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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 46  |  Issue : 4  |  Page : 177-181

Primary vaginal gestational trophoblastic neoplasia treated with uterine angiographic embolization and Etoposide, Methotrexate, Actinomycin D, Cyclophosphamide, and Vincristine: Philippines' first reported case


Department of Obstetrics and Gynecology, St. Luke's Medical Center, Quezon City, Philippines

Date of Submission07-Mar-2022
Date of Acceptance25-May-2022
Date of Web Publication7-Oct-2022

Correspondence Address:
Maria Concepcion D. Cenizal-Santos
Doble Cenizal-Santos, 181 Cordillera Street, Quezon City 1114
Philippines
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/pjog.pjog_34_22

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  Abstract 


Gestational trophoblastic neoplasia (GTN) in itself is an uncommon condition, much so is primary extrauterine GTN. The incidence of GTN in the Philippines is at 22.4/40,000 pregnancies. However, no report has been made for primary extrauterine GTN. Only two cases of primary vaginal choriocarcinoma are reported in literature. This is a case of a 26 year old G1P0 (0010) who came in for profuse vaginal bleeding. Serum beta-human chorionic gonadotropin (β-hCG) was elevated and ultrasound showed hypervascular vaginal mass and an empty uterus. A primary vaginal GTN was considered and the patient was treated with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMACO) regimen. During the course of chemotherapy, there was a note of profuse vaginal bleeding which was controlled by angiographic uterine artery embolization. A normal β-hCG level was achieved after six cycles of EMACO. The patient was able to have three successful pregnancy outcomes thereafter. Primary vaginal GTN is a rare condition that requires a high index of suspicion. In a nulliparous patient complicated with profuse vaginal bleeding, angiographic embolization is an effective fertility-sparing procedure that can manage the said complication.

Keywords: Angiographic embolization, extrauterine gestational trophoblastic neoplasia, vaginal gestational trophoblastic neoplasia


How to cite this article:
Cenizal-Santos MC, Chua AA, Aquilizan LF. Primary vaginal gestational trophoblastic neoplasia treated with uterine angiographic embolization and Etoposide, Methotrexate, Actinomycin D, Cyclophosphamide, and Vincristine: Philippines' first reported case. Philipp J Obstet Gynecol 2022;46:177-81

How to cite this URL:
Cenizal-Santos MC, Chua AA, Aquilizan LF. Primary vaginal gestational trophoblastic neoplasia treated with uterine angiographic embolization and Etoposide, Methotrexate, Actinomycin D, Cyclophosphamide, and Vincristine: Philippines' first reported case. Philipp J Obstet Gynecol [serial online] 2022 [cited 2022 Dec 6];46:177-81. Available from: https://www.pogsjournal.org/text.asp?2022/46/4/177/358081




  Introduction Top


Gestational trophoblastic neoplasia (GTN) encompasses the malignant end of the spectrum of gestational trophoblastic disease. The incidence of GTN varies in different regions of the world. Incidence of one in 40,000 was reported in Europe and North America and 3.3–9.2 in 40,000 pregnancies in Southeast Asia.[1] In the Philippines, the incidence of GTN remained to be almost constant at 22.4 per 40,000 pregnancies.[2] However, the incidence of primary extrauterine GTN has not been reported. To date, only two cases of primary vaginal choriocarcinoma are reported in the literature. Profuse vaginal bleeding as a complication of GTN can be catastrophic and even fatal when not managed promptly. Patient's desire to preserve fertility leads to the utilization of innovative procedures to address both life-threatening hemorrhage and the patient's chance for future pregnancy.


