Teaching Case
Breakages at YWHAE, FAM22A, and FAM22B loci in uterine angiosarcoma: A case report with immunohistochemical and genetic analysis

https://doi.org/10.1016/j.prp.2013.09.009Get rights and content

Abstract

Described herein is the first reported case of a uterine angiosarcoma with breakages at three loci, YWHAE (17p13), FAM22A (10q23) and FAM22B (10q22). A 62-year-old postmenopausal woman was found to have endometrial thickening of her uterus. An endometrial biopsy indicated a malignant, spindle cell neoplasm. A total hysterectomy with bilateral salpingooophorectomy was performed. Histologic examination of the uterine specimen showed a malignant tumor consisting of irregular rudimentary vascular channels and solid small nests diffusely infiltrating to the middle of the myometrial wall. The tumor cells were epithelioid, and displayed eosinophilic cytoplasm and vesicular nuclei in some areas of the tumor. Immunohistochemically, the tumor cells showed vascular differentiation; they were diffusely positive for CD31 and D2-40 but were negative for factor VIII and CD34. In the course of the procedure of differential diagnoses, we included fluorescence in situ hybridization analysis for detection of a FAM22B-YWHAE fusion gene resulting from t(10;17)(q22;p13), recently reported in a series of endometrial stromal sarcoma, and unexpectedly identified breakages at three loci, i.e. YWHAE (17p13), FAM22A (10q23) and FAM22B (10q22). Collectively, these findings suggest that abnormality in the loci of YWHAE, FAM22A and FAM22B, which are known to be associated with oncogenesis of endometrial stromal sarcoma, may contribute to the development of uterine angiosarcoma.

Introduction

Uterine sarcomas other than leiomyosarcomas and endometrial stromal sarcomas (ESS) are uncommon [1], [12]. In particular, uterine angiosarcoma is very rare, and fewer than 20 cases with sufficient immunohistochemical or electron microscopy findings have been reported in the medical literature over the past 20 years [3], [4], [10], [12], [13], [17]. Most patients were postmenopausal and generally presented with heavy uterine bleeding, weight loss, and a pelvic mass [3], [12], [13]. Uterine angiosarcomas are usually highly aggressive and extend beyond the uterus, sometimes recurring within weeks to months after the initial diagnosis [3], [12], [13]. Unfortunately, the oncogenesis of uterine angiosarcomas is unknown.

Tumor is caused by accumulation of genomic abnormalities, including single-nucleotide variations, copy number changes and fusion genes [8], [11], [14], [21]. Thus, their detection is of critical importance for fully understanding oncogenesis, improvement of diagnosis, as well as the development of novel therapeutics. Unfortunately, compared with hematological disorders, our knowledge of the karyotypic features of solid tumors is fragmentary at best. All solid tumors, benign and malignant, account for only 27% of the total number of cases with an abnormal karyotype reported in the literature [11]. However, to date, new technologies, including second-generation sequencer, have been shown to provide powerful methods to detect genomic abnormalities [21], and have confirmed that recurrent fusion genes characterize significant subsets of sarcomas [8], [11]. For example, a YWHAE-FAM22 fusion gene resulting from t(10;17)(q22;p13) was recently reported in a series of ESS [6], [7], [8]. During evolving this surveillance, we checked this fusion gene in the series of uterine mesenchymal tumors, including not only ESS but also others (data not shown). To date, contributory molecular alterations for uterine angiosarcomas have not been reported. In this article, we describe the first reported case of uterine angiosarcoma with breakages at three loci, i.e. YWHAE (17p13), FAM22A (10q23) and FAM22B (10q22), which is serendipitously encountered in the procedure of extended surveillance for uterine mesenchymal tumors.

Section snippets

Clinical summary

A 62-year-old postmenopausal woman sought medical advice because of uterine bleeding. A pelvic ultrasound revealed endometrial thickening (1.02 cm). An endometrial biopsy was positive for a malignant, epithelioid cell neoplasm. A computed tomography (CT) scan and magnetic resonance imaging examination performed at the time of hospitalization revealed a mass in the posterior wall of the uterus and no other mass lesion. A total hysterectomy with bilateral salpingooophorectomy was performed.

