Three atypical presentations of choriocarcinoma, occurring during and shortly after a coexistent viable pregnancy
- Nadia A. du Fossé ,
- E. Margo Lutke Holzik and
- Cor H. de Kroon
- Obstetrics and Gynaecology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
- Correspondence to Nadia A. du Fossé; n.a.du_fosse@lumc.nl
Abstract
Gestational choriocarcinoma is a malignant tumour originating from the trophoblastic tissue that can arise during or after any type of pregnancy, but most of the time follows a molar pregnancy. Characteristic for this tumour is its rapid haematogenous spread to various organs, causing atypical presentations often attributable to metastatic disease. We review three cases that occurred during and shortly after a coexistent intrauterine pregnancy. The patient of Case 1 presented with neurological symptoms due to hypercalcaemia, in Case 2 there was initially suspicion of appendicitis and the third patient presented with acute respiratory insufficiency. This case series illustrates that, although highly effective chemotherapy is available, choriocarcinoma can be life-threatening and accurate diagnosis is challenging but critical.
Background
Choriocarcinoma is a rare and highly malignant tumour, belonging to the group of gestational trophoblastic neoplasia (GTN). The aggressive neoplasm arises from the villous trophoblastic tissue and produces human chorionic gonadotropin (hCG). The gestational form of choriocarcinoma has an incidence of approximately 1 in 30 000 pregnancies in Europe and North-America and most commonly develops after a complete molar pregnancy (about 50% of cases), but can follow any type of pregnancy (approximately 25% after abortion or ectopic pregnancy and 25% after normal pregnancy and delivery).1 Due to the trophoblastic cells’ high tendency for vascular invasion, choriocarcinoma is associated with rapid haematogenous spread to various organs. Approximately 30% of patients present with metastatic disease, with the most common sites for metastasis being the lungs, vulvovaginal region, liver and brain.2 When arising after a molar pregnancy, the diagnosis is usually based on a rising serum hCG or abnormal uterine bleeding. However, in many cases, the link with a previous pregnancy is less clear and patients present with various atypical symptoms, often originating from metastatic sites and the diagnosis is delayed. Choriocarcinoma is extremely responsive to chemotherapy, but due to the diagnostic challenge and rapid haematogenous spread, the disease is often already in advanced clinical stage by the time it is diagnosed. Despite the existence of an effective therapy, this diagnostic delay negatively impacts prognosis. We present three exceptional cases of choriocarcinoma with divergent manifestations, but all of them with a fulminant course of disease. In Cases 1 and 2, the patient started having symptoms during a coexistent intrauterine pregnancy and Case 3 presented shortly after an uncomplicated delivery.
Case 1
Case presentation
A 31-year-old pregnant multiparous woman (Gravida 5, Para 2) at 24 weeks of gestation presented with complaints of fatigue, nausea, vomiting, confusion and (hetero-anamnestic) incoherent thoughts in January 2017. These complaints started 3–4 weeks ago and were increasing. She had an obstetrical history of one spontaneous abortion, two consecutive uneventful deliveries and a molar pregnancy one and a half year ago for which she had undergone vacuum evacuation. After this molar pregnancy, her hCG level was monitored and decreased to <0.1 U/L (hCG values over time for each case are shown in table 1). Extensive diagnostic workup showed microcytic anaemia and severe hypercalcaemia. Ultrasonographic examination revealed a solid mass with a diameter of 11 cm next to the right side of the uterus. The fetus had a normal biophysical profile, with normal growth and Doppler-flow assessments. The patient was referred to our hospital (tertiary centre) because of clinical findings and premature gestational age.
