Partial Molar Ectopic Pregnancy: A diagnostic challenge.

Here, we present a rare case of a primigravida who presented to us with symptoms and signs suggestive of an ectopic gestation, which turned out to be a partial mole in histopathological examination. Since it is a very rare occurrence, we would like to publish the case details in this case report.

Pregnancy, Obstetrics and gynaecology, Reproductive medicine

Partial molar ectopic pregnancy is a very rare entity, with tubal molar pregnancies accounting for only about 40 cases in the available literature. The patient usually presents with symptoms and signs of a classical ectopic pregnancy, and the diagnosis is usually not established unless histopathological results arrive. Hence, there is a need for histopathological studies and cytogenetics for all cases of surgical management of ectopic pregnancy and β-hCG (Beta-human chorionic gonadotropin) follow-up for all cases conservatively managed or treated with methotrexate. Case presentation A primigravida, in her 20s, married for 1.5 years and conceived after ovulation induction, which she had taken since she was very anxious to conceive due to societal reasons, presented to our casualty at 6+4 weeks gestation with pain in the abdomen and vaginal bleeding for 2 days. She had an ultrasound with her, which revealed an ectopic pregnancy. She had regular 30-day menstrual cycles with a flow of 3–4 days. Her medical, past, surgical and psychosocial histories were insignificant, with no known comorbidities, other than a significant history of fever with lower abdominal pain associated with white discharge per vaginum, suggesting pelvic inflammatory disease 1 year ago, for which she had taken treatment. Her last menstrual period was 1.5 months ago. Physical examination revealed a stable, afebrile individual with a pulse rate of 102/min and a blood pressure of 122/72 mm Hg. She had mild pallor on examination. The abdomen was soft on examination, with minimal suprapubic tenderness and no guarding or rigidity. A speculum examination of the cervix revealed minimal bleeding through the external os. Investigations Urine pregnancy test was positive. Haemoglobin turned out to be 102 g/L with a total leucocyte count of 19.87 x10ˆ9/L, and platelet count of 413 x10ˆ9/L. Serum β-hCG was 8962 mIU/mL. A transvaginal sonography was done at our hospital, which revealed a heterogeneous mass measuring 1.2×1.3 cm with a ring of fire appearance suggestive of an ectopic pregnancy. No evidence of any intrauterine pregnancy with an endometrial thickness of 18 mm. A right adnexal cystic mass of size 2.3×2 cm, suggestive of a right ovarian cyst with no colour flow, was noted, probably the corpus luteum. The left ovary was normal, and free fluid was noted in the pouch of Douglas. Differential diagnosis Since ultrasound showed a heterogeneous mass in the tube with free fluid in the pouch of Douglas and the patient had pain in the abdomen and bleeding per vaginum with elevated β-hCG levels, we made the diagnosis of an ectopic pregnancy. Treatment Keeping in view the above findings, the decision was made for an emergency laparotomy after getting the patient’s consent, as laparoscopy services were not available during emergency hours in our centre. Intraoperative details A transverse suprapubic incision was given, and the abdomen was opened in layers. The uterus was 6–8 weeks in size. On examination of the tubes, a right-sided ampullary ectopic pregnancy with some products of conception that looked like vesicles was seen at the fimbrial end of the tube. 100 mL of haemoperitoneum and 50 cc of clots were removed. A right-side salpingostomy was done in view of an unruptured ectopic pregnancy in the ampullary end, and the contents were sent for histopathological examination. Salpingostomy was preferred over salpingectomy in view of the patient’s previous history of pelvic inflammatory disease, the unruptured ectopic pregnancy present in the ampullary end and also taking into account the patient’s wish and consent to conserve the tubes. Moreover, gestational trophoblastic neoplasia or gestational trophoblastic disease (GTD) was not suspected at the time of the surgery.1 The left tube and ovary were looking grossly normal. Outcome and follow-up The surgery was uneventful. 48 hours postsurgery, serum β-hCG was reduced to 780.20 mIU/mL (90% decline). The patient recovered uneventfully and was discharged after 3 days of admission. A follow-up plan was made to check weekly β-hCG values until below the detection levels were achieved, followed by monthly testing for 6 months since the histopathology turned out to be a partial molar pregnancy. β-hCG 2 weeks later was 11.41 mIU/mL and became below detection range 3 weeks postsurgery. She was advised to avoid pregnancy and use contraception, for which she opted for barrier contraception, until her β-hCG levels remain below detection levels for 6 months. Histopathological examination report Microscopic findings Sections examined revealed a focal area showing first-trimester chorionic villi, with many of them showing villous oedema and hydropic changes, and occasional villi showing focal trophoblastic proliferation. Immunohistochemistry or cytogenetics could not be done in this case due to the non-availability of the services. Impression Partial hydatidiform mole (HM).