  Case Report Top


This is the case of a 26-year-old gravida 1 para 0 (0-0-1-0) with a chief complaint of profuse vaginal bleeding 3 months after having a complete abortion. A consult was initially done in Guam where she underwent work-up. Complete blood count showed anemia (hemoglobin 7.6 g/dl) which was corrected with transfusion of 3 units of packed red blood cells (hemoglobin 11.4 g/dl). Elevated serum beta-human chorionic gonadotropin (β-hCG) at 320, 279 mIU/ml was noted. The patient underwent pelvic ultrasound which revealed a heterogeneous, globular, and highly vascular mass in the area of the vagina. The uterus was normal in size with thin endometrium. No lesion was seen in the uterus. Initial consideration at that point was GTN. The patient opted to continue her medical care in the Philippines; hence, she was discharged after 2 days with a repeat hemoglobin of 11.4 g/dl and repeat β-hCG of 465, 000 mIU/ml and was transferred to a tertiary hospital in the Philippines. With the history of profuse vaginal bleeding and an ultrasound finding of highly vascular vaginal mass, speculum examination and internal examination were not performed to avoid manipulation of the said lesion. A repeat β-hCG was still elevated at 513, 551 mIU/ml. The patient underwent careful transvaginal ultrasound which revealed an irregular vascular vaginal mass located caudal to the cervix, measuring 5.6 cm × 4.9 cm × 3.7 cm. The uterus was normal in size, with no lesions. With these findings, a diagnosis of Primary Vaginal GTN (II:8) was made. The patient was then referred to a GTN specialist. Combined chemotherapy in the form of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMACO) was started. On EMACO I day 5, the patient experienced profuse vaginal bleeding, in which hemodynamic stabilization was done. An attempt to control the bleeding with vaginal packing was unsuccessful; hence, a referral to interventional radiologist was made, who then considered doing pelvic angiography. Angiography showed hypervascular vaginal mass mainly supplied by the dilated and tortuous bilateral uterine arteries [Figure 1]; hence, a bilateral uterine artery angiographic embolization was performed [Figure 2]. The procedure was completed uneventfully and was tolerated well by the patient. Vaginal bleeding was completely controlled by the procedure. Chemotherapy with EMACO was continued. Serial monitoring of β-hCG was done until a normal result was achieved after six cycles of EMACO and after three clean-up courses, the patient achieved complete remission [Table 1]. Doppler ultrasound of the mass done after EMACO I [Figure 3] was compared with that done after EMACO VIII (Clean up course II), which showed a significant decrease in the size of previously noted complex mass at the upper vagina [Figure 4].
Figure 1: Pelvic angiography: Dotted lines outline the hypervascular vaginal mass mainly supplied by the dilated and tortuous bilateral uterine arteries

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Figure 2: Uterine artery angiographic embolization: (a) Tortous right uterine artery before embolization, (b) right uterine artery showing complete embolization after the procedure, (c) tortous left uterine artery before embolization, and (d) left uterine artery showing complete embolization after the procedure

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Figure 3: Sonographic image of the vaginal mass (marked by dotted cirle) measuring 4.2 cm × 6.5 cm × 4.5 cm after the first cycle of EMACO. EMACO: Etoposide, Methotrexate, Actinomycin D, Cyclophosphamide and Vincristine

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Table 1: Serial beta-human chorionic gonadotropin showing a significant decreasing trend in the values of the patient from the time of consult until the end of the third clean up course

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Figure 4: Sonographic image of the vaginal mass (marked by dotted circle) measuring 1.7 cm × 1.0 cm × 0.7 cm after the eighth cycle of EMACO. EMACO: Etoposide, Methotrexate, Actinomycin D, Cyclophosphamide and Vincristine

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The patient had regular follow-up and serial β-hCG monitoring which remained to be normal. The fertility of the patient was preserved as evidence in her succeeding obstetric history. She had a total of three pregnancies thereafter, all of which were carried to term, delivered vaginally without fetal and maternal complications encountered. Following chemotherapy and uterine artery embolization performed, succeeding pregnancies were delivered as follows: first, pregnancy was delivered 2 years and 4 months after, the second was delivered 4 years and 9 months after, and third pregnancy was delivered 6 years from chemotherapy and uterine artery embolization.


  Discussion Top


Clinical presentation

Extremely rare cases of primary extrauterine GTN, with the cervix as the most identified site of lesion, are reported in the literature.[3] Some theories suggest that it may have arisen from a uterine cavity tumor that spontaneously regress after it spread to other sites.[4] Clinical manifestations of GTN differ according to the site affected by the disease, vaginal bleeding being the most common initial symptom. In rare cases of primary GTN outside the uterus, clinical signs and symptoms are more nonspecific as it may mimic other more common diseases considered in the site of the lesion. Vaginal metastasis may have the same manifestation as that of primary vaginal GTN. Both can present as a bluish cystic vaginal mass which has deep pelvic anastomosis; hence, biopsy should never be attempted since it can cause intractable bleeding. There were two cases of primary vaginal choriocarcinoma published in the literature. First case was that of a postmenopausal woman reported by Sonobe, who presented with atypical vaginal bleeding 23 years after her last pregnancy.[5] The second case was that of a 33 years old who presented with lower abdominal pain and urinary retention who on work-up was noted to have elevated β-hCG and an anterior vaginal mass.[6]

