Choriocarcinoma is a rare malignancy that occurs mainly in women between 20 and 50 years of age, with a mean incidence of 1 in 40 000 pregnant women (1–3). Etiologically, choriocarcinoma may derive from any pregnancy; however, it is most commonly associated with a molar pregnancy or a miscarriage (4). A complete or partial hydatidiform mole increases the risk of developing choriocarcinoma with the incidence of 3 in 1000 pregnancies (5). Less frequently, choriocarcinoma may also result from non-gestational tumors and may be a part of poorly differentiated germ cell tumors (6). The initial symptom of choriocarcinoma is abnormal uterine bleeding (2). Before the disease is symptomatic, the diagnosis can be established based on an abnormally high level of serum human chorionic gonadotropin (hCG). However, a choriocarcinoma has high metastatic potential, for which an affected patient can present with symptoms derived from distant metastases - hemoptysis, neurological symptoms, or uncontrolled internal bleeding (6). Symptoms related to metastases may emerge first before a precise diagnosis of choriocarcinoma. The common locations of metastases are the lungs (80%), brain (39%), vagina (30%), pelvis (20%), and liver (10%) (6, 7). Metastatic invasive trophoblastic disease during concomitant normal pregnancy is exceptionally uncommon, which occurs in 1 in 160 000 pregnancies. So far, only 19 cases of metastatic choriocarcinoma during pregnancy have been reported in literature (6). Here, we present a rare case study of choriocarcinoma in pregnancy which was complicated with massive intra-abdominal and intrapleural hemorrhage due to metastasis. Following an emergency cesarean section at 29 weeks of gestation, the patient was managed in the intensive care unit, underwent abdominal surgeries due to recurrent hemorrhage, and subsequently received chemotherapy.

Choriocarcinoma is a rare malignant disease. It can be divided into gestational and non-gestational. The former originates from trophoblasts, whereas the latter originates from pluripotent germ cells (8, 9). Due to the frequent presence of paternal genetic material, gestational choriocarcinoma evokes a more intense immune response and is sensitive to chemotherapy (10). This disease subtype is characterized by high survival rates ranging from 91% to 100%, depending on the risk group (1). Non-gestational choriocarcinoma is derived from germ cells, has a much worse prognosis, and is less sensitive to chemotherapy (11). It is unrelated to pregnancy and was reported to have primary sites in the ovaries, lungs, cervix, endometrium, breast, bladder, and gastrointestinal tract (9). Due to the similarities in clinical and histological features, the differentiation between these two types can only be achieved by genetic testing which identifies the presence of paternal DNA in gestational choriocarcinoma (12). In the case of our patient, it remains unclear whether choriocarcinoma derived from her previous pregnancy. It is also hard to rule out that the patient might have had an early miscarriage that was interpreted as delayed menses.

It is challenging to establish the diagnosis of choriocarcinoma during an ongoing pregnancy. The general symptoms of malignancy can be improperly interpreted during gestation (13). Choriocarcinoma was considered in the differential diagnosis in our patient due to the high value of human chorionic gonadotropin (131 087 mlU/ml). It significantly exceeded the reference concentrations in 29 weeks of gestation, which, according to the Korevaar et al. study, usually is not higher than 74 719 mlU/ml after 25 weeks - hCG concentration during pregnancy typically reaches the maximum at the end of the first trimester and steadily decreases with the remaining gestation time (8). The complete disappearance of hCG was observed between 11 to 16 days (13) and 8 to 24 days (14). Cesarean section as a delivery method can influence the hCG concentration around the time of the procedure but does not impact the pace of its decrease (14).

Based on the clinical presentation of this patient, it was difficult to establish the diagnosis of choriocarcinoma during the ongoing pregnancy before the result of the histopathological examination was available. Bleeding from internal organs often occurs in metastatic disease (15, 16); however, it is not specific to choriocarcinoma. Moreover, women with choriocarcinoma during pregnancy, like in this case, do not demonstrate a typical clinical presentation of GTN, such as vaginal bleeding, uterine enlargement and the enlargement of bilateral ovaries or some of those can be attributed to pregnancy (17). Therefore, we could only rely on the disproportionately elevated hCG level and the multiple bleeding vascular lesions of her lungs and liver detected by the radiological imaging to support our clinical suspicion of a choriocarcinoma and initiate chemotherapy before the report of histopathological examination was available.

