Introduction
Vascular anomalies are extremely frequent in childhood. In many cases they cannot be traced in adulthood, while in other cases these congenital defects, which are almost insignificant at birth, develop in time, growing and getting serious with a progression that cannot easily be foreseen and which can at times be devastating.
In 1987 a dermatologist paediatrician, while conducting an extensive survey of the children born in an American hospital, observed that at least one pigmented cutaneous lesion could be noted in 57% of the newborn: in 44% these lesions could be labelled as congenital vascular defects, angiomas or vascular malformations. This strange and perhaps unexpected statistical data (which would deserve an epidemiologic survey in our country too) enables us to stress the great incidence of vascular anomalies. Despite their rate of incidence, even today these pathologies seem to be unknown, and hence they are often diagnosed late and labelled incorrectly with an outdated nomenclature, the heritage mostly of common imagination (strawberry mark, port-wine stain, the stork’s mark or angel’s kiss).

On the other hand their clinical terms too have little to do with the anatomic and pathological substrate (tuberous, cavernous or cirsoid angiomas) and lastly we find eponyms of mostly historical importance (Klippel-Trenaunay syndrome, Sturge-Weber syndrome etc). In a diversified picture of vascular defects of various types and seriousness, which can concern any part of the body, the terminology and classification problem is not a small matter and least of all an academic matter. An improper “nomenclature” of the vascular anomalies can in fact be misleading for the prognosis but especially in regards to the organization of the type of treatment and its “timing”. Then again the incorrect or non-specific nature of labels of certain vascular anomalies complicates the discussion between various specialists consulted to define the best therapeutic course. And in regards to therapy we must state beforehand that the term “course”, at least in the more serious vascular malformations, is extremely appropriate: the corrective treatment which is often multidisciplinary, surgical or of another type, is almost a route marked by laps that can be more or less close in time.

The patient and his parents must hence be informed as concerns this necessity and they must be psychologically prepared to face it. But let us return to the classification. Angiomas and vascular malformations are habitually discussed in medical literature in the same chapter, though they are entirely different problems (despite their often similar clinical signs and symptoms): angiomas are in fact benign tumours, the most frequent tumours in childhood, with a typical evolution cycle - they represent an exclusively paediatric problem; vascular malformations instead are defects that have taken place during embriogenesis, they gradually grow in childhood, persist and as a rule get serious in time. Histologically speaking, angiomas - more precisely haemangiomas - are characterized by an accelerated angiogenesis with high indexes of endothelial cell proliferation and the subsequent formation of new channels formed by capillaries and sinusoids with a high blood flow. Histologically, vascular malformations do not present a high proliferation of endothelial cells and they are distinguished in various typologies according to the distinctive features typical of the blood vessels concerned (thus we will have capillary, venous, lymphatic, arterious and combined forms of malformations) and haemodynamic characteristics (low and high flow malformations). The foundations of this classification introduced in 1982 by J.B. Mulliken, a Bostonian maxillofacial surgeon, and based on a revolutionary biological study on the turnover of endothelial cells, can be found in the classification officially adopted in 1996 by the ISSVA (International Society for the Study of Vascular Anomalies) which we quote in table 1. A few years earlier, at the end of the ’70s, little after the decease of the Italian vascular surgeon Edmondo Malan (who was a pioneer in the study and treatment of congenital vascular defects), Mulliken took the initiative in creating and sponsoring an international study group formed by specialists in a variety of fields.

