Ectopic Gestational Trophoblastic Disease

Introduction

Gestational choriocarcinoma associated with ectopic pregnancy is an extremely rare event with a reported incidence of 1.5/1,000,000 births. ¹ Gestational trophoblastic disease (GTD) is characterized by abnormal proliferation of trophoblasts during pregnancy. It comprises a spectrum of conditions, ranging from hydatidiform mole (which can be complete or partial) to choriocarcinoma. Hydatidiform mole affects 1 in 500–1000 pregnancies. ² The incidence of ectopic pregnancy in the United Kingdom is 11.1/1000. This makes ectopic GTD extremely rare, and only a few cases have been reported in the literature.^3–6

Case

An 18-year-old woman, gravida 3, para 0+2 (terminations of pregnancy), presented with amenorrhea of 6 weeks duration, abdominal pain, and minimal vaginal bleeding to the emergency gynecology assessment unit of the Dudley Hospitals NHS Foundation Trust, Dudley, West Midlands, United Kingdom. A pregnancy test was performed on a urine specimen from the patient, and was positive for pregnancy. The patient's general physical and neurologic examination results on admission were completely normal.

A transvaginal ultrasound scan suggested that the left adnexal region contained an irregularly shaped solid mass that was noted to be quite vascular when color Doppler was applied during the scan. This area measured 62.2×42.7×42.8 mm. There was no evidence of an intrauterine gestational sac or retained products of conception. There was no free fluid in the pouch of Douglas, and the possibility of an ectopic pregnancy could not be excluded.

The patient was subjected to a diagnostic laparoscopy, during which a left-sided cornual ectopic pregnancy was diagnosed with evidence of hydrosalpinx in the proximal part of the left tube. The patient was counseled regarding the diagnosis, and her case was discussed in a gynecologic oncology multidisciplinary meeting, with an onward referral (per national guidance) for the patient to the Regional Trophoblastic Disease Referral center at Charing Cross Hospital in London, United Kingdom, for further follow-up of her β–hCG level. Staging scans performed Charing Cross Hospital—including magnetic resonance imaging of her brain and pelvis, computed tomography of her chest/abdomen, and Doppler ultrasound scanning of her pelvis—all showed normal results.

An attempted laparoscopic resection of the cornual ectopic pregnancy caused excessive bleeding, so the procedure was converted to a transverse suprapubic laparotomy, with left cornual ectopic resection and left salpingectomy. The surgery was uneventful.

This patient recovered well from the surgery and was discharged to go home the next day. In the meantime, the excised specimen was sent for histologic assessment, which, via microscopic examination, revealed the presence of a a choriocarcinoma and confirmed this via immune staining. Quantitative β–human chorionic gonadotropin (β-hCG) testing revealed that her level was 8296 IU/L 2 days after her surgery. This level then dropped further to 3795 2 days later.

Results

This patient had a good recovery and follow-up has been ongoing for the last 9 months, as of this writing. She has dropping β-hCG levels and no indications for chemotherapy so far. Seven weeks following surgery, her β-hCG levels had fallen to normal levels. The patient's general physical and neurologic assessments remained normal following surgery.

Discussion

Gestational choriocarcinoma associated with ectopic pregnancy is an extremely rare event with a reported incidence of 1.5/1,000,000 births. ¹ GTD is characterized by abnormal proliferation of trophoblasts during pregnancy. GTD comprises a spectrum of conditions, ranging from hydatidiform mole (which can be complete or partial) to choriocarcinoma. Hydatidiform mole affects 1 in 500–1000 pregnancies. ² The incidence of ectopic pregnancy in the United Kingdom is 11.1/1,000. This makes ectopic GTD extremely rare, and only a few cases have been reported in the literature.^3–6

Choriocarcinoma is a malignant tumor arising from the epithelium of the chorionic villi and is frequently present in the uterus. Its association with ectopic pregnancy is rare and usually quite aggressive. Histopathological diagnosis of ectopic GTD is difficult, and it is often overdiagnosed.^7,8