Histopathologic and immunohistochemical examination

All the tissues were fixed in 10% buffered formalin and embedded in paraffin after routine processing, sectioning, and staining with hematoxylin and eosin (H&E). Immunostaining was performed using antibodies for the following antigens: bcl-2 (DAKO, Glostrup, Denmark), CD10 (Leica Biosystems, Newcastle, United Kingdom), caldesmon (DAKO), calponin (DAKO), CD31 (DAKO), CD34 class II (DAKO), cyclinD1 (Nichirei, Tokyo, Japan), cytokeratin AE1/AE3 (DAKO), D2-40 (DAKO), epithelial membrane antigen

Pathologic findings in the uterus

The uterus weighed 140 g and measured 7.5 cm × 5.5 cm × 3.5 cm. The uterus contained an ill-circumscribed endometrial tan-gray mass measuring 3.0 cm at its largest dimension; another additional 4 nodules were found in the myometrium (Fig. 2a). The cervix and adnexa were unremarkable.

Histologic examination of the uterine specimen showed an endometrial malignant tumor diffusely infiltrating the endometrium, and this tumor invaded the half thickness of the myometrium (Fig. 2b); the tumor had an irregular

Discussion

Uterine angiosarcoma is very rare as compared with ESS or leiomyosarcoma [1], [12]. Microscopically, angiosarcoma contains incomplete vascular channels lined by atypical cuboidal cells and solid areas with atypical epithelioid cells that exhibit eosinophilic cytoplasm and round nuclei, and does not show the angiocentric pattern, which is commonly observed in epithelioid hemangioendothelioma. However, the microscopic recognition of angiosarcoma arising in the endometrium may pose diagnostic

Conflict of interest

The authors have no conflict of interest to declare.

Acknowledgments

We appreciate Ms. Kiyoko Nagura and Mr. Hisaki Igarashi for technical assistance. This case was presented at the Japanese Pathological Society Chubu Meeting on December 15, 2012, in Nagoya.

This contribution was supported, in part, by Grants-in-Aid for the U.S.-Japan Cooperative Medical Science Program; the National Cancer Center Research and Development Fund; Grant for priority areas from the Japanese Ministry of Education, Culture, Sports, Science and Technology [221S0001]; and Grants-in-Aid

References (21)

There are more references available in the full text version of this article.

Cited by (16)

  • Endometrial stromal sarcomas and related neoplasms: new developments and diagnostic considerations

    2018, Pathology
    Citation Excerpt :

    On that note, smooth muscle differentiation has not been seen in YWHAE-NUTM2A/B HGESS. Also, there has been a uterine angiosarcoma showing breakages at YWHAE, FAM22A, and FAM22B.124 However, both reports did not confirm the presence of a YWHAE-NUTM2A/B fusion transcript.

  • Epithelioid angiosarcoma arising in a uterine leiomyoma with associated elevated CA-125: A case report

    2017, Gynecologic Oncology Reports
    Citation Excerpt :

    Pelvic examination reveals an enlarged uterus presenting as a pelvic mass in almost all cases. Grossly, the majority of cases have been described as spongy and hemorrhagic masses which fill the uterine cavity and, by microscopy, diffusely infiltrate the myometrium (Suzuki et al., 2014; Cardinale et al., 2008; Konishi et al., 2007). In a minority of cases, the neoplasm is described as well circumscribed (Cardinale et al., 2008; Medina et al., 2001; Schammel and Tavassoli, 1998; Ongkasuwan et al., 1982).

  • NUTM2A-CIC fusion small round cell sarcoma: a genetically distinct variant of CIC-rearranged sarcoma

    2017, Human Pathology
    Citation Excerpt :

    Uterine HGESS is categorized as the primary uterine sarcoma with a phenotype of endometrial stromal cells and specific fusion genes of YWHAE-NUTM2A/B [11]. These fusion genes have never been found except for one reported case of uterine angiosarcoma [12]. To our knowledge, NUTM2A rearrangement is mostly limited to uterine HGESS, and the NUTM2A-CIC fusion sarcoma in our study is the first case demonstrating NUTM2A rearrangement in non–uterine sarcomas.

  • Primary epithelioid angiosarcoma of endometrium

    2023, Polish Journal of Pathology
  • Angiosarcoma of the Uterus: A Systematic Review

    2022, International Journal of Gynecological Pathology
  • Genetic variation of YWHAE gene—“Switch”of disease control

    2022, Journal of Central South University (Medical Sciences)
View all citing articles on Scopus
View full text