To the Editor: We describe a case of uterine carcinosarcoma, mainly composed of angiosarcoma as a mesenchymal element. The patient was an 82-year-old ...
Pathology International 2016
doi:10.1111/pin.12455
Letter to the Editor Uterine carcinosarcoma including angiosarcoma: A short case report
To the Editor: We describe a case of uterine carcinosarcoma, mainly composed of angiosarcoma as a mesenchymal element. The patient was an 82-year-old woman who complained of vaginal bleeding. Smear cytology of the endometrium did not detect any malignant cells. Magnetic resonance imaging and computed tomography of the pelvis revealed a mass in the anterior wall of the uterus. Total transabdominal hysterectomy and salpingo-oophorectomy were carried out. Grossly, the tumor occupied the almost whole myometrium without tumorous lesion at the endometrial surface, suggesting that it was of myometrial origin. The patient died 7 months after the operation, attributed to intra-abdominal neoplastic spread and multiple lung metastases. An autopsy was not conducted. The uterine cavity of the resected uterus was filled with bloody materials. The endometrium was thin with partial erosion with hemorrhage and necrosis. The cut surfaces of the uterus showed the thickened anterior wall with hemorrhagic nodules (Fig. 1a and Fig. S2d), and the tumor measured 5 × 6 × 4.5 cm in size. The tumor did not show a polypoid growth protruding into the uterine cavity, which is a typical feature of uterine CS.
Histologically, it was a biphasic tumor consisted of mesenchymal component mainly composed of angiosarcoma and epithelial component. The angiosarcoma were immunopositive for Factor VIII, CD31, CD34, and Erythroblast transformation specific related gene (ERG). Another mesenchymal component demonstrated features of undifferentiated sarcoma (Fig. S1). On the other hand, the epithelial component showed poorly differentiated carcinoma consisted of various-sized nests of polygonal cells with atypical round nuclei and eosinophilic cytoplasm, focally showed squamous differentiation positive for cytokeratin, p63 and p40 and negative for ER, PgR, synaptophysin, and chromogranin A by immunohistochemistry (Fig. S1). The tubular structures were immunoreactive for CEA and also contained Periodic-acid-Schiff stain and Alcian blue-positive secretion, suggesting glandular differentiation. Both the epithelial and mesenchymal components were immunohistochemically negative for hCG. The results of the immunohistochemical studies are summarized in Table S1. Venous invasion of the angiosarcoma was diffusely distributed in the myometrium, and the epithelial component also revealed vascular and lymphatic invasion. Transitions from the epithelial component to angiosarcoma were seen in several foci (Fig. S2a–c). For other findings, multiple adenomyotic foci were widely distributed throughout the myometrium and inside the tumor (Fig. 1b–d), leading to a diagnosis of carcinosarcoma associated with adenomyosis, FIGO Stage IIIC. Some of them had irregular architecture with nuclear enlargement. These
Figure 1 (a) Gross appearance of the resected uterus. The uterine anterior wall was enlarged and thickened. The endometrial surface was smooth, though partially erosive due to hemorrhage and necrosis. On the cut surface, a tumor with massive hemorrhage and necrosis, and multiple hematomatous nodules were observed. (b,c) Adjacent to the CS, adenomyosis was observed in the uterine myometrium. (c) High magnification of endometrial stroma surrounding the benign glands were shown (inset), which is immunopositive for CD10 and ER. (d) Atypical glands in the adenomyosis adjacent to the angiosarcoma were observed. The border between a part of the gland and angiosarcoma was unclear (pointed by arrow). © 2016 The Authors Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
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Letter to the Editor
