Endometrial carcinoma with yolk sac tumor-like differentiation and elevated serum β-hCG: a case report and literature review
A 28-year-old, nulligravid, married Chinese woman presented in December 2010 with a 14-month history of abnormal vaginal bleeding. The patient had been on barrier contraception, and to her knowledge had never been pregnant. Past medical history included epilepsy and hypothyroidism due to thyroidectomy. In October 2010, a diagnostic curettage specimen revealed endometrial adenocarcinoma with glandular squamous metaplasia, and an exploratory laparotomy was performed in a local hospital. A large omental mass and diffuse miliary nodules in the pelvic peritoneum made exposure of the surgical field difficult, so biopsy of the mass and peritoneum only was performed and histologic examination showed endometrial adenocarcinoma with yolk sac tumor-like differentiation. Chemotherapy, including intravenous paclitaxel 120 mg, adriamycin 60 mg, and intraperitoneal cisplatin 150 mg for one course, was administered at the local hospital. The patient was then referred to our hospital, where laboratory tests showed serum alfa-fetoprotein level of 1,522 ng/mL (normal value ≤20 ng/mL), β-hCG 518.9 mIU/mL (normal value ≤5 mIU/mL, chemiluminescent technology, Advia Centaur™ XP immunoassay system, Siemens, Erlangen, Germany), and CA 125 129 U/mL (normal value ≤35 U/mL). A chest computed tomography scan was negative.\nThe patient underwent cytoreductive surgery, including total abdominal hysterectomy, bilateral salpingo-oophorectomy with pelvic lymphadenectomy, omentectomy, appendectomy, partial sigmoidectomy with anastomosis, and resection of abdominal and pelvic metastases, without residual visible metastases. The uterus measured 10 × 8 × 5 cm and the cavity was filled with a cauliflower-like tumor measuring 6 × 3 × 2.5 cm and containing areas of ulceration (see ). This solid tumor had a grayish-white cut surface and moderate texture. Histopathologic examination of the uterine tumor revealed well to moderately differentiated endometrial adenocarcinoma with yolk sac tumor-like differentiation intraendometrially, with a close transition between the two components (). No trophoblastic component was found. The metastases were identical to the primary lesion on histology. The myometrium, cervix, appendix, bilateral adnexa, and iliac lymph nodes were negative for tumor. Periodic-acid Schiff stain was positive in yolk sac tumor cells. Immunohistochemical analysis revealed that both endometrial adenocarcinoma and yolk sac tumor components were positive for AE1/AE3. The yolk sac tumor component was strongly positive for alfa-fetoprotein, while the endometrial adenocarcinoma was relatively negative (). The endometrial adenocarcinoma component was positive for EMA, CA125, and CK7, suggesting epithelial neoplasms. There was focal positive staining for p53. Estrogen receptor and progesterone receptor status were both negative, as were hCG and β-hCG.\nTwo days after surgery, serum alfa-fetoprotein and β-hCG levels decreased dramatically to 166.4 ng/mL and 13.7 mIU/mL, respectively, and the CA125 level dropped into the normal range. Six courses of intravenous chemotherapy with paclitaxel 175 mg/m2 per day followed by carboplatin for an area under the concentration-time curve of 5 mg/mL per minute were administered every 21 days. Serum alfa-fetoprotein dropped to the normal range after three courses, while β-hCG fluctuated in the range of 5–20 mIU/mL despite two additional courses of chemotherapy with etoposide, methotrexate, actinomycin D, etoposide, and cisplatin followed by two courses with bleomycin, etoposide, and platinum. The persistent slightly elevated β-hCG was considered due to abnormal pituitary feedback, so chemotherapy was stopped. Unfortunately, β-hCG and alfa-fetoprotein rose again 2–3 months later. Despite salvage chemotherapy with two cycles of floxuridine, dactinomycin, etoposide, and vincristine, serum alfa-fetoprotein reached 311.1 ng/mL and β-hCG reached 2,716.5 mIU/mL. After the final course with oxaliplatin 200 mg and cyclophosphamide 800 mg, the patient abandoned further treatment and was lost to follow-up.