Original contributionPresence of a distinct neural component in congenital vascular malformations relates to the histological type and location of the lesion
Introduction
Vascular malformations are mass-forming lesions composed of mature but often dysplastic blood and/or lymphatic vessels that result from aberrant vasculogenesis during embryogenesis [1]. Consequently, they are already present at birth, but many become clinically manifest later in life. The growth pattern of most vascular malformations is very slowly progressive, usually commensurate with the growth of the child, and, in contrast to hemangiomas, vascular malformations never regress. Disproportionate growth may occur during infections, hormonal changes such as puberty, or trauma. Life-threatening complications result from obstruction of vital structures or extensive hemorrhage. Regression never occurs, a feature which clearly discriminates vascular malformations from the involuting types of infantile hemangiomas that are present in approximately 10% of all young children [2].
Histologically, vascular malformations are categorized according to the dominant types of vessels that make up the lesion (capillary, arteriovenous, venous, or lymphatic). Arteriovenous malformations (AVM) are the most dangerous types of vascular malformations because of the presence of one or more arteriovenous fistulas. AVM with extensive fistulation can be recognized clinically as so-called high-flow lesions. Apart from the local increase in blood vessels that characterizes the lesion, many vascular malformations also show an abundant extracellular matrix component, which consists of adipose, hyalinized, or myxoid tissue, or combinations, indicating that the composition of vascular malformations is usually more complex [3]. Information on potential involvement of nervous tissues in the component makeup of vascular malformations is scarce. Abnormal innervation patterns have been described in capillary malformations (port wine stains), which are characterized by dilated post capillary venules [4] and a significant decrease in nervous innervation [5]. However, capillary malformations have a relatively normal vasculature [6], and even the amount of vessels in the malformation is not increased compared to the normal skin, which clearly separates them from vascular malformations composed of large vessels. Another study documented the presence of nerve bundles in 91% of cases of AVM versus no intralesional nerves in hemangioma, which according to the authors may be helpful in the differential diagnosis of both lesions [7]. In this study, the different phases in infantile hemangiomas were not delineated.
Congruency of the development of peripheral nerves and blood vessels has been well described, and usually, the nerves and blood vessels follow each other during development [8], [9]. Surprisingly, the literature is replete with regard to investigations of neural involvement in vascular malformations.
In this study, we systematically investigated the presence and extent of nerve bundles in resected specimens of 130 patients who were treated for symptomatic vascular malformations of soft tissues and skin. Vessel types and presence of nerves were visualized by (immuno)histochemistry, and nerve involvement of lesions was correlated with demographic data of patients and the histological type of vascular malformations.
Section snippets
Selection and histomorphologic classification of surgical specimens
For this study we reviewed all case records of patients who were treated for symptomatic vascular malformations between 1984 and 2005 in the Academic Medical Center of the University of Amsterdam, which is a tertiary referral center for the diagnosis and treatment of vascular anomalies. For inclusion in this study, the following criteria needed to be fulfilled: initial resection or amputation specimen 3 cm or larger and availability of adequately sampled paraffin-embedded tissue blocks for
Results
Anti–GLUT-1 immunostaining of endothelium was absent in all specimens, excluding the presence of infantile hemangiomas in the study material. Presence of nerves was evaluated in anti-S100 immunostained sections. Reference materials of normal skin and underlying soft tissues contained less than 10 nerve bundles per 0.58 cm2 mainly adjacent to vessels or skin adnexa. Typically, arteries in normal skin and subcutaneous tissue showed small nerve fibers (twigs) around the smooth muscle layer. These
Discussion
Vascular malformations are congenital lesions that are believed to result from aberrant vasculogenesis. Accordingly, the histological description and classification are focused only on the vasculature [14], [15]. Numerous studies have proposed that peripheral blood vessels and nerves use a shared patterning mechanism during development, leading to the term “neurovascular bundle” [16], [17], [18], [19], [20]. With this knowledge, we systematically screened large series of clinically and
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2013, Annals of Vascular SurgeryCitation Excerpt :The etiology is still unknown, and several theories have been advanced, including a contribution of nerve bundles in congenital vascular malformations of soft tissues. Acquired somatic mutations and aberrant vasculogenesis in adults have also been proposed as possible causes.3,4 In addition, the role of the endothelial progenitor cells should be considered as a potential cause of exacerbation.
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