Hobnail hemangiomas (targetoid hemosiderotic hemangiomas) are true lymphangiomas

BACKGROUND: Hobnail hemangioma (targetoid hemosiderotic hemangioma) is a small benign vascular tumor of the superficial and mid-dermis. In contrast to its well-characterized histology, it has been unclear whether this tumor arises from blood vessel endothelial cells (BECs) or lymphatic vessel endothelial cells (LECs). METHODS: We analyzed 10 hobnail hemangiomas by immunohistochemistry, using the recently described lymphatic endothelial cell marker, D2-40. For comparison, CD31, CD34, and alpha-smooth muscle actin expression were studied in consecutive sections of the paraffin-embedded tissues. RESULTS: In all analyzed vessels, D2-40 labeled exclusively LECs, whereas BECs were consistently negative. In contrast to capillary BECs, either neighboring the tumors or intermingled, neoplastic endothelial cells of all 10 hobnail hemangiomas were strongly labeled by D2-40. CONCLUSIONS: The results suggest a lymphatic origin for hobnail hemangiomas. This view is further supported by the CD34 negativity of endothelial cells and the lack of actin-labeled pericytes in hobnail hemangiomas, both characteristic of lymphatic vessels. Moreover, our analysis revealed that microshunts between neoplastic lymphatic vascular channels and small blood vessels occur, explaining some features of hobnail hemangiomas, such as aneurysmatic microstructures, erythrocytes within and beneath neoplastic vascular spaces, inflammatory changes, scarring, and interstitial hemosiderin deposits.     

The genetics of vascular birthmarks

One in 10 infants are born with a vascular birthmark each year. Some vascular birthmarks, such as infantile hemangiomas, are common, while vascular malformations, such as capillary, lymphatic, venous, and arteriovenous malformations, are less so. Diagnosing uncommon vascular birthmarks can be challenging, given the phenotypic heterogeneity and overlap among these lesions. Both sporadic and germline variants have been detected in various genes associated with vascular birthmarks. Identification of these genetic variants offers insight into both diagnosis and underlying molecular pathways and can be fundamental in the discovery of novel therapeutic approaches. The PIK3/AKT/mTOR and RAS/MEK/ERK signaling pathways, which mediate cell growth and angiogenesis, are activated secondary to genetic variations in vascular malformations. Somatic variants in TEK (TIE2) and PIK3CA cause venous malformations. Variants in PIK3CA also cause lymphatic malformations as well as a number of overgrowth syndromes associated with vascular anomalies. Variants in GNAQ and GNA11 have been identified in both so-called “congenital” hemangiomas and capillary malformations. RASA1 and EPHB4 variants are associated with capillary malformation-arteriovenous malformation syndrome. This review discusses the genetics of vascular birthmarks, including the various phenotypes, genetic variants, pathogenesis, associated syndromes, and new diagnostic techniques.     

Treatment of hemangiomas of infancy

Hemangiomas of infancy are the most common tumors of childhood. They are clinically heterogeneous and as such require individualized treatment plans. Although there are no Food and Drug Administration (FDA)-approved agents for treatment of hemangiomas of infancy, there are many widely used therapeutic options available. This review highlights the treatments currently in use and the factors that direct treatment.     

Potential complications of segmental hemangiomas of infancy

Although the majority of hemangiomas of infancy can be expected to follow a benign course, a significant subset may result in serious complications. Recently, hemangiomas of segmental morphology, or those which are large, plaque-like, and patterned in distribution, have been recognized as important markers for potential complications. PHACE syndrome represents the best known example of the variety of problems that can occur in this setting. The PHACE acronym, which stands for posterior fossa brain malformations, segmental cervicofacial hemangiomas, arterial anomalies, cardiac defects and coarctation of the aorta, and eye anomalies, is sometimes referred to as PHACE(S) when ventral developmental defects such as sternal clefting and supraumbilical raphe are present. This article reviews the specific manifestations of PHACE, reflects on pathogenesis, and discusses appropriate work-up and future directions for this complex and fascinating syndrome. We also discuss other complications associated with hemangiomas of segmental morphology, including ulceration, potential visceral involvement, and underlying anomalies related to the lumbosacral location.     

