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Malignant Ovarian Germ Cell Tumors in Postmenopausal Patients: the Royal Marsden Experience and Literature Review

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Malignant Ovarian Germ Cell Tumors in Postmenopausal Patients: the Royal Marsden Experience and Literature Review ANTICANCER RESEARCH 35: 6713-6722 (2015) Malignant Ovarian Germ Cell Tumors in Postmenopausal Patients: The Royal Marsden Experience and Literature Review STERGIOS BOUSSIOS1, AYOMA ATTYGALLE2, STEVE HAZELL2, MICHELE MOSCHETTA1, JENNIFER MCLACHLAN1, ALICIA OKINES1 and SUSANA BANERJEE1 1Gynaecology Unit, The Royal Marsden NHS Foundation Trust, London, U.K.; 2Department of Histopathology, Royal Marsden Hospital, London, U.K. Abstract. Background: Ovarian germ cell tumors (OGCT) components, or alone as a pure YST (3). The majority of account for 2-5% of ovarian malignancies, with an annual patients reported with YST are under 30 years of age (4). As incidence of 1:100,000, and typically occur in young germ cells are not histologically identified in the ovaries of women and adolescents. The yolk sac tumor (YST) is the postmenopausal patients, an origin of YST from germ cells is second most common subtype of OGCTs and has an most unlikely in this age group. aggressive phenotype. Their rarity in postmenopausal Four theories describing the pathogenesis of women has the potential to cause initial diagnostic postmenopausal YST have been described: the teratoma uncertainty and lead to delayed or sub-optimal treatment. theory, retrodifferentiation, the collision theory, and the In this article, we report two cases. The first case is a 67- neometaplasia theory (5-7). Neo-metaplasia, also called year-old woman with a pure YST and the second refers to a aberrant differentiation, refers to carcinomas having the 59-year-old patient with YST with neuroendocrine capability for germ cell differentiation, and the germ cell differentiation. We also review and summarise the current component is thought to derive from somatic mesodermal literature. Discussion: YSTs in older women, either in cells rather than germ cells (8). The majority of YSTs in association with ovarian epithelial tumors or without an postmenopausal patients are associated with epithelial identifiable epithelial precursor, are a challenging clinical ovarian carcinoma and appear to be associated with a situation. The disease is aggressive and the outcome poorer outcome. Endometrioid carcinoma is the commonest remains poor. Thirty-seven cases, including the two reported precursor lesion and is usually associated with an reported in this article, have been described in the endometriotic cyst. The stage of disease and the presence literature to date. 12/ 37 described patients with malignant of elevated tumor markers at diagnosis correlate with OGCTs died within 8 months of diagnosis. Conclusion: prognosis. Most reported patients died within 8 months of Ovarian cancer with a YST component in postmenopausal diagnosis and only a few cases of mainly mixed YSTs were women has an aggressive behaviour and adjuvant platinum- disease-free more than 2 years from the diagnosis. The based chemotherapy should be considered. immunohistochemical markers which are most useful in the differential diagnosis of these cases are α-foetoprotein Ovarian germ cell tumors (OGCTs) comprise approximately (AFP) and sal-like protein 4 (SALL4), which are positive 15% to 20% of all ovarian neoplasms and 2% to 5% of all in YST and negative in primary ovarian or metastatic ovarian malignancies (1). The most common forms of intestinal carcinomas. Glypican-3, which also stains some malignant OGCTs are dysgerminoma, yolk sac tumor (YST) clear cell carcinomas, is thus less useful in the differential and immature teratoma (2). YSTs usually occur in young diagnosis. women, either occurring in combination with other In this study, we report two cases of YST in post menopausal women and also review and summarise the current literature on this topic. A PubMed search was carried out for eligible articles Correspondence to: Dr. Susana Banerjee MBBS MA RCP, Ph.D., published from January 1976 until December 2014 using The Royal Marsden NHS Foundation Trust, Gynaecology Unit, combinations of the following free-text key words: Yolk sack Fulham Rd, London, SW3 6JJ, United Kingdom. Tel: +44 tumors, ovarian germ cell tumors, postmenopause, AFP. 2086613979, e-mail: [email protected] Original articles, review articles and case reports were Key Words: Yolk sac tumor, ovarian germ cell, postmenopausal, included. The references cited in these articles were also α-fetoprotein. reviewed. 