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CASE REPORT
Year : 2021 | Volume
: 24
| Issue : 3 | Page : 446-451
An unusual presentation of choriocarcinoma co-existing with pregnancy, successful delivery, and treatment: A case report and literature review
EP Igbodike1, CA Adepiti2, KO Ajenifuja2, UU Onwudiegwu2, GB Adejuyigbe3, IK Mogaji4
1 Post Part II Fellow of the West African College of Surgeons; Department of Obstetrics, Gynaeconology and Perinatology, Ile Ife, Nigeria
2 Department of Obstetrics, Gynaeconology and Perinatology, Obafemi Awolowo University Teaching Hospital, Ile Ife, Nigeria
3 Department of Morbid Anatomy, Gynaeconology and Perinatology, Obafemi Awolowo University Teaching Hospital, Ile Ife, Nigeria
4 Department of Preventive Dentistry, Gynaeconology and Perinatology, Obafemi Awolowo University Teaching Hospital, Ile Ife, Nigeria
Correspondence Address:
Dr. E P Igbodike
Department of Obstetrics, Gynaecology and Perinatology, Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife
Nigeria
Source of Support: None, Conflict of Interest: None
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1DOI: 10.4103/njcp.njcp_625_19
Abstract
Choricarcinoma co-existing with pregnancy is rare often misdiagnosed with great potential for hemorrhagic complications and death. We present a case of a 34-year-old woman diagnosed with choriocarcinoma in her 3rd pregnancy with vaginal and pulmonary metastasis. Her first episode of vaginal bleeding was in the third trimester which was misdiagnosed. She had spontaneous vaginal delivery at 34 weeks of a healthy neonate. She was refered to gyneoncology unit of our hospital 5 weeks into puerperium from a nearby State hospital due to continouos vaginal bleeding and a growth from the postero-lateral wall of the lower third of the vagina. She had five courses of EMA-CO regimen. Her beta-human chorionic gonadotropin (hCG) has fallen from pretreatment value of 168,266 mIU/ml to <5 mIU/ml by the 5th course and the metastaic lesion regressed. She however developed WHO Stage III Oral Mucositis (with Oroesophageal Candidiasis) due to the side effects of chemotherapy which was co-managed successfully with the oral medicine specialist. She was subequently discharged home with follow-up visits. The quantitative beta-hCG has remained undetectable during her follow-up visits. Choriocarcinoma co-existing with pregnancy is rare, diagnosis often missed and confused with antepartum hemorrhage. Early and correct diagnosis can be life saving. High index of suspicion is needed to make the diagnosis. The role of chemotherapy and close follow-up with quantitative beta-hCG assays are key to survival.
Keywords: Chemotherapy, choriocarcinoma, pregnancy, puerperium, wide tumour excision
Introduction 
Gestational trophoblastic disease (GTD) constitutes a spectrum of tumors and tumor-like conditions characterized by abnormal proliferation of pregnancy-associated trophoblastic tissue of varying propensities for invasion and spread.[1] It ranges from molar pregnancy (partial hydatidiform mole, complete hydatidiform mole, and invasive mole); benign lesion (exaggerated placental site, placental site nodule); malignant form (choriocarcinoma, placental site trophoblastic tumor and epitheloid trophoblastic tumor).[2]
The quoted incidence for choriocarcinoma is 0.133 per 100,000 woman years decreasing by 2.8% per year.[3] An incidence of 1 per 160,000 pregnancies is reported for choriocarcinoma occuring concurrently with pregnancy.[3],[4] The lungs are the most common metastatic site[5] in trophoblastic tumors followed by the vagina.[6] The hypervascular and naturally friable lesion of a vaginal metastatic lesion places the patient at risk for severe hemorrhage, however they do not shed cells, a known intrinsic property of trophoblasts which challenges the cytologic study of these tumors.[5]
Most choriocarcinomas may arise as primary uterine tumors in mature women with majority of trophoblastic tumors involving the vagina as metastatic.[5] Choriocarcinoma however may co-exist with or follow abortion, ectopic pregnancy, hydatidiform mole, or term gestation.[7]
Choriocarcinoma co-existing with an intrauterine gestation is exceedingly rare and carries a very high mortality rate of 62% and 65% for the pregnant mother and fetus, respectively.[8]
Vaginal bleeding from choriocarcinoma in early gestation may be confused with a threatened miscarriage while placenta praevia or placenta abruption may be considered in second trimester and retained products of conception in puerperium.[8]
In most cases, the patient may be a multipara, thus the origin of the choriocarcinoma may be from an earlier gestation.[4]
The mainstay of treatment for vaginal metastasis remains chemotherapy.[6] The use of effective chemotherapeutic agents, prompt recognition of prognostic factors, and the use of sensitive quantitative human chorionic gonadotropin (hCG) assays have made gestational trophoblastic neoplasia (GTN), a curable human malignancy.
