Journals | Policy | Permission

Journal of Clinical Medicine Research

Review

Volume 10, Number 4, April 2018, pages 294-301

Primary Small Intestinal Angiosarcoma: Epidemiology, Diagnosis and Treatment

Angiosarcomas are uncommon, aggressive mesenchymal sarcomas of endothelial cell origin with high mortality. It accounts for 1-2 % of soft tissue sarcoma. These tumors can arise from any location in the body due to the ubiquity of blood vessels and lymphatics, but most commonly found in skin and subcutaneous tissues [1]. There are cutaneous, visceral, and soft tissue subtypes of angiosarcomas, among which the visceral angiosarcomas comprise 15% to 47% of such neoplasms and are more difficult to diagnose than other subtypes [2-4]. Angiosarcomas have been reported in the breast, heart, lung, liver, spleen, adrenal glands, ovaries, and rarely in the gastrointestinal tract especially the small intestine, which have only been found in scattered case reports and small series [1, 5-45].

In addition to the rarity of the small intestine angiosarcoma, the nonspecific early clinical findings including nausea, vomiting, abdominal pain, gastrointestinal (GI) bleeding, anemia, fatigue, and weakness may further decrease the suspicion of such tumors and delay the diagnosis. The management of small intestine angiosarcomas would be improved by a better knowledge of such fatal neoplasms. We report a case of angiosracoma in the duodenum and jejunum in a 73-year-old man. In addition, the epidemiology, diagnosis, treatment modalities, and survival of small bowel angiosarcoma of previous reported cases are analyzed.

The previously reported cases before July 2016 of small intestine angiosarcoma were included in this study. The age, gender, symptoms on admission, anatomical locations, tumor markers used for diagnosis, subsequent therapies, and survival time of total of 47 cases are analyzed. There are two cases with indeterminate primary sites, one patient was found to have angiosarcoma in both skin and duodenum [5]; the other had operation on cardiac angiosarcoma 5 years before the diagnosis of the angiosarcoma in jejunum, and the authors thought the jejunal angiosarcoma as recurrent, however, a primary small bowel angiosarcoma is also possible after a 5-year interval since the diagnosis of the cardiac angiosarcoma [41]. The Wilcoxon two-sample test was used to compare the age distribution between male and female genders. The log-rank test was used to compare the survival times between different groups.

A 73-year-old man presented with chest pain, dyspnea, melena, weakness, and fatigue for 3 days, and melena for 7 days since the discharge from a prior 3-month-long hospitalization for GI bleeding. No fever, chills, abdominal pain, nausea, or vomiting was reported. During the previous hospitalization, patient had received multiple blood transfusions and undergone endoscopy and push enteroscopy that revealed Los Angeles Grade A erosive esophagitis, small sliding hiatal hernia, two erosions in the bulb, two cratered ulcers with adherent clots in D1 and D2, a fungating mass in D3. The biopsy of the mass showed acute-on-chronic inflammatory cells with granulation tissue. Patient had no prior radiation or polyvinyl exposure and no family history of GI malignancy. He was a former smoker. Vital signs were within normal limits on admission and physical exam showed a non-distended, non-tender abdomen with decreased bowel sounds and no organomegaly.

After admission, the patient received blood transfusions, and underwent multiple enteroscopy, with the biopsy from a bleeding ulcer in D3 revealed poorly differentiated high grade sarcoma. Subsequently, a pylorus-preserving pancreaticoduodenectomy was performed; the pathology demonstrated multiple ulcerated mucosal and submucosal nodules up to 1cm in size of high grade angiosarcoma involving duodenum and jejunum, and metastatic angiosarcoma in 10 of 14 peripancreatic and mesenteric lymph nodes. The positivity for CD34, vimentin, Wilm’s tumor-1, and vWF supported the angiosarcoma diagnosis. Postoperative chest computed tomography (CT) showed masses in both lungs highly suspicious for metastasis that was absent 1 month prior. Patient survived 16 days after surgery on mechanical ventilation before family decided to discontinue treatment.

There are 29 male and 18 female included in this study, the male to female ratio is 1.6:1. The ages of 18 female and 28 male patients are obtainable. The ages of female patients range from 25 to 85 years, with median value of 63.5 years; the ages of male patients range from 25 to 87 years, with median of 69.5 years (Fig. 1, Table 1). There was no significant difference in the age distributions between the two genders (n = 28 female vs. 18 male; P = 0.772, Wilcoxon two-sample test).