0250-7005/2015 $2.00+.40 6713 ANTICANCER RESEARCH 35: 6713-6722 (2015) Case Reports Case 1. A 67-year-old woman presented with a 2-month history of lower abdominal discomfort, and an abdominal mass was palpable on examination. Family history included her father being diagnosed with colorectal cancer and brother with bladder cancer. She had no children, had never taken hormone replacement therapy and was an ex-smoker, having stopped 35 years earlier. Magnetic resonance imaging (MRI) demonstrated a pelvic mass inseparable from the left ovary which was compressing the uterus, peritoneal deposits, free fluid in the pelvis and upper abdominal disease in the splenic hilum. Preoperatively, cancer antigen 125 (Ca125) was raised (700 U/ml), and AFP was not tested. The patient underwent primary debulking surgery with total abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy (BSO), pelvic lymphadenectomy, appendectomy, and partial omentectomy and peritonectomy without macroscopic residual disease. Surgical findings included a mass arising from the left ovary with involvement of the rectum and pelvic peritoneum. Histopathological findings. The initial pathological examination reported this tumor to be a high-grade clear cell carcinoma affecting the left ovary. Upon review at our Institution, the histological diagnosis was revised to a YST with metastatic deposits in the rectum, both parametria and sigmoid mesentery. Most of the right ovary had a glandular morphology whilst other areas showed solid and papillary patterns (Figure 1). A few perivascular formations (Schiller- Duvall bodies) were identified. There was abundant periodic acid-Schiff (PAS)-positive diastase-sensitive material, consistent with glycogen within the cytoplasm of the neoplastic cells. Many hyaline globules were present which were PAS-D positive. The tumor showed strong diffuse positivity for SALL4 (Figure 2). It also showed patchy strong positivity for glypican- 3 and AFP (Figure 3). There were focal glandular structures that resembled embryonic gut structures. Many of which were positive for caudal-related homeobox gene 2 (CDX2). They also showed focal positivity for epithelial membrane antigen (EMA), cytokeratin 7 and 20. The tumor was negative for Figure 1. Haematoxylin and eosin-stained section of the tumour shows octamer 3/4 (OCT3/4), CD30, estrogen receptor (ER), Wilm’s nests, some of which are cribriform, composed of neoplastic cells which tumour 1 protein (WT1), Ca125 and calretinin. The tumors, have well-demarcated cell margins and pale to clear cytoplasm. Nuclei both primary and metastatic, showed no evidence of a are large with distinct nucleoli. Mitoses are frequent. Original magnification, ×300. carcinomatous component. Outcome. The postoperative computed tomographic (CT) imaging performed one month after the surgery demonstrated An MRI scan revealed a good response after 1 cycle of large-volume peritoneal disease, mainly in the lesser chemotherapy. However, in light of the revised diagnosis, the omentum, serosal liver and splenic involvement, as well as recommendation was to change to bleomycin, etoposide and moderate left hydronephrosis secondary to the peritoneal cisplatin (BEP) chemotherapy. Postoperative AFP was noted to disease. After an uneventful postoperative recovery, be 31,014 kU/l and β-human chorionic gonadotrophin (βhCG) carboplatin in combination with paclitaxel was initially 43 mIU/l. Despite the marked clinical response and the dramatic commenced. reduction in AFP (15 kU/l) and βhCG (<2 mIU/l) following 6714 Boussios et al: Two Cases of Yolk Sac Tumours in Postmenopausal Women Figure 2. The neoplastic cells show diffuse and strong positivity for sal-like protein 4. Figure 3. The tumour is positive for α-foetoprotein. 6715 ANTICANCER RESEARCH 35: 6713-6722 (2015) Table I. Demographics of 35 postmenopausal patients with ovarian germ cell tumours. Author Year of No. of Age at Stage Histology Endometriosis Treatment Chemotherapy Outcome (Ref) publication cases diagnosis (years) Arai et al. (1) 1999 1 71 (I) Mixed: MC cystadeno- No TAH, BSO EP DOD at 6M carcinoma-YST Kamoi et al. (5) 2002 1 54 IC Mixed: YST + EM Yes Tumour Ca(ip) followed DF at 21M debulking by PeEP × 5 Lopez et al. (6) 2003 1 51 IC Mixed: EM -YST, Yes TAH, BSO, BEP × 3 DOD at 10M MC cystadenoma omentectomy Rutgers et al. (7) 1987 1 50 IA Mixed: EST + EM Yes TAH, BSO, MOC×5 pre- DOD at 8M omentectomy, operatively and peritoneal washings VP×1 post- operatively Abe et al. (8) 2008 1 52 IC Mixed: YST + EM No TAH, BSO, BEP × 3 DF at 20M omentectomy, pelvic followed and para-aortic by TCa × 3 lymphadenectomy Brown et al. (9) 1976 1 57 III Pure: EST No TAH, BSO, None DOD at 3M omentectomy Ferracini et al. (10) 1979 1 63 N/A Pure: EST No TAH, tumour None DOD 2D post- debulking operatively Cisło et al. (11) 1984 1 50 IC Pure: EST No TAH, BSO MOC DOD at 22M Mazur et al. (12) 1988 1 82 IA Mixed: MC No TAH, BSO, None DF at 24M cystadenofibroma-YST omentectomy Kinoshita et al. (13) 1990 1 62 IA Pure: EST No TAH, BSO, VPeP × 5 N/A omentectomy Pliskow et al. (14) 1993 1 54 N/A Pure: EST No TAH, BSO, BEP × 3 DF at 24M omentectomy Kammerer-Doak 1996 1 53 N/A Mixed: EST + No TAH, BSO, BEP × 3 DF at 60M et al. (15) embryonal carcinoma omentectomy, appendicectomy, pelvic and para- aortic LN Bx Takizawa et al. (16) 1996 1 69 III Mixed: EST + No BSO, partial P × 2 (ip) DOD at 24M papillary serous omentectomy followed by carcinoma CAP × 6. Second line CaE × 2 due to biochemical recurrence Nogales et al. (17) 1996 4 64 IA Mixed: EST + EM No TAH, BSO MOC × 3 DOD at 14M 71 IA Mixed: EST + Yes TAH, BSO P-based × 6 DF at 12M EM + EAF 71 III Mixed: EST + EM No TAH, BSO P-based × 1 DOD at 3M 73 III Mixed: EST + No LSO, omentectomy, None DOD at 5M carcinosarcoma appendicectomy, and uterine Bx Horiuchi et al.
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