The Journal of Reproductive Medicine®
Ectopic Gestational Trophoblastic Disease A Case Series Review Ayman Hassadia, M.D., Fiona M. Kew, M.D., John A. Tidy, M.D., Michael Wells, M.D., and Barry W. Hancock, M.D.
OBJECTIVE: To highlight the clinical presentation, nosed. Presentation is the same as for conventional ectreatment, histological review and outcome of patients topic pregnancy. Central review of the histology should referred to the Sheffield Centre with possible ectopic gesbe undertaken, especially in cases where there is clinical, tational trophoblastic disease (GTD). hCG level or histopathologic concern. Conventional cheSTUDY DESIGN: A retromotherapy for gestational spective case note review of trophoblastic neoplasia is Histopathological diagnosis of patients with possible ectopic effective. Prognosis remains GTD referred to the Sheffield ectopic GTD is difficult, and it is excellent. (J Reprod Med Centre between 1997 and 2012;57:297–300) often overdiagnosed. 2010 was performed. RESULTS: During the 13 Keywords: ectopic pregyears of this retrospective study 6,708 patients were regnancy, gestational trophoblastic disease, hydatidiistered at the Centre with GTD, of whom 42 had form mole, molar pregnancy. possible ectopic GTD. Most patients presented with abdominal pain and/or vaginal bleeding (67%). Ectopic Gestational trophoblastic disease (GTD) is characpregnancy was diagnosed by ultrasound scan in 19%. terized by abnormal proliferation of the trophoblast Laparoscopic removal of ectopic pregnancy was carried during pregnancy. It comprises a spectrum of conout in 50% of cases; the rest underwent laparotomy for ditions ranging from hydatidiform mole (which can removal of ectopic conceptus. Histological review of be complete or partial) to choriocarcinoma. Hydaslides was performed in 19 cases for whom there was tidiform mole affects 1 in 500–1,000 pregnancies.1 clinical concern. This resulted in 12 confirmed cases of The incidence of ectopic pregnancy in the UK is ectopic GTD: 4 choriocarcinomas, 5 partial moles and 3 11.1/1,000.2 This makes ectopic GTD extremely complete moles. No evidence of metastasis was recorded rare, and only a few cases have been reported in the in any of the cases. Three patients diagnosed with ectopic literature.3-7 In the UK, all cases with suspected choriocarcinoma needed chemotherapy. Two responded GTD are registered with 1 of 3 centers. to methotrexate and 1 needed second-line chemotherapy. The aim of this study is to record our recent exAll patients are alive and free of disease. perience with ectopic GTD by reporting new cases CONCLUSION: Ectopic GTD is rare and still overdiagand updating our case series published in 2004.8 We From the Departments of Gynaecological Oncology and of Histopathology, Royal Hallamshire Hospital, Sheffield, and the Sheffield Centre for Trophoblastic Disease, Weston Park Hospital, Sheffield, U.K. Presented at the XVIth World Congress on Gestational Trophoblastic Diseases, Budapest, Hungary, October 16–19, 2011. Address correspondence to: Ayman Hassadia, M.D., Department of Gynaecological Oncology, Royal Hallamshire Hospital, Sheffield, U.K. (
[email protected]). Financial Disclosure: The authors have no connection to any companies or products mentioned in this article.
