Tumori, 93: 619-621, 2007
DUODENAL EPITHELIOID ANGIOSARCOMA: IMMUNOHISTOCHEMICAL AND CLINICAL FINDINGS. A CASE REPORT Chiara Mignogna1, Sara Simonetti1, Giuseppe Galloro2, Luca Magno2, Rossella De Cecio1, and Luigi Insabato1 1 Department of Biomorphological and Functional Sciences, Pathology Section, and 2Department of General Surgery, Special Section of Digestive Surgical Endoscopy, University of Naples “Federico II”, Naples, Italy
Angiosarcomas are uncommon malignant tumors of vascular endothelium that represent less than 1% of all sarcomas. The epithelioid variant of angiosarcomas is exceptionally rare, and the gastrointestinal tract is rarely involved. Angiosarcomas mainly involve skin and soft tissue and rarely occur in breast, liver, bone, and spleen. We present the case of a 30-year-old man who underwent an upper gastrointestinal endoscopy for melena. A
duodenal reddish polypoid lesion was found, which on microscopic examination turned out to be an epithelioid angiosarcoma. The immunohistochemical features of the lesion supported this diagnosis.The patient died eight months after the diagnosis. Epithelioid angiosarcoma is an aggressive variant of angiosarcoma and must be considered in the differential diagnosis of gastrointestinal tumors.
Key words: angiosarcoma, duodenal, epithelioid.
Introduction
Angiosarcomas are uncommon malignant tumors of vascular endothelium that represent less than 1% of all sarcomas1. They may vary from highly differentiated to high grade tumors, making them difficult to distinguish from carcinomas or melanomas. Immunohistochemical expression of endothelial markers such as CD31 and factor VIII could be useful to identify the vascular nature of the tumor. There is a variant, the socalled epithelioid angiosarcoma, that expresses also keratin, which makes the distinction from a carcinoma problematic2. Angiosarcomas mainly involve the skin and soft tissue and rarely occur in breast, liver, bone, and spleen3. Angiosarcomas of the gastrointestinal tract are exceptionally rare; they may arise in the esophagus, stomach, small intestine, appendix, and rectum4. The tumors are often multicentric from the outset and tend to have disseminated to the liver, omentum and peritoneum by the time they are detected. Here we describe a rare case of primary duodenal epithelioid angiosarcoma. Case presentation
In July 2003, a 30-year-old white man with a history of anemia was admitted to the gastroenterology unit of our university hospital presenting melena. Laboratory findings were hemoglobin 6.2 g/dL (normal range, 12-17.5 g/dL), red blood cells 2.3 x 106/µL (normal range, 4.2-5.6), hematocrit 19.2% (normal range, 3754), mean corpuscular volume 88.1 fl (normal range, 80-97), iron 18 µg/dL (normal range, 45-150), and erythrocyte sedimentation rate 45 mm/h.
Upper gastrointestinal endoscopy (UGE) (Olympus GIF Q140, Tokyo, Japan) was performed. A sessile polypoid lesion of 1 cm in diameter in the third part of the duodenum with an irregular surface and red-purple color was found (Figure 1A). The lesion was not bleeding at the time but showed signs of recent hemorrhage. Two days later a new UGE with polypectomy by crescent snare was performed, resulting in good control of hemostasis. A new dramatic hemorrhage presenting with melena occurred 6 days later. UGE showed bleeding from the base of the previously resected polypoid lesion. This was treated with argon plasma coagulation until complete resolution of the hemorrhage. A capsule endoscopy (Given M2A, Given Imaging, Ltd., Yoqneam, Israel) showed no other lesions in the jejunum and ileum. Histological examination revealed a malignant tumor with a destructive pattern ulcerating the surface epithelium (Figure 1B). It was composed of epithelioid cells with round to oval nuclei and huge nucleoli. The cells were prevalently arranged in a solid pattern, featuring epithelial growth (Figure 1C). Mitoses were seen but no necrosis was found. Immunohistochemically, the neoplastic cells were strongly positive for CD31 (Figure 1D), factor VIII (Figure 1E), and vimentin, and they were focally positive for keratin (Figure 1F). CD34, S-100 protein, and EMA were negative. Staging at the time of biopsy was T1, N0, M0; grade 3; stage II B5. Four months later a CT scan of the abdomen and chest showed irregular thickening of the posterior gastric wall below the esophagogastric junction, which was not separable from the homolateral crus. The scan also showed coarse consolidation of the left basal posterior
Correspondence to: Luigi Insabato, MD, PhD, Department of Biomorphological and Functional Sciences, Pathology Section, University of Naples “Federico II”, Via S Pansini 5, 80131 Naples, Italy. Tel +39-081-7463442; fax +39-081-7463475; e-mail
[email protected] Received September 25, 2006; accepted January 18, 2007.