hCG values over time
| Case 1 | hCG (U/L) | Case 2 | hCG (U/L) | Case 3 | hCG (U/L) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| *Postdetermination: result obtained 1 week after diagnosis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 8 months before diagnosis (monitoring after molar pregnancy) |
<0.1 | Day 1 (diagnosis, 36 days postpartum) |
463 540 | Day 1 (diagnosis, 19 days postpartum, start first course of EMA-CO) |
300 973 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Day −8 (25 6/7 weeks’ gestation) |
22 256* | Day 16 (1 day after start paclitaxel monotherapy) |
107 452 | Day 12 | 48 300 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Day −7 (26 weeks’ gestation) |
23 957* | Day 22 | 14 199 | Day 19 | 6864 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Day −6 (26 1/7 weeks’ gestation, day of CS; hCG postdetermination in blood collected after CS) |
6178* | Day 28 | 2049 | Day 26 (start second course of EMA-CO) |
2150 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Day −5 | 2436* | Day 42 | 158 | Day 33 | 594 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Day −4 | 677* | Day 63 | 18 | Day 47 | 49 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Day 1 (diagnosis, based on pathology report) |
Unknown | Day 91 (start first course of EMA-CO) |
5.6 | Day 68 | 38 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Day 6 | 7.8 | Day 143 (end of fourth course of EMA-CO) |
1.3 | Day 82 | 11 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Day 13 | 0.4 | Day 170 | 0.8 | Day 95 | 2.8 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| From day 64 onwards |
<0.1 | From day 280 onwards | <0.1 | From day 217 onwards | <0.1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigations
The patient presented with a haemoglobin of 4.3 mmol/L, a calcium level of 4.0 mmol/L, a decreased parathyroid hormone (PTH) of 0.4 pmol/L and an elevated parathyroid hormone-related protein (PTHrp) of 2.7 pmol/L. Liver and kidney functions were normal. MRI of the brain, conducted because of the neurological symptoms, did not show any abnormalities. After the ultrasonographic finding of an abdominal mass, MRI of the abdomen (figure 1) was performed and revealed a lobed retroperitoneal mass (14×10×12 cm) with an intermediated signal on T2-weighted image and low signal on T1-weighted image. The mass did not appear to have a relation with the serosal lineage of the uterus.
T2-weighted MRI abdomen demonstrating a lobed retroperitoneal mass (14×10 cm) right to the uterus (Case 1).
Differential diagnosis
Following radiological findings, the abdominal process was presumed to be most suspect for a retroperitoneal sarcoma, the second most likely option being a paraganglioma. The hypercalcaemia was thought to be caused by PTHrp produced by the tumour. However, paragangliomas are not known to produce PTHrp and metanephrines levels were not increased in a way consistent with the presence of a paraganglioma. Taking her history of molar pregnancy into account, the possibility of choriocarcinoma was considered, but ruled out based on the radiological findings. The differential diagnosis with respect to the hypercalcaemia further included granulomatous disease, tuberculosis (chest X-ray was normal), lymphoma (no lymphadenopathy), multiple myeloma (unlikely because of young age, excluded by M protein assessment).
Treatment
Initially, the patient was symptomatically treated for the hypercalcaemia with furosemide, calcitonin and hyperhydration with sodium chloride. Blood pressures were strictly monitored since maternal hypotension comprised a potential danger for the fetus because of a likely calcified placenta. The condition of the patient was deteriorating (fever), most likely caused by bacterial translocation from the intestine, as blood culture was positive for Streptococcus anginosus. In addition, calcitonin therapy for the hypercalcemia was no longer seen as sustainable management because of need for hyperhydration (6 L/24 hours) and potential teratogenic effects of high dose calcitonin. Tumour excision was thought to be the optimal treatment. Tumour excision with continuation of the pregnancy was not considered feasible because of the extensive surgery and perioperative risks, that is, massive bleeding with direct effect on haemodynamics and thereby placental perfusion, would imply intrauterine risks for the fetus. After a course of antenatal steroids for fetal lung maturation and magnesium sulfate for fetal neuroprotection a combined procedure was performed (26 weeks’ gestation): an uncomplicated caesarean section by median lower abdominal incision and a resection of the retroperitoneally located tumour and lymph nodes. A right hemicolectomy and right adnex extirpation were carried out due to tumour adhesion to the colon and right adnex.