血管性胎记相关综合征的遗传学研究进展

血管性胎记主要有婴幼儿血管瘤和血管畸形,婴幼儿血管瘤有家族聚集性发病倾向,部分患儿与特应性皮炎等过敏性疾病伴发,患儿在瘤体增生期和消退期均存在基因突变。血管畸形可表现为散发或常染色体显性遗传,动静脉畸形常因RASA1突变导致。静脉畸形可散发,可呈不完全显性遗传或常染色体显性遗传。常染色体显性遗传性静脉畸形基因Tie2/Tek突变导致。此外,约1,2散发静脉畸形会出现Tie2体细胞突变。有关血管性胎记分子水平的研究能为临床诊治提供新的思路。     

Flashlamp-pumped pulsed dye laser for hemangiomas in infancy: treatment of superficial vs mixed hemangiomas

OBJECTIVE: To study in a compared manner the efficacy of flashlamp-pumped pulsed dye laser (FPDL) therapy for superficial and mixed hemangiomas. DESIGN: Nonrandomized control trial. SETTING: Department of Lasermedicine, General Hospital Neuk?lln, Berlin, Germany. PATIENTS: To investigate variation in response to treatment, a prospective study of 165 children with 225 separate hemangiomas treated with the FPDL was undertaken. Patients were aged 2 days to 7 years; mean follow-up was 5 months. INTERVENTIONS: During a 2 1/2-year period, we administered 332 treatments, for a mean+/-SD of 2.0+/-1.1 treatments per patient. MAIN OUTCOME MEASURE: Patients received therapy until the lesion was almost clear or until the lesion did not respond to treatment. Evaluation was performed by comparing pretreatment and posttreatment photographs. In addition, pathologic flow of vessels and thickness were determined before, during, and after completion of therapy with color-coded duplex sonography. RESULTS: In the first group of 100 patients with 153 flat cutaneous hemangiomas, 52 hemangiomas (34%) had excellent results; 80 (52%) had good results; and 21 (14%) showed proliferation of the subcutaneous component, although these lesions were flat at first presentation. Of the 54 mixed hemangiomas, 33 (61%) had continued proliferation of the subcutaneous component. The cutaneous component responded to therapy in 21 hemangiomas (39%), whereas the subcutaneous component of the mixed hemangiomas remained unchanged. No lesions in this group involuted completely, and therapy was discontinued because of relatively poor response. Twelve (67%) of 18 patients with superficial hemangiomas in the involution phase had excellent results and 6 (33%) had good results. CONCLUSIONS: Treatment with the FPDL is effective and may be the treatment of choice for superficial cutaneous hemangiomas at sites of potential functional impairment and on the face. Hemangiomas with a deep component do not benefit from FPDL treatment because the efficacy of the FPDL is limited by its depth of vascular injury. Furthermore, early therapeutic intervention with the FPDL may not prevent proliferative growth of the deeper or subcutaneous component of the hemangioma despite early intervention.     

血管瘤与脉管畸形分类进展

【摘要】 血管瘤和脉管畸形从最原始的形态学分类到现在的生物学特性分类历经数百年的历史。2018年国际血管异常研究会（ISSVA）在1996版、2014版分类基础上，对血管肿瘤进行细化及补充，增添了15种少见的血管肿瘤；脉管畸形中，对毛细血管畸形亚型进行重新分类，将“疣状血管瘤”更名为“疣状血管畸形”，增添了“肢体毛细血管畸形合并先天性非进展性肢体过度发育” 、“CLAPO综合征”等疾病，并增加了PIK3CA相关的过度增殖性疾病谱这一类疾病。本文阐述血管瘤与脉管畸形的分类萌芽、传统分类及现代分类，比较1996版、2014版及2018版ISSVA分类的异同，并阐述血管瘤与脉管畸形的现代分类对诊断和治疗的意义。     

婴儿血管瘤和血管畸形的治疗

婴儿血管瘤（草莓状血管瘤）和血管畸形是婴幼儿常见的血管异常,两种疾病对患儿的健康和美观有很大的影响。婴儿血管瘤具有自然消退的生物学特征,血管畸形则不会自行消退。关于婴儿血管瘤和血管畸形的治疗一直存在争议,有观点认为可以观察不需积极治疗,但有学者认为,应早期积极治疗。概述婴儿血管瘤和血管畸形在治疗与否、治疗时机和治疗方法上的选择。     

普萘洛尔治疗婴儿血管瘤的临床疗效及作用机制研究现状

婴儿血管瘤是常见的婴幼儿良性肿瘤,对于增生期的血管瘤应早期治疗,防止严重并发症的发生.普萘洛尔是临床常用的非选择性β肾上腺素受体阻滞剂.近年来,越来越多的研究报道普萘洛尔治疗婴儿血管瘤取得较好的疗效,其可能机制包括抑制血管内皮生长因子的生成、抑制低氧诱导性因子-1a-血管内皮生长因子-A血管发生轴、促使基质金属蛋白酶的下调、以及降低血管瘤的内皮一氧化氮合酶等.     