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Figure 1 - A) A polypoid hemorrhagic lesion was found at upper gastrointestinal endoscopy. B) Polypoid tumor with ulceration of the surface epithelium (×40). C) Neoplastic cells showing epithelioid features. A gland is entrapped in the tumor (×400). D) Neoplastic cells strongly immunoreactive for CD31. Notice the negative glandular epithelium (arrow). E) Factor-VIII-positive immunostaining in tumor cells. Some negative glands are entrapped. F) Tumor cells were focally positive for keratin. The glandular epithelium serves as a positive internal control (arrow).
segment of the lung extending proximally to the bifurcation between the posterior-basal and lateral-basal bronchius; it was largely vascularized and inhomogeneous and had irregular edges. At this time disease stage was T2, N0, M0; stage III5. The patient refused surgical treatment and underwent radiotherapy treatment in another hospital; he died 4 more months later. No autopsy was performed.
Discussion
Although formerly regarded as a tumor of the elderly, an increasing number of angiosarcomas are being recognized in younger adults and even children3. The most frequent sites of involvement are skin and superficial soft tissue of head and neck (over 60%). Angiosarcoma of deep soft tissue is rare, and its typical presentation
DUODENAL EPITHELIOID ANGIOSARCOMA
consists of a deep-seated soft tissue mass located in the lower extremities6. Other, albeit smaller, clinical subsets have emerged, particularly a group arising in the abdominal cavity, which is often of the epithelioid type6,7. Interestingly, an epithelioid morphology was first described in cutaneous and thyroid angiosarcomas8,9, and successively reported in soft tissue. In a larger series of angiosarcoma of soft tissue the epithelioid morphology was described as the most frequently observed pattern6. The pure epithelioid variant of angiosarcoma in the gastrointestinal tract is extremely rare. There are scattered case reports and small series describing the epithelioid variant of angiosarcoma in the gastrointestinal tract10-12. Moreover, a small series of 3 cases of gastrointestinal tract angiosarcomas occurring many years after historic evidence of cutaneous Kaposi’s sarcoma was reported13. Here we report on the case of a young man with duodenal epithelioid angiosarcoma. This angiosarcoma variant is predominantly composed of large, epithelioid neoplastic endothelial cells, exhibiting abundant eosinophilic cytoplasm and vesicular nuclei with huge nucleoli. An epithelioid morphology can also be found in vascular tumors that vary considerably in their presentation and behavior. In 1979, authors initiated the controversies regarding angiolymphoid hyperplasia with eosinophilia, Kimura’s disease and epithelioid hemangioendothelioma, spindle cell hemangioendothelioma, epithelioid angiosarcoma, and epithelioid (bacillary) angiomatosis14. Likely a spectrum of lesions exists that includes benign lesions such as epithelioid heman-
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gioma, low-grade malignancies such as epithelioid hemangioendothelioma, and the highly aggressive epithelioid angiosarcoma. The latter is sometimes difficult to distinguish from epithelioid hemangioendothelioma. However, the presence of a solid growth pattern should be generally regarded as a diagnostic clue in favor of epithelioid angiosarcoma 3 . The distinction from metastatic carcinoma, melanoma, and proximal-type epithelioid sarcoma is based particularly on immunohistochemistry. Finally, epithelioid angiosarcoma may mimic the angiomatous variant of epithelioid sarcoma, both in morphology and by the occasional expression of cytokeratin. However, angiosarcoma is more pleomorphic and usually expresses CD31 and factor VIII. Endoscopically, the appearance of a polypoid, hemorrhagic lesion as in the present case could be confused with hemorrhagic necrosis of an adenocarcinoma. Very recently an intraperitoneal disseminated angiosarcoma developing in a capsule of a foreign body has been described15. Furthermore, a small intestinal angiosarcoma leading to perforation and acute abdomen16 and a case of angiosarcoma of the colon and rectum have been reported4. Epithelioid angiosarcoma is a very aggressive mesenchymal neoplasm with a poor prognosis. In the gastrointestinal tract it is very rare but if it does occur, it has a very aggressive growth pattern and symptoms, including the tendency to bleed. Pathologists should keep in mind the possibility of an angiosarcoma in the differential diagnosis of gastrointestinal tumors, even if the tumor is composed of epithelioid cells with a solid growth pattern.
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