Click for large image

Figure 1. Age distribution in male and female patients of small intestinal angiosarcoma. There is no significant difference in age distribution between male and female genders (P = 0.677, Wilcoxon two-sample test, n = 28 and 18, respectively; the age of one male patient is missing).

Click to view

Table 1. Age and Gender Characteristics of Patients With Small Intestinal Angiosarcoma

The clinical symptoms and signs on initial presentation are nonspecific. The common clinical features (in descending order of frequency) include abdominal pain, anemia, GI bleeding, fatigue/weakness, weight loss, dyspnea, abdominal distension/bowel obstruction, anorexia, nausea/vomiting, acute abdomen, and bowel perforation (Table 2).

Click to view

Table 2. Symptoms and Signs in Patients With Small Intestine Angiosarcoma

The development of angiosarcoma has been related to history of radiation exposure, certain environmental toxins or foreign bodies, chronic lymphedema, and genetic factors [3, 4]. There are 17 patients who had previous radiation exposure, among which 16 with therapeutic radiation, one with a 30-year-long exposure to both occupational radiation and polyvinyl chloride. The onset of radiation exposure is available in14 cases, ranging from 3 to 30 years prior to the diagnosis of angiosarcoma, with median latency of 9.5 years. In addition, there was one case with hemodialysis for 21 years (Table 3). Therefore, based on the current data, previous heavy radioactive exposure is likely the most common preventable environmental risk factor for small intestinal angiosarcoma.

Click to view

Table 3. Risk Factor for Small Intestinal Angiosarcoma in Reported Cases

The location of the angiosarcoma in small bowel as reported were (percentage of the 47 cases, in descending order): ileum only (29.8%), jejunum only (27.7%), unspecified small intestine (23.4%), duodenum/jejunum (10.6%), duodenum only (4.3%), jejunum/ileum (2.1%) and duodenum/jejunum/ileum (2.1%) (Table 4). The jejunum and ileum are the most common locations for small intestinal angiosarcoma.

Click to view

Table 4. Location of Small Intestinal Angiosarcoma

Among the 47 patients reported, 26 had metastatic disease, three patients with stage III, and four patients with stage II, others indeterminate. The metastatic sites include liver (11/26, 42.3%), lung (11/26, 42.3%), peritoneum (5/26, 19.2%), spleen (4/26, 15.4%), bone (3/26, 11.5%), stomach (3/26, 11.5%), mesentery (3/26, 11.5%), two cases of kidney (2/26, 7.7%), abdominal wall (2/26, 7.7%) and retroperitoneal (2/26, 7.7%); and one case for each of these sites: brain, oropharynx, thoracic cavity, pleura, pancreas, omentum, gall bladder, urinary bladder, appendix and skin (1/26, 3.8%).

The diagnosis of small bowel angiosarcoma may be very challenging due to the non-specific clinical, radiological and histopathological features as seen in our and previously reported cases [1, 5-45]. Imaging studies including CT, magnetic resonance imaging (MRI), positron emission tomography (PET) scan, and ultrasound can be used to define the extent of abdominal angiosarcoma prior to operation. Endoscopy and enteroscopy help detect the source of bleeding. Although the biopsy done by endoscopy and/or enteroscopy may lead to the appropriate diagnosis, it may be overlooked initially as in our case. Surgical resection and subsequent immunohistochemical studies are therefore required for a definitive diagnosis [3, 4].

Histological characteristics of angiosarcoma may provide useful clues for diagnosis. Angiosarcoma can be classified into different subtypes based on the cytologic appearance: spindle-shaped endothelial cells, epithelioid with large rounded or polygonal cells, and pleomorphic or mixed phenotypes as in most angiosarcoma [21]. Areas of irregular anastomosing vasculature lined by atypical endothelial cells are readily identifiable in histology study. However, the existence of anaplasia in most of angiosarcomas makes it challenging to distinguish such tumors from other undifferentiated ones such as melanoma or carcinoma. Therefore immunohistochemistry is mandatory to establish the definitive diagnosis of angiosarcoma. Expression of endothelial markers CD31, CD34, von Willebrand factor (vWF), Ulex europaeus agglutinin 1 (UEA-1), Friend leukemia integration 1 (Fli-1), endothelin-1, vascular endothelial growth factor (VEGFR), and erythroblast transformation specific related gene (ERG) can help identify angiosarcomas, each with different sensitivity and specificity (Table 5, [2, 46-51]), among which the vWF, UEA-1 and CD31 are considered the most useful for the diagnosis of poorly differentiated cases [1].

