Presence of a distinct neural component in congenital vascular malformations relates to the histological type and location of the lesion

Summary

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. Although little is known about the existence of a substantial neural component in vascular malformations, we investigate the presence of an intralesional component of nerve bundles in congenital vascular malformations of soft tissues. Resection specimens of 130 congenital vascular malformations of soft tissue were retrospectively screened for the presence and extent of intralesional mature nerves bundles. Lesions were histologically categorized in arteriovenous malformations (n = 83), pure venous malformations (n = 33), and lymphatic-venous malformations (n = 14). For identification of nerves, all sections were immunostained with anti-S100. GLUT-1 immunostaining excluded the presence of infantile hemangiomas in these series. Of 130 cases, 96 (74%) showed a substantial increase of intralesional nerves in close apposition to the vessels. The nervous component appeared to be more extensive in the head and neck region and upper extremities than in malformations of other topographic sites. Most cases of arteriovenous malformations showed an increase in nerve elements (87% of all arteriovenous malformations), which was more than in pure venous malformations (55%). In cases of lymphatic-venous malformations, the areas composed of lymphatic vessels showed an almost complete absence of nerves. Prior surgery in the malformation gave no different nerve pattern compared to cases that were surgically treated for the first time. The abundant presence of intralesional mature nerves in most congenital vascular malformations suggests that at least in a large subset of lesions, neural components are an integral part of the developmental disorder. This is particularly evident in the arteriovenous type of malformations and lesions that arise in the head and neck region of the body.

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.