Venous malformation: causes, symptoms, diagnosis, treatment and prognosis

A venous malformation is a congenital vascular anomaly characterized by abnormally developed veins with slow blood flow. It is not a vascular tumor or an "infantile hemangioma" in the old sense. The current classification of the International Society for the Study of Vascular Anomalies classifies it as a slow-flow vascular malformation, not a tumor. Older terms like "cavernous hemangioma" are considered imprecise and are no longer recommended for clinical use. [1]

Most of these malformations are present from birth, but they don't always become immediately noticeable. A small lesion may initially appear as a barely noticeable bluish spot or soft nodule, but then begin to enlarge as the child grows, during puberty, pregnancy, after an injury, or due to thrombosis within the malformation itself. This pathology rarely resolves spontaneously: unlike infantile hemangiomas, venous malformations do not regress. [2]

The clinical picture varies greatly. For some people, it's merely a cosmetic defect, while for others, it can cause chronic pain, swelling, limited mobility, bleeding, anemia, and speech, swallowing, vision, or gait impairment. This is why venous malformations are now viewed not as "a birthmark on a vein," but as a chronic condition that can seriously impact quality of life and sometimes requires multi-stage treatment in a specialized center. [3]

According to current understanding, most cases are caused by postzygotic mutations (that is, mutations that arise after fertilization) in vascular developmental signaling pathways, primarily in the TEK and PIK3CA genes. This explains why some patients have lesions limited to a single site, while others experience tissue overgrowth, multiple lesions, or syndromic forms. Genetics is gradually changing treatment: in addition to sclerotherapy and surgery, targeted approaches are being developed. [4]

Code according to ICD-10 and ICD-11

The International Classification of Diseases, 10th revision, does not have a separate, unique code for isolated peripheral venous malformations. In practice, such cases fall under the category of congenital malformations of the peripheral vascular system. If the diagnosis is specified, code Q27.8 is typically used – "other specified congenital malformations of the peripheral vascular system," and if the wording is too general, code Q27.9 – "congenital malformation of the peripheral vascular system, unspecified" – is used. This is an important feature of the classification: it is less detailed than the International Classification of Diseases, 11th revision. [5]

The International Classification of Diseases, 11th revision, has refined the classification. Current classification sources list peripheral venous malformations as LA90.2 Peripheral venous malformations. Certain rare variants, such as vein of Galen malformation or congenital portosystemic shunt, are indexed as subcategories within or adjacent to this block, so the code should always be clarified based on the specific anatomy and diagnosis. [6]

Table 1. Codes most commonly used for venous malformation

System	Code	When to use
ICD 10	Q27.8	Specified congenital malformation of the peripheral vascular system
ICD 10	Q27.9	Unspecified malformation of the peripheral vascular system
ICD 11	LA90.2	Peripheral venous malformations
ICD 11	LA90.20	Special sub-variants, such as vein of Galen malformation, when specifically indicated
ICD 11	LA90.21	Congenital portosystemic shunt as a separate subcategory

Basis for the table: current pages of the International Classification of Diseases 10th and 11th revisions and their mirrors, where block LA90.2 is indicated for venous malformation. [7]

Epidemiology

Venous malformation is considered one of the most common vascular malformations of slow blood flow. According to modern reviews, its estimated incidence at birth ranges from 1 to 5 cases per 10,000 newborns, and its prevalence in the population is estimated at approximately 1%. In specialized centers, this form accounts for a significant proportion of visits for vascular anomalies. [8]

According to GeneReviews, venous malformations are often considered the most common subtype of vascular malformations observed in specialized clinics, and the birth incidence in some sources is described as 1 case in 2,000-5,000 live births. The range of figures is explained by different recording criteria: small cutaneous forms may not be included in registries for a long time, while deep lesions are sometimes detected in adulthood. [9]

No significant ethnic predisposition has been identified. Gender differences are also not considered consistent, although in some clinical series, there were slightly more women. This does not mean that the disease is more genetically prevalent in women: some of the differences are likely due to the fact that symptoms often worsen during periods of hormonal changes, including pregnancy. [10]

More than 90% of venous malformations are sporadic and isolated. Familial forms are significantly less common. In specialized centers, mucocutaneous venous malformation associated with the hereditary variant TEK accounts for less than 1% of venous anomalies, and blue rubber bleb nevus syndrome remains a rare entity. [11]