Click to view

Table 5. Sensitivity and Specificity of Some Markers for Angiosarcoma Diagnosis [2, 46-51]

However, some of these markers may be lost due to progressive tumor dedifferentiation. Otherwise, epithelioid angiosarcoma may express cytokeratins, which makes it difficult to distinguish it from poorly differentiated carcinomas. Therefore, a number of other markers with different tissue specificity including lymphatic endothelial (lymphatic vessel endothelial hyaluronan receptor-1/Lyve-1 or podoplanin/D2-40), smooth muscle (desmin), neural (S100, SOX10), epithelial (keratin), stromal (CD117, DOG1), melanocytic (HMB-45, melan-A), human herpes virus 8 (HHV-8), and mesothelial (calretinin, CK5/6, HBME-1 and WT-1) can be used to distinguish angiosarcoma from other tumors such melanoma [3, 26, 48].

The markers used in the reported cases of small intestinal angiosarcoma are summarized in Table 6. Among which, collagen IV, a marker for basal lamina collagen has proven to be a powerful tool in the identification of endothelial neoplasm in combination with other markers [52]. Overexpression of vimentin, a marker for epithelial-mesenchymal transition, is linked to accelerated tumor growth, tissue invasion, and poor outcome [53].

Click to view

Table 6. Markers Used for Immunohistochemical Studies in Reported Cases

The expression of those endothelial markers is heterogeneous in different types of vessels of various organs [49, 54]. Also, unusual expression patterns and loss of endothelial markers are common findings in angiosarcomas [55]. Therefore, a combination of multiple markers may markedly improve the sensitivity and specificity in the diagnosis in challenging angiosarcoma cases (Table 7, [2, 50, 56-58]).

Click to view

Table 7. Markers Useful for Angiosarcoma Differentiation [2, 50, 56-58]

The treatment modalities are available in 45 patients with small intestinal angiosarcoma (Table 8), among which 31 patients underwent resection alone (26 cases with obtainable survival times); eight had resection/chemotherapy (seven with survival times); two with surgery/chemotherapy/radiation therapy (both with survival times reported); one patient received surgery, but it is unclear if other treatment modality was added subsequently (with survival time); one patient received chemotherapy only (with survival time); one had chemotherapy/radiation (with survival time), and one patient treated was Argon plasma coagulation (APC, with survival time), the treatment for two patients are unavailable (with survival time). The chemotherapy agents used as single or in combination are anthracycline (three cases), paclitaxel (three cases), dacarbazine (two cases), cisplatin (one case), thalidomide (one case), vincristine (one case), and cyclophosphamide (one case).

Click to view

Table 8. Therapeutic Modalities in Reported Cases

Among the 26 patients treated with surgery alone and included for survival analysis, 16 had metastatic disease at diagnosis, two with stage III, while the stages of the other eight patients indeterminate. Six out of the seven patients treated with surgery plus chemotherapy were found to have metastatic lesions at diagnosis, while the other one was indeterminate. Furthermore, almost all of the patients with metastatic small bowel angiosarcoma underwent surgical resection with or without additional treatment modalities: surgery alone (18/26, 69.2%), surgery plus chemotherapy (6/26, 23.1%), surgery plus chemotherapy and radiation (1/26, 3.8%), and only one patient was treated with APC (1/26, 3.8%).

The median survival times are obtainable for 41 patients (as reported or from personal communications). The median survival time is 150 days (range 9 to more than 3,720 days) days after diagnosis (Fig. 2a). The median survival times are 300 days for female (n = 15) and 120 days for male patients (n = 26), with no significant difference between the genders (log-rank test: z = 0.17; P = 0.86; Fig. 2b). The overall 1-, 2-, 3-, and 5- year survival rates are 36.6%, 14.6%, 12.2%, and 2.4% respectively. The survival rates are markedly lower than that of the primary soft-tissue sarcomas (5-year survival of 50-60%), and overall angiosarcomas (5-year survival of about 35%) [1].

