Akiko Abe, MD, Department of Obstetrics and Gynecology, University of Tokushima, School of Medicine, 3-18-15, Kuramoto-cho, Tokushima 770-8503, Japan. Email: firstname.lastname@example.org
Endometrioid adenocarcinoma of the ovary coexists very rarely with yolk sac tumor (YST). This unusual mixed tumor is thought to be a rare variant of endometrioid ovarian carcinoma because of its aggressive behavior, lack of response to chemotherapy, and unfavorable prognosis. We report a case of ovarian endometrioid adenocarcinoma with a YST component in a postmenopausal woman. The patient was treated by surgery and a combination of bleomycin, etoposide, and cisplatin and taxol and carboplatin. She has been clinically free of tumor for 20 months. Immunohistochemically, the YST component reacted for alpha-fetoprotein. YST areas were negative for both CA125 and sex-hormone receptors. Cytokeratin7 and epithelial membrane antigen were negative in YST, but positive in endometrioid adenocarcinoma. The occurrence of this unusual case suggests that even somatic carcinomas may acquire an extraembryonal germ cell differentiation.
Yolk sac tumor (YST) is a malignant germ cell tumor characterized by endodermal differentiation(1). YST usually occurs in girls and young women, either in combination with other components in mixed germ cell tumor or alone in a pure form(2). Teilum(3) delineated five patterns of YSTs as microcystic, endodermal sinus, solid, alveolar–glandular, and polyvesicular vitelline. YST coexisting with a variety of histologic patterns have been described, but that with an epithelial malignant component is extremely rare(4). It has been suggested that this rare tumor represents an adenocarcinoma with aberrant differentiation because it occurs in the same age range as epithelial ovarian carcinoma (EOC) and shows an aggressive behavior and poor prognosis(5). Although chemotherapy is effective for pure YST(6), YST with endometrioid adenocarcinoma does not respond to chemotherapy(4).
We describe a case of an ovarian endometrioid adenocarcinoma with a YST component in a postmenopausal woman. The standard chemotherapy for YST consists of bleomycin, etoposide, and cisplatin (BEP), whereas that for EOC is a combination of taxane and platinum. The patient received three courses of BEP followed by three courses of taxol and carboplatin. She has been clinically free of tumor for 20 months.
A 52-year-old postmenopausal woman developed lower abdominal pain in January 2004. She consulted a doctor with complaints of increasing abdominal girth and severe abdominal pain on November 4, 2004, and referred to our clinic on November 8, 2004. A large unilateral pelvic mass and ascites were detected by computed tomography and magnetic resonance imaging. Computed tomography did not detect any sign of distant metastasis or lymphadenopathy. She underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, omentectomy, pelvic lymphadenectomy, and para-aortic lymphadenectomy. The ascitic fluid (600 mL) was hemorrhagic and positive for cytologic examination. The left ovary was replaced by a tumor, 10 cm in size, which was free of adhesions. Pathologic examination demonstrated endometrioid adenocarcinoma with a YST component confined to the left ovary without extraovarian spread. She was staged as pT1cNoMo.
Postoperative treatment consisted of three courses of BEP and three courses of taxol and carboplatin. We obtained two written consents before surgery and chemotherapy.
Before surgery, some of the tumor markers were elevated. Serum–fetoprotein: 24,518 (normal: <20 ng/mL), CA125: 8439 U/mL (normal: <35 U/mL), SLX(Sialyl Lex−i): 3379 U/mL (normal: <38 U/mL), and CA72-4: 138 U/mL (normal: <4 U/mL). The serum level of these markers declined rapidly after surgery, and remained within the normal range. The patient is alive with no evidence of disease for 20 months postoperatively.
The left ovarian tumor was 10 cm in diameter with a smooth outer surface. The cyst contained bloody serous fluid. There was a 7-cm solid tumor within the cyst with necrotic change and hemorrhage and many small papillary tumors inside the cyst.
The tumor consisted of two components: a well differentiated endometrioid adenocarcinoma with squamous differentiation and a YST component. The ratio between the YST component and the endometrioid adenocarcinoma was approximately 3:7. Many small papillary tumors inside the cyst consisted of a YST component. The predominant pattern of the YST component was reticular, and there were numerous hyaline globules and extracellular eosinophilic material (Fig. 1A). There was also a glandular pattern consisting of a single layer of atypical columnar cells (Fig. 1B). The endometrioid adenocarcinoma showed mature squamous metaplasia (Fig. 1C). The contralateral ovary was unremarkable as well as the fallopian tubes and the uterus. The pelvic and para-aortic lymph nodes were free of tumor. And there was no endometriosis in the resected organs except adenomyosis. Endometrium was atrophic and unremarkable.