The meetings promoted by this group, informal workshops, followed at two-year intervals, encouraging a profitable exchange of experiences on the most serious and complex clinical cases and the acquisition of a common language that at last enabled a real comparison between clinical case histories and the formulation of diagnostic and therapeutic guidelines for each type of vascular defect. This common effort concretized in the formation of a scientific organ dedicated to the study of vascular anomalies (The International Society for Study of Vascular Anomalies – Budapest, 1994) and lastly, after years of discussion among its members, the above-mentioned classification was officially adopted (Rome, 1996). Haemangiomas and other vascular tumours Haemangiomas are the most common vascular tumours that can occur in 10-12% of newborn infants. Higher percentages (up to 20%) can be noticed in pre-term babies. Females are more often affected by it. Besides those noticeable in pre-term babies and the rare cases of congenital haemangioma, a haemangioma generally develops on a flat cutaneous lesion which is often insignificant (it looks like a telangiectatic or bluish patch) a few weeks after birth, when it begins its evolution cycle. Essential stages can be identified in this cycle:
1) proliferative phase - it ends generally after the first 12 months of life;
2) involutive phase - it is slower and more variable, persisting in some cases for 6-7 years;
3) effects - characterized by the presence of fibrous excrescences and a telangiectatic, hypopigmented or atrophic skin area.

During the proliferative phase some blood and urine tests prove an accelerated angiogenesis: basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). From a histological viewpoint, while in the proliferative stage there prevail concentrations of endothelial cells, in the involutive stage there is a prevalence of mastocytes and pericytes. In the rare but not exceptional congenital haemangiomas (detectable at times during pregnancy by means of echography or prenatal MRI), the proliferative phase ends generally in the womb - even the largest angiomas will regress in a few weeks or months. Cutaneous haemangiomas, which interest the papillary and reticulated dermis, clinically appear with the typical “strawberry” aspect; the deeper ones, still called “cavernous”, are covered by normal skin; the diagnosis in such cases is left to ultrasound investigations. Both in superficial haemangiomas and the deeper ones, the flow signal (which can be detected by a simple pocket continuous wave Doppler apparatus) is similar to the one recorded in malformations and arteriovenous fistulas: it is a high speed signal with a high diastolic component.

The diagnosis of haemangiomas is almost always clinical. The Doppler and eco-Doppler are however useful investigations when it is necessary to differentiate between an angiomatous tumefaction, a venous malformation and a lymphangioma. Angiographic investigations add nothing to this, while MRI is adviced in the most problematic haemangiomas such as the laringeal ones (which can interfere with respiratory functions) or the hepatic ones (which cause a cardiac overload due to their size and the subsequent shunt they form). In regards to hepatic haemangiomas, it must be stated that they are generally associated with cutaneous haemangiomas only in the so-called multiple rash-type haemangiomatosis, an extremely rare syndrome in which the newborn’s skin is spotted with little angiomas. Hence there is no meaning in systematically performing hepatic (or cerebral) echographies when only one strawberry or tuberous haemangioma is noted. Treatment of haemangiomas Given the natural tendency to involute, the great majority of haemangiomas does not require any treatment. This conservative attitude is open to many exceptions: in case of a rapidly growing haemangioma (which can exceed 3cm in diameter) and, notwithstanding their size, in case of haemangiomas localized in critical sites where they obstruct certain functions. Besides the already mentioned larynx, critical sites are localized in the ano-genital area (due to the risk of ulcerations and bleeding), the lips and nose and lastly the periorbital area, where even a temporary mechanical obstruction to the visual functions can cause astigmatic amblyopia or strabismus. Oral treatment with Prednisone in doses of 2-4 mg/kg, given in repeated cycles of 3-4 weeks, has proved effective in a percentage that can be assessed between 30 and 40 % of cases. A temporary arrest of body growth represents the most common side-effect (not entirely unimportant) of this kind of treatment. More rarely there are iatrogenic effects such as bone alterations, cushingoid appearance and infections. Intralesional cortisone treatment is a valid alternative to systemic oral treatment and it is, in our experience, more efficacious and less exposed to side-effects and complications.