Click for large image

Figure 2. (a) Survival analysis of patients with small intestinal angiosarcoma. (b) There is no gender difference in the survival times between male and female patients (0 = female, 1 = male; Log-rank test, z = 0.17, P = 0.86, n = 15 and 26, respectively).

The survival times in different treatment groups are further summarized (median survival time) as showed in Figure 3. There is a significant difference in the survival times between patients treated with surgical resection only (range 8 - 3,720 days; median 96.5 days, n = 26) compared with surgery/chemotherapy (range 150 - 1,080 days, median 420 days, n = 7; log-rank test, z = 2.2; P = 0.0275). Due to the small number of cases for other treatment modalities, only range and median survival times are provided here: surgery/chemotherapy/radiation (range 1,020 - 1,440 days, median 1,230 days, n = 2); upfront surgery but with unknown subsequent therapy (1,080 days, n = 1); chemotherapy only (median 120 days, n = 1); chemotherapy/radiation (540 days, n = 1), APC (42 days, n = 1); unspecified treatment (range 120 - 510, median 315 days, n = 2).

Click for large image

Figure 3. Survival times in different treatment groups. The survival time is longer in patients received resection/chemotherapy compared to that in patients underwent surgery alone (*P = 0.0275; Log-rank test; n = 7 and 26, respectively). The survival times in other treatment groups are not compared due to the limited case numbers. *Compared to treatment with patients treated with surgery only. APC: argon plasma coagulation; Chemo: chemotherapy; NA: the other modality not available; Rad: radiation therapy; Surg: surgery.

The incidence, risk factors, symptoms, diagnosis, treatment, and survival time of total of 47 cases of small bowel angiosarcoma reported in English literature are analyzed (including our case). Most of the patients demonstrated nonspecific GI symptoms upon initial presentation and at advanced cancer stages, which might contribute to the late diagnosis and resultant short survival time. The prompt diagnosis not only requires high index of vigilance, but the use of markers such as vWF, UEA-1, and CD31 [1]. The ages at diagnosis range from 25 - 87 years, with median of 68.5 years. Prior radiation exposure was reported in 36% of cases included, with a median latency of 9.5 years, suggesting a causal role of radiation in the carcinogenesis of small bowel angiosarcoma. The overall median survival time is 150 days. Although there is no significant difference in the survival time between the two genders, the median survival time in female seems to be longer than that of male patients (300 vs. 120 days, respectively; P = 0.86). The lack of statistical significance might be related to the small number of cases included.

Due to the rarity of the small intestinal angiosarcoma there remains a lack of randomized clinical trials and recommendations for the treatment. Generally the management includes initial control of anemia and bleeding followed by resection and/or chemotherapy. Surgery is the first line modality for localized resectable tumors, which may also be used for palliative relief in patients with metastatic disease. For localized angiosarcoma, complete radical resection (R0) with wide margins is the primary treatment of choice. However, involved margins (R1 or R2 resection) are common due to diffuse tissue infiltration, and often multifocal characteristics of angiosarcoma, which leads to a worse prognosis, therefore adjuvant radiation therapy may be employed. Radiation therapy alone is largely inadequate, and further radiotherapy is usually avoided for radiation-induced angiosarcomas. The role of neoadjuvant or adjuvant chemotherapy for angiosarcoma is unclear [1]. The adjuvant therapy regimens are generally empiric and based on the protocols for cutaneous angiosarcoma [17, 21, 31]. Neoadjuvant chemotherapy may be considered in patients with adequate functional status, while adjuvant chemotherapy can be continued in patients responding to initial neoadjuvant chemotherapy.

Although the evidence is limited, the metastatic angiosarcoma is primarily treated with cytotoxic chemotherapy. The drugs used for the treatment of angiosarcoma include paclitaxel, docetaxel, vinorelbine, sorafenib, sunitinib, and bevacizumab [59-65]. The recommended treatment for unresectable or stage IV intra-abdominal soft tissue sarcoma is to downstage the tumor first with combination chemotherapy, chemoradiation or radiation therapy, followed by subsequent treatment based on the resectability. If the tumor is resectable based on the imaging assessment, treatment with surgery, or preoperative radiation or chemotherapy then surgery may be used; if unresectable, palliative treatment with chemotherapy, radiation therapy, surgery for symptomatic control, supportive care can be considered, or observation in asymptomatic patients [65]. However, as described above, the vast majority of the patients with metastatic small bowel angiosarcoma underwent surgical resection with or without additional treatment modalities (25/26, 96.2%).

