Gestational choriocarcinoma FIGO stage III, score 8 (high-risk) in 38-year-old woman four weeks postpartum

Introduction

Gestational trophoblastic disease comprises a spectrum of pre-malignant (complete and partial hydatidiform moles) to malignant conditions (invasive mole, choriocarcinoma, rare placental site trophoblastic tumor, epithelioid trophoblastic tumor). The malignant forms are known as gestational trophoblastic tumors or neoplasias [1].

Choriocarcinoma is a rare and malignant gestational trophoblastic neoplasia with direct invasion into the myometrium and frequent hematogenous metastasis into the lungs, brain, liver, pelvis and vagina, kidney, intestines and spleen. Choriocarcinoma is categorized into two different forms: gestational and non-gestational. Gestational choriocarcinoma is the most common type and might occur after any pregnancy. In 50 % of cases it stems from hydatidiform moles, in 25 % it occurs after abortion or tubal pregnancy, in 25 % it occurs after a normal pregnancy. Only 2–3 % of hydatidiform moles progress to choriocarcinoma [2].

Intraplacental choriocarcinoma as a variant of gestational choriocarcinoma involving both infant and mother is extremely rare. Infantile choriocarcinoma usually becomes symptomatic at the age of 0–6 months with anemia, hepatomegaly, hemorrhagic syndromes. Typical metastases are located in the liver, lungs, brain and skin [3].

In Europe and North America, the incidence of gestational choriocarcinoma is 1:40,000 pregnancies. In Southeast Asia the incidence is higher (3.3–9.2:40,000), as well as in Indian Americans, African Americans and Hispanics [2], 4]. Ethnicity, advanced maternal age, prior spontaneous abortions and molar pregnancies, long-term contraceptive use and blood group A might be risk factors for choriocarcinoma. Non-gestational choriocarcinoma arises from pluripotent germ cells and can appear in women and men, for example in the gonads [5]. It has a much worse prognosis and is also less chemosensitive [5]. Gestational choriocarcinoma usually has a paternal chromosomal pattern while non-gestational choriocarcinoma has the patient’s chromosomal pattern, occasionally with karyotype variations [6].

This case report highlights the differential diagnoses of postpartum hemorrhage and underscores the importance of thoroughly examining the placenta. When a sonographic diagnosis suggests retained placental tissue, it should be followed by regular ultrasound monitoring and beta-hCG surveillance. If bleeding persists or sonographic findings raise concern, surgical removal and histological analysis are necessary to rule out gestational trophoblastic neoplasia.

Methods

Case presentation

A 38-year-old woman (2 Gravida, 2 Para) of South American origin presented at our clinic four weeks after her second cesarean section with persistent vaginal bleeding and decreasing hemoglobin from 10.7 to 6.8 mg/L within four weeks. Past medical history included a cesarean section in 2015 due to fetal breech position, tonsillectomy and nasal septum surgery. The patient was breast feeding without complications, had no somatic symptoms and vital parameters were normal. Ultrasound findings included a small 1 × 2 × 3 cm diffusely perfused inhomogenous intrauterine structure (Figure 1) initially assessed to be either a blood clot or retained placental tissue as well as a small amount of approximately 8 mL intraabdominal liquid.

Figure 1:

Ultrasound findings four weeks after delivery. The ultrasound findings four weeks after delivery revealed a normal sized uterus with a small 1 × 2 × 3 cm intrauterine diffusely perfused inhomogenous structure.

Aside from normocytic normochromic anemia and slightly elevated CRP, routine blood tests were unremarkable. Due to rare anemic symptoms a conservative management with misoprostol and intravenous iron infusions was performed for four days. Finally, due to consistent vaginal bleeding and falling hemoglobin a curettage was performed. The histopathological result of the evacuated tissue revealed a gestational choriocarcinoma invading the myometrium (CK18 positive, HPL positive, beta-hCG positive, p63 negative, PLAP positive, Ki67 (MIB-1)>80 %). Beta-hCG was 50,607 IU/L first measured after the histopathological diagnosis was established (course Figure 2). Unfortunately, beta-hCG values had not been assessed at the first presentation of the patient with postpartum vaginal bleeding. Beta-hCG increased to 276,424 IU/L until chemotherapy was started and quickly went back to normal rates.

Figure 2:

Beta-hCG levels over time. Monitoring of beta-hCG levels with marked medical events of cesarean section, curettage and diagnosis, start and end of chemotherapy, as well as emergency embolization. After the start of chemotherapy beta-hCG quickly decreased back to normal values.

Another ultrasound control 7.5 weeks after delivery revealed an enlarged intrauterine inhomogenous hyperechogenous structure about 4 × 4 × 3 cm in size, now with hyperperfusion and potential invasion of the myometrium (Figure 3).

Figure 3:

Ultrasound findings after histopathological diagnosis 7.5 weeks after delivery. The ultrasound findings 7.5 weeks after delivery revealed an intrauterine inhomogenous hyperechogenous structure about 4 × 4 × 3 cm in size, now with hyperperfusion and potential invasion of the myometrium (*).

The computed tomography (CT) scan for staging revealed several small bilateral pulmonary metastases. There were no metastases to the liver, lymph nodes, skeleton or brain (Figure 4).

Figure 4:

Tumor staging. Computed tomography (CT) scan revealed several small bilateral pulmonary metastases (arrows).