0024-7758/12/5707-8–0297/$18.00/0 © Journal of Reproductive Medicine®, Inc. The Journal of Reproductive Medicine®
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aim to highlight the clinical presentation, treatment and outcome of patients diagnosed with ectopic GTD registered with the Sheffield UK Centre. Materials and Methods A search of the Sheffield Centre database was performed for patients referred with ectopic GTD from 1997 to 2010. The following details were collated retrospectively for each case: maternal age at registration, past obstetric history, clinical presentation, initial diagnosis, risk factors for ectopic pregnancy, initial treatment, gestational age, central review of histology, use of chemotherapy, final outcome, subsequent pregnancy and duration of follow-up. Descriptive statistics have been used in view of the small number of cases. Follow-up and management protocols of GTD have been discussed elsewhere.8,9 Results During the 13 years of the study 6,708 patients were referred to the Sheffield Centre with GTD. Of those, 42 (0.6%) cases were suspected ectopic GTD. The mean age at registration was 30 years and the mean gestational age at presentation was 6 weeks. Thirty patients were white, 5 Asian, 3 Chinese and 1 of Middle Eastern origin. The figures below refer to all 42 patients unless stated otherwise. Risk factors for ectopic pregnancy were documented in 8 cases: previous tubal surgery (3), previous ectopic pregnancy (4) and pelvic inflammatory disease (1). The majority of patients presented with abdominal pain and/or vaginal bleeding (67%). Ectopic pregnancy was confirmed by ultrasound scan in 19%, suboptimal serial human chorionic gonadotropin (hCG) rise in 20%, and 1 presented to the emergency department clinically in shock. Primary treatment of the ectopic pregnancy was undertaken in the referring hospital. Ectopic pregnancy was removed laparoscopically in half of the patients. Laparotomy was performed in 18 patients (18/42). In 2 cases there was no documentation regarding mode of surgery. The site of ectopic was recorded in 7 cases. Two were in the ampulla, 2 in the cornua and 3 in the ovary. The ectopic pregnancy was ruptured in 10 cases (23.8%). Of the 42 cases registered 18 were referred as ectopic partial moles, 3 complete moles, 6 choriocarcinomas and 11 as showing possible molar changes. One patient was referred with persistently lowlevel elevation of hCG despite having had normal
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histological appearances of the ectopic conceptus. Slides were available for expert histological review in 19/42 cases. This confirmed 4 choriocarcinomas, 3 complete moles and 5 partial moles. Table I demonstrates the demographics and clinical features of the ectopic GTD cases diagnosed after expert review of the histopathology. None of the patients with choriocarcinoma presented with metastatic disease, and all were considered “low risk” according to the WHO prognostic scoring system. Three patients were treated with low-dose intramuscular methotrexate, and 1 did not need chemotherapy. Patient 4 (Table I) did not respond to methotrexate; second-line chemotherapy with intravenous bleomycin, etoposide and cisplatin was given in view of the possibility of nongestational choriocarcinoma. However, subsequent genetic analysis confirmed the choriocarcinoma to be gestational in origin and likely to have arisen in a complete mole of monospermic origin. The patient responded to chemotherapy and is in remission. She went on to have a total abdominal hysterectomy a year later for persistent abdominal pain likely related to polycystic ovarian syndrome. Subsequent pregnancy was recorded in 15/42 cases. Six patients delivered normally and 2 had terminations. Outcome of pregnancy was not recorded in 7 cases. Postnatal urinary hCG follow-up was normal in 8 patients. Seven patients failed to send urinary hCG results. All patients referred to the center and those reported by Gillespie et al8 are in remission. The average follow-up is 16.5 months. Discussion Ectopic GTD is exceptionally rare. Confirmed cases account for only 0.2% of referrals during the 13 years of study. We were able to add 10 new cases of confirmed ectopic GTD to our previous series, which reported 6 cases,8 and have also updated the outcome in the earlier cases. Histopathological diagnosis of ectopic GTD is difficult, and it is often overdiagnosed.10,11 As demonstrated in our study, only 12/19 (63%) of patients were correctly diagnosed as having ectopic molar pregnancy by the referring hospital. This compares favorably with other series in which correct diagnosis was made in 15%10 and 6%.11 The recent improvement in accuracy of diagnosis might be as a result of these earlier studies, highlighting the fact that ectopic molar pregnancy was and probably still is overdiagnosed. Those authors also out-
