Incidentally diagnosed epithelioid trophoblastic tumor immediately after delivery : a case report

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INTRODUCTION
G estational trophoblastic disease (GTD) constitutes an abnormal proliferation of placental trophoblasts, and exhibits specific pathogenesis and clinical features (1) .The modified classification of GTD by the World Health Organization defines complete and partial hydatidiform moles as benign lesions of GTD, and invasive moles, choriocarcinoma (CC), and epithelioid trophoblastic tumors (ETT) as malignant lesions of GTD.ETT is difficult to recognize as a trophoblastic disease because of its very low incidence, and its growth pattern that simulates a poorly differentiated carcinoma and other GTDs (1,2) .Most cases of ETT occur in women who are of reproductive age and have a prior gestational history.The reported interval between the previous gestation and the diagnosis of the tumor ranges from 0 to 264 months (mean, 84 months) (3)(4)(5) .ETT found in the immediate postpartum period is extremely rare; it has been reported only once previously (5) .Here we report a case of ETT found immediately after delivery.

CASE REPORT
A 42-year-old Korean woman (gravida 2, para 2) was transferred to our hospital for antenatal care because she was pregnant at an advanced maternal age and had gestational diabetes mellitus.Her obstetric history was uncomplicated: she had delivered by cesarean sections earlier, 4 and 5 years before, and we had no prior knowledge of her other medical history.Preoperatively, her serum HbA1C level (5.7%) and other laboratory findings were unremarkable.At 38 weeks of gestation, she underwent a repeat cesarean section, and a healthy infant weighting 5010 g was delivered.Unexpectedly, during surgery, we saw the lower uterine segment bloated with active bleeding and uterine atony.Therefore, we made a decision to perform hysterectomy to control bleeding; there were no postoperative complications.Grossly, the uterus appeared to have nonspecific findings (Fig. 1).Pathological examination revealed that a minute portion of the endometrium exhibited aberrant proliferation of trophoblasts, and these tumor cells were epithelioid with occasional mitotic figures (Fig. 2A).On immunohistochemical staining, these cells were strongly positive for p63 (Fig. 2B) and CD10 (Fig. 2C).In addition, the proliferation index, as assessed by the Ki-67 labeling index, was higher than 10%, and lymphocytic infiltration was not conspicuous (Fig. 2D).These histological and immunohistochemical findings were consistent with features of ETT.Postoperatively, computed tomography of the abdomen, pelvis and chest was performed for ruling out metastases.It revealed no significant findings.Although the preoperative serum-B-human chorionic gonadotropin levels of the patient were not checked, the postoperative levels were normal.She was followed-up regularly every 3 months by blood tests for complete blood cell count, liver and kidney function tests and chest radiography.There was no clinical evidence of tumor recurrence for 5 years after surgery.

DISCUSSION
ETT is a rare tumor composed of chorionic-type intermediate trophoblasts, and was initially described as an atypical choriocarcinoma in patients with lung metastases in 1998 by Whin and Kurman (1,2,6,7) .Patients with ETT are usually of reproductive age, ranging from 15 to 50 years of age (mean, 34.9 years), and have had previous gestations, including, full-term deliveries (67%), molar pregnancies (16%) and abortions (16%) (6,8) .The interval between the antecedent gestational events and the diagnosis of ETT ranges from 0 to 264 months (mean, 84 months) (5) .It is extremely rare to find ETT immediately after delivery, as was the case with our patient (5,9) .Tab. 1 compares the intervals from antecedent pregnancies in several case reports of ETT before 2016 (1,(3)(4)(5)9,10) . Tab.  compares the previous history, documented in the literature published in English, which summarizes the factors of mixed GTD.It documents the shortest intervals from antecedent pregnancy for mixed GTD cases before 2015, the shortest of which was 7 months after term delivery (8) .The most common symptom of ETT is abnormal vaginal bleeding.Other symptoms are amenorrhea and irregular menstruation (2,5) .Fifty percent of ETTs are located in the lower uterine segment of the cervix; 30%, in the uterine corpus; and 20%, in extrauterine sites including the lungs and the small bowel (4) .It is reported that 25% of patients with ETT develop metastases, most frequently in the lungs.Ten percent of patients die of the disease.Therefore, exact diagnosis is very important (2) .

Reference Number Age (years) Antecedent pregnancy
Interval from antecedent pregnancy (months)  On immunohistochemical staining, these cells were strongly positive for p63 (B, ×400) and CD10 (C, ×400).In addition, the proliferation index, as assessed by the Ki-67 labeling index, was higher than 10%, and lymphocytic infiltration was not conspicuous (D, ×400)

Tab. 2. Cases of mixed gestational trophoblastic disease (GTD) in women of reproductive age with prior gestation
ETT can be misdiagnosed as other forms of GTD or as squamous cell carcinoma of the cervix because of the resemblance in behavior and the epithelioid appearance of tumor cells.Immunohistochemical staining for cytokeratin 18 and inhibin helps to distinguish ETT from these forms of disease, as these markers are positive in ETT but negative in squamous cell carcinoma (2,11) .Additionally, the Ki-67 proliferative index can be useful for differential diagnosis, because it is low in placental site trophoblastic tumor (PSTT) (15-25%) and ETT (10-25%), but relatively high (>50%) in squamous cell carcinoma and CC (12) .Raised serum β-hCG levels in most cases of ETT are associated with a large mass and high mitotic activity (2,9) .In addition, p63 is expressed in chorionic-type intermediate cells of ETT, but not in PSTT (8) .
In summary, we have reported an ETT found incidentally in a patient undergoing hysterectomy for treatment of uterine atony.As is seen in Tabs. 1 and 2, ETT is associated with a prior gestational history, but its pathogenesis is yet unclear.Additional cases need to be studied to determine the relationship between the occurrence of ETT and previous gestations.Therefore, our patient deserves attention not only because she had a rare disease, but also because she was diagnosed with ETT immediately after delivery by cesarean section.