Hemangioma and vascular malformation Hemangioma (hemangiorna) and vascular malformation (vascular malformation) is a congenital abnormality of vascular development, and the pathology belongs to misshapen tumor rather than true tumor. In the past 20 years, the etiology, pathology, classification and diagnosis of hemangioma and vascular malformation have been studied in depth, and the clinical efficacy has improved significantly. The use of academic terms, classification principles and diagnostic and therapeutic criteria are gradually standardized. Epidemiology] Hemangioma is a common disease in children, with an incidence rate of 2.5% to 12%, l.1% to 2.6% in the neonatal period, and the highest incidence rate of l0% to l2% in infancy and childhood. The incidence rate is high in females, with a male to female ratio of 1:2 to 1:5. The incidence rate of ultra-low birth weight children with birth weight less than 1000g can be as high as 30%. There is no significant difference in the incidence of hemangioma among different races. Hemangioma can occur in all parts of the body, and 15% to 30% of children have multiple hemangiomas. The causes and pathogenesis of hemangioma are still unclear. The following two theories are generally accepted. 1. Embryonic residual theory Embryonic blood vessels grow in two ways: ① embryonic hematopoietic stem cells differentiate to form vascular endothelial cells, which further proliferate to form cell masses, with the central cells differentiating into blood cells and the outer layer gradually differentiating into vascular lumen; ② vascular endothelial cells form new vascular buds under the stimulation of vascular growth factor, which further develop to form neovascularization. The infantile vascular endothelial cells remaining after birth maintain some of the growth characteristics of embryonic stem cells, and the cells proliferating with the participation of cytokines eventually form hemangiomas. 2.Estrogen theory Research proves that the serum estradiol level of children with hemangioma is higher than that of normal children of the same age, and it is also found that the estrogen receptor of hemangioma tissue is significantly higher than that of normal tissue. In animal experiments, estrogen supplementation helps the formation of hemangioma. Significantly higher estrogen levels in pregnant women could explain the increased incidence of hemangiomas during pregnancy. In addition, certain biologic factors that promote angiogenesis such as vascular endothelial growth factor (VEGF), fibroblast growth factor (bFGF) can promote vascular endothelial proliferation and excessive blood vessel formation. Studies suggest the isolation of cytomegalovirus from hemangioma tissue. Animal experiments have confirmed that polyomavirus gene fragments can establish a nude mouse model of hemangioma. These factors may be the etiology of hemangioma. In 1982, Muliken and Glowacki classified hemangiomas in terms of pathology, cell biology, clinical manifestations, development and regression of hemangiomas. True hemangioma is mainly characterized by normal skin at birth and lesions appearing weeks or months later, with gradual growth of the tumor that continues to develop for 6 to 8 months, which is the growth phase. Then the growth of the tumor slows down or even stops, which is the stationary phase. Then the tumor gradually becomes smaller and darker and enters the receding phase, and finally the tumor fades away on its own, leaving only pigmentation, a small amount of fibrous tissue formation or mild dilatation of local skin capillaries. 50% of children with hemangioma completely fade away by the age of 5, and 90% of them can heal on their own by the age of 9. In contrast to true hemangiomas, all vascular malformations are present from birth and gradually increase in size with age, but the lesions do not change much in extent, darken in color, and do not fade completely. Vascular malformations can be classified as capillary malformations, venous malformations, arteriovenous malformations, and arteriovenous fistula malformations. The incidence of true hemangioma is high, while vascular malformation is relatively rare; true hemangioma lesions are in the skin and subcutaneous, and vascular malformation can also affect muscles and internal organs; true hemangioma does not damage the skeletal system, while vascular malformation can involve bones; most true hemangiomas are treated non-surgically, while vascular malformation is generally treated surgically. 