The addition of chemotherapy to surgery appears to have a survival benefit. The survival time in patients received surgery plus chemotherapy is longer than that in ones underwent surgery only (420 days, n = 7 vs. 96.5 days, n = 26, respectively; P = 0.0019). Although the survival may be affected by the disease stages at diagnosis, it is less likely to explain the difference described above, since a higher percentage of cases received surgery and adjuvant chemotherapy was metastatic (6 out of 7, 85.7%), in contrast to that treated with surgery only (16 out of 26, 61.5%). However, due to the small sample size, the difference in the survival times between those treatment groups may not reflect the true effects of the specific treatment modalities. Further studies are required to determine the optimal treatment strategy for this rare disease entity.

The information provided in this study would help the physicians, especially gastroenterologists, to better understand clinical feature and management of small intestine angiosarcoma and maintain a high level of vigilance, which is essential for the early recognition of this rare but fatal disease. Further studies are needed for the development of better approaches for prevention, early diagnosis, and effective therapy.

1. Young RJ, Brown NJ, Reed MW, Hughes D, Woll PJ. Angiosarcoma. Lancet Oncol. 2010;11(10):983-991.
   doi
2. Hart J, Mandavilli S. Epithelioid angiosarcoma: a brief diagnostic review and differential diagnosis. Arch Pathol Lab Med. 2011;135(2):268-272.
   pubmed
3. Juan CJ, Yu CY, Hsu HH, Chian CP, Huang GS, Fan HC, Chen CY. Visceral and nonvisceral angiosarcomas: Imaging features and clinical correlation. Chinese J Rad. 2000;25(5):183-189.
4. Lucas DR. Angiosarcoma, radiation-associated angiosarcoma, and atypical vascular lesion. Arch Pathol Lab Med. 2009;133(11):1804-1809.
   pubmed
5. Al Ali J, Ko HH, Owen D, Steinbrecher UP. Epithelioid angiosarcoma of the small bowel. Gastrointest Endosc. 2006;64(6):1018-1021.
   doi pubmed
6. Al-Daraji W, Husain E, Zelger BG, Zelger B. A practical and comprehensive immunohistochemical approach to the diagnosis of superficial soft tissue tumors. Int J Clin Exp Pathol. 2009;2(2):119-131.
   pubmed
7. Allison KH, Yoder BJ, Bronner MP, Goldblum JR, Rubin BP. Angiosarcoma involving the gastrointestinal tract: a series of primary and metastatic cases. Am J Surg Pathol. 2004;28(3):298-307.
   doi pubmed
8. Aitola P, Poutiainen A, Nordback I. Small-bowel angiosarcoma after pelvic irradiation: a report of two cases. Int J Colorectal Dis. 1999;14(6):308-310.
   doi pubmed
9. Berry GJ, Anderson CJ, Pitts WC, Neitzel GF, Weiss LM. Cytology of angiosarcoma in effusions. Acta Cytol. 1991;35(5):538-542.
   pubmed
10. Butron Vila T, Garcia Villar O, Alonso Garcia S, Bonachia Naranjo O, Perez Espejo G, Lomas Espadas M, Hidalgo Pascual M. Angiosarcoma in the small intestine. Apropos of a particular case. Hepatogastroenterology. 2005;52(64):1139-1142.
    pubmed
11. Chami TN, Ratner LE, Henneberry J, Smith DP, Hill G, Katz PO. Angiosarcoma of the small intestine: a case report and literature review. Am J Gastroenterol. 1994;89(5):797-800.
    pubmed
12. Chen JL, Mok KT, Tseng HH, Wang BW, Liu SI, Chen CW. Duodenal angiosarcoma: an unusual cause of severe gastrointestinal bleeding. J Chin Med Assoc. 2007;70(8):352-355.
    doi
13. Chen KT, Hoffman KD, Hendricks EJ. Angiosarcoma following therapeutic irradiation. Cancer. 1979;44(6):2044-2048.
