A gastrointestinal hemorrhage is a potentially dangerous condition that warrants a quick diagnosis and decisive treatment. The vast majority of these bleeding events are due to either upper or lower gastrointestinal bleeding, and only 5% cannot be localized endoscopically[35
]. These bleeding events typically occur from the small intestine. The most common cause of small intestinal bleeding is a vascular abnormality such as angioectasia, followed by tumors and, more infrequently, small bowel ulcers and aortoenteric fistulas[36
]. Angiosarcoma of the small intestine is an extremely rare but potentially life-threatening cause of such bleeding.
Angiosarcomas typically occur in skin and superficial soft tissue, rather than in the gastrointestinal tract, and compromise < 2% of all sarcomas[37,38
]. Consequently, only 33 cases of small intestinal angiosarcoma have been reported in the English literature over the past 42 years (Table ).
Table 1 Literature overview: Angiosarcoma of the gastrointestinal tract (modified from Grewal et al and Policarpio-Nicolas et al)
The precise predisposing factors remain unknown. Exposure to vinyl chloride, thorotrast, arsene, and radiation have been associated with the pathogenesis[9,31,39-41
]. Of the 33 cases reported, 14 describe patients developing an angiosarcoma after being treated with radiation for a malignant tumor, including ovarian carcinoma[39,42
], ovarian dysgerminoma[40
], squamous cell carcinoma of the uterine cervix[43-46
], endometrial adenocarcinoma of the uterus[41,47
], and Hodgkin’s disease[48
]. The first report of an angiosarcoma of the small intestine after postoperative irradiation was published in 1979[39
]. That patient developed an angiosarcoma in the terminal ileum 8 years after irradiation for an ovarian carcinoma. Since then, 13 more angiosarcoma cases following radiation have been published (Table ). In one case, an angiosarcoma occurred after exposure to irradiation and polyvinyl chloride[31
], but predisposing factors could not be identified in the remaining 19 cases. The patient presented in this report also did not have any known malignancy or exposure to irradiation, vinyl chloride, or other chemicals known to induce angiosarcomas such as thorotrast or arsene.
Categorization by sex and age does not reveal any clear-cut distribution. The average age of patients with this type of angiosarcoma was 62 years (range, 25-87 years), and 18 patients were male and 15 were female (Table ).
The clinical manifestations of patients with angiosarcomas of the small intestine include lethargy, weakness, altered intestinal function, nonspecific abdominal pain, severe melena, anemia, acute abdominal signs and/or ileus symptoms, and even nonspecific chest pain (Table ). In 15 of the 33 cases, the patient had signs of gastrointestinal bleeding[30,31,37,49,50
], similar to the patient described in this report. This variability in clinical manifestations makes it even more difficult to reach a quick and correct diagnosis. Furthermore, currently available diagnostic modalities, including CT, capsule endoscopy, double-balloon enteroscopy, magnetic resonance imaging, and positron emission tomography-CT all fail to detect the bleeding site, let alone lead to a diagnosis.
Angiosarcomas are classified as well-differentiated, poorly differentiated, and epithelioid tumors. A histological diagnosis can be challenging because angiosarcoma of the small intestine shows high architectural and cytological variability. The epithelioid morphology is typical but can be easily confused with other entities such as a poorly differentiated carcinoma[4,47
]. Immunohistochemical expression analysis for the endothelial markers CD31, CD34, and factor VIII-associated antigen is crucial. The majority of cases listed in Table were positive for these antigens. Other antigens show limited relevance and can cause confusion with other carcinomas. There is some controversy about the relevance of cytokeratin, which has been reported positive by some authors[32,37,49,51
]. However, most authors have reported no such expression by intestinal angiosarcomas[29-31,48,52
The current therapy for angiosarcoma includes bleeding control and symptomatic therapy to stabilize the patient, followed by radical tumor resection.
Six patients in the literature received adjuvant chemotherapy[39,41,48,49,52
], and three patients were treated with combination chemotherapy and radiation[40,49,53
]. Adjuvant therapy with paclitaxel was intended in the present case; however, the patient died before starting chemotherapy. All adjuvant therapy protocols are generally empiric and based on studies of cutaneous angiosarcoma, as randomized clinical studies on gastrointestinal angiosarcomas are lacking due to their rarity. The first case published received combination chemotherapy consisting of doxorubicin, vincristine, dacarbazine, and cyclophosphamide, after operative resection of the terminal ileum. That patient survived 14 mo[39
]. Another combination therapy that has been used is doxorubicin and dacarbazine, which led to 5 mo survival after diagnosis[48
]. Monotherapy with doxorubicin showed survival of 21 mo, at which time the tumor was widely disseminated[41
]. Furthermore, thalidomide therapy was initiated as an experimental measure after operative resection in one case[52
]. That patient was still alive 1 year after the initial diagnosis. No recommendation can usually be made, but paclitaxel and/or thalidomide are currently commonly considered[52,54,55
]. The newest studies suggest administering doxorubicin and paclitaxel weekly for cutaneous angiosarcoma, which seem to provide longer progression-free survival[56-58
Despite all efforts, survival of patients with small bowel angiosarcoma is generally poor. Survival usually ranges from several days after surgical intervention to 2 years. The majority of patients die within 6 mo to 1 year after being diagnosed (Table ). Only two reported patients survived > 2 years after resection and adjuvant (radio-) chemotherapy[2,53
One major cause of this poor outcome seems to be that the diagnosis is difficult, and many tumors are diagnosed only in the late stages of the disease. Therefore, a quick diagnosis using endoscopy and imaging procedures, as well as fast and decisive surgical intervention and adjuvant chemotherapy are necessary.