The infiltration of Triamicinolone (in doses of 1-3 mg/kg) is practiced in various points of the angiomatous mass by means of a fine needle (30 G). This treatment, performed by us under anaesthesia, can be repeated after 4-6 weeks and can be combined with pulsed dye-laser photocoagulation. Opinions differ on how advisable it is to sistematically treat all haemangiomas with pulsed dye-laser treatment: the effect of dye-laser photocoagulation is manifest only on superfical blood-vessels (depth < 1mm), hence this treatment could be prescribed only in the prodromal stages of the haemangioma’s growth (when it looks like a superficial mark). The efficacy of photocoagulation laser treatment in ulcerated haemangiomas is universally agreed with, and confirmed by our experience too. Few repeated sittings can encourage the cicatrization of the ulcer. In giant haemangiomas which do not respond to cortisone treatment by mouth or by infiltration, Interferon–alpha 2A is resorted to, at a dosage of 2-3 millions of units/mq of body surface. The high cost and the potential neurotoxicity of Interferon makes it suitable only for selected cases. Lastly, surgical excision remains the simplest and most radical solution for most haemangiomas:
1) those who show a poor tendency to natural involution;
2) the pedicellated ones located in exposed and easily excisable areas;
3) those for which a visible scar can be foreseen, due to their size.
Particular haemangiomas: Capillary lobular haemangioma (granuloma pyogenicum) These are small acquired vascular tumours which are extremely common in childhood (but not infrequent in the adult and in pregnant women). Of uncertain etiopathogenesis (the term granuloma pyogenicum seems to imply an infective pathogenesis which has never revealed itself), they appear as raised papules which are at times pedicellated, and they bleed easily. The Doppler probe has detected high flow signals even in these peculiar vascular lesions; this explains their conspicuous bleeding when subject to minor traumas. Surgical excision is almost always the only solution. Other vascular tumours: kaposiform endothelial sarcoma, angioblastoma, haemangioendothelioma and haemangiopericytoma.

The other vascular tumours are extremely rare in childhood. This report limits us to only mention kaposiform endothelial sarcoma and angioblastoma (otherwise defined “tufted angioma”). We mention them because these vascular tumours can by associated with the so-called Kasabach-Merritt syndrome, an extremely serious and often fatal thrombopenic coagulopathy which was thought to complicate bigger haemangiomas, till recent years. On the contrary to haemangiomas, serological indexes (VEGF and bFGF) are kept low in these tumours. Vascular malformations “Low flow” vascular malformations Capillary malformations These are very common. The incidence of 0.3%-0.5% in the population is probably underestimated as concerns anomalies which are incorrectly considered only of aesthetic importance. They can in fact be associated with complex congenital vascular defects as in the so-called Sturge-Weber syndrome in which the capillary malformation, in the form of a red mark localized on the forehead (in the site of the I branch of the trigeminal nerve), is associated with meningeal and ocular lesions (mental retardedness and glaucoma); or in the Klippel-Trenaunay syndrome in which islands of angiodysplastic skin are spread along the lateral surface of the lower limb, which as we will see, is generally hypertrophic in all its components and it also presents superficial and deep venous anomalies. Even when they represent isolated vascular defects, especially when localized on the face, their clinical impact goes far beyond the presumed aesthetic disfigurement, due to the obvious psychological effects which, already in the preschooling age, can seriously disturb the formation of the child’s personality and self-confidence.

Capillary malformations are designated with various terms which are more or less fanciful: birthmarks, plane angiomas, naevi flammei, Port-Wine stains, etc. The term capillary malformation too is to be considered incorrect. In fact these are congenital dilations which concern the post-capillary venulas and not the real capillary bed. Already present at birth, as every other type of congenital vascular defect, capillary malformations do not regress; if at all they tend with the years to take on a darker shade of colour and to become hypertrophic (there appear raised warts on the angiodysplastic skin: “cobblestones”). Only in certain diffuse capillary malformations in the newborn, there can be an attenuation in a few months along the midline of the head (Unna’s naevus is the term that defines the not infrequent telangiectatic patches of the nape and the centre of the forehead, otherwise commonly known as “angel’s kiss” or “Stork marks”). Even the so-called spider angioma (or spider naevus) must be considered small vascular anomalies, even if their congenital origin has not been ascertained. Extremely frequent (present in 10-15% of the population) and innocuous, they are characterized by microscopic arteriovenous shunts which can be easily detected by applying a Doppler probe to the lesion. But let us come to the treatment. The pulsed dye-laser photocoagulation technique (flashlamp-pumped pulsed dye-laser), perfected only in recent years, has completely replaced all the various types of treatment proposed in the past for capillary malformations. The equipment currently in use enables the modulation of various parameters, according to the characteristics of the vascular lesion to be treated: 1) wavelength (from 585 to 600 nanometres); 2) the duration of the impulse (400-1500 microseconds); 3) the energy level (up to 10 joule). A cooling apparatus which can produce cold air (up to –31° C) helps minimize the undesired effects of heat on the treated skin. Treating extensive skin areas requires multiple sittings. The results are exceptionally good in smaller children for whom our protocols foresee hospitalized treatment or day-hospital, in order to perform the laser sittings under anaesthesia. The child generally accepts the treatment well if “he does not feel pain”, if the hospital environment is adapted to his needs, if the anaesthetists and other non-medical staff who work regularly in the paediatric ward know how to use all their specific professional skills with the small patient. Lymphangiomas (lymphatic malformations)

