Cavernous hemangioma, also called cavernous angioma, venous malformation, or cavernoma, is a type of venous malformation due to endothelial dysmorphogenesis from a lesion which is present at birth. A cavernoma in the brain is called a cerebral cavernous malformation or CCM. Despite its designation as a hemangioma, a cavernous hemangioma is a benign (but not harmless) condition, not a malignant tumor, as it does not display endothelial hyperplasia. The abnormal tissue causes a slowing of blood flow through the cavities, or "caverns". The blood vessels do not form the necessary junctions with surrounding cells, and the structural support from the smooth muscle is hindered, causing leakage into the surrounding tissue. It is the leakage of blood (hemorrhage) that causes a variety of symptoms associated with the condition.
Symptoms People with this condition in the brain may or may not experience symptoms. Some complications of the condition are life-threatening or cause major disruptions to normal functioning. Dangerous seizures due to compression of the brain, bleeding inside the brain tissue, vision problems, difficulty with speaking or using words, memory loss, ataxia, or hydrocephalus can occur. Less serious symptoms may include headaches and weakness or numbness in the arms or legs, though these symptoms alone do not indicate a person has the condition. In the eye, it may cause disruption or damage to the extraocular muscles and optic nerve which may manifest as double vision, progressive proptosis, decreased visual acuity, or other vision changes. It can lead to partial or complete blindness. When the condition occurs in the liver it usually does not cause symptoms, but some may experience pain in the upper right abdomen, a feeling of fullness after eating only a small amount of food, decreased appetite, nausea, or vomiting.
In those with cerebral cavernous malformations about 50% have focal seizures and 25% have focal neurologic deficits, according to the location of the CCM.
Presentation Cavernous hemangiomas can arise nearly anywhere in the body where there are blood vessels. They are sometimes described as resembling raspberries because of the appearance of bubble-like caverns. Unlike capillary hemangiomas, cavernous ones can be life-threatening and do not regress.
Causes Most cases of cavernomas are thought to be congenital; however they can develop over the course of a lifetime. While there is no definitive cause, research suggests that genetic mutations cause the condition. Congenital hemangiomas that appear on the skin are known as either vascular or red birthmarks.
Familial cerebral cavernous malformations are known to occur. The mutations may be inherited in an autosomal dominant fashion or occur sporadically. Overall, familial disease is thought to be responsible for one-third to one-half of cases.Mindea SA, Yang BP, Shenkar R, Bendok B, Batjer HH, Awad IA (2006) Cerebral cavernous malformations: clinical insights from genetic studies. Neurosurg Focus; 21(1):e1. In the US, approximately 50% of Hispanic patients with cerebral cavernous malformations have a familial form. In contrast, the familial form of the condition accounts for only 10 to 20% of cases in Caucasians. The reason for this difference is not presently known.
Several genes – K-Rev interaction trapped 1 (ССМ1), malcavernin (CCM2) and programmed cell death protein 10 (ССМ3) – have been identified as having mutations thought to be related to these lesions. These genes are located at 7q21.2 (chromosome 7 long arm), 7p13 (chromosome 7 short arm) and 3q25.2-q27 (chromosome 3 long arm) respectively. These lesions are further discussed in the Online Mendelian Inheritance in Man site – the reference numbers are OMIM 116860, OMIM 603284 and OMIM 603285 respectively.
Variations
Cerebral cavernomas Symptomatic intracranial hemorrhage is the main concern in the clinical course of a CCM. A meta-analysis of individual patient data from 1,620 people with untreated lesions estimated the 5-year hemorrhage risk at 15.8% overall. The risk was lowest, at 3.8%, for lesions outside the brainstem in people who had not presented with hemorrhage or a focal neurological deficit, and highest, at 30.8%, for brainstem lesions in people who had. The two main predictors of future bleeding were presentation with hemorrhage or focal deficit and brainstem location; age, sex, and the number of lesions had no independent prognostic value.
A CCM may occur next to a developmental venous anomaly. People with an associated anomaly are less likely to present with hemorrhage, and their hemorrhage risk during follow-up is similar to that of people without one. Somatic mutations in MAP3K3 and PIK3CA have been identified in sporadic lesions; familial disease arises from germline mutations in the CCM genes. In 2025, an expert panel convened by the Alliance to Cure Cavernous Malformation published updated consensus guidelines for diagnosing and managing cavernous malformations of the brain and spinal cord.
The first industry-sponsored randomized Phase II trial of a drug therapy for symptomatic cerebral cavernous malformation, the SYCAMORE trial of the oral superoxide scavenger REC-994, met its primary endpoint of safety and tolerability in 2024, but the sponsor discontinued development in May 2025 after long-term extension results did not confirm early imaging and functional trends.
Liver cavernous hemangioma Cavernous hemangiomas are erroneously called the most common benign tumors of the liver. Usually one malformation exists, but multiple lesions can occur in the left or right lobe of the liver in 40% of patients. Their sizes can range from a few millimeters to 20 centimetres. Those over 5 cm are often referred to as giant hemangiomas. These lesions are better classified as venous malformations.
