EA is a rare endothelial cell malignancy. Epithelioid endothelial cell tumors include epithelioid hemangioma, epithelioid hemangioendothelioma (EHE), and EA [17]. Epithelioid hemangioma is a benign tumor while EHE is a low-grade malignancy. EA is the least common type, and it is a high-grade malignancy characterized by atypical, multilayered or solid endothelial proliferation and a vasoformative architecture on microscopic findings. EA displays a greater degree of nuclear pleomorphism and mitotic activity than does EHE and frequently shows areas of necrosis [18-19]. Proposed criteria for distinguishing EA from other histopathological entities include a multilayered endothelium and an infiltrative growth pattern. Poorly differentiated angiosarcomas are best distinguished from other spindle cell sarcomas or carcinomas by immunohistochemistry. In particular, CD31 is the most sensitive endothelial marker [17-20].
Angiosarcoma may be difficult to diagnose because of its various clinical and pathological characteristics [2]. Differential diagnoses include hemangioma, pyogenic granuloma, Kaposi’s sarcoma, melanoma, and metastatic disease [14, 17-19]. In the present case, primary EA of the mandibular gingiva was initially diagnosed as pericoronitis involving the mandibular third molar. In addition, CBCT suggested a hyperplastic dental follicle or a dentigerous cyst, and there were no signs of malignancy in imaging studies. Generally, radiographic findings for angiosarcoma may include osteolytic changes with a mild periosteal reaction [21]. In these cases, although the lesion may have originated from bone tissue, a relatively well-defined margins may simulate a benign osteolytic lesion such as a cyst or an odontogenic tumor. There was a possibility that this tumor originated from bone tissue, however, the only clinical signs in the present case were gingival swelling and oozing, which is justified considering the origin of the tumor. The tumor enlarged rapidly after biopsy. Traumatic irritation by the antagonist teeth might accelerate the tumor growth, however, there is a possibility that this finding was due to the natural course of this rare aggressive tumor. Definitive diagnosis of angiosarcoma is challenging because of its rarity and clinical, radiographic, and histopathological resemblance to other diseases. Immunohistochemistry is generally required to identify this tumor, particularly the epithelioid and spindle cell types [2].
In immunohistochemistry, positive staining for factor VIII, CD34, and CD31, which are endothelial markers, indicates that the tumor has endothelial characteristics. The lesion in our patient showed positivity for factor VIII, CD31, and vimentin. In particular, CD31, a membrane glycoprotein that is important for endothelial cell-cell interactions and vascular adhesion of leukocytes, is considered the best marker for the endothelial phenotype, especially the poorly differentiated variant [22]. Our patient also exhibited a very high Ki67 index (>40%).
Most authors believe that surgery in combination with radiotherapy and/or chemotherapy offers the best chance of survival [17]. Angiosarcomas exhibit a strong tendency for local recurrence and metastasis [14]. These characteristics reflect the highly aggressive nature of this tumor. Our patient received postoperative adjuvant chemotherapy because of the aggressive preoperative course of the lesion. The prognosis of angiosarcoma is unfavorable, although the tumor size and site and the histopathological grade may influence survival [23]. In particular, a poor prognosis is associated with advanced age, larger tumors, the tumor location, and a Ki67 index of >10% [24]. Radical surgery should be performed as soon as possible for improvement of the prognosis [2].