Overgrowth-associated vascular anomalies – PROS, PTEN, PROTEUS: Sometimes there is excessive growth of bone and soft tissue in a child’s limb or body segment, associated with an arteriovenous malformation (AVM—an abnormal tangle of blood vessels connecting arteries and veins), and/or arteriovenous fistula (an abnormal connection between an artery and a vein). In most cases, an underlying genetic change causes the condition. For example, some individuals with Parkes Weber Syndrome (PWS), in which vascular anomalies such as AVMs and arteriovenous fistulas occur together with overgrowth of a limb, have a mutation of the RASA1 gene. Another example is PTEN-related conditions, where mutations of the PTEN gene are sometimes associated with both vascular malformations and a disproportionate growth of one part of the body. Patients with PIK3CA mutation related vascular anomalies often have features of overgrowth as well, known as (PROS), PIK3-related overgrowth syndrome. Specific treatments can be beneficial based on the underlying genetic causes.
Capillary malformation and associated syndromes: Sturge Weber syndrome; CM-AVM (RASA mutation): In addition to the above mentioned PTEN and RASA1-related syndromes, several other genetic disorders are also associated with vascular malformations. Capillary malformation-arteriovenous malformation (CM-AVM) syndrome, PIK3CA-related conditions, and hereditary hemorrhagic telangiectasia (HHT) are three of the more common ones we see in the clinic. Our team of experts can evaluate if there is an underlying genetic condition and then treat the manifestations based on that condition, with access to genetic counseling.
Lymphatic malformation & lymphatic disorders: A lymphatic malformation is a mass of abnormal lymphatic vessels. Lymphatic vessels are small canals that lie near blood vessels and help carry tissue fluids from within the body to the lymph nodes and back to the bloodstream.
Venous malformation (non-complicated and complicated): A venous malformation is a disorganized growth of veins, the blood vessels which normally return blood to the heart. Frequently venous malformations can be diagnosed clinically because of characteristic features: bluish color, soft texture, and compressible nature. Venous malformations generally decrease in size when elevated, and enlarge when placed in a gravity dependent position.
Vascular tumors
Benign lesions
Infantile hemangiomas: Sometimes called “strawberry marks,” infantile hemangiomas are the most common type of vascular tumor in infancy, affecting 5 percent of newborns. These benign growths are made of proliferations of cells that line the blood vessels. Girls and children with lighter skin or were premature have the highest risk of developing infantile hemangiomas. Infantile hemangiomas are often superficial; involve the skin of the head and neck, trunk, or extremity; and are bright red. However, some infantile hemangiomas occur in the subcutaneous tissues or internal organs, such as the liver; these appear bluish or have no overlying skin discoloration.
While they may be present at birth, most are not identified until 2 weeks of age, and deeper lesions may not be revealed until 3 months of age. During the first nine months of life, infantile hemangiomas enter a proliferative phase and grow rapidly. Between 9 and 12 months of age, infantile hemangiomas are usually stable and known as "plateaued" before they enter an “involuting phase,” in which they begin to shrink, fade and flatten. After 5 years of age, half of infantile hemangiomas are no longer visible. Those that remain, however, may have residual stains or deformity due to underlying scar tissue, that can be treated with a laser or surgery.
Most infantile hemangiomas are diagnosed by a history and physical examination. Ultrasound may be used to support the diagnosis. Less than 1 percent of infantile hemangiomas require biopsy. Ninety percent of children with infantile hemangiomas are treated with observation, topical therapies, or intralesional laser therapies, when the lesions are small and localized, and do not involve important areas. However, large infantile hemangiomas can cause significant problems in the proliferative phase when they are located near vital structures in the head and neck, or when they involve the liver, and they should be managed by a multidisciplinary group of vascular anomalies specialists.
Congenital hemangiomas: These benign vascular tumors form in utero and are present at birth. There are two types: rapidly involuting congenital hemangiomas (RICH) and non-involuting congenital hemangiomas (NICH). A RICH, as the name implies, involutes rapidly after birth. Half of them regress by 7 months of age and the other half involute by 14 months. Most congenital hemangiomas can be diagnosed by history and physical examination and are simply observed, requiring no treatment unless they are symptomatic. Treatments for problematic lesions include embolization or surgical resection to minimize scarring.
