLC1, EPHA3, PIK3CA, and THBS2 across diverse cell types in the human developing heart by incorporating chromatin accessibility (scATAC-seq) and gene expression (scRNA-seq) datasets. We observed that AFF2, EPHA3, PIK3CA, and THBS2 are co-expressed in the vascular smooth muscle cells in the fetal heart, whilst AFF2, EPHA3, and PIK3CA are co-expressed in the vascular endothelium. These findings suggest oligogenic variants in RAS pathway genes may contribute to the developmental vascular abnormalities in PHACE.

Lymphatic Research and BiologyVol. 20, No. 1 Literature WatchUpdate February 2022Francine BleiFrancine BleiNYU Langone Health, Grossman School of Medicine, New York, NY, USA.Search for more papers by this authorPublished Online:28 Feb 2022https://doi.org/10.1089/lrb.2021.29118.fbAboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 20Issue 1Feb 2022 InformationCopyright 2022, Mary Ann Liebert, Inc., publishersTo cite this article:Francine Blei.Update February 2022.Lymphatic Research and Biology.Feb 2022.89-114.http://doi.org/10.1089/lrb.2021.29118.fbPublished in Volume: 20 Issue 1: February 28, 2022Online Ahead of Print:February 14, 2022PDF download