Clinically, it's also important to note that not all malformations behave the same way. Small superficial lesions can remain virtually stable for years, while diffuse muscular, visceral, or combined forms are more complicated, often accompanied by pain, thrombosis, bleeding, and local coagulopathy. Therefore, the epidemiology here is closely linked not only to the incidence but also to the subtype structure of the disease. [12]

Table 2. What is known about the prevalence of venous malformations

Indicator	Grade
Frequency at birth	1-5 per 10,000 newborns
Alternative frequency assessment	1 in 2,000-5,000 live births
Estimated population prevalence	about 1%
Proportion of sporadic and isolated cases	more than 90%
Place among vascular malformations	one of the most common, often the most common form of slow blood flow

Table based on: contemporary reviews and GeneReviews.[13]

Reasons

The main cause of venous malformation is a disruption in the formation of the venous system during embryonic development. This is a congenital, not an acquired, pathology. It is not caused by diet, lifestyle, normal physical activity, or parental errors. In most cases, the defect is associated with mosaic genetic changes that arise early in tissue development. [14]

The TEK and PIK3CA genes have been the most studied. Current data show that somatic activating mutations in TEK are found in more than 50% of sporadic unifocal venous malformations, and approximately 20% of cases are associated with PIK3CA mutations. Both variants alter vascular wall growth signaling pathways and lead to the formation of abnormal venous channels. [15]

Hereditary forms exist, but are much less common. Mucocutaneous venous malformation can be inherited in germline variants of TEK, while some multiple and syndromic forms are associated with other genetic mechanisms. However, even a hereditary predisposition does not mean the disease is equally severe in all family members: the size, number of lesions, and clinical manifestations vary greatly. [16]

Sometimes, venous malformations are part of more complex syndromes, such as those associated with tissue overgrowth, epidermal nevi, and bone and spinal anomalies. In such cases, the clinical picture is broader than an isolated vascular lesion, and the examination and treatment plan must consider not only the vascular lesion itself but the entire syndrome as a whole. [17]

Precipitating events such as trauma, infection, hormonal changes, or intralesional thrombosis are usually not the primary cause of the disease. Rather, they make an existing malformation more noticeable, painful, or larger. Therefore, the clinical "onset" after trauma should not be misleading: more often, it is the manifestation of a congenital anomaly that previously went unnoticed. [18]

Table 3. Main causes and genetic mechanisms

Cause or mechanism	Clinical significance
Disruption of embryonic vein formation	Basic innate mechanism
Somatic TEK mutations	A common cause of sporadic unifocal lesions
Somatic mutations of PIK3CA	Associated with isolated and syndromic forms
Germline mutations in familial forms	Explains multiple and inherited cases
Syndromic forms	Often associated with excess tissue growth and other abnormalities
Trauma, infection, hormonal changes	Usually not the primary cause, but a factor in manifestation and deterioration

Basis for the table: reviews on the genetics and pathogenesis of venous malformations. [19]

Risk factors

For congenital venous malformations themselves, there are no classic acquired risk factors, as with atherosclerosis or varicose veins. However, there are factors that increase the likelihood of severe symptoms, enlargement of the lesion, pain, coagulopathy, and functional impairment. Therefore, in this regard, it is more appropriate to speak not so much about the risk of "onset" but rather about the risk of progression and complications. [20]

These factors include a large lesion, deep location, muscular or visceral involvement, the presence of phleboliths, and connection to the deep venous system. Large and deep malformations are more often accompanied by localized intravascular coagulopathy, thrombosis, pain, and bleeding. They are more likely to cause problems with walking, limb movement, breathing, speech, or swallowing, depending on the location. [21]

A separate group of factors concerns hormonal periods. Venous malformations typically grow proportionally to the body, but accelerated growth and increased symptoms are often noted during puberty and pregnancy. This is associated with the influence of sex hormones on angiogenesis and vascular proliferation. Clinically, this means that a lesion that appears stable in childhood may become much more noticeable in adolescence. [22]

Trauma, local inflammation, and recurring microthromboses within the malformation also exacerbate symptoms. These often lead to the development of dense, painful areas, increasing swelling and pain, and, over time, phleboliths forming in the tissue. To the patient, this appears as a sudden worsening, although in reality, it is a worsening of an existing congenital lesion. [23]