Eye cavernous hemangioma In the eye, it is known as orbital cavernous hemangioma and is found in women more frequently than men, most commonly between the ages of 20–40. This neoplasm is usually located within the muscle cone, which is lateral to the optic nerve. It is not usually treated unless the patient is symptomatic. Visual impairment happens when the optic nerve is compressed or the extraocular muscles are surrounded.
Mechanism There are several known causes for cavernous hemangiomas, but some cases are still unknown. Radiation treatment used for other medical conditions has been suggested to cause cavernous malformation in some patients. Hemangioma tumors are a result of rapid proliferation of endothelial cells and pericytic hyperplasia, or the enlargement of tissue as a result of abnormal cell division pericytes. The pathogenesis of hemangioma is still not understood. It has been suggested that growth factors and hormonal influences contribute to the abnormal cell proliferation. Cavernous liver hemangiomas are more commonly diagnosed in women who have been pregnant. As a result of this, it is believed that estrogen levels may play a role in the incidence of liver cavernomas. Genetic studies show that specific gene mutations or deletions are causes for the disease. The genes identified for cerebral cavernous hemangiomas (or malformations), are CCM1 (also KRIT1), CCM2 (also MGC4607, malcavernin) and CCM3 (also PDCD10). The loss of function of these genes is believed to be responsible for cerebral cavernous malformations. Furthermore, it is also believed that a "second hit mutation" is necessary for the onset of the disease. This means that having a mutation in one of the two genes present on a chromosome is not enough to cause the cavernous malformation, but mutation of both alleles would cause the malformation. Additionally, research on hemangiomas in general has shown that loss of heterozygosity is common in tissue where hemangioma develops. This would confirm that more than a single allele mutation is needed for the abnormal cell proliferation. KRIT1 has been shown to act as a transcription factor in the development of arterial blood vessels in mice. CCM2 has overlapping structure with CCM1 (KRIT1) and acts as a scaffolding protein when expressed. Both genes are involved with MAP3K3 and thus appear to be a part of the same pathway. CCM2 has been shown to cause embryonic death in mice. Lastly, the CCM3 gene has been shown to have similar expression to CCM1 and CCM2, suggesting a link in its functionality. no experiments have determined its exact function. The lack of function of these genes in control of a proliferative signaling pathway would result in uncontrolled proliferation and the development of a tumor. In 2018, it was theorized that proliferation of endothelial cells with dysfunctional tight junctions, that are under increased endothelial stress from elevated venous pressure provides the pathophysiological basis for cavernous hemangioma development.
In 2017 a team demonstrated that negative regulation of MAP3K3 (MEKK3), KLF2, and KLF4 are implicated in the pathogenesis of CCM. Additionally, they identified endothelial Toll-like receptor 4 (TLR4) and it's relationship with the gut microbiome as a driving factor in CCM formation.
Diagnosis
Gradient-echo T2WI magnetic resonance imaging (MRI) is the most sensitive method for diagnosing cavernous hemangiomas. MRI is such a powerful tool for diagnosis that it has led to an increase in diagnosis of cavernous hemangiomas since the technology's advent in the 1980s. The radiographic appearance is most commonly described as "popcorn" or "mulberry"-shaped. Computed tomography (CT) scanning is not a sensitive or specific method for diagnosing cavernous hemangiomas. Angiography is typically not necessary, unless it is required to rule out other diagnoses. Additionally, biopsies can be obtained from tumor tissue for examination under a microscope. It is essential to differentially diagnose cavernous hemangioma because treatments for these lesions are less aggressive than that of cancerous tumors, such as angiosarcoma. However, since MRI appearance is practically pathognomonic, biopsy is rarely needed for verification.
On ultrasound, cavernous haemangiomas in liver appear as homogenous, hyperechoic lesions with posterior acoustic enhancement. On CT or MRI scans, it shows peripheral globular/nodular enhancement in the arterial phase, with portions of attenuation of enhancing areas. In the portal venous phase, it shows progressive centripetal enhancement. In delayed phase, it shows retention of contrast. It shows a high signal on T2 weighted images.
Treatment Asymptomatic lesions may not require treatment but may need to be monitored for any change in size. A change in size of lesions in the nose, lips, or eyelids can be treated with steroid drugs to slow progress. Steroids can be taken orally or injected directly into the tumor. Applying pressure to the tumor can also be used to minimize swelling at the site of the hemangioma. A procedure that uses small particles to close off the blood supply, known as sclerotherapy, promotes tumor shrinkage and pain reduction; however, it is possible for the tumor to regrow its blood supply after this procedure. If the lesion caused by the cavernous hemangioma is destroying healthy tissue around it, or if the patient is experiencing major symptoms, surgery can be used to remove the cavernoma piecemeal. A common complication of the surgery is hemorrhage and the loss of blood. The hemangioma may also recur after its removal. Stroke or death is a possible risk.