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Table I Cases of Ectopic GTD Confirmed After Expert Histological Review Type Age of Risk Gravidity/ Case (y) GTD score parity Presentation 1*
38
CC
2
5/3
PV bleeding
2*
17
CC
3
4/0
3
36
CC
1
2/0
PV bleeding, abdo pain PV bleeding
4
35
CC
0
3/2
5
28
CM
––
2/1
6
30
CM
––
3/1
7
33
CM
––
4/3
8
19
PM
––
1/0
9
30
PM
––
3/2
10
27
PM
––
2/1
11
29
PM
––
2/1
12
29
PM
––
6/1
Abdo pain, abnormal USs PV bleeding, abnormal USs Abnormal USs Abnormal USs PV bleeding PV bleeding, abnormal USs N/K PV bleeding, abdo pain, abnormal USs PV bleeding, abnormal USs
Mode of evacuation Open salpingectomy Open salpinggectomy Laparoscopic salpingectomy Laparoscopic oophorectomy
Gestational age (wks)
Treatment at Centre
Wks until Persis- Remission/ normal tent follow-up Subsequent hCG GTD (mos) pregnancy
8
None
5
No
Yes/123
N/K
100,000 IU/L. None of the patients in this series presented 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. Ruptured ectopic pregnancy was recorded in 10 (23%) cases. This is proportionately lower than previously reported by Gillespie et al8 (60%). This could be due to the use of modern ultrasound machines and serial serum hCG levels (according to standard protocols) for the diagnosis and management of possible ectopic pregnancy. At least half of the patients in the present series had the ectopic conceptus removed laparoscopically. Based on our small numbers, the mode of surgery does not seem to affect the prognosis or time taken for hCG levels to normalize. Most of the patients in this series did not develop persistent disease after surgical removal of the ectopic GTD. Also, whereas Muto et al7 reported 4 of 6 patients with ectopic (fallopian tube) choriocarcinoma presenting with metastases, none of the patients in our series presented with or developed metastases. Three patients required chemotherapy, all of whom are in remission. Only 1 needed secondline chemotherapy. This demonstrates the excellent prognosis of this condition. In conclusion, ectopic GTD is rare and is still overdiagnosed. Presentation is the same as that of
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normal ectopic pregnancy. Expert review of the histopathology should be carried out, especially in cases where there is clinical, hCG level or histologic concern. Conventional chemotherapy for GTN is effective. The prognosis remains excellent. References 1. Smith HO, Kim SJ: Epidemiology. In Gestational Trophoblastic Disease. Edited by BW Hancock, RS Berkowitz, ES Newlands, et al. Second edition. Available at: www.isstd. org. 2. Lewis G: Saving mothers’ lives: Reviewing maternal death is to make motherhood safer 2003–2005. London, CEMACH, 2007, pp 93–94 3. Hwang JH, Lee JK, Lee NW, et al: Molar ectopic pregnancy in the uterine cornus. Minim Invasive Gynecol 2010;17:239– 241 4. Soares PD, Costa OL, Costa LA, et al: Gestational trophoblastic neoplasia following molar ectopic pregnancy: A case report. J Reprod Med 2008;53:579–582 5. Chauhan S, Diamond MP, Johns DA: A case of molar ectopic pregnancy. Fertil Steril 2004;81:1140–1141 6. Zite N, Lipscomb G, Merrill K: Molar cornual ectopic pregnancy. Obstet Gynecol 2002;99(5 Pt 2):891–892 7. Muto MG, Lage JM, Berkowitz RS, et al: Gestational trophoblastic disease of the fallopian tube. J Reprod Med 1991;36: 57–60 8. Gillespie AM, Lidbury EA, Tidy JA, et al: The clinical presentation, treatment and outcome of patients diagnosed with possible ectopic molar gestation. Int J Gynecol Cancer 2004; 14:366–369 9. Fisher PM, Hancock BW: Gestational trophoblastic diseases and their treatment. Cancer Treatment Rev 1997;32:1–16 10. Burton JL, Lidbury EA, Gillespie AM, et al: Over-diagnosis of hydatidiform mole in early tubal ectopic pregnancy. Histopathology 2001;38:409–417 11. Sebire NJ, Lindsay I, Fisher RA, et al: Overdiagnosis of complete and partial hydatidiform mole in tubal ectopic pregnancy. Int J Gynecol Pathol 2005;24:260–264