Immunohistochemical stains were performed by the streptavidin–biotin method. The primary antibodies were alpha-fetoprotein (AFP) (DAKO Glostrup, Denmark), CA125 (Novocastra, Newcastle, UK), CA19-9 (DAKO Corporation), estrogen receptor (ER) (Immunotech, Marseille, Cedex, France), progesterone receptor (PR) (Immunotech), epithelial membrane antigen (EMA) (DAKO Corporation), and cytokeratin7 (CK7) (DAKO Corporation).
Immunohistochemical studies demonstrated that the YST component was positive for AFP, but negative for CA125, CA19-9, ER, PR, CK7, and EMA. In contrast, the endometrioid adenocarcinoma was stained diffusely positive for PR, CA125, CA19-9, CK7, and EMA, but it was negative for AFP and ER (Fig. 2). Ramalingam et al.(2) reported that CK7 and EMA were essentially negative in YST, but were positive in endometrioid adenocarcinoma. Both of these markers were negative in the YST component (Fig. 2). The IHC staining patterns differed between the two components, suggesting that this case was not an endometrioid variant of YST but an endometrioid adenocarcinoma with a YST component.
Between the two components, there was a transition area positive for AFP, CA125, CA19-9, ER, PR, CK7, and EMA. (Fig. 3).
We describe a rare case of ovarian endometrioid adenocarcinoma with a YST component occurring in a 52-year-old postmenopausal woman. YSTs rarely coexist with EOC. The clinicopathologic profile of YST arising in association with endometrioid adenocarcinoma differs from that of pure YST. The patients’ age ranges same as EOC, whereas YST usually occurs in young girls. Nogales et al.(5) reported that the patients’ age ranges from 31 to 73 years (average; 53). BEP regimen has generally been accepted for germ cell tumors(7). A case of mixed ovarian endometrioid tumor and YST, that recurred as pure YST, has been reported, and the author speculated that regimens for YST may be appropriate in these rare tumors(8). However, in previously reported cases that were treated by cisplatin-based chemotherapy, no objective response was observed in any of them(4,5). Therefore, in this case, we chose a combination of BEP and taxol and carboplatin. She has been clinically free for 20 months. Although no conclusion could be obtained from this case report, the fact that this particular tumor is more similar to EOC than YST in clinical behavior suggests that a combination of taxol and carboplatin should be compared with BEP. This case should be distinguished from the so-called endometrioid-like variant of YST because AFP is negative in the endometrioid component. The presence of ovarian clear cell carcinoma may be confused with the YST because the latter may have clear cells and glandular arrangements that mimic clear cell carcinoma. In this case, the tumor is distinguished from the clear cell carcinoma because of the presence of AFP, Schiller–Duval bodies, and negative staining for CK7 and EMA.
In our case, IHC demonstrated striking differences between the endometrioid adenocarcinoma and YST component. Whereas the former was positive for CA125 and PR, the YST areas were negative. The YST component was characterized by a glandular pattern positive for AFP, while the endometrioid adenocarcinoma component was negative. CK7 and EMA were essentially negative in YST, but positive in endometrioid adenocarcinoma as reported by Ramalingam et al.(2).
Ovarian endometrioid tumors with a YST component should be considered as a rare variant of endometrioid adenocarcinoma and distinguished from the so-called endometrioid-like variant of YST. Nogales et al.(5) reported that the development of extraembryonal germ cell tissue from tumors of somatic origin is a rare event in the female genital tract and occurs mainly in the aerodigestive and urinary tracts. Although the exact explanation for this biologic behavior is not known, four theories including the teratoma theory, retrodifferentiation, collision theory, and neometaplasia theory have been proposed(7–9).
Because of absence of other teratoma components, and the different histopathologic features of both endometrioid and YST components, it is difficult to explain this case by the teratoma theory. Whereas the yolk sac is an early endodermal derivative, EOC has the somatic nature of the endometrioid adenocarcinoma and is mesodermal in origin. Therefore it is unlikely that YST arose from endometrioid adenocarcinoma by retrodifferentiation. The collision theory is also unlikely because there was a transition zone between the endometrioid and YST component immunohistochemically. It has been suggested that somatic carcinomas have the ability to acquire a germ cell differentiation, and the germ cell component is thought to derive from somatic mesodermal cells and not from germ cells(4,5,8). This phenomenon could be explained by neometaplasia (aberrant differentiation), which appears to be the most reasonable theory to explain the histogenesis of this tumor.