In the case presented, the only attributable risk factor that could predispose her to develop tumor is the history of spontaneous abortion. The patient presented with profuse vaginal bleeding with associated vaginal mass and increased β-hCG. Based on the criteria made by Saito, in their extensive survey on extrauterine GTN,[7] we considered this case as a primary ectopic GTN. The criteria include: (1) Absence of focus of choriocarcinoma in the uterine corpus as the sonographic imaging of the patient showed normal-sized uterus without note of any mass or lesion and (2) exclusion of extrauterine choriocarcinoma coexisting with hydatidiform mole or intrauterine pregnancy. Furthermore, part of the criteria is that an intramural choriocarcinoma in the uterine corpus should not be considered ectopic choriocarcinoma, which was not present in the patient. The last criterion are a histopathological diagnosis confirmed as choriocarcinoma. However, this could not be done in the index case because biopsy of the vaginal mass was not performed to avoid possible intractable hemorrhage.

Diagnosis

Diagnosis of GTN is based on clinical presentation, hormonal assay, and imaging studies. Histopathologic diagnosis is not always possible, as with the index patient wherein further manipulation of the vaginal mass is avoided to prevent further intractable hemorrhage. In other cases, these factors contribute to the difficulty in making accurate clinical diagnosis and eventually may lead to delayed appropriate management. The most important factor in the recognition of GTN is a high index of suspicion and consideration for its possibility. In the case presented, to denote the extent of the disease, as that of primary uterine GTN, the FIGO anatomical staging and WHO scoring system were applied.

Management

GTN is unique compared to other malignant tumors since treatment can be initiated even without histologic confirmation. Just like in cases of primary uterine and metastatic GTN, the cornerstone in the treatment of this patient's vaginal GTN is chemotherapy. However, due to the highly vascular nature of the tumor, hemorrhage can persist and worsen even with the initiation of chemotherapy, as what transpired with the index patient. In a young and nulliparous patient such as in this case, an innovative procedure to address both life-threatening hemorrhage and the patient's chance for future pregnancy is warranted. This leads to the consideration of angiographic embolization, a minimally invasive procedure that can address massive bleeding while preserving the patient's fertility.

Due to the rarity of the condition of interest, there is the scarcity of studies on the relationship between uterine artery angiography and succeeding fertility among patients who had GTN treated with the said procedure. McGrath et al. reviewed 19 GTN patients with bleeding vaginal metastases who underwent polyvinyl alcohol particle-based radiological embolization via femoral artery approach at Charing Cross Hospital in London from 2000 to 2009. Control of hemorrhage was achieved in 18 out of 19 patients while only one patient necessitated surgical intervention. Pelvic pain requiring opiate administration was the most common morbidity of the procedure. Out of the 19 patients reviewed, nine had successful pregnancy outcomes.[8] A study conducted by Keepanasseril in 2011 included eight women diagnosed to have GTN who presented with massive vaginal hemorrhage. All women underwent angiography, and embolization was performed in seven of the eight patients. Bilateral internal iliac artery embolization was done on two patients, bilateral uterine artery embolization was done on four patients, and one patient underwent bilateral uterine and hepatic artery embolization. In 85.7% of the patients, embolization was successful in managing massive hemorrhage. Chemotherapy was administered to all patients. Five out of the eight patients were in remission, while three succumbed to the disease. Out of the two who tried to get pregnant, one delivered a term infant, while the other had a miscarriage.[9] A case report by da Silva in 2021 presented a 23-year-old G1P0 (0010) with GTN III: 7 complicated by severe vaginal hemorrhage whose uterus was rescued by utilizing uterine artery embolization.[10] These cited cases and reports showed that angiographic embolization, with low short-term toxicity, is a safe procedure that could be considered among patients with GTN who present with massive vaginal hemorrhage and are still desirous of getting pregnant since the procedure showed no obvious detrimental effect on the future fertility. The first reported angiographic embolization utilized in a GTN patient in the Philippines was reported by Yap and Soriano-Estrella in 2016.[11] Angiographic embolization was done in the bilateral internal pudendal artery branches and obturator artery branches of a choriocarcinoma patient with metastasis to the labia.

