Case of a chronic ectopic pregnancy misdiagnosed as pelvic inflammatory disease

Abstract

The definition of a chronic ectopic pregnancy (CEP) is poorly defined in the literature and making a timely diagnosis can be incredibly challenging. This is primarily due to its broad range of clinical presentations and conflicting biochemical and sonographic results. Often, CEPs are mistaken for ovarian malignancies, pelvic inflammatory disease (PID), uterine fibroids or endometriosis, therefore, leading to a delayed diagnosis. We present a case report of a woman who was initially misdiagnosed with PID and then later preoperatively diagnosed with a CEP. This case particularly highlights the diagnostic dilemma posed by CEPs and raises awareness of the key clinical symptoms, biochemical and sonographic investigations which in combination can contribute towards making a timely preoperative diagnosis.

Background

In the UK, the incidence of ectopic pregnancies is 11 per 1000 pregnancies. According to the 2019 MMBRACE report, five women died following complications relating to their ectopic pregnancies between 2015 and 2017.¹ Ectopic pregnancies can be categorised into either acute or chronic forms. While the former is well known and swiftly recognised in early pregnancy units (EPU), the latter tends to be an enigma where there is often a delayed diagnosis.²

The definition of a chronic ectopic pregnancy (CEP) is ill defined in the literature, however, it is usually an ectopic pregnancy presenting with gradual tubal wall disintegration with repeated episodes of haemorrhaging. This results in the formation of a complex pelvic mass.³ CEP is thought to account for 6% of all ectopic pregnancies.⁴ According to a systematic review of 399 patients, the most common presenting symptom in women with CEP is abdominal pain (71%), followed by irregular vaginal bleeding (55%) and fever (5%).³ An asymptomatic presentation is found in 18% of cases.³

Furthermore, the pathogenesis of CEP is not fully understood.⁴ It is thought to occur when trophoblastic tissue degenerates and destroys the tubal wall gradually resulting in repeated haemorrhage.⁴ Bleeding may accumulate within the tube itself to form a haematosalpinx or trickle into the peritoneal cavity to form a haematocele.⁴ This may in turn promote an inflammatory reaction giving rise to adhesions and therefore a complex adnexal mass.⁴ The use of transvaginal ultrasound scanning is partially sensitive in the diagnosis of CEP as this can be seen in 48% of cases.³ However, it is not specific as several alternative diagnoses can give rise to a sonographic appearance of a non-homogeneous adnexal mass.⁵ For example, in one case report, a young woman was diagnosed histologically with a CEP only following laparotomy when she was initially investigated for a likely germ cell tumour.² In view of the protracted clinical course before the diagnosis is achieved, these patients often suffer from chronic pelvic pain which therefore impacts on their quality of life. In rare circumstances, the CEP can rupture leading to life-threatening complications.³ Hence, it is imperative to work towards obtaining a timely preoperative diagnosis.

In this paper, we report the case of a woman who was initially misdiagnosed with pelvic inflammatory disease (PID) and then later preoperatively diagnosed with a CEP. This is one of the few case reports where an accurate preoperative diagnosis was made, hence paving the way for consideration of a certain set of investigations which should be considered when there is an atypical sonographic appearance of an adnexal mass.

Case presentation

A 31-year-old woman, gravida 1, para 0 (presumed miscarriage), presented with a 3-month history of lower abdominal (mainly suprapubic) pain. There was no relevant past medical or surgical history. She denied smoking, contraceptive use or any previous sexually transmitted infections.

Three months prior to her presentation, the patient had a positive urine pregnancy test (UPT) followed by an episode of heavy vaginal bleeding and pelvic pain with a subsequent negative UPT. In view of this, she was presumed to have had a miscarriage. Prior to this, the patient never had an ultrasound scan to confirm the location of the pregnancy.

However, she continued to have irregular ongoing vaginal bleeding and persistent severe left sided pelvic pain following on from her miscarriage. Hence she was reviewed in the EPU 4 weeks later. Her UPT in the unit was negative. A transvaginal scan was unremarkable with no evidence of retained products of conception or adnexal masses. She was, therefore, reassured and discharged.

A few weeks later, the patient then represented to the emergency department due to ongoing left-sided pelvic pain and abdominal bloating. On this occasion, she did not report any vaginal blood loss and her UPT was once again negative.

