Venous malformation, which used to be called cavernous hemangiomas, is the most common low-flow vascular malformation, consisting of dilated veins of varying sizes that grow in proportion to the body, develop gradually throughout life, and do not subside on their own. The incidence of venous malformations is about 1:5,000 to 10,000, with about 40% occurring in the head and neck, the vast majority being sporadic, with the oral cavity, airway, and intramuscularly common. It not only affects facial appearance, but also complicates pain, ulceration, bleeding or compression, invasion of adjacent tissue structures, and subsequently affects language, swallowing and respiratory function, and even the risk of death by hemorrhage and asphyxiation.
1.Etiology and pathogenesis
Venous malformation is a developmental malformation rather than a true tumor, and its etiology and pathogenesis are still unclear. TIE2 receptor mutations have been found in some patients with venous malformation syndromes (e.g., blue rubber bubble nevus syndrome) and multiple cutaneous mucosal venous malformations. Familial venous malformations are clinically rare, are autosomal dominant, and are associated with mutations at the 9P locus. Further studies revealed the presence of somatic mutations in the proangiogenic receptor TEK in many solitary or multiple venous malformations. This mutation leads to loss of TIE2 receptor function and upregulation of other vascular growth factors such as βTGF and βFGF expression, resulting in increasing lesion severity.
In some venous malformation lesions, a significant increase in the number of neuronal cells was found, but the exact role of this needs to be further investigated. In addition, the recent finding of high expression of matrix metalloproteinase 9 (MMP-9) in intramuscular venous malformations suggests that venous malformations may exhibit infiltrative growth and angiogenic properties while slowly expanding due to increased hydrostatic pressure. The high expression of luteinizing hormone receptors in venous malformation lesions may be one of the reasons for the rapid enlargement of the lesions in response to altered hormone levels in vivo.
2. Clinical manifestations
Venous malformations can occur superficially or deeply; they can be solitary or multiple. They occur in the cheek, neck, eyelid, lip, tongue, soft palate, parapharynx or floor of the mouth. The location varies in depth; if the location is deep, the skin or mucosa is normal in color; superficial lesions appear blue or dark purple. The borders are indistinct, soft and compressible, and sometimes venous stones can be found. When the child cries or when the head is below the level of the heart, the lesion area is obviously congested and enlarged; when the normal position is restored, the swelling then shrinks and returns to its original state, which is called a positive postural shift test.
Most venous malformations are detected at birth, and when the size of the lesion is not large, there are usually no conscious symptoms. If the lesion continues to develop and increase in size, it may cause deformities and dysfunction of the face, lips and tongue. In case of trauma, secondary infection, sudden internal bleeding or change of hormone level in the body, it may cause pain, swelling and even bleeding. Venous malformations occurring in the parapharynx, tongue root, and soft palate may be associated with swallowing, speech, and respiratory dysfunction.
Venous malformations can occur within the muscle tissue (e.g., temporalis, bite, tongue) and are called intramuscular angiomas or, more accurately, intramuscular venous malformations. Most of these malformations are located between the muscles and may extend from the affected muscle into the surrounding tissue. Although histologically identical to venous malformations, they have a completely different clinical presentation than non-intramuscular venous malformations. It is most often found in the 20s or 30s and occasionally presents earlier or later. It presents as a progressively growing palpable muscle mass with or without pain. There is good reason to believe that intramuscular venous malformations are actually microvenous-venous malformations, with markedly thickened inflowing arteries visible on arteriography. In some cases, they occur in the anatomic gaps of the face, such as the pterygopalatine fossa and infratemporal fossa, and are not easily detected early. When the head is below the level of the heart, blood rapidly fills the diseased sinus, causing the corresponding area to swell and the mass to become visible.
Venous malformations can also occur in bone, most commonly in the mandible, followed by the maxilla, nasal bone, parietal bone, and frontal bone, and Sadowsky et al. referred to lesions involving the maxilla and mandible as “central hemangiomas. The mandibular lesion usually presents as a painless, slow-growing mass with loose teeth and enlarged gaps due to gingival bleeding and/or swelling of the buccal bone cortex and thinning of the bone. The first sign of intraosses venous malformations may be post-extraction hemorrhage, and further radiographic examination may reveal soap bubble-like or honeycomb bone changes; in addition to direct intraosseous involvement, they may also show bone hypertrophy and/or deformity, which can be caused by mechanical, physiological, and developmental factors, and soft tissue hypertrophy is also more common, especially in lesions that are Soft tissue hypertrophy is also common, especially in those with diffuse lesions. Microscopically, a large number of bleeding dilated veins between the bone tissues are visible.