Pyogenic granulomas: Deep P6 can enlarge significantly and cause local destruction. These benign vascular tumors, also called lobular capillary hemangiomas, typically appear between the ages of 2 and 10 years as a solitary red skin lesion that grows rapidly and attach to skin via a stalk. Most of these lesions are less than 1 cm. Bleeding is common, and many pyogenic granulomas ulcerate and regrow. Diagnosis is made by history and physical examination, although biopsy may be indicated. Due to the risks of bleeding, ulceration and deformity, pyogenic granulomas should be removed.
Intermediate, locally aggressive lesions
Kaposiform hemangioendotheliomas (KHE): These are rare vascular tumors that are locally aggressive but do not metastasize to other parts of the body. Sixty percent are noted in the neonatal period, and 90 percent are diagnosed in infancy. Most KHE involve the skin, but they can also occur in the abdominal or chest cavities or in muscles and bones. Seventy-five percent of KHE are associated with a life-threatening phenomenon called Kasabach-Merritt, in which clotting factors are affected, resulting in hemorrhage. Most KHE are diagnosed by history and physical examination. MRI is used for diagnostic confirmation and to evaluate the extent of a tumor. Due to the degree of local invasion and risk of bleeding, surgery is rarely possible in KHE, and systemic therapies must be used. These include steroids, mTOR inhibitors and chemotherapeutic agents. A clinical trial open at Lucile Packard Children’s Hospital Stanford is currently recruiting patients with KHE to optimize therapies (NCT02110069).
Tufted angiomas (TA): Tufted angiomas are rare vascular tumors that are locally aggressive but do not metastasize to other parts of the body. They generally appear in infancy and early childhood, most commonly as a pink-red raised lesion on the trunk or an extremity. Like KHE, tufted angiomas are associated with Kasabach-Merritt, a life-threatening phenomenon in which clotting factors are affected, resulting in bleeding. Most TA are diagnosed by history and physical examination; however, MRI and biopsy may be needed to distinguish TA from KHE and other vascular tumors. Surgery may be used for symptomatic tumors that are localized, but systemic therapies such as steroids, mTOR inhibitors and chemotherapy can be used to treat diffuse or complicated lesions for which surgery is not an option.
Cutaneovisceral angiomatosis with thrombocytopenia (CAT): Also called multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT), these vascular tumors primarily affect young children. Most cases appear before 2 years of age, with red-brown skin lesions; however, tumors can also occur in the brain and spinal cord, lungs, gastrointestinal tract, liver, spleen, muscle and bone. CAT or MLT is associated with low platelet counts (called thrombocytopenia), which increases the risk of bleeding. History and physical examination may be insufficient for diagnosis, and therefore MRI and biopsy, when feasible and safe, are used for confirmation. Because these lesions spread, surgery is often not possible, and systemic therapies using steroids and chemotherapeutic agents, are required.
Malignant lesions
Angiosarcomas: These malignant or cancerous vascular tumors are extremely rare in the pediatric population. In children, they generally occur in the deep tissues and internal organs, including the mediastinum, liver and spleen. Tumors are often greater than 5 cm. It is very common for them to spread to lymph nodes in the colon area or the lungs. Biopsy is necessary for diagnosis, and imaging is required to determine the extent of the cancer. Despite treatment with surgery when possible, radiation and chemotherapy, mortality is unfortunately high.
Epithelioid hemangioendotheliomas (EHE): These are rare vascular tumors with an unpredictable clinical course. Lesions can occur in multiple locations, including the skin, lung, liver and bone. Biopsy is necessary for diagnosis, and imaging is required to determine the extent of the cancer. EHE may remain stable, grow slowly, or progress rapidly with metastases, and therefore treatment is based on the clinical behavior of the tumor. Enlarging or metastasizing lesions are treated with therapies including surgery when possible, radiation and chemotherapy.
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