On physical examination, her abdomen was soft with mild suprapubic tenderness. There was no adnexal tenderness or cervical excitation. Biochemical investigations showed mildly elevated inflammatory markers: white cell count (WCC) was 9.0×10⁹/L and C reactive protein (CRP) 12 mg/L. A transvaginal ultrasound scan performed on the day of her presentation showed a right haematosalpinx, a left hydrosalpinx and a vascular solid structure just inferior to the left hydrosalpinx. Triple swabs from the vagina and cervix were obtained. She was treated as a presumed pelvic infection, commenced on oral antibiotics for PID and discharged home with a plan to be reviewed in the gynaecology outpatient clinic with a follow-up pelvic ultrasound scan after 6 weeks.

The follow-up scan showed a large vascular heterogeneous mass adjacent to the left ovary and she was referred to the on-call gynaecology team. Once again, her UPT was negative. Cervical swabs from her previous admission were negative for chlamydia and gonorrhoea.

Observations were stable. On physical examination, her abdomen was soft and non-tender. Biochemical investigations showed β-human chorionic gonadotropin (β-HCG) 18 mIU/mL, progesterone 30 ng/mL, WCC 8×10⁹/L and CRP 1 mg/dL. On further questioning, she denied any unprotected sexual intercourse since her presumed miscarriage 3 months ago.

At this point, the possibility of a CEP was suggested and hence the patient was admitted with a view to repeating the scan the following morning by the gynaecological Consultant. The scan confirmed the presence of a vascular inhomogeneous conglomerate mass measuring 38×37×34 mm in the isthmic part of the left fallopian tube, separate to the ipsilateral ovary. The mass appeared to contain thick, cystic and echogenic trophoblastic tissue and the left salpinx was slightly distended with blood (figure 1). The patient was informed of the likely diagnosis of a CEP and subsequently consented for a laparoscopic salpingectomy.

Figure 1.

Transvaginal ultrasound scan confirming the presence of a vascular inhomogeneous conglomerate mass in the left adnexa and a left haematosalphinx.

On surgical exploration, the laparoscopic approach was converted to a laparotomy due to dense pelvic adhesions involving the omentum. A left salpingectomy was performed with minimal complications. Postoperative recovery was unremarkable.

Outcome and follow-up

After being discharged a few days later, the patient has remained well and has since provided a patient perspective encounter of her overall experience.

Histological analysis was in keeping with the clinical diagnosis of a chronic ectopic tubal pregnancy. Figure 2 demonstrates the macroscopic view of the three pieces of tissue with the largest being a grossly cystically dilated length of fallopian tube which was rounded and measured 45×40×35 mm. Figure 3 demonstrates the microscopic changes of a grossly dilated fallopian tube showing a few residual viable chorionic villi on a background of scanty infarcted chorionic villi and extensive blood clot within the lumen. Further analysis of the second fragment (figure 4) presumably originally attached to the dilated fallopian tube at the site of defect showed extensive fibrotic and fibrinous tissue with acute on chronic inflammation, macrophages and haemosiderin deposition in keeping with a chronic inflammatory process. There was no evidence of fetal tissue or gestational trophoblastic disease.

Figure 2.

Macroscopic view of the tissue showing the cystically dilated fallopian tube with haemorrhage and necrosis and a defect on the surface (black arrow) where the inflammatory piece (red arrow) was attached. Small third fragment was normal fallopian tube.

Figure 3.

Microscopic view of the fallopian tube containing extensive blood clot on the left side of picture alongside viable chorionic villi present on the right side of the picture (arrowed).

Figure 4.

Microscopic view of the tissue demonstrating inflammation and fibrotic changes with blood clot and haemosiderin deposition.

Discussion

CEP is a diagnosis which requires lateral thinking, as well as some prior experience in its identification. In the field of gynaecology, there are well-recognised pathways to narrow down a minefield of diagnoses when a patient presents with pelvic pain. This relies on the use of routine biochemical and sonographic investigations. The use of the UPT is usually first line as this is a cost-effective tool used to rule out an ectopic pregnancy. However, in the case of a CEP, the small proportion of live chorionic villi renders a low serum HCG level.² Hence, in these cases, the UPT can still be negative which can falsely divert one’s suspicion away from the diagnosis of a CEP.