Molar pregnancy in an ectopic gestation is a very rare event. The incidence is reported to be around 1–5/200 000.2 The diagnosis of this extremely rare condition is completely dependent on histopathological studies. HM was first described as ‘dropsy of the uterus’ by Hippocrates around 400 BCE. It is characterised by trophoblastic proliferation and villous hydropic changes.3 It happens due to aberrations in fertilisation. Complete molar pregnancy arises as a result of an empty ovum being fertilised by a haploid sperm, followed by duplication of the paternal chromosome, with 90% of cases being 46 XX. Whereas a partial mole forms when two sperms fuse with a haploid ovum, resulting in triploidy, which could be 69 XXY (70% cases), 69 XXX (27% cases) or 69 XYY (3% cases). This can occur in ectopic gestations as well since the pathogenesis is entirely before implantation and has no relation to the implantation site for its occurrence. Such ectopic molar pregnancies have been reported in the uterine cornua,4 fallopian tubes, cervical canal,5 and even in the ovaries and peritoneum.6 Since molar tubal ectopic occurrence is very rare, there has been no study to date establishing its risk factors. The risk factors for ectopic pregnancy, such as pelvic inflammatory disease, a history of ectopic pregnancy, intrauterine contraceptive devices, tubal surgery, are applicable for tubal molar pregnancies as well. Molar tubal pregnancies present with similar complaints as ectopic pregnancies, with no features specific to distinguish them either clinically or sonographically.7 8 But it is essential to differentiate between molar and non-molar ectopic pregnancy since the former has the inherent ability of invasion and metastasis.9 The rate of rupture in molar ectopic pregnancies accounts for around 67% when compared with non-molar ectopics, which fall between 25% and 29%.10 This is essentially due to the high invasive capacity of trophoblasts in molar pregnancies. Preoperative diagnosis is not possible. There is no definite β-hCG correlation for tubal molar pregnancies since they are implanted in tubes, and tubal vascularity is limited to producing more β-hCG. Hence, using β-hCG as a tool to differentiate molar and non-molar ectopic pregnancy is not useful. Imaging modalities such as transvaginal sonography, Doppler colour flow have not shown efficacy in diagnosing molar ectopics. Hence, postoperative histopathology is the gold standard for the diagnosis of molar ectopic pregnancy.11 The diagnosis of partial mole is usually made with the observation of abnormal nonpolar circumferential trophoblastic proliferation, often showing a vacuolated phenotype. A more specific diagnosis of a partial mole can be established using immunohistochemistry with P57KIP2, which is expressed only in partial moles.12 Ploidy identification using flow cytometry can perfectly distinguish diploid and triploid moles.13 It is mentioned in the RCOG guidelines on ectopic pregnancy that higher rates of subsequent intrauterine pregnancy have been found if salpingotomy is performed rather than salpingectomy in women with a history of fertility-reducing factors (previous ectopic pregnancy, contralateral tubal damage, previous abdominal surgery, previous pelvic inflammatory disease), but, due to the risk of subsequent ectopic pregnancy and persistent trophoblastic disease, it was concluded that in women with a tubal ectopic pregnancy and a healthy contralateral tube, salpingotomy does not significantly improve fertility prospects compared with salpingectomy.14 15 I want to acknowledge the fact that the management adopted in this case was not according to UK practice due to resource unavailability, as a laparoscopic surgical approach should