Ovarian endometrioid carcinoma with yolk sac component in a young patient: A diagnostic and therapeutic dilemma

Abstract

Endometrioid carcinomas (EC) are mullerian epithelial tumours, most common in older patients. In contrast yolk sac tumours (YST) are malignant germ cell tumours (GCT) that recapitulate the yolk sac and its derivatives microscopically and are found, essentially, in young patients. Yolk sac tumours may be pure or admixed with other types of germ cell neoplasia. An ovarian endometrioid tumour with YST component is distinctly rare. Endometrioid carcinoma with YST occurs in the same age range (31–73 years) as endometrioid adenocarcinoma, often coexisting with benign endometriotic lesions.1–3 To our knowledge, only 10 cases have so far been reported in the English language medical literature and all in elderly patients (Medline search).1–5 Our patient is unusual in that she is the youngest (23 years old) among all reported cases to date. It is important to recognise these tumours in view of their aggressive behaviour and poor response to standard platinum-based chemotherapy admimistered for ovarian carcinoma.1 A 23-year-old woman presented with abdominal pain for the past 6 months. Ultrasonography showed a left adnexal mass. After a total abdominal hysterectomy, bilateral salpingo-ophorectomy and omentectomy were performed in another hospital, she was referred to our hospital with a histopathology report of adenocarcinoma of the left ovary. Her general physical examination was unremarkable. On pelvic examination, multiple nodules were palpable in the vault. Per rectal examination was normal. Tumour marker CA 125 was 85 U/mL (normal: <35 U/mL) and α-fetoprotein (AFP) was 2726 ng/mL (normal: 0.5–35 ng/mL) on the 12th postoperative day. Carcino-embryonic antigen and human chorionic gonadotrophin (hCG) were within normal ranges. A computed tomography (CT) scan of the abdomen and pelvis showed multiple peritoneal deposits. Her histopathology slides and blocks were reviewed. Her final revised histopathology report was grade I ovarian endometroid adenocarcinoma with yolk sac component and omental metastases. We administered four cycles of combination chemotherapy consisting of bleomycin, etoposide and cisplatin (BEP) in line of GCT followed by two cycles of cisplatin. Post chemotherapy her AFP level was within normal range and CT scan of the abdomen and pelvis showed no abnormality. The patient is alive and disease free, 12 months after the last cycle of chemotherapy. Histologically, the tumour was partly solid and partly cystic. The solid area was composed of well-differentiated EC. Many squamous morules were seen protruding in the lumina of neoplastic glands (Fig. 1). The tumour originated from a cyst lined by an endometrial type of columnar epithelium (Fig. 2). Intimately admixed with EC were foci of YST, composed mainly in a papillary pattern (Fig. 3). An occasional focus exhibited classical reticular pattern and eosinophilic hyaline globules. The omental nodule was composed exclusively of yolk sac component and exhibited a papillary pattern. Solid portion of tumour showed well-differentiated endometrioid carcinoma with squamous morules. Cystic portion of the tumour lined by stratified atypical endometrial epithelium. Immunohistochemical staining for α-fetoprotein, shows focal positive staining (arrow) of cells of yolk sac component. Note papillary pattern and primitive nuclei of tumour. Extensive epithelial and GCT markers were tested for immunohistochemically with the use of avidin and biotin method. The YST cells stained positively with AFP, polyclonal cytokeratin (CK) and stained negatively for CK7, epithelial membrane antigen (EMA), CA 125, oestrogen receptor (ER), progesterone receptor (PR), CK 20 and hCG. In contrast, the EC cells stained positive with CK7, EMA, CA 125, ER, PR and were negative for CK 20, AFP and hCG. Thus, two distinct components of YST and EC in the ovarian tumour were confirmed immunohistochemically. Yolk sac tumours are malignant GCT exhibiting differentiation, primarily in the direction of extra embryonic yolk sac structures. Although most of these tumours have germ cell origin, rarely do they originate within somatic cell tumours; they predominantly occur in the organs of endodermal origin. Somatic mullerian epithelial tumours arising in the female