Imaging manifestations: ultrasonography can initially identify venous malformations from other soft tissue vascular tumors and high-flow arteriovenous malformations. Ultrasound gray-scale sonograms of venous malformations usually show well-defined, irregularly shaped, heterogeneous internal echogenicity. If the lesion is predominantly a dilated vein, ultrasound shows a cystic, hypoechoic lumen that may be compressed. If the vein wall cells are predominant, the lesion tissue is more echogenic and much less compressible. Venous stones are strongly echogenic and accompanied by acoustic shadowing. Color Doppler as well as spectral waveform analysis can show slow blood flow within the lesion with normal surrounding arterial flow and a high resistance index. The limitations of ultrasound are that it is not effective in visualizing deeper lesions and when the lesion is obscured by bone. Ultrasound can also help guide puncture localization when sclerotherapy is performed for deeply located venous malformations. After sclerotherapy, ultrasound can also detect incompressible thrombus echoes in the lesion to determine if there is an unembolized portion of the venous malformation and to help re-treat it at a different point. Painless and non-invasive is the greatest advantage of ultrasonography.
Venous malformations of the face and neck are often found clinically and on plain radiographs as venous stones. The lesion sometimes involves the jawbone or is located entirely within the jawbone, and the X-ray shows a soap bubble-like or beehive-like hypodense image of the jawbone.
Magnetic resonance imaging (MRI) is the imaging modality of choice, or the gold standard, for confirming the extent of venous malformations and aiding in the development of treatment plans. Venous malformations appear as solid masses of moderate signal intensity on MRI T1-weighted images and as high-signal, homogeneous masses on T2-weighted images. Large venous malformations are often associated with venous stones, which show better on CT as scattered high-density calcified images; they appear as low-signal areas on T1-weighted images and T2-weighted images on MRI.
On T2-weighted images, limited lesions of venous malformations can form “venous lakes”, which have the effect of lumpectomy. The MRI cross-sectional images can avoid tissue overlap and show the relationship between the lesion and deeper structures, so it is significantly better than the lumpectomy in showing the extent of the lesion and its relationship with normal tissue. MRI can show the extent of the lesion and its relationship with the surrounding structures, especially the T2-weighted image (compression lipid image). ct can well show the venous stone in the venous malformation, but the lesion itself has no obvious enhancement, and it is difficult to show the relationship between the lesion and the surrounding tissues.
In recent years, the application and development of 64-layer spiral CT angiography (CTA) combined with virtual endoscopy (VE) technology has provided patients with a non-invasive vascular examination method that has certain advantages in the diagnosis of venous malformations. It can display the scope of the lesion, the characteristics of the blood supply, the relationship with the adjacent blood vessels, muscle, bone and other structures (multi-angle and three-dimensional), which not only reduces the pain suffered by the patient during the examination, but also makes the clinician’s diagnosis of the lesion more accurate and rapid.
3.Diagnosis and differential diagnosis
Most of the venous malformations are easy to diagnose according to the medical history, clinical manifestations and imaging features. Venous malformations occurring in superficial areas are easily diagnosed by clinical examination, while those located deep in the face and neck are sometimes difficult to be correctly diagnosed by clinical examination alone and need to be diagnosed with the aid of puncture examination or imaging examination (ultrasound, MRI, MRA, etc.). Dark red venous blood can be extracted during puncture and can be left for a period of time to coagulate, which is the most reliable clinical diagnosis indication. Color Doppler ultrasound and MRI are very helpful in the diagnosis of deep venous malformations, especially MRI T2-weighted images, which have unique advantages in diagnosing venous malformations and can clearly show the extent of the lesion, which is a guide for the development of treatment plans. Compared with MRI, CT has no significant advantage in diagnosing venous malformations.
Based on the imaging characteristics of the refluxing veins, venous malformations are classified into four types: type I with no obvious refluxing veins, type II with normal refluxing veins, type III with thickened refluxing veins, and type IV with dilated refluxing veins. This classification has important reference value for the development of treatment plan of venous malformation and prevention of complications during treatment, clinically type I and II venous malformations account for the majority.
Figure 1. Imaging classification of venous malformations
Venous malformations deep in the tissue need to be differentiated from hemangiomas, especially in infantile patients. In rare cases, hemangiomas can be present in the same or different sites as venous malformations or arteriovenous malformations, making the differential diagnosis more difficult. Venous malformations occurring in the palate often present as a deep blue mass in the mucosa, similar to mucous epidermoid carcinoma in this area, and require attention. Dark red venous blood from a puncture can be used for differentiation. Venous malformation also needs to be differentiated from jugular venous dilatation and gill slit cysts.