Low-risk GTN can be cured with first-line and second-line single-agent chemotherapy, while up to 75–85% of patients with high-risk GTN can achieve cure using etoposide containing combination regimen.[9]
Case Report We present a 34-year-old unbooked lady who had her first episode of vaginal bleeding at a gestational age of 30 weeks. A differential diagnosis of low lying placenta was made but ultrasound features did not confirm diagnosis. Subsequent vaginal examination revealed a nodule located in the distal third of the left vagina wall about 3 cm from the introitus measuring about 2 × 2 cm in its widest diameter necessitating excision at the referring centre. The histology of the excised mass revealed eccrine tumor.
She had spontaneous rupture of fetal membranes at 34 weeks and had spontaneous vaginal delivery of a live male neonate weighing 1.55 kg with good APGAR scores. There was no associated primary postpartum haemorrhage.
She however developed a regrowth of the vaginal tumor and significant vaginal bleeding 4 weeks after the initial vaginal growth excision following which she was referred to the gyne-oncology unit of Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria.
Patient upon arrival to our hospital was pale. The abdominal findings were however unremarkable. Vaginal examination revealed an exophytic sessile mass with a bulb-like base originating from the distal third of the left vaginal wall 3 cm from the introitus with the extent of growth limited just at the introitus. The mass bled easily on contact.
There were wide areas of necrosis, ulcerations, and sloughs. It was tender to touch and friable. It was however possible to get above and below its bulb-like base [Figure 1]. The cervix and the parametrium could not be examined as the mass was excuriatingly tender. The rectovaginal space was however preserved with the rectum containing hard fecal matter. The sphicteric tone was normal with no palpable rectal mass. There were no other significant findings.
Figure 1: Metastasis to the lungs lungs (arrows showing cannon ball metastasis)Her hemoglobin level was 4.3 g/dl, abdominopelvic ultrasound performed with emphasis on the liver, spleen, and intestine revealed no evidence of metastasis. The bulky uterus, measured 13.4 × 14.3 cm in its lateral and anteroposterior dimensions. The myometrial echogenicity was heterogenous and the endometrial plate could not be delineated. There were oval shaped structures seen in the adnexae with several small cysts measuring 6.89 × 7.28 cm in its lateral and anteroposterior dimensions. The liver span was enlarged at 19.1 cm with no obvious metastasis.
She was transfused six units of blood and counselled on tumor excision on the weight of the histology from the referral centre. A wide excision was done under general anesthesia [Figure 2] and the excised mass sent for histology. On the third postoperative day, the mass was observed to be regrowing again. A week after the surgery, the histology report was received confirming choriocarcinoma [Figure 3].
A serum quantitative beta-hCG was immediately requested which came as 112,387 mIU/ml. The chest radiograph revealed two near oval shaped soft tissue density masses, the first was a paratracheal mass projecting on the 4th and 5th right posterior ribs and the medial clavicular end with smooth lateral but obscured medial margin, while a second smaller oval mass was projecting on the 7th right anterior rib with features consistent with canon ball metastasis to the lungs [Figure 4].
A diagnosis of choriocarcinoma with vaginal and lungs metastases was confirmed on the weight of current histology report, serum beta-hCG, and chest X-ray. She was further transfused six units of blood postoperatively which raised the hematocrit to 8.3 mg/dl. A repeat hematocrit over a 24 h period was 5.7 mg/dl. She had addition 4 units of packed cell which raised her hematocrit to 9 mg/dl.
The risks and benefits of treating the disease were discussed with the patient. She was assessed to be in FIGO anatomic stage III since GTD extends to the lungs with a vaginal involvement. Her risk profile was calculated based on the modified World Health Organization prognostic scoring system adapted by FIGO Committee report 2002 and she was assessed to be in the high-risk profile group with a total score of 9 (Stage 3:9) qualifying her for combination regimen with EMA-C0.
The recurrent mass continued to bleed and she was transfused additional nine units of blood making a total of 25 units of blood in all and this raised her packed cell volume to 30%, the minimum required for chemotherapy.
A repeat beta-hCG prior to chemotherapy was 168,266 mIU/ml. She tolerated the first course of chemotherapy satisfactorily with a repeat beta-hCG a day after the first course of 9,395 mIU/ml. A repeat beta-hCG a day after the 2nd course was 355 mIU/ml [Figure 5].
Figure 5: Beta hCG Regression curve following EMA/CO treatment of the index patientThis treatment plan was to continue the chemotherapy until the serum beta-hCG fell below 5 mIU/ml, and then for a further additional three courses of the chemotherapy. The beta-hCG was monitored weekly. She was advised to avoid pregnancy for the next 1 year following completion of treatment since most relapses occur within the first year.