atypical glands and the tumor cells of the CS were negative immunostaining for PTEN, while the normal endometrial glands and adenomyosis with no atypical glands were positive. We performed a genetic analysis of the PTEN, using the Vysis PTEN/CEP10 FISH probe (Abbott, Tokyo, Japan). The deletion of PTEN by FISH analysis was not found in any lesion. In addition, P53 and K-ras mutations were analyzed. Four minute targets representing normal tissue, adenomyotic lesion, carcinoma and sarcoma were sampled directly unstained sections, and genomic DNA was extracted from each representative lesion. Exons 5–8 of the p53 gene and exon 1 of the K-ras gene were examined by direct sequencing of PCR products. No mutation of the analyzed p53 and K-ras gene was detected in any lesion. The present case of uterine CS showed two unique aspects, the nature of the tumor's mesenchymal component and the location of the tumor. In this case, the mesenchymal component was mainly composed of angiosarcoma with focal undifferentiated sarcoma. This histological pattern is characteristic of the gross findings demonstrating hemorrhagic tumors closely resembling uterine choriocarcinoma, although the tumor did not include choriocarcinoma element. Only two cases of CS with angiosarcoma of the fallopian tube and ovary have been reported,1 and no cases of uterine CS have ever been reported to include angiosarcoma components. The several recent studies about CS have suggested the combination theory to explain the histogenesis of uterine CS by genetic analysis.2 But in this case, gene alterations such as p53, PTEN, K-ras were not detected in any lesion, which were reported to be associated with tumorigenesis in uterine endometrial cancer and other tumors. Another interesting aspect is the association between the CS and adenomyosis. Forty-four cases of malignant neoplasms or borderline malignancy tumors arising from uterine adenomyosis have been reported.3 However, CS arising from uterine adenomyosis is extremely rare.4 In the present case, the tumor growth was mainly within the myometrium, resulting in a thickening of the wall. In addition, the atypical epithelial cells in the adenomyosis adjacent to the CS were focally observed. CS of this case might arise from adenomyosis, but the histogenesis of this tumor was not demonstrated by genetic analysis. In summary, we report an unusual case of uterine CS with angiosarcoma component. This is the first report of uterine CS demonstrating mainly angiosarcoma as a mesenchymal component.
DISCLOSURE STATEMENT None declared.
Tomoko Uchiyama,1 Maiko Takeda,1 Kohei Morita,1 Tokiko Nakai,1 Masato Takano,1 Kinta Hatakeyama,1 Junko Takahama,2 Fuminori Ito,3 Hiroshi Kobayashi3 and Chiho Ohbayashi1 1 Departments of Diagnostic Pathology, 2Radiology, and 3 Gynecology and Obstetrics, Nara Medical University, Kashihara, Nara, Japan
REFERENCES 1 Lim BJ, Kim JW, Yang WI, Cho NH. Malignant mixed mϋllerian tumor of fallopian tube with multiple distinct heterologous components. Int J Gynecol Cancer 2004; 14: 690–3. 2 Wada H, Enomoto T, Fujita M et al. Molecular evidence that most but not all carcinosarcomas of the uterus are combination tumors. Cancer Res 1997; 57: 5379–85. 3 Kawamura K, Kaneki E, Ogawa S et al. Primary uterine mϋllerian mucinous borderline tumor (MMBT) associated with adenomyosis: A case report. Int J Gynecol Pathol 2014; 33: 146–50. 4 Kiuchi K, Hasegawa K, Kanamori A et al. Carcinosarcoma arising from uterine adenomyosis: A case report. J Obstet Gynaecol Res 2016; 42: 358–62.
SUPPORTING INFORMATION Additional Supporting Information may be found in the online version of this article at the publisher’s website: Figure S1 Microscopic appearance and immunohistochemical analysis of the CS. (a) Angiosarcoma. (b) Angiosarcoma was immunoreactive to ERG. (c) Undifferentiated sarcoma composed of atypical spindle cells. (d) For AE1/AE3, spindle cells were negative and epithelioid nests were focally positive. (e) The lesion with squamous differentiation in the epithelial component. (f) The majority of polygonal epithelial cells were positive for p40. (g) The lesion with glandular differentiation in the epithelial component. (h) Alcian blue-positive secretion in the epithelial component was observed. Figure S2 (a-c) These figures show transition between epithelial component and angiosarcoma. (d) The illustration of the distribution of the tumor and the adenomyosis on the cut surface. Table S1 Summary of immunohistochemical analysis.
© 2016 The Authors Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