    doi
14. Cilursu AM. Massive hemorrhage due to angiosarcomatosis diagnosed by intraoperative small bowel endoscopy. Endoscopy. 1991;23(4):245.
    doi pubmed
15. de Mascarenhas-Saraiva MN, da Silva Araujo Lopes LM. Small-bowel tumors diagnosed by wireless capsule endoscopy: report of five cases. Endoscopy. 2003;35(10):865-868.
    doi pubmed
16. Delvaux V, Sciot R, Neuville B, Moerman P, Peeters M, Filez L, Van Beckevoort D, et al. Multifocal epithelioid angiosarcoma of the small intestine. Virchows Arch. 2000;437(1):90-94.
    doi pubmed
17. Zacarias Fohrding L, Macher A, Braunstein S, Knoefel WT, Topp SA. Small intestine bleeding due to multifocal angiosarcoma. World J Gastroenterol. 2012;18(44):6494-6500.
    doi pubmed
18. Fraiman G, Ganti AK, Potti A, Mehdi S. Angiosarcoma of the small intestine: a possible role for thalidomide? Med Oncol. 2003;20(4):397-402.
    doi
19. Grewal JS, Daniel AR, Carson EJ, Catanzaro AT, Shehab TM, Tworek JA. Rapidly progressive metastatic multicentric epithelioid angiosarcoma of the small bowel: a case report and a review of literature. Int J Colorectal Dis. 2008;23(8):745-756.
    doi pubmed
20. Hansen SH, Holck S, Flyger H, Tange UB. Radiation-associated angiosarcoma of the small bowel. A case of multiploidy and a fulminant clinical course. Case report. APMIS. 1996;104(12):891-894.
    doi pubmed
21. Huntington JT, Jones C, Liebner DA, Chen JL, Pollock RE. Angiosarcoma: A rare malignancy with protean clinical presentations. J Surg Oncol. 2015;111(8):941-950.
    doi pubmed
22. Hwang TL, Sun CF, Chen MF. Angiosarcoma of the small intestine after radiation therapy: report of a case. J Formos Med Assoc. 1993;92(7):658-661.
    pubmed
23. Khalil MF, Thomas A, Aassad A, Rubin M, Taub RN. Epithelioid angiosarcoma of the small intestine after occupational exposure to radiation and polyvinyl chloride: a case report and review of literature. Sarcoma. 2005;9(3-4):161-164.
    doi pubmed
24. Kelemen K, Yu QQ, Howard L. Small intestinal angiosarcoma leading to perforation and acute abdomen: a case report and review of the literature. Arch Pathol Lab Med. 2004;128(1):95-98.
    pubmed
25. Knop FK, Hansen MB, Meisner S. Small-bowel hemangiosarcoma and capsule endoscopy. Endoscopy. 2003;35(7):637.
    doi pubmed
26. Liu DS, Smith H, Lee MM, Djeric M. Small intestinal angiosarcoma masquerading as an appendiceal abscess. Ann R Coll Surg Engl. 2013;95(1):e22-24.
    doi pubmed
27. Mohammed A, Aliyu HO, Liman AA, Abdullahi K, Abubakar N. Angiosarcoma of the small intestine. Ann Afr Med. 2011;10(3):246-248.
    doi pubmed
28. Maeyashiki C, Nagata N, Uemura N. Angiosarcoma involving solid organs and the gastrointestinal tract with life-threatening bleeding. Case Rep Gastroenterol. 2012;6(3):772-777.
    doi pubmed
29. Nanus DM, Kelsen D, Clark DG. Radiation-induced angiosarcoma. Cancer. 1987;60(4):777-779.
    doi
30. Navarro-Chagoya D, Figueroa-Ruiz M, Lopez-Gomez J, Nava-Leyva H, Alvarez-Ponce CE, Guzman-Sombrero G, Velazquez-Garcia J. Obscure gastrointestinal bleeding due to multifocal intestinal angiosarcoma. Int J Surg Case Rep. 2015;10:169-172.
    doi pubmed
31. Ni Q, Shang D, Peng H, Roy M, Liang G, Bi W, Gao X. Primary angiosarcoma of the small intestine with metastasis to the liver: a case report and review of the literature. World J Surg Oncol. 2013;11:242.
    doi pubmed