Finally, syndromic forms and genetic variants with multiple lesions have an unfavorable profile. These have a higher risk of recurrence, multi-stage treatment, and systemic complications than small, isolated cutaneous venous malformations. Therefore, genetic evaluation and management in a multidisciplinary center are increasingly recommended for multiple, familial, or combined lesions. [24]

Table 4. What increases the risk of severe disease

Factor	Why is this important?
Large volume of the hearth	Higher risk of pain, swelling and coagulopathy
Deep location	More difficult diagnosis and treatment
Connection with the deep venous system	Higher risk of thrombosis and embolic complications
Phleboliths	Often associated with pain and thrombosis
Puberty and pregnancy	Accelerated growth and increased symptoms are possible.
Trauma and inflammation	They provoke an exacerbation
Multiple and syndromic forms	More often, complex and lengthy treatment is required.

Basis for table: contemporary reviews, studies on pain and coagulopathy, and consensus patient management pathways.[25]

Pathogenesis

Normally, the venous network is formed as an orderly system of vessels with relatively stable walls, valves, proper connections to the deep veins, and predictable hemodynamics. In venous malformations, this process is disrupted: dilated, tortuous, slowly draining venous channels form, which are poorly organized and do not ensure normal blood flow. As a result, blood stagnates in them. [26]

At the cellular level, such lesions are associated with disruption of endothelial and vascular wall signaling pathways. The TIE2-PI3K-AKT-mTOR pathway is particularly important. Its excessive activation leads to vessels becoming not just dilated, but structurally abnormal: large channels, thin walls, unevenly distributed smooth muscle, and easily involved tissue. [27]

Due to slow blood flow within the lesion, local intravascular coagulopathy occurs. In other words, microthrombi constantly form and partially disintegrate within the malformation. This leads to increased D-dimer levels, phlebolith formation, pain, and sometimes the depletion of coagulation factors. In large malformations, this process can become clinically significant and complicate any intervention. [28]

The pathogenesis of pain associated with venous malformations is multifactorial. Pain arises not only from tissue stretching, but also from thrombosis within the lesion, pressure on nerve structures, involvement of muscles, joints, and fascia, and the inflammatory response following episodes of microthrombosis. Therefore, the severity of pain does not always strictly correspond to the external size of the bluish spot on the skin. [29]

If the malformation connects to the deep venous system or is located in vital areas, the pathogenesis becomes more complex. Then, in addition to local problems, there is the risk of embolism, bleeding, anemia, organ dysfunction, and significant cosmetic consequences. For this reason, a venous malformation cannot be assessed solely by skin color: its anatomical volume and depth are decisive. [30]

Symptoms

The classic presentation is a soft, compressible, non-pulsating bluish mass that may enlarge with straining, crying, bending, physical activity, or prolonged standing. Sometimes it is a barely noticeable spot, sometimes a large nodule or diffuse enlargement of part of a limb or face. Superficial lesions are usually more visible, while deeper lesions can long be disguised as "swelling," "cyst," "muscle problem," or "unclear pain." [31]

Pain is one of the most common and most underestimated symptoms. It can be dull, aching, burning, or stabbing. It often intensifies in the evening, after exertion, prolonged sitting, or standing. With thrombosis within the lesion, the pain becomes more severe, and dense areas or phleboliths may be palpated within the tissue. [32]

Swelling and a feeling of heaviness are particularly characteristic of limb involvement. If muscles, fascia, and joint areas are involved, limited motion, fatigue, lameness, and difficulty with fine motor skills or sports may occur. Hand involvement can impair grip, while knee involvement can impair walking and extension, and extensive femoral and ankle involvement can impair weight bearing. [33]

When localized in the head and neck area, completely different complaints are possible: cosmetic deformity, speech impairment, chewing, swallowing, breathing, pain in the tongue, cheek, floor of the mouth, and orbit. With visceral forms, symptoms depend on the organ: gastrointestinal lesions can cause occult or overt bleeding and chronic iron deficiency anemia, while genitourinary lesions can cause macrohematuria or other episodes of blood loss. [34]

For some patients, complaints remain primarily psychological for a long time. A visible lesion on the face, neck, lips, or exposed areas of the body can lead to low self-esteem, social anxiety, and avoidance of communication. For children and adolescents, this aspect is often no less important than physical pain and should also be considered when choosing treatment. [35]

