1 Introduction
Yolk sac tumors (YSTs), also known as endodermal sinus tumors, are malignant germ cell tumors that secrete alpha-fetoprotein (AFP). These tumors, which commonly develop in infants, young children, and young women, often originate in the gonads and are distributed along the central axis of the body.[1] [2] [3] [2]
2 Case report
The patient was a 38-year-old woman of childbearing age with a history of regular menstruation, gravidity 3, and parity 1. She underwent a B-mode ultrasound examination at a local hospital to evaluate the complaint of prolonged menstruation and increased menstrual bleeding of a duration exceeding 2 months. The results of the examination indicated the presence of a lesion in the intrauterine space. The patient underwent diagnostic curettage, and a pathological examination of the tissue specimen indicated the possibility of sarcoma. Accordingly, the pathological specimen was sent to the Department of Pathology of our hospital, and the pathological report indicated the presence of a mixed-type endometrial adenocarcinoma (approximately 80% clear cell carcinoma and 20% poorly differentiated endometrioid adenocarcinoma) accompanied by mucinous adenocarcinoma.
A pelvic examination revealed uterine enlargement at approximately 50 days after conception. The uterine surface was soft and smooth without tenderness, and no other abnormalities were observed. Tumor marker evaluations revealed a high level of carbohydrate antigen (CA) 125 (58.5 U/mL), and normal levels of AFP, carcinoembryonic antigen (CEA), CA199, and human chorionic gonadotropin (HCG). A magnetic resonance imaging examination indicated a slight expansion of the uterine cavity and a patchy area of abnormal signal intensity suggestive of uterine bleeding. The left obturator lymph node, which was approximately 0.8 cm × 0.5 cm in size, was relatively larger than the right node, and no other abnormalities were found. The patient was diagnosed with mixed-type endometrial adenocarcinoma.
On December 9, 2016, the patient underwent a laparoscopic extrafascial hysterectomy, bilateral adnexectomy, pelvic lymphadenectomy, abdominal para-aortic lymphadenectomy, omentectomy, and appendectomy. Intraoperatively, the uterus remained enlarged at approximately 50 days after pregnancy, and a 0.3-cm nodule was observed on the left side of the peritoneal reflection of the bladder. No abnormalities were observed in the bilateral ovaries or oviducts, and no enlargement or hardening of the pelvic and abdominal para-aortic lymph nodes was observed. However, scattered hard nodules (size: 0.5–0.8 cm) were observed in the greater omentum. Furthermore, a postoperative uterus evaluation observed hard nodules (size 2.5 cm × 1.2 cm) in the left posterior wall of the uterine cavity. Postoperative pathology revealed a stage IVB endometrial YST with tumor metastasis to the greater omentum.
Postoperatively, the patient was administered 6 courses of chemotherapy with the bleomycin–etoposide–cisplatin (BEP) regimen. Although she developed adverse reactions, such as grade IV neutropenia and vomiting, during chemotherapy, these symptoms improved after treatment. She was followed up regularly for 24 months after completing chemotherapy, and no tumor recurrence occurred during this period.
3 Pathological findings
The endometrial YST (Fig. 1 ) invaded to a depth corresponding to less than half of the full muscularis layer; specifically, only a thin layer of tissue had been infiltrated. In the muscle wall, tumor thrombosis was observed in a vessel adjacent to the tumor, and the tumor itself had metastasized to the greater omentum (Fig. 2 ). No metastasis was found elsewhere. Immunohistochemistry yielded the following positive results: cytokeratin (CK)18+++, SALL-4+++ (Fig. 3 ), multifocal AFP+, multifocal CD56+, unifocal CD15+, unifocal P16+, P-CK+++, glypican 3+++ (Fig. 4 ), unifocal CEA+, β-catenin (membrane)++, P53++, Ki67 positivity rate of approximately 90%, Mutl homolog (MLH)1+++, MutS protein homolog (MSH)2++, PMS2++ (PMS2 Postmeiotic Segregation), and MSH6+++. Additionally, the tumor yielded negative results for estrogen receptor (Fig. 5 ), progesterone receptor (Fig. 6 ), OCT3/4 (octamer-binding transcription factor), CK7X3, EMAX3 (Mpithelial Membrane Antigen), CD30, CD117, CRX2, WT-1X2 (Wilm's tumor), VIMX2 (Vimentin), CD146, Melan-A, HMB45 (Human Melanoma Black), human placental lactogen, HCG, synaptophysin, cyclin D1, napsin-AX2, CD10, and CK5/6.
Figure 1: Images of an endometrial yolk sac tumor . A, 40×; B, 100×; C, 200×; and D, 400× magnification.
Figure 2: Infiltration by the yolk sac tumor into the greater omentum.
Figure 3: Immunohistochemical staining for SALL-4 (positive result).
Figure 4: Immunohistochemical staining for glypican 3 (positive result).
Figure 5: Immunohistochemical staining for estrogen receptor (negative result).
Figure 6: Immunohistochemical staining for progesterone receptor (negative result).