The term lymphangioma or cystic hygroma generally in use is incorrect. The suffix –oma seems to designate a proliferative component which can be justified concerning haemangiomas but not these localized cystic tumefactions mostly of the head and neck. Lymphangiomas of the neck, real congenital defects, seem to originate from a defective connection between the rudimental lymphatic system (jugular trunks) and the underlying primitive lymphatic system. These congenital vascular defects are quite rare. In our experience, in the past 3 years, on a total of 395 patients hospitalized for vascular malformations, 22 were lymphangiomas, equal to 5.6 %. In some cases, lymphangiomas of a certain size can be detected during pregnancy by means of echography or prenatal MRI; in other cases they may not be obvious at birth but do appear later with a sudden swelling. The diagnosis of lymphangioma is not hard to make. In the deeper ones the lymphangiomatous nature of a suspicious tumefaction can be proved with MRI. In weighted MRI T2 sequences, the lymphangioma is characterized by a clear sign which, on the contrary to venous malformations, is not increased by injecting a contrast medium. MRI enables a precise assessment of the relations of the malformation with nearby organs in order to programme the best suited treatment. In childhood, lymphangiomas can vary in volume in relation with inflammatory events. Cases of spontaneous regression have also been reported. In most cases they are subject to treatment, especially when they can mechanically obstruct breathing. As an alternative to surgical excision, which requires great precision (especially if the lymphangioma mass invades the vascular bundle of the neck), the infiltration of sclerosant substances can yield good results. Japanese authors have recently proposed the use of OK 432, a product derived from the Streptococcus. Venous malformations Venous malformations (also defined venous dysplasias) are quite frequent. They are bluish, spongy tumefactions or venous dilations. Raising empties the parts concerned while inclined positions make them congested. They can interest any part of the body, including limbs and internal organs; the majority of the so-called hepatic angiomas are venous malformations. As in haemangiomas and lymphangiomas, venous malformations too (oropharynx, tongue, larynx) can mechanically obstruct vital functions when in certain localizations, hence they require speedy treatment. Episodes of thrombosis inside the angiodysplastic mass cause sudden painful symptoms in previously asymptomatic individuals. In some cases X-rays of the parts concerned detect small (phleboliths) or extensive calcifications. In recent years, thanks to MRI, infiltrating venous malformations have been found in a single muscle or in an extensive group of muscles - malformations once unrecognized or interpreted as oncologic pathologies. Only in certain cases these malformations are connected with superficial venous ectasias, which can be the “sign” of a deeper involvement. Besides surgical excision, we increasingly resort to ultrasound guided sclero-embolization with percutaneously injected saline techniques to treat them, suiting the products used to the situation (Ethylene-polydecanol, Sodium tetradecylsulphate, Ethanol, etc). Combined and complex malformation syndromes The eponym Klippel-Trenaunay syndrome designates one of the best known malformation syndromes.

