Caesarean scar ectopic pregnancy masquerading as gestational trophoblastic disease.

Cesarean scar ectopic pregnancy (CSEP) is a very rare form of ectopic pregnancy in which implantation occurs at the site of the previous cesarean scar with low or absent beta-human chorionic gonadotropin (hCG) levels. It has various differential diagnoses on gross and microscopic examination. A delay in the identification and management of this condition may lead to life-threatening complications. Here, we discuss the incidence and clinicopathological features of chronic CSEP, its types, and differential diagnoses.

Introduction

Chronic ectopic pregnancy is a rare form of ectopic pregnancy in which the serum beta-human chorionic gonadotropin (hCG) levels are either low or absent. Cesarean scar pregnancy is an ectopic pregnancy implanted in the myometrium at the site of a previous cesarean section scar, rare, although lately, its incidence is increasing due to an increased rate of cesarean section deliveries. It has various differential diagnoses on both, gross as well as microscopic examination, which include choriocarcinoma, placenta accreta/increta, cervical ectopic pregnancy, placental site trophoblastic tumor, epithelioid trophoblastic tumor, and invasive mole. Serum beta hCG levels help to rule out some of these conditions. Early diagnosis and management of this entity are important as it may lead to serious complications such as uterine rupture and hemorrhage which may be important causes of secondary infertility or even maternal mortality. Here, we present a case of chronic cesarean scar ectopic pregnancy (CSEP) masquerading as gestational trophoblastic disease, describing the clinical presentation, gross features, microscopic findings, and differential diagnosis along with a review of the literature.

Clinical Presentation, Investigations, and Provisional Diagnosis

A 27-year-old female, P2L2A1 non-tubectomized with a history of previous two lower segment cesarean section (LSCS) deliveries, came with complaints of intermittent bleeding per vaginum with lower abdominal pain and foul-smelling vaginal discharge. On detailed evaluation, the patient had a history of consumption of pills from the medical termination of pregnancy (MTP) kit consisting of mifepristone and misoprostol, for termination of pregnancy at home due to the positive status of the urine pregnancy test (UPT). This was followed by intermittent bleeding for 15 days, for which she consulted a private hospital where her UPT was repeated, which was again positive. Her dilatation and curettage were done twice by the hospital in view of the repeated positive status of UPT to rule out retained products of conception (histopathology report was not available). During both the procedures, the patient gave a history of heavy bleeding during and after the procedure for which she was given an injection of tranexamic acid. A month later, she visited another hospital for a second opinion where her repeat UPT was negative. The ultrasonography was suggestive of scar site ectopic pregnancy with a large heterogeneous residual trophoblastic tissue at the scar site. The beta hCG levels were 22.5 mIU/mL and a single dose of injection methotrexate was given to the patient.

The patient visited our hospital for further evaluation and management. On examination, she was vitally stable and there was no bleeding per vaginum. Per abdomen was soft and non-tender and the pelvic examination revealed a uterus of around 6–8 weeks in size, retroverted, and displaced to the left. Repeat beta hCG value was 7.87 mIU/mL, and the ultrasonography was suggestive of invasive molar pregnancy and the magnetic resonance imaging (MRI) confirmed the diagnosis with the presence of vascular invasion.

Management

The patient again started complaining of heavy vaginal bleeding on day 4 post-admission which was not responding to injection tranexamic acid. Two-pint packed red cells were transfused and a decision of total abdominal hysterectomy was taken due to clinical diagnosis of gestational trophoblastic disease. The patient was completely asymptomatic during the entire postoperative period and was discharged on day 10.

Pathology Findings and Differential Diagnosis

Gross examination: The uterus with cervix measured 11 cm × 6 cm × 3 cm. The serosa was unremarkable. On the cut section, the endometrial cavity was slit-like with an endometrial thickness of 0.3 cm. There was the presence of a well-defined, soft tumor-like mass measuring 6 cm × 3 cm × 2.5 cm in the lower uterine segment near the endocervix which appeared to be infiltrating almost full thickness of the myometrium on both the anterior and posterior walls with a thin rim of intact myometrium. The mass appeared fleshy with areas of hemorrhage and necrosis [Fig. 1]. The first differential diagnosis on gross examination was choriocarcinoma due to the presence of tumor-like mass with extensive areas of hemorrhage and necrosis. However, it was ruled out based on the low levels of beta hCG. The other differential diagnoses on gross examination were placental site trophoblastic tumor and epithelioid trophoblastic tumor due to low levels of beta hCG. Ectopic pregnancy was considered low down in the list of differential diagnoses because of radiology findings.