Cornual gestation is one of the most hazardous types of ectopic gestation. The diagnosis and treatment are challenging and frequently constitute a medical emergency. In general, the death rate associated with ectopic pregnancy has not declined since the Confidential Enquiry into Maternal and Child Health report for 2000–2002 and has increased since the rates for 1991–1993 were published. ⁹ Cornual pregnancy accounts for 2%–4% of ectopic pregnancies and is said to have a mortality rate in the range of 2.0–2.5%. ⁹

The interstitial part of the Fallopian tube is the proximal portion that lies within the muscular wall of the uterus. It is 0.7-mm wide and ∼1–2 cm long, with a slightly tortuous course, extending obliquely upward and outward from the uterine cavity. Pregnancies implanted in this site are called interstitial (cornual) pregnancies. They pose a significant diagnostic and therapeutic challenges and carry a greater maternal mortality risk than ampullary ectopic pregnancies. As a result of myometrial distensibility, cornual pregnancies tend to become evident relatively late, at 7–12 weeks of gestation. Significant maternal hemorrhage leading to hypovolemia and shock can result rapidly from cornual rupture. Clinically, risk factors are as for other types of ectopic pregnancy: contralateral salpingectomy; previous ectopic pregnancy; and in vitro fertilization. ¹⁰

Sixty three % (63%) of patients were correctly diagnosed as having ectopic molar pregnancy by the referring hospital (Charing Cross Hospital, London, UK). This compares favorably with other series in which correct diagnoses were made in 15% and 6% of cases, highlighting the fact that ectopic molar pregnancy was and probably still is overdiagnosed.^7,8

Tubal choriocarcinoma is very rare but very aggressive. In 75% of cases, it stems from distant metastasis; therefore, a histologic examination of the Fallopian tubes must be performed in all patients who have ectopic pregnancies. These patients need close follow-up with regarding to serum levels of β-hCG per trophoblastic regional centre protocol and need effective contraception for 1 year. ¹¹

The presentation of ectopic GTD is similar to normal ectopic pregnancy. Abdominal pain and vaginal bleeding are the most common symptoms. Most patients if not all, do not present with symptoms/signs typical of molar pregnancy or choriocarcinoma. As in conventional ectopic pregnancy, the presence of risk factors—such as pelvic inflammatory disease, previous ectopic pregnancy or previous pelvic surgery—would appear to be strongly associated with ectopic GTD pregnancy. ¹⁰

Because of its location, early diagnosis of cornual pregnancy has historically been difficult. The eccentric position of the gestational sac and thinning of the myometrial mantle means that differentiation between eccentric intrauterine and cornual pregnancy is often difficult. ¹²

Although histologic diagnosis is possible in most cases, DNA flow cytometry or digital-image analysis is useful to determine ploidy status. Genetic analysis plays a role in distinguishing between a gestational trophoblastic tumor and a nongestational germ-cell tumor. The importance of expert review of the histology in cases of suspected ectopic moles has been highlighted in previous publications.^7,13

In general, laparoscopic techniques involve cornual resection, cornuostomy, salpingostomy, or salpingectomy. Even in women with ectopic pregnancy with significant hemoperitoneum, laparoscopic surgery has been safely conducted by experienced laparoscopists, with intraoperative autologous blood transfusion, if hemodynamic stability is achieved by perioperative management. ¹⁴

Cornual excision or hysterectomy used to be the traditional treatment for such cases. Conservative management has, however, been increasingly practiced successfully. This includes laparoscopic conservative treatment and pharmaceutical treatment with systemic methotrexate.

Sonographically guided, minimally invasive treatment can be a safe and effective alternative to surgical and systemic pharmaceutical therapy. Appropriate individual counseling is needed regarding risks of future pregnancy and mode of delivery. ¹⁵

Most patients in a case review of a series did not develop persistent disease after surgical removal of the ectopic GTD. ¹⁰

Conclusions

Ectopic GTD is rare and is still overdiagnosed. Presentation is the same as that of a typical ectopic pregnancy. Expert review of the excised specimen's histopathology should be carried out. Conventional chemotherapy for GTD is effective. The prognosis remains excellent for these cases.