Classification, forms and stages

Modern classification begins with the principle of blood flow. Venous malformations are considered slow-flow malformations. This fundamentally distinguishes them from arteriovenous malformations, which have rapid blood flow and an arterial component. This is why errors in terminology lead to treatment errors: the approach to slow and fast blood flow is different. [36]

According to the International Society for the Study of Vascular Anomalies, venous malformations can be simple, meaning venous in nature, or combined, where the venous component is combined with capillary, lymphatic, or other components. Furthermore, malformations associated with other anomalies and syndromes are also separately identified. This approach is convenient because it immediately links anatomy with diagnostic and treatment strategies. [37]

According to the VASCERN consensus classification, patients are conveniently divided into sporadic single venous malformations, sporadic multiple venous malformations, familial multiple venous malformations, and combined and syndromic forms. This is a clinically useful scheme: a single small lesion and multiple familial lesions are not the same situation in terms of prognosis, genetics, and the extent of examination. [38]

Based on prevalence, lesions can be localized or diffuse. Based on location, lesions can be cutaneous, subcutaneous, muscular, bony, articular, mucous, visceral, or mixed. Based on the course of the disease, one can roughly speak of asymptomatic, symptomatic, or complicated forms, although there is no strictly universal staging system, as with tumors, for all venous malformations. In practice, severity is determined by pain, coagulopathy, bleeding, impact on function, and relationship with critical structures. [39]

For the clinician, this is usually sufficient: to understand whether the venous malformation is isolated, multiple, familial, part of a syndrome, whether there is a coagulopathy, how deep it extends, and whether it threatens organ function. It is from these answers that the patient's entire subsequent care pathway is constructed. [40]

Table 5. Practical classification of venous malformations

Sign	Options
By blood flow	Slow blood flow
By structure	Simple venous, combined
By number of outbreaks	Single, multiple
By origin	Sporadic, familial
According to clinical context	Isolated, syndromic
By prevalence	Localized, diffuse
By localization	Skin, subcutaneous tissue, muscles, bones, joints, mucous membranes, internal organs

Basis for table: ISSVA 2025 and VASCERN consensus path. [41]

Complications and consequences

The most common complication is chronic pain associated with phlebothrombosis within the lesion, local coagulopathy, and mechanical pressure on the tissue. This is often the reason for seeking medical attention, even for seemingly "small" malformations. If the lesion is deep, the pain may be misdiagnosed for years as an orthopedic, neurological, or rheumatological problem. [42]

The second major group of complications is related to blood clotting. Large and deep venous malformations are characterized by localized intravascular coagulopathy with elevated D-dimer, sometimes decreased fibrinogen, platelets, and other parameters. Severe cases are dangerous because any intervention, prolonged immobilization, hormonal changes, or major surgery can tip the balance toward bleeding or generalized coagulation. [43]

When the deep venous system is involved, the risk of thrombosis and, less commonly, pulmonary embolism increases. When internal organs are affected, chronic blood loss and anemia are possible. With lesions in the head and neck area, complications affect breathing, swallowing, speech, and vision. With extensive limb damage, persistent limitation of movement, gait disturbance, and decreased exercise tolerance develop. [44]

Cosmetic and psychosocial consequences are also not unimportant. In some patients, they determine the severity of the disease more than laboratory parameters. Changes in appearance, anxiety about bleeding, fear of pain and recurrence, multi-stage procedures, and long-term follow-up significantly impact quality of life. [45]

Finally, there is a risk of diagnostic errors. If a venous malformation is repeatedly referred to as a hemangioma, lymphangioma, cyst, soft tissue tumor, or varicose vein, the patient may receive inappropriate treatment. For this pathology, incorrect terminology is not just a formality but a real source of complications. [46]

When to see a doctor

You should consult a doctor as soon as a soft, bluish lesion appears, slowly enlarges, becomes painful, swells, becomes harder after exercise, or interferes with movement. Even if the lesion has been present for a long time, a change in symptoms requires a reassessment of the diagnosis. This is especially important for children and adolescents, who may rapidly progress during their growth period. [47]

More urgent consultation is necessary in the event of a sharp increase in pain, the appearance of dense, painful nodes, sudden growth of the lesion, repeated bleeding, severe limb swelling, symptoms of anemia, deterioration in limb function, episodes of shortness of breath, and if the lesion is located on the face, in the oral cavity, pharynx, orbit, or near the respiratory tract. In such situations, the risk of functional complications is high. [48]

