Small Intestinal Angiosarcoma Leading to Perforation and Acute Abdomen: A Case Report and Review of the Literature Open Access

The small intestine constitutes about 75% of the gastrointestinal tract, but only 1% to 1.6% of all gastrointestinal malignant tumors originate in this site. The 3 most frequent malignancies in the small intestine are neuroendocrine tumors, adenocarcinomas, and leiomyosarcomas.1 Angiosarcomas represent 1% to 2% of soft tissue sarcomas and most frequently occur in the subcutis. They may affect internal organs, such as the heart, liver, and spleen, and only rarely do they emerge in the gastrointestinal tract. Although their etiology is unclear, vinyl chloride, arsenic, and thorium dioxide exposure has been shown to be associated with angiosarcomas of the liver,2,3 and external-beam irradiation has preceded several reported cases of abdominal angiosarcomas.4–6 Similar to other malignant tumors of the gastrointestinal tract, intestinal angiosarcomas most often present with abdominal pain, gastrointestinal bleeding, and obstruction. The pathologic diagnosis may be a challenge, and immunohistologic markers are needed to differentiate the tumor from poorly differentiated carcinomas. We report a case of advanced ileal angiosarcoma with no previous exposure to radiation and with the unusual presentation of small bowel perforation and acute abdomen.

A 76-year-old Hispanic man presented at the emergency room with complaints of abdominal pain, poor appetite, and fatigue. He had been sick for several months with abdominal pain, anorexia, and weight loss. He denied vomiting, melena, rectal bleeding, or hematuria. His medical history included chronic anemia, duodenal ulcers, heart disease, hypertension, and diabetes. He had no history of abdominal surgery or radiation therapy. He did not smoke or consume alcohol.

Physical examination showed a thin, cachectic, chronically ill–appearing man in no apparent distress. He had a temperature of 38.3°C, heart rate of 107 beats per minute, respiratory rate of 20 breaths per minute, and blood pressure of 114/60 mm Hg. Significant findings were pale conjunctiva and epigastric tenderness with guarding.

Laboratory data showed a hemoglobin level of 5 g/dL, hematocrit of 16.8%, white blood cell count of 16 000/μL, platelet count of 233 × 10³/μL, albumin was low at 1.7 g/dL, prothrombin time was elevated at 15 seconds, and partial thromboplastin time was 30 seconds.

A computed tomographic scan of the abdomen and chest showed bilateral small pleural effusions and multiple small foci of ill-defined hypodensities in the liver (Figure 1). The spleen, gallbladder, and pancreas were unremarkable. The small intestine showed dilated loops with transitions to nondilated loops, suggesting an obstruction in the mid to distal small bowel. A small amount of ascites surrounded the liver and several small collections of apparent free air were evident within the abdomen (Figure 2).

An exploratory laparotomy revealed large amounts of free air and purulent fluid in the peritoneal cavity, a liver with multiple large masses, and multiple tumor nodules in the small intestinal wall and in the mesentery. An ileal segment showed a perforation. A loop of small intestine containing a tumor nodule was densely adherent to the bladder. The small bowel was mobilized from the bladder wall, resulting in penetration into the bladder. After the bladder wall was repaired, a 14-cm-long segment of small intestine was removed. The postoperative course was remarkable for bacterial sepsis, high demand for blood transfusions, and progressive deterioration of the patient's cardiorespiratory status. Because of the widespread metastatic disease and the patient's unstable condition, further surgical intervention was not considered. The patient's condition continued to deteriorate, and on the ninth day after surgery he died of cardiac arrest. Postmortem examination was not granted.

The pathology department received a 14-cm-long segment of small intestine showing a perforation measuring 2.5 × 2.0 cm. The overlying serosal surface was covered by yellow-green, fibrinopurulent exudate (Figure 3). Microscopic examination showed a malignant neoplasm in an area of perforation, which involved the full thickness of the intestinal wall (Figure 4). The neoplasm consisted of interlacing small vascular channels, spindle cells focally forming a sheetlike pattern, focal red blood cell extravasation, and extensive necrosis. There was evidence of vascular invasion, and 2 of 4 regional lymph nodes showed metastatic tumor (Figure 5).

Representative paraffin-embedded, formalin-fixed blocks were cut, and the tissue was stained using the streptavidin-biotin method with primary antibodies against cytokeratin 7 (Dako Corporation, Carpinteria, Calif), cytokeratin 20 (Dako), CAM 5.2 (Becton Dickinson, San Jose, Calif), S100 (Dako), factor VIII (Dako), Ulex europaeus (UEA-I; Sigma, St Louis, Mo), CD34 (Dako), and CD31 (Dako). The tumor cells showed diffuse strong positive reaction with the CD31 marker (Figure 6). Staining with all other antibodies was negative. These results support the diagnosis of an angiosarcoma.