4.Treatment
Treatment of venous malformations includes conservative treatment such as head of bed elevation and compression therapy, surgery, sclerotherapy, laser therapy, cryotherapy, electrocoagulation, electrochemical therapy, etc. All these methods have advantages and disadvantages. Cryotherapy and electrocoagulation can leave scarring on the skin and mucous membranes and have poor therapeutic effects, so they are rarely used in clinical practice. Because of the variety of treatment methods and the different manifestations of patients, it is recommended that multidisciplinary treatment teams be formed by several related disciplines to treat complex patients.
Conservative treatment is primarily indicated for the management of small, isolated, asymptomatic venous malformations, as well as for the control of growth and symptoms of large lesions treated by other means. Elevation of the head is important to reduce the hydrostatic pressure that can cause distension of the malformation and is also useful in reducing symptoms of airway obstruction, swelling and pain. Other helpful conservative treatment measures include local compression, anti-infection, and pain relief.
Sclerotherapy is the removal of abnormal veins by injection of sclerosing agents, traditionally liquid sclerosing agents that are chemically stimulating to the endothelium, followed by the formation of a thrombus and the eventual transformation of the vein into a fibrous streak that then disappears. Sclerotherapy has now replaced surgery as the mainstream treatment for venous malformations today, either as a single treatment or in combination with surgery and laser. For large lesions, the number of sclerotherapy injections is high, and the chance of recurrence after treatment is greater. The goal of treatment is to control the lesion and improve its shape and function. The sclerosing agents reported in the literature include 5% sodium cod liver oil acid, sodium tetradecyl sulfate, ethanolamine oleate, corn alcohol soluble protein (ethiblock), hypertonic saline, pantothenic acid, hypertonic glucose, tetracycline, OK-432, etc. Currently, the commonly used sclerosing agents are pinyamycin, anhydrous ethanol, and polyglaucine (polydocanol). The choice of sclerosing agent depends on the experience and preference of the physician, as well as the site, extent and type of lesion.
Laser treatment is suitable for the treatment of superficial venous malformations of the skin and oral mucosa, commonly used Nd:YAG laser, also can use KTP laser.Nd:YAG laser wavelength is 1064nm, for the invisible light of infrared segment, can be transmitted through the thin optical fiber, to reach any part of the oral cavity and throat, its main mechanism is the absorption of laser energy by the hemoglobin in the lesion, which generates high temperature locally and produces coagulation effect and immediate tissue crumpling. Endovascular and percutaneous modalities have allowed the extension of laser treatment to many other venous malformations.
In most cases, surgical treatment is only an adjunctive treatment with the primary goal of improving facial shape and function. Localized, non-aesthetic areas of venous malformation may be surgically excised; in extensive cases, partial excision may be performed after injection of sclerosing agents to correct the appearance. Preoperative lesion imaging or MRI (MRA) is advisable to fully understand the extent of the lesion and collateral circulation for reference in surgical design. Blood loss should be fully estimated and measures should be taken accordingly to avoid irreparable damage. Larger tissue defects after lesion excision can be repaired with skin graft or flap. After sclerotherapy with anhydrous ethanol for giant venous malformations, patients with facial skin laxity, which affects aesthetics, can be treated surgically by removing excess tissue to improve facial morphology, and intraoperative laser treatment can be performed for residual lesions. Due to the pre-sclerotherapy, the venous malformation of the reflux veins and the lesion cavity are occluded, and the intraoperative bleeding will be significantly reduced, but due to the formation of scar in the tissue, the dissection of nerves and well-known vessels will be more difficult, so the operator should have a full estimate before surgery.
In addition to the above methods, some scholars have also tried to use high frequency electrocoagulation and copper needle embolization to treat venous malformations with good results.
Large venous malformations are clinically difficult to treat because of their wide range and involvement of multiple layers of tissue (skin, mucosa, muscle) and important tissue structures (large blood vessels, nerves), and a combination of methods is currently advocated, with attention to keeping the patient’s upper airway open during treatment.
Attachment: When in upright position, the lesion is not obvious. When the head is forcefully lowered and the head position is below the level of the heart, the lesion becomes congested and enlarged because of poor local venous return and large amount of venous blood stagnation in the lesion. When gradually returning to upright position, the lesion shrinks rapidly or slowly and returns to the original state, which is called positive postural shift test. This is the most typical clinical manifestation of venous malformations swell when the area involved is lowered below the level of the heart-a dependent position.