Lesions harboring PIK3CA mutations are frequently associated with overgrowth of adjacent tissues, as seen in patients with Klippel-Trénaunay syndrome. In most cases, PIK3CA mutations are identical to canonical cancer mutations. Another one-third of venous malformations, and nearly all lymphatic malformations, are caused by somatic mutations in PIK3CA. Approximately one-third to one-half of venous malformations result from somatic or, rarely, germline mutations in the TEK (or TIE2) gene. Patients with low-flow malformations are the most likely to present for oncological treatment this will normally occur after conventional treatments have failed. Only a low level of evidence supports the choice of treatment between these options, and the recurrence rates for large lesions are relatively high. Ideally, a multidisciplinary vascular anomalies team is involved in the treatment of these patients. Treatment for patients with both high-flow and low-flow malformations is usually either surgery, endovascular intervention, or some combination of the two. Capillary malformations include port-wine stains and a number of less common lesions. In patients with large lesions, there is a risk of pulmonary embolism. The symptoms in patients with low-flow malformations most often relate to the bulk of the lesion, episodic thrombosis, or bleeding, which causes pain. Low-flow lesions may be venous, lymphatic, or mixed. High-flow lesions, arteriovenous malformations are the most aggressive type, but they are relatively rare. In the International Society for the Study of Vascular Anomalies (ISSVA) classification, vascular malformations are subdivided according to vessel type. Nonetheless, endothelial cells isolated from vascular malformations have been found in vitro to have some tumor-like behaviors, such as increased growth, migration, and resistance to apoptosis. They tend to grow in proportion to the child and are generally stable in adulthood. Vascular malformations are distinguished from vascular tumors by their low cell turnover and lack of invasiveness. Generally, vascular tumors are proliferative, while malformations enlarge through expansion of a developmental anomaly without underlying proliferation. Vascular anomalies are a spectrum of rare diseases classified as vascular tumors or malformations. Therefore, it is important for oncologists to have some understanding of the biology and clinical management of common vascular malformations.

While information about vascular malformations is covered at the beginning of this summary, the remainder of this summary focuses on neoplasms, not malformations.Īlthough not considered neoplasms, many vascular malformations are caused by targetable somatic mutations this discovery means that pediatric oncologists will be asked to be involved in management of these lesions.

Single site mutant protein turnover