In the index patient, percutaneous right transfemoral 5F Cordis Pigtail catheterization of the lower abdominal aorta was performed for the aortoiliac study, and 5F Impress Berenstein and 3F Terumo Progreat selective and superselective catheter-contrast examination of the bilateral common iliac, internal iliac, and uterine circulations was done. The procedure revealed a hypervascular vaginal mass mainly supplied by the dilated and tortuous bilateral uterine arteries. Minor collateral blood supplies were noted to be coming from the adjacent pelvic vessels. The rest of the visualized internal iliac circulations showed normal intimal outline and branching pattern. Sequential superselective catheterization of the left then the right uterine arteries facilitated embolization using Boston Contour Polyvinyl Alcohol particles. This provided complete resolution of the profuse vaginal hemorrhage.

GTN is a rare tumor, much so is a primary extrauterine GTN, in the case presented, a primary vaginal GTN. To date, this is the first case of primary vaginal GTN reported in our country, and the third in the world. Although staging and prognostication seem to be the same for primary vaginal GTN and metastatic GTN to the vagina, primary vaginal GTN is still worth reporting as it may raise the index of suspicion of the attending physician in diagnosing GTN in the absence of uterine lesion or mass. Knowledge of such cases may lead to proper diagnosis and, in turn, prompt and appropriate management of GTN patients who are presented with extrauterine mass and normal empty uterus.

The angiographic embolization presented in this article is the first reported case performed in a clinically diagnosed primary vaginal GTN with the purpose of sparing fertility. Angiographic embolization is a life-saving procedure in managing acute hemorrhage in a GTN patient who is still desirous of future pregnancy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Lawrie TA, Alazzam M, Tidy J, Hancock BW, Osborne R. First-line chemotherapy in low-risk gestational trophoblastic neoplasia. Cochrane Database Syst Rev 2016:CD007102. doi: 10.1002/14651858.CD007102.pub4.  Back to cited text no. 1
    
2.
Cagayan MS. Changing trends in the management of gestational trophoblastic diseases in the Philippines. J Reprod Med 2010;55:267-72.  Back to cited text no. 2
    
3.
Kairi-Vassilatou E, Papakonstantinou K, Grapsa D, Kondi-Paphiti A, Hasiakos D. Primary gestational choriocarcinoma of the uterine cervix. Report of a case and review of the literature. Int J Gynecol Cancer 2007;17:921-5.  Back to cited text no. 3
    
4.
Sorbi F, Sisti G, Pieralli A, Di Tommaso M, Livi L, Buccoliero AM, et al. Cervicoisthmic choriocarcinoma mimicking cesarean section scar ectopic pregnancy. J Res Med Sci 2013;18:914-7.  Back to cited text no. 4
    
5.
Sonobe H, Taguchi K, Ogawa K, Yoshioka T. Latent vaginal choriocarcinoma in a postmenopausal woman. Acta Pathol Jpn 1976;26:611-8.  Back to cited text no. 5
    
6.
Wong T, Fung EP, Yung AW. Primary gestational choriocarcinoma of the vagina: Magnetic resonance imaging findings. Hong Kong Med J 2016;22:181-3.  Back to cited text no. 6
    
7.
Saito N. On ectopic choriocarcinoma. World Obstet Gynecol 1965;17:459-84.  Back to cited text no. 7
    
8.
McGrath S, Harding V, Lim AK, Burfitt N, Seckl MJ, Savage P. Embolization of uterine arteriovenous malformations in patients with gestational trophoblastic tumors: A review of patients at charing cross hospital, 2000-2009. J Reprod Med 2012;57:319-24.  Back to cited text no. 8
    
9.
Keepanasseril A, Suri V, Prasad GR, Gupta V, Bagga R, Aggarwal N, et al. Management of massive hemorrhage in patients with gestational trophoblastic neoplasia by angiographic embolization: A safer alternative. J Reprod Med 2011;56:235-40.  Back to cited text no. 9
    
10.
Silva AC, Passos JP, Signorini Filho RC, Braga A, Mattar R, Sun SY. Uterine rescue in high-risk gestational trophoblastic neoplasia treated with EMA-CO by uterine arteries embolization due to arteriovenous malformations. Rev Bras Ginecol Obstet 2021;43:323-8.  Back to cited text no. 10
    
11.
Yap B, Soriano-Estrella A. Bilateral internal pudendal artery angiographic embolization of labial metastasis from gestational trophoblastic neoplasia. Philipp J Obstet Gynecol 2016;40:27-31.  Back to cited text no. 11
    


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