A separate reason for consultation is preparation for any planned intervention on a large venous malformation. Before sclerotherapy, surgery, or sometimes even major non-vascular surgery for extensive lesions, an assessment of hemostasis, the deep venous system, and the anatomy of the lesion is required to reduce the risk of bleeding and thrombosis. [49]

Diagnostics

Diagnosis begins with a clinical examination and a thorough medical history. The doctor will determine whether the lesion was noticeable from birth, how it has changed over time, whether symptoms worsen with exertion, straining, or standing, and whether there have been episodes of pain, thrombosis, bleeding, anemia, pregnancy, family history, or syndromic signs. Even at this stage, it is possible to suspect a slow flow malformation. [50]

The next step is a physical examination. Venous malformations are characterized by softness, compressibility, lack of pulsation, a bluish tint, and enlargement during tests that increase venous pressure. Phleboliths are sometimes detected during palpation. The examination should be systemic rather than local: assessing the skin, mucous membranes, limb volume, joint function, neurological status, and signs of combined or syndromic forms. [51]

The first instrumental technique used is usually ultrasound with Doppler ultrasonography. Recent reviews cite it as the preferred first-line method, especially for superficial soft tissue lesions. It allows visualization of compressible hypoechoic lesions, slow blood flow, venous cavities, and phleboliths. For many patients, this is the best initial test because it is accessible, noninvasive, and helps quickly differentiate venous malformations from other causes of swelling. [52]

If the lesion is deep, large, located in a complex area, treatment is planned, or doubts remain, magnetic resonance imaging (MRI) is performed. It is considered the gold standard for assessing the lesion's size, depth, and connections to muscles, fascia, joints, bones, and adjacent organs. If necessary, dynamic MRI with contrast is added to more accurately assess the vascular architecture and rule out rapid blood flow. [53]

Laboratory tests are not required for everyone, but rather as indicated. In cases of large malformations, pain, phleboliths, a planned procedure, or suspected local coagulopathy, it is recommended to examine the coagulogram, platelet count, fibrinogen, and D-dimer levels. An elevated D-dimer is particularly typical of local intravascular coagulopathy. In cases of bleeding and visceral forms, hemoglobin and iron stores are also assessed. [54]

Genetic testing is most useful for multiple, familial, combined, and syndromic forms, as well as for severe cases, when targeted therapy is considered. Modern patient management directly includes differentiation into sporadic single, multiple, familial, and syndromic forms, taking into account associated genes. This is no longer an academic luxury, but rather a part of personalized treatment. [55]

Table 6. Step-by-step diagnosis of venous malformation

Stage	What are they doing?	What does this give?
1	Anamnesis	Allows one to suspect a congenital malformation
2	Inspection and palpation	Evaluates compressibility, color, depth, function
3	Ultrasound examination with Dopplerography	First-line method for superficial lesions
4	Magnetic resonance imaging	Gold standard for prevalence assessment
5	Coagulation tests, fibrinogen, D-dimer	Local intravascular coagulopathy is detected
6	Genetic testing as indicated	Helps with multiple, familial and severe forms

Basis for table: 2024 review and VASCERN consensus. [56]

Differential diagnosis

The first thing to distinguish a venous malformation from is an infantile hemangioma. A hemangioma typically undergoes a rapid growth phase after birth and then tends to regress. A venous malformation is present from birth, does not regress, and grows with the individual. It is this confusion that has historically led to many misdiagnoses such as "cavernous hemangioma." [57]

The second major competitor is lymphatic malformation and mixed venous-lymphatic forms. These also involve slow blood flow, but their imaging and clinical presentation may differ by the presence of macrocysts, episodes of inflammation, a different consistency, and a lower incidence of phleboliths. In real-life practice, this is one of the most common complex variants, especially in the head and neck region. [58]

It's imperative to rule out arteriovenous malformations. This is a lesion affecting fast blood flow. It can pulsate, produce noise, localized temperature increase, more aggressive growth, and carry other risks of complications. Mistakes here are especially dangerous: the methods and procedures for treatment are fundamentally different. Ultrasound and magnetic resonance imaging are particularly helpful in distinguishing between slow and fast blood flow. [59]

