On Uterine Angiosarcomas: 2 Additional Cases

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To the Editor:
We read with great interest the paper titled “Uterine Angiosarcoma: A Case Report and Literature Review” published in the May issue of 2016 1. We wish to report 2 additional cases of uterine angiosarcoma, including one with cytogenetic studies.
A 63-yr-old presented with postmenopausal bleeding. Magnetic resonance imaging showed cystic endometrial degeneration, and an endometrial biopsy contained only benign inactive endometrium. Her past medical history included myomectomies 30 and 2 yr prior. Hysterectomy and bilateral salpingo-oophorectomy with staging biopsies were performed. On gross examination the uterus weighed 1134 g and measured 18×15×14 cm, with distortion by >10 leiomyomata. There was a 14×7.5×5.0 cm intracavitary polypoid lesion with a fleshy, yellow-tan cut surface (Fig. 1A). A frozen section analysis on the polyp was reported as atypical stroma, cannot rule out carcinosarcoma. The polyp was examined in a total of 25 cassettes. Microscopically the stroma of the polypoid lesion showed a poorly differentiated malignant spindled cell proliferation, that in areas showed focal slit-like spaces, and anastomosing irregular vascular spaces lined by atypical cells (Fig. 1B). The tumor invaded 50% of the myometrium; tumor necrosis was <5%. The mitotic rate was 19/10 high-power fields. The background polyp was a benign endometrial polyp without evidence of adenosarcoma or adenocarcinoma. The cervix, tubes and ovaries, lymph nodes, and omentum were benign. The following immunohistochemical stains were positive: vimentin, CD31, CD34, D2-40, p16, ETS transcription regulator, cMYC, and BCL-1. The following stains were negative: CD10, CD117, desmin, pancytokeratin (AE1/AE3), epithelial membrane antigen, estrogen receptor, progesterone receptor, S-100, HMB45, chromogranin, synaptophysin, and CD56. Reticulin stain showed cords and groups of cells surrounded by reticulin fibers. Karyotyping revealed 46,X,t(X;12)(p22.1;q15)[5]/46,XX[15], that is a clone with X;12 translocation. The patient was treated with docetaxel and is disease-free at 1-yr follow-up.
The second patient presented at 61 yr of age with postmenopausal bleeding and underwent hysterectomy with bilateral salpingo-oophorectomy and bilateral pelvic node sampling. On gross examination, the uterus weighed 2034 g and measured 19.5×16×15 cm, and was distorted by numerous leiomyomata. There was a 15 cm dark-brown necrotic mass with a homogenous appearance involving the endometrial cavity but also extending to over 50% of the myometrial thickness (2.4 cm). Frozen section showed a high-grade malignant spindle cell neoplasm. Histologically, the lesion was composed of short spindle to oval cells with enlarged nuclei, coarse chromatin, and prominent nucleoli. There was brisk mitotic activity and extensive geographic tumor necrosis. Carcinomatous elements were not identified. In retrospect, a collection of ill-defined vascular channels and extravasated blood can be appreciated (Figs. 2A–C). Immunostains for ERG and CD31 were diffusely positive while cytokeratin AE1/AE3, CAM 5.2, EMA, D2-40, and CD10 were negative, supporting the diagnosis of angiosarcoma (Fig. 2D). The patient developed lung metastasis and died of disease 11 months after diagnosis, despite 6 cycles of chemotherapy with carboplatin and paclitaxel. This case was initially identified during a review of uterine sarcomas for a different project; performance of endothelial immunohistochemical markers (ERG, CD31, and D2-40) on 22 archived cases of uterine sarcomas (endometrial stromal sarcomas, leiomyosarcomas, and undifferentiated uterine sarcomas) to highlight areas of vascular invasion, yielded a case that was reclassified based on its diffuse expression of both markers 2.
Angiosarcomas primarily arising in the uterus are rare with 13 cases reported 1. We report 2 additional cases, 1 with a novel translocation (X;12)(p22.1;q15). This karyotype, to our knowledge, has not been previously reported in uterine or extrauterine angiosarcomas. The 12q15 chromosome locus includes HMGA2 and MDM2, 2 genes affected in sarcomas, in particular adipocytic tumors 3. HMGA2 gene rearrangements are also common in uterine leiomyomata, endometrial polyps, and vulvar aggressive angiomyxoma 4.
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