32. Ogawa S, Minowa O, Ozaki Y, Kuwatsuru R, Sumi Y, Maehara T. Small bowel intussusception caused by intestinal angiosarcomatosis: usefulness of MR enteroclysis with infusion of water through a nasojejunal catheter. Eur Radiol. 2002;12(3):534-536.
    doi pubmed
33. Ordonez NG, del Junco GW, Ayala AG, Ahmed N. Angiosarcoma of the small intestine: an immunoperoxidase study. Am J Gastroenterol. 1983;78(4):218-221.
    pubmed
34. Policarpio-Nicolas ML, Nicolas MM, Keh P, Laskin WB. Postradiation angiosarcoma of the small intestine: a case report and review of literature. Ann Diagn Pathol. 2006;10(5):301-305.
    doi pubmed
35. Selk A, Wehrli B, Taylor BM. Chylous ascites secondary to small-bowel angiosarcoma. Can J Surg. 2004;47(5):383-384.
    pubmed
36. Siderits R, Poblete F, Saraiya B, Rimmer C, Hazra A, Aye L. Angiosarcoma of small bowel presenting with obstruction: novel observations on a rare diagnostic entity with unique clinical presentation. Case Rep Gastrointest Med. 2012;2012:480135.
    doi
37. Su CC, Jin YT, Chien CH, Yu CY, Lin PW. Postirradiation angiosarcoma of the terminal ileum. Zhonghua Yi Xue Za Zhi (Taipei). 1991;48(2):147-152.
38. Suzuki F, Saito A, Ishi K, Koyatsu J, Maruyama T, Suda K. Intra-abdominal angiosarcomatosis after radiotherapy. J Gastroenterol Hepatol. 1999;14(3):289-292.
    doi pubmed
39. Takahashi M, Ohara M, Kimura N, Domen H, Yamabuki T, Komuro K, Tsuchikawa T, et al. Giant primary angiosarcoma of the small intestine showing severe sepsis. World J Gastroenterol. 2014;20(43):16359-16363.
    doi pubmed
40. Taxy JB, Battifora H. Angiosarcoma of the gastrointestinal tract. A report of three cases. Cancer. 1988;62(1):210-216.
    doi
41. Turan M, Karadayi K, Duman M, Ozer H, Arici S, Yildirir C, Kocak O, et al. Small bowel tumors in emergency surgery. Ulus Travma Acil Cerrahi Derg. 2010;16(4):327-333.
    pubmed
42. Usuda H, Naito M. Multicentric angiosarcoma of the gastrointestinal tract. Pathol Int. 1997;47(8):553-556.
    doi pubmed
43. Watanabe K, Hoshi N, Suzuki T, Suzuki T. Epithelioid angiosarcoma of the intestinal tract with endothelin-1-like immunoreactivity. Virchows Arch A Pathol Anat Histopathol. 1993;423(4):309-314.
    doi pubmed
44. Wolov RB, Sato N, Azumi N, Lack EE. Intra-abdominal "angiosarcomatosis" report of two cases after pelvic irradiation. Cancer. 1991;67(9):2275-2279.
    doi
45. Zemheria E, Engina P, Ozkanlia S, Ozemir IA. Primary angiosarcoma of small intestine presenting with intestinal perforation: a case report. J Med Cases. 2014;5(2):113-115.
    doi
46. Fanburg-Smith JC, Furlong MA, Childers EL. Oral and salivary gland angiosarcoma: a clinicopathologic study of 29 cases. Mod Pathol. 2003;16(3):263-271.
    doi pubmed
47. Folpe AL, Chand EM, Goldblum JR, Weiss SW. Expression of Fli-1, a nuclear transcription factor, distinguishes vascular neoplasms from potential mimics. Am J Surg Pathol. 2001;25(8):1061-1066.
    doi pubmed
48. Miettinen M, Lindenmayer AE, Chaubal A. Endothelial cell markers CD31, CD34, and BNH9 antibody to H- and Y-antigens - evaluation of their specificity and sensitivity in the diagnosis of vascular tumors and comparison with von Willebrand factor. Mod Pathol. 1994;7(1):82-90.
    pubmed
49. Ohsawa M, Naka N, Tomita Y, Kawamori D, Kanno H, Aozasa K. Use of immunohistochemical procedures in diagnosing angiosarcoma. Evaluation of 98 cases. Cancer. 1995;75(12):2867-2874.
    doi