Clinically similar lesions may also include glomovenous malformations, soft tissue tumors, cysts, hematomas, varicose veins, intra-articular lesions, and, if localized in the salivary glands, sialoliths. The presence of phleboliths, slow blood flow, typical softness, and a congenital nature helps differentiate these conditions, but with deep localization, it's easy to make a mistake without visualization. [60]

Finally, with multiple lesions, one must consider not only "many individual malformations," but also a hereditary or syndromic form. This is already part of the differential diagnosis between an isolated lesion and a systemic disease. Therefore, with multiple mucocutaneous lesions, combined with tissue hypertrophy or a family history, the diagnosis must be broader than the usual local approach. [61]

Table 7. What most often has to be excluded

State	What is similar?	What helps to distinguish
Infantile hemangioma	Visible vascular formation	Hemangiomas are characterized by postnatal growth and regression.
Lymphatic malformation	Soft swelling, slow blood flow	Different structure, cysts, less typical phleboliths
Arteriovenous malformation	Vascular formation	Rapid blood flow, pulsation, different risk profile
Glomovenous malformation	Bluish spots and pain	Other clinical and genetic features
Cyst, hematoma, soft tissue tumor	Volumetric formation	Visualization shows vascular nature
Varicose changes	Venous nature of complaints	Venous malformation is congenital and has a different architecture

Table based on ISSVA, current reviews and clinical publications on imaging.[62]

Treatment

Treatment of venous malformations is always individualized. There is no universal procedure that will permanently eliminate any lesion. The primary goal in most cases is not the complete removal of all pathological vessels, but rather the reduction of pain, swelling, and the risk of thrombosis and bleeding, as well as the preservation of function and improvement of quality of life. For small, localized lesions, almost complete control can sometimes be achieved, but larger and diffuse lesions often require a stepwise, combined strategy. [63]

The most gentle level of therapy is conservative treatment. For symptomatic limb lesions, compression garments are important, as they reduce venous congestion, pain, and swelling. Painkillers and anti-inflammatory medications are also used as clinically indicated. Compression does not "remove" the malformation, but in some patients it significantly reduces the frequency of painful episodes and improves tolerance to daily activities. [64]

If a patient has signs of focal intravascular coagulopathy, treatment should also take this component into account. Current reviews indicate that low-molecular-weight heparins help reduce pain and the severity of coagulopathy, especially in the perioperative period and with large foci. Direct oral anticoagulants are also increasingly being discussed. In a 2024 study of 29 patients, pain improvement was noted in 85%, and a decrease in D-dimer by at least a quarter was observed in 86%; major bleeding was not observed. This does not mean that anticoagulants are necessary for everyone, but in the case of coagulopathy, they become an important part of treatment. [65]

Sclerotherapy remains the primary and first-line invasive treatment for most venous malformations. The procedure involves percutaneous injection of a sclerosing agent into the affected veins under ultrasound, fluoroscopy, or magnetic resonance imaging (MRI) guidance. The agent damages the endothelium, causing thrombosis and subsequent scarring of the vascular cavities. This is why sclerotherapy is particularly effective for lesions that are technically difficult to remove entirely surgically. [66]

The choice of sclerosant depends on the depth, size, drainage, and anatomical location. Ethanol, sodium tetradicyl sulfate, ethanolamine oleate, and, increasingly, bleomycin are used in clinical practice. Ethanol is more potent and effective, but has a higher risk of complications. Bleomycin is less inflammatory and therefore particularly useful for cervicofacial malformations, the hand, forearm, and other "tight" spaces where it is important to reduce the risk of massive swelling, compression syndrome, and damage to surrounding structures. [67]

Improvement after sclerotherapy does not occur immediately. Pain and swelling may increase during the first 24 hours or even several days, due to induced thrombosis and inflammation within the lesion. Symptoms then gradually subside. Post-procedure pain relief, cold, elevation of the limb, and subsequent rehabilitation are important. If compression syndrome is suspected, immediate reassessment is required. For large malformations, treatment almost always requires multiple sessions. [68]

Surgical treatment is used when the lesion is small, accessible, well-demarcated, and does not involve critical structures, or when symptoms that interfere with function persist after other methods. Surgery is often part of a staged approach, that is, a multi-stage protocol with preliminary sclerotherapy. Such preparation can reduce blood loss and improve visualization. For certain types of lesions that respond poorly to sclerotherapy, resection may be preferable. However, surgery should not be performed as a "simple removal of the lichen lichen": without proper preoperative assessment, the risk of bleeding and recurrence is too high. [69]