be the preferred mode when available. In this case, the patient had a history of previous pelvic inflammatory disease, and considering the patient’s consent and wish to conserve the tubes, a salpingostomy was performed after explaining the pros and cons of it and also about the β-hCG follow-up. But this case unexpectedly turned out to be a partial molar ectopic on histopathology, hence, we are reporting this case. Also, it is important to note that although the patient had a history suggestive of PID previously, this could have resulted in damage to the tube that contained the ectopic pregnancy. Hence, it is prudent to say that laparoscopic salpingectomy would be the preferred surgical option for tubal ectopic pregnancies in the presence of a healthy contralateral tube and also to prevent the other consequences mentioned above. The risk of persistent trophoblastic disease in tubal molars is no less than in uterine molar pregnancies. It is approximately 0.5% for partial moles and 15% for complete moles.16 Hence, the need for adequate follow-up is important to diagnose persistent GTD early.17 Jwa et al mention in one of their case reports that a 34-year-old conceived postovulation induction, similar to our case, presented with clinical features of ectopic pregnancy, and diagnostic laparoscopy followed by salpingectomy was performed, which on histopathological examination revealed the presence of tubal choriocarcinoma. The patient was then subjected to chemotherapy.18 This proves the possibility of the occurrence of any form of GTD, ranging from complete and partial mole to extrauterine tubal choriocarcinoma. The prognosis of choriocarcinoma is better in tubes than in the uterus because it can be removed intact.19 Hence through our case report, we wish to emphasise that it is of utmost importance to have a histopathological examination done on the products of conception in all surgically managed ectopic pregnancies. Learning points. The most important learning point is that, although very rare, gestational trophoblastic neoplasia (GTN)/gestational trophoblastic disease (GTD) could occur in ectopic pregnancies, and this should be factored in when counselling patients with ectopic pregnancies about their different management options and the small potential risk of having GTN, which could alter the patient’s decision in choosing her management option. All surgically managed ectopic pregnancies must be put under histopathological screening to identify molar components. Referral to GTD centres would be a good choice in this case. Tissue karyotyping and immunohistochemistry would have made the diagnosis better. Footnotes Contributors: The following authors were responsible for drafting of the text, sourcing and editing of clinical images, investigation results, drawing original diagrams and algorithms, and critical revision for important intellectual content: VK involved in diagnosis, treatment and follow-up of the patient, has written this case report, edited and is the main author. Pathology images from SP and MS. The following authors gave final approval of the manuscript: SS, professor had played a role in diagnosis, treatment and also guided in final editing of the manuscript. Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy. Competing interests: None declared. Provenance and peer review: Not commissioned; externally peer reviewed. Ethics statements Patient consent for publication Consent obtained directly from patient(s).