So far, only less than 20 cases of choriocarcinoma during pregnancy have been reported in the literature. Among them, there were three cases with pulmonary and liver metastases, which were also observed in our patient (6). Ding et al. described a pregnant patient with choriocarcinoma metastasizing to the vagina, lungs, and liver. The patient received two cycles of antenatal chemotherapy with EP regimen (etoposide and cisplatin), followed by a caesarean section at 31 weeks and 5 days of gestation and six cycles of EMA-CO regime postnatally. The patient responded well; the mother and child had no clinical symptoms in 4 years of observation. Although chemotherapy can be given during antenatal period, it was not feasible in our case because she had life-threatening internal bleeding, for which the surgical interventions were mandatorily required. In the case published by Kristiansen et al., the pregnant patient was diagnosed with choriocarcinoma metastasizing to the liver and the lungs. The patient underwent a cesarean section and hysterectomy at 22 + 3 weeks. The child died shortly after the procedure, and the mother was qualified for chemotherapy. One course of methotrexate and actinomycin-D was ineffective; therefore, the regimen was changed to BEP (Bleomycin, Etoposide, Cisplatin), which resulted in a complete response (18). Another case described by Brudie et al. presents metastatic choriocarcinoma in a pregnant patient with lung, liver, and brain lesions. The patient received four cycles of chemotherapy with the EMA-CO regimen before the planned induction at 32 weeks of gestation and continued the therapy afterward. The disease and treatment resulted in a persistent left-sided decrease in patients’ peripheral vision. There were no complications in the child (19).

It remains unclear whether an episode of blurred vision observed in our patient could be related to choriocarcinoma. The symptom could be caused by transient cerebral venous thrombosis (CVT). May et al. reported a case of a patient with choriocarcinoma and CVT. The authors indicate an increased risk of developing CVT in conditions predisposing to thrombosis, such as concomitant pregnancy and malignancy, as in the case of our patient (20).

Although the neurological signs and symptoms in our patient were attributable to a cerebral venous sinus thrombosis, it is important for clinicians to have an initial strong suspicion of brain metastasis (21–24), which happens in 39% of cases (6, 7). The imaging modalities of choice for the diagnosis of brain metastasis include CT and MRI. If the imaging tests are inconclusive, a serum: cerebrospinal fluid hCG concentration ratio below 60 can be used as an alternative method to diagnose brain metastasis (21, 25).

Avoiding massive bleeding from liver metastases during chemotherapy was a therapeutic challenge in managing our patient. According to Lurain et al., massive hmorrhage is the most common cause of death in patients with metastatic gestational choriocarcinoma (26). The highest risk of bleeding is at the beginning of chemotherapy due to the tumors high chemosensitivity resulting in rapid necrosis of the lesions (27). Instead of administering the standard EMA-CO regimen for our patient with a metastatic choriocarcinoma and a FIGO risk score of more than 7 (FIGO risk score = 14) (28), an initial single-agent chemotherapy with MTX before escalating it to EMA-CO regimen was decided upon. The rationale of this alternative approach was to reduce her risk of bleeding from the liver lesions by slowing down the rate of vascular necrosis. This similar strategy has also been described by Ding et al, in which a lower dose of chemotherapy with EP regimen (etoposide and cisplatin) was utilized in an antenatal mother to reduce the risk of massive bleeding from metastatic lesions, multiorgan failure and fetal complications (6). The emergency treatment option for massive bleeding from liver metastases is a selective temporal catheterization of the arteries supplying the metastases, which is considered a safer and more efficient method of bleeding control than packing or suturing (27, 28). Nevertheless, an arterial embolization does not completely eliminate the risk of recurrent bleeding. In our case, the multidisciplinary approach, which included surgical bleeding control, the correction of anemia and coagulopathy and assisted radiological embolization, has enabled her to achieve a fast recovery from the life-threatening condition, which rendered her eligible for the curative chemotherapy.

Choriocarcinoma during normal pregnancy is extremely uncommon, and its clinical presentation may not be straightforward. If diagnosed, the disease is potentially curable; however, its complications during treatment can be severe and difficult to manage. Therefore, managing this type of cases requires multidisciplinary team management.

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.

Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

KJ, CM, AF, EN-M, and MPZ contributed to the conception and design of the study. KJ, CM, EP, and MPZ organized the data. KJ and CM wrote the first draft of the manuscript. KJ, CM, and MPZ wrote sections of the manuscript. All authors contributed to the article and approved the submitted version.