Ablative methods are used in some patients. Cryoablation is considered an option for painful lesions resistant to sclerotherapy and can be performed under ultrasound, CT, or MRI guidance. In review data, the average lesion volume reduction was approximately 92%, pain reduction was approximately 77%, and overall clinical benefit was observed in most patients. Laser is sometimes used as an adjunct for superficial lesions, and high-intensity focused ultrasound under MRI guidance is showing promise in some centers. [70]

If the malformation is extensive, deep-seated, multiple, syndromic, or poorly accessible to local treatments, systemic therapy is considered. Sirolimus, an inhibitor of the mechanistic target of rapamycin (MORR) pathway, has been the most studied. A 2025 review found significant clinical benefit in patients for whom sclerotherapy and surgery were either impossible or insufficiently effective, and side effects were often reversible and mild. Earlier data from a European multicenter study also showed significant clinical improvement, although symptom recurrence is possible after drug discontinuation. [71]

The most recent approach is mutation-targeted therapy. For PIK3CA- and TEK-related lesions, alpelisib, an inhibitor of phosphatidylinositol 3-kinase alpha, is receiving increasing attention. A 2024 study of 25 patients with lesions resistant to conventional therapy showed improvement in all patients, with the median lesion volume, as measured by magnetic resonance imaging, decreasing by approximately 33.4% in PIK3CA-related lesions and by 27.8% in TEK-related lesions over 6 months. While this treatment should still be considered highly specialized and genetically targeted, it is precisely these approaches that likely represent the future of management of severe venous malformations. [72]

Table 8. Main methods of treatment of venous malformation

Method	When needed	Key benefits	Restrictions
Compression	Symptomatic lesions of the extremities	Reduces pain and swelling	Does not eliminate the source itself
Pain relief and anti-inflammatory therapy	Pain, inflammatory component	Improves well-being	Does not change the architecture of the malformation
Low molecular weight heparins	Coagulopathy, pain, perioperative preparation	Control of local coagulopathy	Individual selection is required
Direct oral anticoagulants	Selected patients with coagulopathy	A possible alternative to heparins	The evidence base is still accumulating.
Sclerotherapy	Most symptomatic lesions	The first invasive method of choice	Repeat sessions are often needed
Surgery	Small, accessible or resistant lesions	Can provide radical control	Risk of bleeding and recurrence
Cryoablation and other ablations	Refractory painful foci	Useful for certain localizations	Not available everywhere
Sirolimus	Extensive, severe, poorly operable forms	Systemic symptom control	Monitoring of side effects is necessary.
Alpelisib	Genetically confirmed forms associated with PIK3CA or TEK	Personalized approach	Highly specialized therapy

Basis for table: contemporary reviews, retrospective and prospective studies. [73]

Prevention

Congenital venous malformations cannot be completely prevented in most cases, as they develop during the development of the vascular system and are most often associated with sporadic mosaic mutations. Therefore, primary prevention is of limited importance. Secondary prevention—preventing pain, thrombosis, bleeding, and functional impairment—is far more important. [74]

For symptomatic lesions in the extremities, compression garments, rational physical activity, avoidance of prolonged immobility, and prompt treatment of episodes of pain and thrombosis are beneficial. For large malformations, especially those with high D-dimer levels, pre-procedural complication prevention should be planned in advance, rather than on the day of the procedure. [75]

Patients with a known venous malformation should avoid traumatic, unauthorized manipulations, unnecessary punctures, and cosmetic procedures without vascular evaluation. During pregnancy, rapid growth of the lesion, new bleeding, and increased pain, a re-evaluation should be promptly performed, as hormonal changes and thrombosis often alter the course of the disease. [76]

If the patient has multiple or familial forms, prevention also includes genetic counseling. Its goal is not to "prohibit pregnancy," but to explain the risk of inheritance, the likelihood of syndromic manifestations, and the rationale for current monitoring. For severe forms, complication prevention is almost always interdisciplinary. [77]

Forecast

The prognosis depends primarily on the size of the lesion, its depth, its relationship to critical structures, the presence of coagulopathy, and the genetic context. Small, localized superficial venous malformations can often be well controlled conservatively, with sclerotherapy, or limited surgery. However, even in such patients, the term "cure" should be used with caution: tissue may respond to hormonal changes and trauma years later. [78]