- 1. Diagnosis and management of ectopic pregnancy. BJOG 2016;123:e15–55. 10.1111/1471-0528.14189 [DOI] [PubMed] [Google Scholar] - 2. Ayyash M, Kole M, Le Q, et al. Partial molar pregnancy presenting as a Tubal ectopic pregnancy. Case Rep Obstet Gynecol 2022. 10.1155/2022/7414190 [DOI] [PMC free article] [PubMed] [Google Scholar] - 3. Soper JT, Mutch DG, Schink JC. American college of Obstetricians and gynecologists diagnosis and treatment of gestational Trophoblastic disease. ACOG Practice Bulletin No53 Gynecol Oncol 2004;93:575–85. 10.1016/j.ygyno.2004.05.013 [DOI] [PubMed] [Google Scholar] - 4. Dagar M, Srivastava M, Ganguli I, et al. Interstitial and Cornual ectopic pregnancy. Conservative Surgical and Medical Management J Obstet Gynecol India 2018;68:471–6. 10.1007/s13224-017-1078-0 [DOI] [PMC free article] [PubMed] [Google Scholar] - 5. Aytan H, Caliskan AC, Demirturk F, et al. Cervical partial Hydatidiform molar pregnancy. Gynecol Obstet Invest 2008;66:142–4. 10.1159/000141647 [DOI] [PubMed] [Google Scholar] - 6. Church E, Hanna L, New F, et al. Ovarian molar pregnancy. Journal of Obstetrics and Gynaecology 2008;28:660–1. 10.1080/01443610802421734 [DOI] [PubMed] [Google Scholar] - 7. Chauhan S, Diamond MP, Johns DA. A case of molar ectopic pregnancy. Fertil Steril 2004;81:1140–1. 10.1016/j.fertnstert.2003.11.022 [DOI] [PubMed] [Google Scholar] - 8. Hasan A, Elhawary A, Abdelaleem MF, et al. Partial Hydatidiform mole in an ectopic Tubal pregnancy. Cureus 2021;13:e15455. 10.7759/cureus.15455 [DOI] [PMC free article] [PubMed] [Google Scholar] - 9. Allen L, Dawson C, Nascu P, et al. A molar pregnancy within the Fallopian tube. Case Rep Obstet Gynecol 2016. 10.1155/2016/4367181 [DOI] [PMC free article] [PubMed] [Google Scholar] - 10. Berlingieri P, Bogdanskiene G, Grudzinskas JG. Rupture of Tubal pregnancy in the Vilnius population. Eur J Obstet Gynecol Reprod Biol 2007;131:85–8. 10.1016/j.ejogrb.2006.03.004 [DOI] [PubMed] [Google Scholar] - 11. Sherer DM, Stimphil R, Hellmann M, et al. Transvaginal Sonographic findings of an isolated intramural uterine Choriocarcinoma mimicking an interstitial pregnancy. J of Ultrasound Medicine 2006;25:791–4. 10.7863/jum.2006.25.6.791 [DOI] [PubMed] [Google Scholar] - 12. Merchant SH, Amin MB, Viswanatha DS, et al. P57Kip2 immunohistochemistry in early molar pregnancies: emphasis on its complementary role in the differential diagnosis of Hydropic Abortuses. Hum Pathol 2005;36:180–6. 10.1016/j.humpath.2004.12.007 [DOI] [PubMed] [Google Scholar] - 13. Tanha FD, ShirAli E, Rahmanpour H, et al. Molar pregnancy presents as Tubal ectopic pregnancy. Int J Fertil Steril 2011;4:184–6. [PMC free article] [PubMed] [Google Scholar] - 14. Becker S, Solomayer E, Hornung R, et al. Optimal treatment for patients with ectopic pregnancies and a history of fertility-reducing factors. Arch Gynecol Obstet 2011;283:41–5. 10.1007/s00404-009-1270-2 [DOI] [PubMed] [Google Scholar] - 15. Diagnosis and management of ectopic pregnancy (green-top guideline No.21). RCOG. [DOI] [PubMed] [Google Scholar] - 16. Seckl MJ, Fisher RA, Salerno G, et al. Choriocarcinoma and partial Hydatidiform moles. The Lancet 2000;356:36–9. 10.1016/S0140-6736(00)02432-6 [DOI] [PubMed] [Google Scholar] - 17. Rotas M, Khulpateea N, Binder D. Gestational Choriocarcinoma arising from a Cornual ectopic pregnancy: a case report and review of the literature. Arch Gynecol Obstet 2007;276:645–7. 10.1007/s00404-007-0394-5 [DOI] [PubMed] [Google Scholar] - 18. Jwa SC, Kamiyama S, Takayama H, et al. Extrauterine Choriocarcinoma in the Fallopian tube following infertility treatment: implications for the management of early-detected ectopic pregnancies. J Minim Invasive Gynecol 2017;24:855–8. 10.1016/j.jmig.2017.03.006 [DOI] [PubMed] [Google Scholar] - 19. Venturini PL, Gorlero F, Ferraiolo A, et al. Gestational Choriocarcinoma arising in a Cornual pregnancy. Eur J Obstet Gynecol Reprod Biol 2001;96:116–8. 10.1016/s0301-2115(00)00412-7 [DOI] [PubMed] [Google Scholar]