1.True hemangioma classification (1)Capillary hemangioma: Strawberry hemangioma is the most common, accounting for about 65%. The growth is fast, and it takes only a few weeks to increase from the size of a spot to several centimeters, and a few may show diffuse proliferation. The lesion is light red or bright red, fading when pressed, protruding from the skin surface, and may be lobulated or nodular, resembling a strawberry, also known as strawberry hemangioma. (2) Spongiotic hemangioma: It accounts for about 15%, mainly located in the subcutaneous area, uniformly elastic, with unclear boundary, mainly composed of proliferating capillary endothelial cells, which can be deformed under pressure, with normal or slightly light blue epidermal color. (3) Mixed hemangioma: A mixture of capillary hemangioma and cavernous hemangioma appears in the same part of the body, accounting for about 20%. In the early stage, only capillary hemangioma is seen. As the tumor grows and expands, the subcutaneous tissue tumor gradually proliferates and the local tissue is obviously elevated. Mixed hemangioma grows rapidly and involves a wide area, which can affect the appearance or even disfigure the face, or cause serious dysfunction if it appears in special areas. According to the size of hemangioma, hemangioma can be divided into small hemangioma, the maximum diameter is less than 3cm; medium-sized hemangioma, the diameter is 3-5cm; large hemangioma, the diameter is 5-10cm; extra-large hemangioma, the diameter is more than locm. 2.Vascular malformation classification (1)Capillary malformation: bright red nevus and wine spot as the representative, commonly seen on head, face and neck, followed by chest and back, trunk and limbs. Rarely seen. The capillary hyperdilation in the innervated area is caused by the abnormal development of peripheral nerves. The pathology is characterized by mature endothelial tissue type capillaries in the dermis, with smooth surface and clear borders. The erythematous skin is darker, fades with pressure, and darkens to a purple-grape color with age. Due to local circulatory disorder, blood retention and poor skin metabolism cause epidermal hyperkeratosis and thickening. (2) Venous malformation: It is the most common vascular malformation, represented by spongy vascular malformation. The hemangioma changes into veins forming luminal spaces of different sizes or spongy sinusoidal changes; the normal morphology of vascular endothelial cells disappears and the function is abnormal. Spongiform vascular malformations can be seen in any part of the body, and the common parts of the body are the extremities, trunk, head and face. Involvement of internal organs such as liver, spleen, gastrointestinal tract and reproductive organs. (3) Arteriovenous malformations: arteriovenous malformations that can be distinguished from true hemangiomas are mainly small arteriovenous malformations, the main types of which are small arteriovenous nevi, mostly seen in school-age children, with the head, face and neck as the prevalent sites, with thin walls and bleeding from scratching. Arteriovenous malformations in which the arteries form masses are less common. (4) arteriovenous fistula: clinically it is manifested as cystic hemangioma, which is less common. The main pathological changes are subcutaneous pulsating tortuous vessels and elevation above the skin surface, pulsation can be found, murmur can be heard, local skin temperature is elevated, the extremities are the preferred sites, and extensive trapezius hemangioma can seriously affect the function of the limbs. About 30% of hemangiomas appear in the neonatal period, and most of them appear in the first few weeks after birth. After 3-6 months of proliferation, the tumor grows rapidly after the formation of speckled lesions, and then enters a relatively stable period with slow growth in 6-18 months. Nearly 30% of the cases have residual hyperpigmentation and skin keratinization, and very few have atrophy or even fibrosis to form scar. The most common sites of true hemangioma are the head, neck and face, accounting for about 60% of cases, followed by the trunk and limbs. About 20% of the cases are multiple hemangiomas, and those located in the viscera are not easily detected, but are diagnosed by chance during physical examination or when corresponding clinical symptoms appear with bleeding. 