The urine HCG Clinitest cassette which is used in our hospital can display either positive, borderline or negative results depending on the HCG level. The results of this test should be interpreted after 2–5 min. According to local laboratory standards, a negative result reflects a HCG level <5 mIU/mL whereas a positive result reflects a HCG level of >25 mIU/mL. In cases where the HCG level is between 5 and 25 mIU/mL, the result should be interpreted as borderline, triggering the need for a serum HCG level. A borderline result is an extremely rare occurrence based on our experience. In this case report, our patient had a documented negative UPT with a serum HCG level of 18 mIU/mL. The lack of serum HCG testing at the first presentation led to the inaccurate diagnosis of PID hence leading to a delayed diagnosis of a CEP. This highlights the inherent inaccuracy and limitation of a UPT which should always be cautiously interpreted in such cases.

Furthermore, inflammatory markers in the blood may be elevated due to the chronic inflammatory process in the abdominal cavity.² Hence the unreliable nature of biochemical investigations often adds to the confusion and misdiagnosis. CEP is, therefore, difficult to differentiate from PID, ovarian malignancies, uterine fibroids and endometriosis.³ Often the diagnosis of CEP is suggested in surgery and confirmed after histopathological evaluation.⁶ In our case, the clinical history and investigations were not typical of PID, however, mildly elevated CRP and the evidence of a haematosalpinx influenced the clinical judgement. The absence of fever and a normal WCC should prompt clinicians to consider other differential diagnoses. If serum HCG testing had been considered in line with the atypical sonographic findings during this occasion, then the diagnosis of a CEP would have been made earlier.

Traditionally, an intrauterine pregnancy can be seen with a transvaginal ultrasound scan when the serum HCG level is over a 1000 IU/L.⁷ However, in the case of a CEP, the HCG level is often very low in keeping with the small amount of live villi. Therefore the sonographic appearance of a CEP can be variable and nonspecific.⁸ In most cases, there is usually a complex heterogeneous adnexal mass which may demonstrate vascularity with doppler flow in the periphery or external to the mass.⁸ As a result, this leads to the possibility of a wide range of diagnoses including ovarian tumours, degenerating fibroids, ectopic pregnancies and tubo ovarian abscesses. The key to identifying the accurate diagnosis lies in the clinical presentation of the varying diagnoses.⁸

Hence, it is vital to consider the holistic picture which includes the history, examination and investigations before arriving at the final diagnosis. As seen in this case report, the patient was mildly symptomatic and had a protracted clinical course where she was seen by multiple healthcare professionals of varying grades. This demonstrates how the diagnosis of a CEP can be easily overlooked and therefore greater awareness is required. Furthermore, this case also demonstrates the importance of follow-up consultations when the final diagnosis is still in question.⁷

To conclude, this case particularly highlights the diagnostic dilemma posed by CEPs and raises awareness of the clinical symptoms, biochemical and sonographic investigations which in combination can contribute towards making a timely preoperative diagnosis.

Patient’s perspective.

Over the months of seeing multiple professionals, one of the most challenging aspects was communicating the severity of pain I was experiencing and having this pain acknowledged. The pain was varied and sometimes transient. At times it was mild, however I also experienced regular episodes of intense pain, almost paralysing, which would cause me to faint. I recollect, with great frustration, during one consultation I was told that ‘you do not seem to be in that much pain’, despite trying to convey this. At times I felt that I was judged to be overly anxious, and I was frustrated that my concerns about the pain and how it was affecting my normal functioning were overlooked.

What I value most from this experience and what I believe to have made a difference are the professionals who took the time to take a thorough history, those who took my views into account and showed empathy. Having been otherwise healthy and symptom free prior to the initial positive UPT and presumed miscarriage, I felt confused by the potential diagnoses put forward. The timeline of my symptoms perhaps suggested a pregnancy related complication early on, and I believe that if more consideration was given to this, it would have helped with coming to a more timely diagnosis. I hope that this report will increase awareness of CEPs and the diagnostic difficulties, but also the importance of good communication and history taking during patient consultations.

Learning points.

• Urine pregnancy tests may be inaccurate when the human chorionic gonadotropin (hCG) level is borderline and a negative urine pregnancy test does not rule out a chronic ectopic pregnancy.

• Serum HCG testing should be requested in cases of atypical ultrasound findings which do not correlate with the clinical symptoms.

• In cases where ultrasound findings are inconsistent with the clinical findings, these patients should ideally be rescanned by an experienced sonographic operator.