Figure 1

Gross photograph of the uterus with cervix showing a well-defined, tumor-like mass in the lower uterine segment seen infiltrating the myometrium. Tumor mass appears fleshy with necrotic and hemorrhagic areas within.

However, the histopathologic examination gave a surprise, showing many ghost and few intact hydropic chorionic villi surrounded by large areas of fibrin and hemorrhage with focal areas of neutrophilic infiltrate and calcification [Fig. 2b-d]. The villi were seen invading deep into the myometrium as well as the cervical wall, resulting in marked thinning of the uterine and cervical walls. The endometrium showed tubular endometrial glands with surrounding compact stroma showing plasma cells and lymphocytes [Fig. 2a]. The differential diagnoses on microscopy now were scar ectopic pregnancy and invasive mole. The invasive mole was ruled out on the basis of low beta hCG levels as well as the absence of any histopathologic features of trophoblastic hyperplasia, cisterns, or markedly enlarged villi. A diagnosis of chronic CSEP was made on the basis of the clinical, radiological, and histopathological findings.

Figure 2

Microphotograph: (a) endometrial gland with plasma cells and lymphocytes in the stroma (HE, X400); (b) and (c) intact and ghost chorionic villi surrounded by hemorrhage, fibrin (HE, X100, and X400, respectively); (d) myometrial fibers (red arrow) and focal areas of calcification (HE, X100).

Discussion

Ectopic pregnancy is an implantation of the embryo outside the uterine cavity. It occurs in 1–2% of the general population and 2–5% of the patients who have conceived using an assisted reproductive technology. The most common site is the fallopian tube with the non-tubal sites being the cervix, myometrium, uterine cornua, ovaries, abdominal cavity, and cesarean scar. Less than 10% of ectopic pregnancies occur at these non-tubal sites.[1] Chronic ectopic pregnancy is a rare variant of ectopic pregnancy, characterized by low or absent levels of serum hCG and methotrexate resistance.[2] CSEP (incidence being 6.1%) occurs when the implantation of the blastocyst occurs on a previous cesarean scar,[3] with the first case of CSEP reported in 1978.[4] Although a rare location for ectopic pregnancy, its incidence is increasing all over the world due to an increase in cesarean section deliveries. It is believed that the implantation occurs at this site due to the migration of the embryo either through the wedge defect in the lower segment of the uterus or a microscopic fistula formed within the scar due to poor healing.[5] It is of utmost importance to diagnose it early as a delay in the diagnosis and management can lead to uterine rupture and related complications causing significant maternal morbidity.[6] There is unclarity regarding its natural history. It may lead to spontaneous abortion after losing its vascular connection, or it may end up as a low-lying adherent placenta with or without invasion of the surrounding organs due to its continuous growth. The presentation of the scar ectopic pregnancy may be at 5–6 weeks to 16 weeks.[7] In the present case, the patient was admitted to our hospital at 12 weeks. The timely decision of hysterectomy prevented further complications. Histopathological examination proved to be of utmost importance to rule out the various differential diagnoses, especially gestational trophoblastic diseases. CSEP should be differentiated from placenta accreta or increta, where the pregnancy is intrauterine with an invasion of the villi into the myometrium while CSEP is gestation within the myometrium, separated from the endometrial cavity.[8] Although medical management modalities may be used in selective cases, the best treatment option may be termination of pregnancy by laparotomy and hysterotomy with uterine scar repair.[6] The important issue to be considered here is the condition of the uterine scar left after medical or conservative surgical treatment and its subsequent behavior in future pregnancies.[9] Other treatment options, though not popular, are (i) dilatation and curettage (D and C) with excision of trophoblastic tissue using laparotomy or laparoscopy, (ii) bilateral hypogastric artery ligation associated with D and C under laparoscopic guidance, (iii) administration of methotrexate locally or systemically with prolonged follow-up of hCG levels.

Conclusion

CSEP is a rare form of ectopic pregnancy, which if not diagnosed and managed early, may lead to serious complications such as uterine rupture. Low beta hCG levels should not exclude the possibility of an ectopic pregnancy. This entity must be a potential differential diagnosis in women with amenorrhea and/or bleeding abnormalities, especially in women with a chronic duration of complaints. Histopathological examination proves to be valuable to differentiate this rare entity from its relatively common differentials. Early diagnosis may even preserve fertility in some cases.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.