Patient, however, developed severe dysphagia with episodic vomiting by the 5th course of her chemotherapy. This was diagnosed as a WHO grade III (severe) oral mucositis and esophageal candidiasis and was co-managed by the oral medicine specialist and Parasitologist. She maintained her remission with serial serum beta-HCG values less than 5 miu/L.
She was discharged home after the 5th course and sucessful treatment of the oral lesion. She is currently on follow-up visits and her beta-hCG has remained undetectable.
Discussion Choriocarcinoma is a relatively rare tumor with an incidence of one case per 40,000 pregnancies; and its occurrence during pregnancy is even rarer, reported as one per 160,000.[10] The documented incidence of gestational choriocarcinoma is in the range of 5–23 cases per 100,000 live birth.[3]
Padmanabhan in 2009 documented that only 30 cases of choriocarcinoma occurring during pregnancy have been reported in the literature and only in six of them did mother and child survive.[11] The case thus described is another reportable case of gestational choriocarcinoma co-existing with intrauterine pregnancy in which both mother and baby survived.
Choriocarcinomas can be classified based on histogenetical origin into gestational (non-teratomatous) and teratomatous tumors.[7] We however believed that the origin of the choricarinoma thus presented was gestational, because of the obstetric history, high serum beta-hCG titer, and the absence of teratomatous components upon histopathological appraisal.
Two main theories have attempted the explanation for the mechanism of ectopic gestational choriocarcinoma. The extrauterine or ectopic choricarcinoma may be a metastatic tumor post-disapperance of the primary tumor in the uterus.[7],[12] Novak et al. described “chorioepithelioma with reference to disappearance of primary uterine tumor.[12] The second theory is transport of chorionic cells as emboli and malignant transformation in distant organs may lead to ectopic choriocarcinomas.[13]
We favor the first explanation probably as the vaginal lesion may have followed the penultimate getatation, though it is difficult to rule out the second theory too. However, judging from the history and clinicopathological evaluations, we presume that the vaginal tumor may have developed after a latent period of 2 years from the last pregnancy when chorionic elements may have probably entered into the bloodstream and got deposited in the vaginal tissue, and thereafter metastasized secondarily to the lungs.
Complex genetic analysis and polymerase chain reaction (PCR) are modalities that have been utilized recently by some scholars to identify the pregnancy responsible for choriocarcinoma.[14],[15] These techniques may become very useful in the future in defining the origin of choriocarcinomas concurrent with normal pregnancies as seen in the patient presented.
The location and the size of the metastatic tumor may be a pointer to patients that are at increased risk of severe haemorrhage.[6]
The initial diagnosis poised a challenge. The histopathological re-apprasial, high levels of beta-hCG, cannon ball metastases on chest radiograph, presence of bilateral “theca lutein cysts” on abdominopelvic ultrasound scan made the diagnosis of vaginal choriocarcinoma certain.
It is important to know that the most used primary chemotherapy for high-risk GTN is EMA/CO[16] with remission rates of up to 71–86%.[17],[18],[19] Lybol introduced the hCG regression normogram in 2012 for high-risk GTN to predict EMA/CO resistance.[20],[21] Attached is a graph depicting the beta-hCG regression curve following EMA-CO chemotherapy for our patient [Figure 5].
The treatment and diagnostic modalities have evolved with time. In the past, only palliative treatments were given with hysterectomy and bilateral salpingo-oophorectomy, the only therapeutic option for patients with choriocarcinoma until the introduction of methotrexate.
It suffices to say, therefore, that the introduction of effective chemotherapy has revolutionalized prognosis, but the need for adequate follow-up cannot be over-emphasized. It is advised that histopathologic examination after curettage for patients with abortion or postpartum hemorrhage and routine histologic examination of the placenta will allow the diagnosis of GTD early enough for a therapeutic intervention and better outcome.
Conclusion It is very difficult to conclude if this choriocarcinoma originated from penultimate pregnancy, the first pregnancy, or from index pregnancy. The development of choriocarcinoma during the index pregnancy and a possible regrowth of a tumor that originated from a previous pregnancy are both possible explanations for this rare disease. Early diagnosis with a high index of suspicion and effective treatment are however imperative for patients' survival.
The advocacy for routine placenta histopathology may not be out of place, however, this may be challenged by the socio-cultural mileau where placentae are taken away post-delivery by the family involved. Awareness campaigns and education of the populace through widespread media may change this socio-cultural pattern over time.
Choriocarcinoma has significant fatal outcome when undiagnosed bearing in mind its unsual presentations; therefore a reappriasal of these clinical signs and symptoms can sharpen the clinicians' index of suspicion.
The presence of vaginal tumor especially if accompanied by bleeding in pregnancy should alert the physician of a possible choriocarcinoma co-existing with pregnancy.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References 
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