In our case the gestational choriocarcinoma was classified as high-risk (score 8) and FIGO III due to its expansion to the lungs. In the FIGO scoring consists of two points for antecedent pregnancy at term, two points for pretreatment hCG level of 276,424 (10⁴–10⁵) IU/L, two points for a maximal tumor size of >5 cm, and two points for >5 pulmonary metastases, resulting in score of 8. Since the prognostic scoring resulted in a high risk of developing a resistance to single-agent chemotherapy, a multi-agent chemotherapy was chosen.

In the course of the inpatient stay a hemodynamically relevant uncontrollable genital bleeding occurred. Therefore, an emergency transcatheter arterial embolization of the uterine artery on both sides was performed (Figure 5). A multi-drug chemotherapy after EMACO-schema was started 9.5 weeks postpartum during 14 days for seven cycles. A CT scan during chemotherapy showed a regression of the tumor mass in the uterus and a complete regression of the pulmonary metastases. A thrombus in the right atrium was identified after the end of chemotherapy, most likely associated with the port catheter. Therefore, anticoagulation with new oral anticoagulants (NOAK) was started. Check-ups since then revealed normal beta-hCG and alpha-fetoprotein levels as well as normal CT scans of the head, thorax, abdomen and pelvis without the suspicious of tumor relapse or metastases. Although not screened, the child did not show any signs of choriocarcinoma.

Figure 5:

Therapeutic radiological intervention. Emergency transcatheter arterial embolization of the left A. uterina was successfully performed due to massive tumor bleeding (A) before intervention and (B) after embolization.

Discussion

Choriocarcinoma is a very rare condition, but still an important and life-threatening diagnosis and might likely be underdiagnosed. Ultrasound plays a key role in the diagnosis, but might not be conclusive. Typical findings of thromboplastic neoplasia include an inhomogeneous invasive structure in the uterine cavity with hyperperfusion and multiple cysts. hCG is a tumor-marker and should be measured when placental histology is absent and vaginal bleeding remains persistent. In gestational trophoblastic disease hCG level is usually above those in normal pregnancies and correlates with the progression of the disease. Risk factors like a prior hydatidiform mole or abortion, Asian, Indian American, African American or Hispanic ethnicity, advanced maternal age (>40 years) or blood group A, and measurement of beta-hCG should be taken into consideration. Histopathological diagnosis can only be performed after curettage or biopsy of the metastatic lesions. Although potential etiological factors have been identified, a definitive cause has yet to be determined. It is likely that both exposure to risk factors and intrinsic defects in gametogenesis and fertilization play a role. Classifying types of gestational trophoblastic disease into specific histologic subsets will help to further characterize potential risk factors. To effectively study environmental and genetic factors across different continents and cultures, it is essential to use accurate reproductive denominators, a standardized classification system, and consistent technology to define index cases. The malignant potential of cases identified through these newer technologies also warrants further investigation; until then, ongoing follow-up of these cases remains advisable [9], 12].

Secondary or late postpartum hemorrhage is defined as severe vaginal bleeding between 24 h and 6 weeks after delivery and affects 1–2 % of all pregnancies [13], 14].

Differential diagnoses include uterine atony, infections, retained placental tissue, arteriovenous malformations or a pseudoaneurysma of the uterine artery, primary or metastatic tumors from other organ systems, or subsequent pregnancy shortly after the last [2], 15], 16].

Uterine atony is the most common cause of primary postpartum hemorrhage (80 % of cases), however it is rarely the cause of secondary postpartum hemorrhage.

Infections, such as endomyometritis, are the most common causes of secondary postpartum hemorrhage (67.5 %) [15]. These conditions are associated with fever, uterine tenderness and pain. Management includes antibiotic therapy and supportive care.

Retained placental tissue causes 21.1 % of cases of secondary postpartum hemorrhage [15]. Management includes conservative treatment with uterotonics, if the bleeding is acceptable and beta-hCG levels are normal, or the removal of the retained placental tissue, sometimes requiring surgical procedure such as curettage.

Arteriovenous malformations and pseudoaneurysmas of the uterine artery may require interventional radiological techniques [16]. Risk factors are previous uterine surgery, such as curettage or cesarean section. Surgical interventions, such as a curettage, might increase the bleeding and should be evaluated carefully.

Bleeding from uterine perforation or metastatic lesions may cause abdominal pain, hemoptysis, melena, or signs of intracerebral or lung metastases [2].

Transcatheter arterial embolization in the clinical management of massive genital bleeding resulting from malignant gynecological neoplasms has significant merits before undergoing subsequent tumor therapy and has been described in the literature [17].

In conclusion, secondary postpartum hemorrhage should be carefully evaluated for potential causes, which require different management strategies.

This case report emphasizes the differential diagnoses of vaginal peripartum bleeding and illustrates the importance of a detailed examination of the placenta. The sonographic diagnosis of presumed retained placental tissue should be followed up with regular ultrasound screenings and beta-hCG surveillance. If the bleeding stays persistent or the sonographic findings are suspect, management requires surgical removal and histology to rule out gestational trophoblastic neoplasia.

What’s already known about this topic?

1. Choriocarcinoma is a very rare and aggressive malignant form of gestational trophoblastic neoplasia.

2. Choriocarcinoma differs in two different subtypes: gestational and non-gestational. Gestational choriocarcinoma is the most common type and might occur after any pregnancy.

What does this study add?

1. We report the case of a gestational choriocarcinoma in the early postpartum period four weeks after delivery.

2. This information can help healthcare providers with the management of postpartum vaginal bleeding and suspected placental residues.