Described in the early years of the last century, it is a capillary, venous and lymphatic malformation of the lower limb, associated with dysmetria or macrosomia of the limb concerned. In this malformative pathology the limb’s skin presents more or less extensive islands of naevi flammei; atypical varicosities with a prevalently lateral course (vena umbilicalis or marginal sinus) are evident; anomalies of the deep venous circulation can be detected with directed eco-colour-Doppler investigations or with a phlebography; from a structural viewpoint dysmetria is typical - the side involved grows various centimetres in length. The traditional, conservative treatment is based on elastic immobilization but in recent years specialized centres tend to treat the malformation early in childhood with a series of corrective operations: removal of superficial venous ectasias, and corrective operations (in selected cases) on anomalies of the deep venous circulation and on bone dysmetria. Among the “low flow” vascular malformation syndromes, the so-called Bean syndrome is worth mention. Otherwise known as blue rubber bleb naevus, it is a rare, mostly hereditary, malformation, characterized by bluish, blackberry-shaped malformations, rubbery in consistence, which dot the skin and the mucous tissues in a variable number. The serious nature of these lesions is due to their localization in the intestine, where they can cause relevant enterorrhagias, which lead to significant anemia. Vascular “high flow” malformations Fistulas and arteriovenous malformations This group includes arterial anomalies (atresias, congenital aneurysmal dilations, etc), arteriovenous fistulas and arteriovenous malformations; in regards to this last group, thousands of parallel fistulas in an angiodysplastic context cause the same haemodynamic effect of a single, direct, arteriovenous connection. The clinical characteristics of arteriovenous malformations are well known: they are warm, pulsating tumefactions, animated by thrills, and they have dilated and twisted afferent and efferent arteries and veins. It must be specified that in the context of all types of vascular malformations, the arteriovenous ones are quite rare. Our recent experience (that of the past 3 years) counts 65 cases of malformations with active arteriovenous shunts on a total of 412 congenital vascular defects of various types, equal to an incidence of 15.7%. Despite their rare incidence, arteriovenous malformations seem to be what the average culture of medical students and doctors, whether they be experts or not in vascular diseases, know best. Every vascular malformation is seen as a possible “arteriovenous fistula” with consequences that can at times by misleading, both from a diagnostic and therapeutic viewpoint - totally unnecessary arteriographic investigations are requested ever too often and embolization treatment is proposed incorrectly even for vascular malformations of the venous type. As we know, arterial embolization consists in the blockage, in most cases only partial, of arteriovenous shunts. This is achieved by using a fine catheter to empty microspheres of polyvinylalcohol or other substances (cyanoacrylate, ethanol, etc) into blood-vessels afferent to the malformation. In practice, far from being the panacea for the treatment of vascular malformations, embolization enables expert hands to reduce the vascularization of the angiodysplastic mass, making its surgical excision easier and safer. In other cases it can be proposed as a palliative repeatable technique which can keep a malformation considered inoperable under control. Summary Angiomas and vascular malformations are frequent pathologies. Despite their incidence, little is still known about them, the attention the scientific world gives them is scarce and the economic resources available to prevent and cure them are poor. In recent years a new and simpler nosological classification, proposed by an international scientific association (International Society for the Study of Vascular Anomalies), has enabled a more rational diagnostic and therapeutic approach by introducing guidelines for each type of congenital defect. The complexity and rare nature of many clinical signs and symptoms often calls for a multidisciplinary approach in specialized centres in order to undertake the best suited corrective intervention early in childhood. The cases investigated at the Vascular Surgery Operative Unit of the “V.Buzzi” hospital in Milan are reported: 305 haemangiomas and 412 malformations of various types (capillary, lymphatic, venous, combined and arteriovenous) were treated in the past 3 years.

Translated by Interpres sas

Gianni Vercellio
Responsabile Unità Operativa di Chirurgia Vascolare Centro Angiomi e Malformazioni Vascolari
Ospedale “V.Buzzi”-Milano
Con la collaborazione di
Vittoria Baraldini
Dirigente Medico –U.O.
Chirurgia Vascolare Ospedale “V.Buzzi”- Milano