Adult cutaneous hemangiomas are composed of nonreplicating endothelial cells

Thirty-four human "cherry" dermal hemangiomas were studied by electron microscopy, immunohistochemistry, and cell culture to assess the neoplastic nature of these lesions. Electron microscopy of nine hemangiomas revealed a pronounced thickening of the basement membrane (0.6 to 14 micron) in 93% of the total 158 vascular structures examined within the lesions. This increase was caused mainly by multiple layers of basal lamina, which were irregular in outline and frequently associated with pericytes. Basement membrane changes were present both in the periphery of the hemangiomas, as well as in the center of the lesions. Immature vessels could not be identified and mitoses were absent in all endothelial cells. Using an immunohistochemical marker (Ki67) specific for proliferating cells in G2 and S phases, positive staining was not found in the endothelial cells lining the hemangiomatous vessels, whereas basal epidermal keratinocytes in the same preparations and cultured microvascular endothelial cells expressed the antigen. Endothelial cells of nine hemangiomas did not stain with an activation-related antibody (E12) specific for endothelial cells. When endothelial cells from 14 hemangiomas were isolated and cultured under conditions that support the growth of normal human skin microvascular endothelial cells, the cells of hemangiomatous origin failed to grow. We conclude that the adult hemangiomas may not be true neoplasms, but a tissue overgrowth composed of mature vessels resembling dermal venules, lined by endothelial cells with virtually no turnover.     

普萘洛尔治疗婴儿重症血管瘤的疗效及不良反应

血管瘤是最常见的婴儿良性肿瘤,重症血管瘤会引起严重的并发症,导致毁容、功能损害甚至危及生命.已有报道普萘洛尔(心得安)治疗重症血管瘤取得较好的疗效.普萘洛尔治疗血管瘤的机制包括收缩血管、抑制血管生成因子如血管内皮生长因子和碱性成纤维细胞生长因子表达,以及促进细胞凋亡.普萘洛尔作为一种非选择性的β-受体阻断剂,服用后可能引起低血压、心动过缓、低血糖、支气管痉挛等不良反应.因此服用时要严密监测生命体征.     

普萘洛尔治疗婴儿重症血管瘤的疗效及不良反应

血管瘤是最常见的婴儿良性肿瘤,重症血管瘤会引起严重的并发症,导致毁容、功能损害甚至危及生命.已有报道普萘洛尔(心得安)治疗重症血管瘤取得较好的疗效.普萘洛尔治疗血管瘤的机制包括收缩血管、抑制血管生成因子如血管内皮生长因子和碱性成纤维细胞生长因子表达,以及促进细胞凋亡.普萘洛尔作为一种非选择性的β-受体阻断剂,服用后可能引起低血压、心动过缓、低血糖、支气管痉挛等不良反应.因此服用时要严密监测生命体征.     

长脉冲1064nm Nd:YAG激光治疗婴幼儿皮肤血管瘤215例疗效分析

目的:观察长脉冲1064nm Nd:YAG激光治疗婴幼儿皮肤血管瘤临床疗效,并探讨影响疗效的相关因素.方法:应用长脉冲1 064 nm Nd:YAG激光治疗婴幼儿皮肤血管瘤215例,其中鲜红斑痣19例,草莓状血管瘤179例,混合型血管瘤17例.分析其疗效与病变类型、瘤体大小、病变部位及治疗次数的关系.结果:215例患儿中治愈133例,显效67例,有效8例,无效7例,痊愈率和有效率分别为61.9％和93.1％.疗效与血管瘤的病变类型、瘤体的大小以及治疗次数有关,但与其病变部位无明显相关性.治疗后暂时性色素沉着、暂时性色素减退、浅表性瘢痕、头部毛发减少或消失的发生率分别为48.8％、8.3％、4.6％和3.7％.结论:长脉冲1064nm Nd:YAG激光治疗婴幼儿皮肤血管瘤疗效好,安全性较高,不良反应轻,可在临床上推广使用.