3.Hemangioma receding time and residual lesions 50% of true hemangiomas recede naturally before the age of 5 years, and the receding tumor is not related to the size, age, location and growth rate. The earlier the tumor regresses, the fewer the complications. If the tumor regresses before the age of 3, it is rarely complicated by residual skin lesions and can even completely restore normal skin. If there is repeated bleeding and infection with ulcer formation, pigmentation and local fibrosis or scar formation will be obvious. Most of the hemangiomas exist independently and their mechanism, pathology and clinical manifestations are single diseases, only a few cases combine other malformations or abnormalities to form various syndromes. (1) Thrombocytopenia syndrome (Kasabach-Merritt syndrome, K-M syndrome): The clinical manifestation is rapidly expanding capillary endothelioma with thrombocytopenia, coagulation abnormalities and extensive bleeding, and the tumor is malignantly proliferating but not metastatic. The pathogenesis of K-M syndrome is still unclear, whether massive bleeding depletes coagulation factors or reduces coagulation factors and causes extensive bleeding is still inconclusive, but studies have shown that some cases of K-M syndrome have bone marrow hematopoietic disorders. (2) K-T syndrome (Klippel-Trenaunay syndrome): varicose bone hypertrophy with vascular nevus syndrome, related to the abnormal development of embryonic mesoderm, clinical manifestations of the typical triad: wine stains, superficial varicose veins, bone and soft tissue hyperplasia. Complications】 1. Local complications are the most common complications (1) Skin breakage and ulcer formation: local skin breakage caused by local irritation, friction and scratching of hemangioma and repeated injury cause ulcers, common sites such as neck, axilla, groin, buttocks and perineum. (2) Infection: Long-lasting skin defects and ulcers often cause infections, which can further develop into cellulitis and sepsis in severe cases. 2.Serious systemic complications (1)Canal obstruction: The rapid proliferation of hemangioma can lead to local canal obstruction and cause serious complications. Oral cavity and tongue body proliferation to promote the regression of hemangioma are now widely used in clinical treatment of hemangioma, and clinical experience proves that Pingyangmycin is more effective when combined with glucocorticoids. Scholars at home and abroad have also applied bleomycin and vincristine to treat hemangioma with certain efficacy. However, as there is still controversy in the theory of anti-cancer drugs for treating benign lesions, their application is also restricted to some extent accordingly. 3.Local injection of sclerosing agent Sclerotherapy has a long history and a wide variety of sclerosing agents, such as anhydrous alcohol, 5% sodium cod liver oil acid, quinineuratan, elimination of hemorrhoids, etc. However, because the optimal dose is difficult to control, it often causes extensive tissue necrosis, ulceration and eventually scar formation, so its application is obviously limited. Urea tumor in vivo injection treatment has obvious advantages over traditional sclerotherapy. Urea is metabolized after injection to form normal metabolites of human body, with small toxic side effects, simple injection method, cheap drug price, and a large number of cases showing satisfactory efficacy. Treatment method: 30%～40% urea, l～ lOml each time, local injection, injection can make the tumor color lighter. 2～3 times/week, l～2 times/day for large lesions, divided into parts of the injection, 10～20 times for a course of treatment, intermittent one month for the second course of treatment. 4.Laser treatment CO2 laser and YAG laser knife surgical excision of hemangioma can reduce bleeding, small epidermal hemangioma is a better indication, the main shortcoming of laser treatment is the obvious scar tissue left after treatment. Laser treatment is not suitable for larger cases. The new laser treatment instrument is continuously used in clinical practice, which is more targeted and has better efficacy. 5.Surgical treatment The main indications for surgical treatment are: ①Vascular malformation will not subside by itself, drug treatment and local injection treatment are not effective, so surgical treatment is the best choice. ②Surgical treatment is the best choice for true hemangioma which is not effective in injection treatment, but the tumor is not large and does not affect the beauty. ③Surgical treatment is appropriate for true hemangioma that has poor effect of injection therapy and seriously affects function. Smaller hemangiomas are expected to be observed and followed up, facial vascular cosmetic requirements are very high, there are various methods available for huge hemangiomas, and cases of surgical treatment of hemangiomas are subject to more restrictions. Other methods Cryotherapy, radiation therapy, microwave therapy, high-energy ultrasound therapy and Chinese herbal medicine have all been used in clinical practice, but their clinical application has been limited due to the defects of the treatment methods themselves. In recent years, biological therapy has gradually emerged, such as γ-interferon, interleukin-l2, etc. Aiming at the mechanism of angiogenesis and vascular endothelial cell proliferation, the inhibitory factor of endothelial cell growth factor was used to treat true hemangioma with significant efficacy in animal experiments and potential clinical value.