In large, diffuse forms, the prognosis is more functional than anatomical. In other words, the goal of treatment is to reduce pain, bleeding, and limitation of motion, even if part of the malformation remains. This approach is now considered more realistic and safer than attempting to completely remove a large lesion at any cost. [79]

The best prognosis typically occurs in patients who are referred to a specialized center early and receive planned, rather than episodic, treatment. Modern interdisciplinary approaches allow for better timing of sclerotherapy, surgery, anticoagulants, and systemic medications. This is especially important for cervicofacial, muscular, visceral, and syndromic forms. [80]

The prognosis is worsened by deep spread, recurrent thromboses, severe local coagulopathy, association with the deep venous system, syndromic variants, and late diagnosis. However, even in these situations, treatment options are greater today than 10-15 years ago, thanks to advances in imaging, safe sclerotherapy, and targeted agents. [81]

Table 9. What the forecast depends on most

Factor	Impact on prognosis
Small localized lesion	Usually a more favorable prognosis
Deep and diffuse damage	Higher risk of pain, relapse and multi-stage treatment
Local intravascular coagulopathy	Complicates procedures and the course of the disease
Involvement of critical areas	Higher risk of organ dysfunction
Early diagnosis in a specialized center	Improves the quality of disease control
Syndromic and multiple forms	More often requires complex long-term treatment

Basis for table: current reviews and consensus pathways. [82]

FAQ

Can a venous malformation go away on its own?
Usually not. Unlike an infantile hemangioma, a venous malformation does not spontaneously regress and usually persists throughout life, although the severity of symptoms may vary. [83]

Is this a tumor or cancer?
No. It is a congenital vascular malformation, not a malignancy. But it can be clinically serious due to pain, bleeding, coagulopathy, and dysfunction. [84]

Is surgery always necessary?
No. For most symptomatic lesions, the first invasive treatment is sclerotherapy, with surgery used selectively, often as part of a combined approach. [85]

Why get a D-dimer test if it's not deep vein thrombosis?
Because with a venous malformation, local thrombus formation and dissolution often occur within the lesion. An elevated D-dimer helps identify local intravascular coagulopathy and better prepare the patient for treatment. [86]

Is it possible to live without treatment if the malformation is small?
Sometimes yes, if there is no pain, growth, bleeding, or functional problems. But even small lesions require proper diagnosis and periodic evaluation, especially if symptoms change. [87]

When is genetic testing needed?
Most often, it's done for multiple lesions, a family history, a combination with tissue overgrowth, a syndrome, or when planning targeted therapy. For a single, small, superficial form, it's not always necessary. [88]

Are sirolimus and alpelisib already the standard?
Sirolimus is increasingly used for severe forms of cancer that are difficult to treat locally, and alpelisib is a promising targeted option for genetically defined subtypes. However, this treatment should be prescribed in experienced centers after a thorough assessment of the indications and risks. [89]

Key points from experts

Professor Anne Dompmartin, MD, PhD, Director of the Department of Dermatology at CHU University Caen Normandie, France, emphasized in the VASCERN materials she coordinated that the diagnosis of venous malformations should not be limited to the lesion itself, but should also classify patients into sporadic, single, multiple, familial, and syndromic subtypes. In practice, this means that in a patient with multiple lesions or an unusual phenotype, it is necessary to look not only for the local problem but also for the genetic context. [90]

Professor Laurence M. Boon, MD, PhD, is coordinator of the Vascular Malformation Center at Saint-Luc University Clinics, chair of ISSVA, and co-chair of VASCERN. Her clinical and organizational work consistently highlights the need for multidisciplinary care of patients with vascular anomalies. The key practical lesson: complex venous malformations cannot be treated piecemeal, with just one procedure or one specialty. A common strategy, imaging, coagulation assessment, and alignment of treatment goals are needed. [91]

Guillaume Canaud, MD, PhD, Professor at the Université Paris Cité and Hôpital Necker Enfants Malades, Head of the Translational Medicine and Targeted Therapies Unit. His work has shown that targeted inhibition of phosphatidylinositol 3-kinase alpha with alpelisib can reduce the volume and clinical severity of vascular malformations associated with PIK3CA and TEK. This is one of the strongest signals that the future of treatment for severe venous malformations will increasingly depend on the molecular profile, and not just on anatomy. [92]