Angiosarcomas of the gastrointestinal tract are rare and their actual incidence is unknown. In a review of 106 cases of gastrointestinal vascular tumors seen at the Mayo Clinic between 1925 and 1944, only 14 angiosarcomas were found. These tumors were distributed as follows: 7 in the stomach, 3 in the small intestine, 2 in the rectum, 1 in the esophagus, and 1 in the appendix.7 More recent reviews on primary tumors of the small intestine have occasionally reported rare cases of gastrointestinal angiosarcomas.8 

The association between angiosarcomas and certain toxic substances or previous external-beam radiation therapy is well documented. Occupational exposure to vinyl chloride, thorotrast, or arsenic was shown to increase the incidence of angiosarcomas of the liver.2,3 The majority of the reported gastrointestinal angiosarcomas followed previous radiation therapy, given either for malignancy (most commonly carcinoma of the cervix or ovary) or for benign lesions, such as eczema or lymphangioma. The dose of prior radiation ranged from 4000 to 8000 rad, and the median time of development of the angiosarcoma was 12.5 years (range, 2.5–50 years).9,10 Postradiation angiosarcomas have been described in the omentum, small intestine, colon, and in the form of diffuse angiosarcomatosis of the entire abdomen.9–11 In addition, foreign bodies were shown to be associated with angiosarcomas in extra-abdominal sites and in the colon.12,13 

Clinically, small intestinal angiosarcomas usually present with gastrointestinal bleeding and/or intestinal obstruction.14 Because of the anatomic location of the small intestine, the identification of the bleeding source is difficult. The conventional diagnostic methods, such as endoscopy, barium studies, and even technetium 99m–labeled erythrocyte scan, might leave the examiner without an answer, and visceral angiogram or laparotomy might be necessary to establish a diagnosis.

We report a case of advanced small intestinal angiosarcoma with the unusual presentation of intestinal perforation and acute abdomen. The patient had no history of toxic exposure or radiation therapy. At the time of the surgery, the disease appeared to be widespread. Several tumor masses were noted in the wall of the ileum, and multiple nodules were scattered through the mesentery. The liver showed multiple masses, suggestive of a metastatic tumor. Because tumor was seen in the wall of small intestine but no other gastrointestinal organ, the primary site of the angiosarcoma was most probably the ileum. The multifocality of the neoplasm does not rule out a primary ileal tumor, as multifocal angiosarcomas have been described previously in the small intestine.6,15 Metastatic involvement of the ileum with another gastrointestinal primary site, however, cannot be excluded.

The identification of gastrointestinal angiosarcomas is a challenge for the pathologist. They can be mistaken for a poorly differentiated carcinoma, lymphoma, or malignant melanoma. Immunohistologic stains are mandatory to establish a diagnosis. The classic microscopic appearance of the tumor is a network of anastomosing, delicate vascular channels lined by atypical endothelial cells. Some of these channels may contain erythrocytes. In many cases, the pattern is obscured by solid sheets of spindle, epithelioid, or undifferentiated cells; spilled erythrocytes; and necrosis. The typical immunohistologic pattern is positivity for vimentin and endothelial markers (eg, factor VIII–related antigen, UEA-I, CD31, and CD34), and negativity for the epithelial markers keratin and epithelial membrane antigen.4 The existence of the so-called epithelioid angiosarcoma, a variant consisting of large, plump, polygonal cells showing little architectural differentiation, positivity with keratin, and similarity to undifferentiated carcinomas, makes the differential diagnosis even more difficult.6,15 In our case, the pattern of immunohistologic staining of the tumor was unusual. The epithelial markers were negative, as were the majority of endothelial stains. Factor VIII–related antigen, UEA-I, and CD34 failed to stain the tumor cells, and only CD31 gave a positive result, supporting the diagnosis of angiosarcoma. These findings suggest that angiosarcomas might show different levels of differentiation and an individual pattern of expression of endothelial markers.

In summary, even though angiosarcomas of the small intestine are rare, they should be taken into consideration in cases of small intestinal perforation or severe gastrointestinal bleeding, especially in an elderly patient. The pathologic diagnosis of these malignant tumors requires immunohistochemical investigations. A broad panel of endothelial markers might be necessary to establish a diagnosis.