4 Discussion and literature review
Primary endometrial YST is very rare, with only 11 cases reported in the literature to date (Table 1 ). Of these, 8 cases involved simple endometrial YST, 2 involved endometrial YST accompanied by endometrial adenocarcinoma, and 1 involved a combination of adenocarcinoma, high-grade stromal sarcoma, and YST. Increased AFP levels have been observed in 10 cases, whereas normal AFP levels were reported in only 1 case.[2–12]
Table 1: Cases of primary endometrial yolk sac tumor .
Four theoretical hypotheses have been suggested to explain the development of endometrial YST tissue: the abnormal migration of primordial germ cells, which are hidden in the endometrial basal layer, during embryogenesis; an undiscovered YST metastasis; residual tissue after an incomplete abortion; and the abnormal differentiation of somatic cells.[3–5,7] [1,2] [13] [3]
YSTs are prone to early metastasis and infiltration into surrounding tissue structures and can metastasize through the bloodstream and lymphatic system. In the current case, although no metastasis was observed in the lymphatic system, implantation metastasis was detected in the greater omentum. Therefore, this extremely rare condition supports the tendency of YST to metastasize early.
Given the rarity of primary endometrial YST, little systematic research has addressed the relevant surgical procedures, postoperative adjuvant therapies, and/or standard treatment regimens. In 1993, Fujita et al[14] [15]
Among the 11 patients reported on in the literature,[2–12]
Although it remains unclear whether the prognosis of endometrial YST is similar to that of ovarian YST, the above studies could serve as references. Notably, the BEP chemotherapy regimen can be administered postoperatively to patients with endometrial YST. Furthermore, AFP is an important and sensitive tumor marker for YST and can often be used to monitor post-treatment metastasis and recurrence. However, despite the crucial role of AFP in the diagnosis, treatment, and follow-up management of YST, we note that a few patients, including the patient in our case, have normal levels of this marker.
5 Conclusion
Primary endometrial YST is extremely rare, and even rarer in the context of a normal AFP level. Most cases are treated with surgery and chemotherapy, which can enable a young patient to retain their endocrine function. Furthermore, the BEP chemotherapy regimen appears to be an effective postoperative chemotherapy regimen for patients with endometrial YST.
Author contributions
Resources: Xiaoxia Wei, Liang Song.
Supervision: Danqing Wang, Kaixuan Yang, Mingrong Qie, Rutie Yin, Qingli Li.
Validation: Xiaoxia Wei.
Writing – original draft: Liang Song.
Writing – review & editing: Liang Song, Qingli Li.
References
[1]. Talerman A. Primary endodermal sinus tumor of the endometrium presenting as “recurrent” endometrial adenocarcinoma. Gynecol Oncol 2002;84:184.
[2]. Spatz A, Bouron D, Pautier P, et al. Primary
yolk sac tumor of the endometrium: a case report and review of the literature. Gynecol Oncol 1998;70:285–8.
[3]. Pileri S, Martinelli G, Serra L, Bazzocchi F. Endodermal sinus tumor arising in the endometrium. Obstet Gynecol 1980;56:391–6.
[4]. Clement PB, Young RH, Scully RE. Extraovarian pelvic yolk sac tumors. Cancer 1988;62:620–6.
[5]. Ohta M, Sakakibara K, Mizuno K, et al. Successful treatment of primary endodermal sinus tumor of the endometrium. Gynecol Oncol 1988;31:357–64.
[6]. Joseph MG, Fellows FG, Hearn SA. Primary endodermal sinus tumor of the endometrium. A clinicopathologic, immunocytochemical, and ultrastructural study. Cancer 1990;65:297–302.
[7]. Rossi R, Stacchiotti D, Bernardini MG, et al. Primary
yolk sac tumor of the endometrium: a case report and review of the literature. Am J Obstet Gynecol 2011;204:e3–4.
[8]. Wang C, Li G, Xi L, et al. Primary
yolk sac tumor of the endometrium. Int J Gynaecol Obstet 2011;114:291–3.
[9]. Abhilasha N, Bafna UD, Pallavi VR, et al. Primary
yolk sac tumor of the endometrium: a rare entity. Indian J Cancer 2014;51:446.
[10]. Patsner B. Primary endodermal sinus tumor of the endometrium presenting as “recurrent” endometrial adenocarcinoma. Gynecol Oncol 2001;80:93–5.
[11]. Oguri H, Sumitomo R, Maeda N, et al. Primary
yolk sac tumor concomitant with carcinosarcoma originating from the endometrium: case report. Gynecol Oncol 2006;103:368–71.
[12]. Ji ML, Lu Y, Guo LN, et al. Endometrial carcinoma with
yolk sac tumor -like differentiation and elevated serum β-hCG: a case report and literature review. Onco Targets Ther 2013;6:1515–22.
[13]. Zhang B, Gao S, Chen Y, Wu Y. Primary
yolk sac tumor arising in the pancreas with hepatic metastasis: a case report. Korean J Radiol 2010;11:472–5.
[14]. Fujita M, Inoue M, Tanizawa O, et al. Retrospective review of 41 patients with endodermal sinus tumor of the ovary. Int J Gynecol Cancer 1993;3:329–35.
[15]. Nawa A, Obata N, Kikkawa F, et al. Prognostic factors of patients with yolk sac tumors of the ovary. Am J Obstet Gynecol 2001;184:1182–8.