genital tract can also develop trophoblastic or yolk sac component. Thus, the development of extra embryonic teratoid type of neoplastic patterns within somatic cell tumours is well known but a rare event encountered mainly in the tumours of aerodigestive and urinary tracts.3,6 An ovarian EC with YST component is rare. It has been postulated that the presence of germ cell elements in a carcinoma that is of somatic origin is a type of neometaplasia and may be a result of tumour heterogeneity. Retrodifferentiation has also been suggested as an alternative explanation for germ cell elements arising from somatic tissues.2 Finally, simultaneous dual differentiation within a tumour from an uncommitted cell line cannot be excluded. Histologically it should not be confused with a ‘endometrioid-like’ variant of ovarian YST which occurs much more frequently. Rutgers et al. reported the first case of EC associated with YST as a foci of ‘a peculiar pattern of clear cell carcinoma’.2 The morphology of the tumour actually corresponds to the pattern named by Clement et al. as ‘endometrioid like’.6 Nogales et al.3 reported six cases, while Horiuchi et al.,1 Kamoi et al.4 and Lopez et al.5 reported one case each of ovarian endometrioid tumours with YST component. All the reported cases were in elderly patients. The age of the patients ranged from 31 to 73 years. Eight patients were above 50 years, one patient was 40 years and one patient was 31 years. Four tumours were stage Ia, two were stage Ic, three were stage III and one was stage IV (according to the International Federation of Gynaecology and Obstetrics (FIGO)). In all cases, cytoreductive surgery was followed by platinum-based chemotherapy. Only two patients were alive at the end of 14 and 21 months.3,4 This illustrates the aggressive behaviour of the tumour. Our patient was the youngest among all reported cases to date in the English language medical literature. She had stage IIIC (FIGO) ovarian cancer. After surgery our patient was administered four cycles of BEP which is standard treatment for GCT followed by two cycles of cisplatin chemotherapy. Post chemotherapy her AFP level was within normal range and CT scan of abdomen and pelvis show no abnormality. The patient is alive and disease free at 12 months after the last cycle of chemotherapy. It has been stressed in the literature that this tumour should be considered as a variant of EC.3 However, it is time to reconsider this assumption, as EC grade 1 of ovary should behave very well. It is the yolk sac component which affects prognosis adversely, and not the EC. Although the primary ovarian tumour showed combination of EC and YST in the current case, the metastatic tumour was purely YST component. Horiuchi et al. reported similar finding in an autopsy study, again explaining YST as an aggressive component.1 Standard chemotherapy for ovarian carcinoma is ineffective. It appears that this tumour is more likely to respond to chemotherapy effective against YST. Therefore, it is worth considering whether the patient should be initially treated by chemotherapy effective along the lines of malignant GCT and additional cycles of platinum-based chemotherapy for ovarian carcinoma. It is worth noting that Kamoi et al. have reported better survival following five cycles of (peplomycin, etoposide and cisplatin) chemotherapy and one cycle of intraperitoneal carboplatin.4 Our patient, who is the youngest, highlights problems encountered in diagnosis as well as adjuvant treatment of such cases. The presence of YST component in an otherwise classical EC of the ovary confers an aggressive behaviour. Hence the pathology should be documented histologically. The pathologist needs to be alert, as small foci of YST with an uncommon papillary-like pattern should not be missed for epithelial tumours. This is more likely to happen in older patients as preoperative GCT markers are not done routinely. Although commonly encountered in older patients, this tumour can also rarely arise in young patients. Hence, the pathologist should be aware of this unusual association in ovarian tumours in patients of all ages and should not label it either as EC or as YST. More cases need to be diagnosed, studied, and followed up in order to evolve ideal treatment policy to improve the dismal outlook associated with this rare tumour.