Endotheliomas

ALSO KNOWN AS: Hemangioendotheliomas, hemangiosarcomas, angiosarcomas, hemangiomas, meningiomas

RELATED CONDITIONS: Soft-tissue sarcoma, benign tumors

DEFINITION: Endothelioma is a general term that describes malignant or benign neoplasms of endothelial tissuethe cells that line blood vessels or lymphatic channels. These tumors can arise in any part of the body and often are referred to by terms specific to their location. For example, meningioma or dural endothelioma is a type of benign brain tumor, hepatic angiosarcoma or hemangioendothelioma is a type of liver cancer, and hemangioma is a tumor that often develops on or just under the skin. All fall under the somewhat broader heading of soft-tissue sarcomas.

Risk factors: There are no identifiable risk factors for malignant endothelioma (angiosarcoma). However, several risk factors associated with soft-tissue sarcomas have been identified. These include exposure to chlorophenols in wood preservatives and phenoxyacetic acid in herbicides, exposure to ionizing radiation, and rare genetic predispositions in some families. Infantile hemangiomas do not appear to have a hereditary origin, and no known food, medication, or activity during pregnancy has been identified as a risk factor.

Etiology and the disease process: The etiology of malignant endothelioma is obscure, although tumors have been known to develop as complications from a preexisting condition. Lymphedema resulting from radical mastectomy may trigger the development of angiosarcoma, and radiation-induced angiosarcomas have developed many years following successful radiotherapy for visceral carcinomas and Hodgkin disease. Environmental carcinogens such as vinyl chloride and thorium dioxide have been shown to induce hepatic hemangioendothelioma. Once initiated in the lining of the blood vessels, the tumor spreads rapidly and builds its blood vessel network.

The causes of infant and neonatal benign hemangioma are also unknown. However, some studies have implicated estrogen signaling in hemangioma proliferation. Other studies suggest that an interaction between fetal skin and the maternal placenta may trigger tumor formation.

Incidence:  In 2024, the Mayo Clinic published that less than one percent of newly diagnosed cancers are soft-tissue sarcomas. Of these, only about two percent are classified as hemangiosarcomas or angiosarcomas. The annual incidence of soft-tissue sarcomas in the United States is approximately one to two cases per one million people. In 2024, the American Cancer Society projected 13,590 new diagnoses of soft tissue sarcomas would emerge. 7,700 would be in males and 5,890 in females. 5,200 fatalities were also anticipated. The most common types of sarcomas in adults would be undifferentiated pleomorphic sarcoma, followed by liposarcoma and leiomyosarcoma. Hemangiomas, on the other hand, are the most common benign childhood tumors, occurring in approximately four to ten percent of white childrenalthough they are much less prevalent in children of other races. They are common in twin pregnancies, and the incidence may be as high as 25 percent in premature infants weighing less than 1,000 grams. Female children are three to five times more likely to be affected than male children.

Symptoms: Symptoms vary greatly depending on tumor location. Soft-tissue sarcomas of the extremities usually present as painless swellings that grow moderately rapidly. Abdominal and thoracic endotheliomas may grow to large masses before detection. Neurologic symptoms may result from the compression of lumbar or pelvic nerves. In the case of liver, heart, or bowel tumors, organ function may be compromised as the tumors grow. Up to one-third of patients may present with anemia or other evidence of recent hemorrhage, including gastrointestinal bleeding, hemothorax, or persistent hematoma.

Infantile hemangiomas present a more predictable growth pattern. Although occasionally present at birth, most arise during the first few weeks after birth and grow rapidly over the next several months. This is followed by a gradual shrinking, which may occur throughout one to seven years. Regression is complete in 50 percent of children by age five and in essentially all children by age twelve.

Screening and diagnosis: Diagnosis of malignant endothelioma in most cases is based on surgical biopsy and direct histological examination of tumor tissue. The characteristic network of blood vessels usually provides an unambiguous identification. Screening tests for industrial workers exposed to vinyl chloride are available. Still, screening programs for people exposed to other environmental carcinogens are not generally available because of the rarity of this type of cancer. Staging of these tumors generally follows the guidelines established by the American Joint Committee on Cancer. These stages are based on the size of the tumor (T), the degree of spread to regional lymph nodes (N), and spread to distant lymph nodes and organs (metastasis, M), as well as its grade.

Treatment and therapy: Treatment of malignant endothelioma varies considerably depending on tumor location. However, surgical removal with wide marginstwo centimetersis recommended whenever possible. However, surgery may be inadvisable for a massive tumor or one extending into vital structures. In these cases and sometimes following successful surgery, chemotherapy, radiation therapy, or both are often recommended.

Most infantile hemangiomas disappear without treatment, often leaving no visible marks or scars. Occasionally, cosmetic surgery may be indicated in large affected areas. Oral corticosteroids may be prescribed, and the direct injection may treat small raised lesions of corticosteroids. In March 2014, the US Food and Drug Administration approved a pediatric formulation of propranolol hydrochloride (Hemangeol) for proliferating infantile hemangioma requiring systemic therapy. By 2021, concerns with propranolol had formed over negative impacts on average growth and development. A study published in the International Journal of Pediatrics the same year suggested that propranolol was well-tolerated and effective.

Pulsed dye laser therapy is deemed helpful in cases of incomplete resolution or flat, superficial lesions in cosmetically significant areas.

Prognosis, prevention, and outcomes: Malignant endotheliomas, like most soft-tissue sarcomas, are clinically aggressive, often challenging to treat, and have a high rate of local recurrence and metastasis. The prognosis is poor, with reported five-year survival rates generally less than 20 percent.

Bibliography

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