50. Poblet E, Gonzalez-Palacios F, Jimenez FJ. Different immunoreactivity of endothelial markers in well and poorly differentiated areas of angiosarcomas. Virchows Arch. 1996;428(4-5):217-221.
    doi
51. Sullivan HC, Edgar MA, Cohen C, Kovach CK, HooKim K, Reid MD. The utility of ERG, CD31 and CD34 in the cytological diagnosis of angiosarcoma: an analysis of 25 cases. J Clin Pathol. 2015;68(1):44-50.
    doi pubmed
52. Schmidt D, von Hochstetter AR. The use of CD31 and collagen IV as vascular markers. A study of 56 vascular lesions. Pathol Res Pract. 1995;191(5):410-414.
    doi
53. Satelli A, Li S. Vimentin in cancer and its potential as a molecular target for cancer therapy. Cell Mol Life Sci. 2011;68(18):3033-3046.
    doi pubmed
54. Pusztaszeri MP, Seelentag W, Bosman FT. Immunohistochemical expression of endothelial markers CD31, CD34, von Willebrand factor, and Fli-1 in normal human tissues. J Histochem Cytochem. 2006;54(4):385-395.
    doi pubmed
55. Rao P, Lahat G, Arnold C, Gavino AC, Lahat S, Hornick JL, Lev D, et al. Angiosarcoma: a tissue microarray study with diagnostic implications. Am J Dermatopathol. 2013;35(4):432-437.
    doi pubmed
56. Gill R, O’Donnell RJ, Horvai A. Utility of immunohistochemistry for endothelial markers in distinguishing epithelioid hemangioendothelioma from carcinoma metastatic to bone. Arch Pathol Lab Med. 2009;133(6):967-972.
    pubmed
57. Kahn HJ, Bailey D, Marks A. Monoclonal antibody D2-40, a new marker of lymphatic endothelium, reacts with Kaposi’s sarcoma and a subset of angiosarcomas. Mod Pathol. 2002;15(4):434-440.
    doi pubmed
58. Lee KB, Lee HS, Lee HE, Park SY, Chung JH, Choe G, Kim WH, Song KY. Immunohistochemical characteristics of Kaposi sarcoma and its mimicries. Korean J Pathol. 2006;40:361-367.
59. Penel N, Bui BN, Bay JO, Cupissol D, Ray-Coquard I, Piperno-Neumann S, Kerbrat P, et al. Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX Study. J Clin Oncol. 2008;26(32):5269-5274.
    doi pubmed
60. Schlemmer M, Reichardt P, Verweij J, Hartmann JT, Judson I, Thyss A, Hogendoorn PC, et al. Paclitaxel in patients with advanced angiosarcomas of soft tissue: a retrospective study of the EORTC soft tissue and bone sarcoma group. Eur J Cancer. 2008;44(16):2433-2436.
    doi pubmed
61. Maki RG, D’Adamo DR, Keohan ML, Saulle M, Schuetze SM, Undevia SD, Livingston MB, et al. Phase II study of sorafenib in patients with metastatic or recurrent sarcomas. J Clin Oncol. 2009;27(19):3133-3140.
    doi pubmed
62. George S, Merriam P, Maki RG, Van den Abbeele AD, Yap JT, Akhurst T, Harmon DC, et al. Multicenter phase II trial of sunitinib in the treatment of nongastrointestinal stromal tumor sarcomas. J Clin Oncol. 2009;27(19):3154-3160.
    doi pubmed
63. Agulnik M, Yarber JL, Okuno SH, von Mehren M, Jovanovic BD, Brockstein BE, Evens AM, et al. An open-label, multicenter, phase II study of bevacizumab for the treatment of angiosarcoma and epithelioid hemangioendotheliomas. Ann Oncol. 2013;24(1):257-263.
    doi pubmed
64. Nagano T, Yamada Y, Ikeda T, Kanki H, Kamo T, Nishigori C. Docetaxel: a therapeutic option in the treatment of cutaneous angiosarcoma: report of 9 patients. Cancer. 2007;110(3):648-651.
    doi pubmed
65. National Comprehensive Cancer Network. Soft tissue sarcoma. Version 2.1.2017. Copy right© National Comprehensive Cancer Network. Inc., 2017, All right reserved.

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Journal of Clinical Medicine Research is published by Elmer Press Inc.