Outcome and follow-up
Following caesarean, a premature daughter was born and admitted to the neonatal intensive care unit (ICU). The postoperative course of the patient was uneventful, except for a positive blood culture for Streptococcus constellatus, which was successfully treated with antibiotics. The pathological results revealed an extensively necrotic choriocarcinoma with ingrowth up to the lumen of the colon ascendens. Margins were free, one omental metastasis was found and resected lymph nodes (18 in total) were tumour-free. The placenta was normally structured and without metastases.
The gestational trophoblastic disease was classified as high-risk since the interval from the molar pregnancy to the time of the diagnosis of the choriocarcinoma was more than 12 months and intestinal and omental metastases were present. However, the patient had undergone complete surgical debulking and a CT chest-abdomen did not show any other metastases. Therefore, chemotherapeutic treatment was not indicated and follow-up consisted of serum hCG monitoring for a period of 2 years. hCG declined following the established regression pattern. In April 2017 it reached a value of <0.1 U/L. The patient had a good recovery and remained in complete remission until now. Her daughter did not suffer any complications of prematurity and shows normal development.
Case 2
Case presentation
A 30-year-old pregnant woman (Gravida 2, Para 1) presented with abdominal pain in March 2008. Besides cholecystitis, she did not have a relevant medical history. Her previous pregnancy had been uneventful. Suspecting appendicitis, a transverse abdominal incision was performed at 17 weeks of gestation. However, the appendix appeared to be without abnormalities. Some blood was seen intra-abdominal and interpreted as a corpus luteum hemorrhagicum. During the continuation of the pregnancy, right-sided abdominal pain persisted. At a gestational age of 34 weeks, an abdominal ultrasound showed a hyperechogenic mass at the right side of the uterus with a diameter of 7 cm, with echolucent areas. Labour was induced at 37 weeks and a healthy son was born in October.
Investigations
Postpartum analysis of the tumour was performed. Laboratory investigations on the first day postpartum showed a hCG of >224 999 U/L (highly elevated) and carcinoembryonic antigen (CEA) of 2.2 ug/L (moderately elevated). Other tumour markers (CA–125, CA 15–3, CA 19–9) were low.
An abdominal CT scan (figure 2) showed a multicystic mass (AP diameter 11.5 cm) in the right lower abdominal quadrant, probably originating from the right adnex Subsequent chest CT revealed bilateral multiple variable-sized lung nodules, particularly located subpleural. The pulmonologist was asked for consultation and a CT-guided lung puncture was performed, which showed chronic inflammation with focal necrosis. Given these non-specific pathological findings, other biopsies were obtained through video-assisted thoracoscopic surgery, which also showed a state of necrosis, without providing a conclusive diagnosis. Four weeks postpartum, hCG was measured again and this was still highly elevated (478 373 U/L).
CT abdomen demonstrating a multicystic mass (anterior-posterior diameter 11.5 cm) in the right lower abdominal quadrant (Case 2).
Differential diagnosis
The joint findings of a tumour originating from the adnex, pulmonary nodules and a highly increased hCG 5 weeks postpartum pointed in the direction of a choriocarcinoma of the ovary with pulmonary metastases. This became even more plausible when tissue obtained by endometrial curettage showed histological features of trophoblastic disease, most likely choriocarcinoma. The patient was referred to our academic hospital.
Treatment
The patient’s condition deteriorated. She developed high fever, unsuccessfully treated with antibiotics. Due to tumour bleeding, the patient went into haemorrhagic shock. Hypotension, probably in combination with nephrotoxicity of gentamycin, nonsteroidal anti-inflammatory drug (NSAID) treatment and radiocontrast agent, leads to acute tubular necrosis. Another abdominal CT showed progression of the tumour, making a quick start of chemotherapeutic treatment desirable. However, treatment with the preferred etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine chemotherapeutic (EMA-CO) regimen was not possible because of poor kidney function and overall condition. It was decided to start with paclitaxel monotherapy, resulting in a decrease of hCG. Two weeks later, the patient developed an acute abdomen and a laparotomy was performed. A large amount of necrotised tumour tissue and 4 L of infected ascites were removed from the abdominal cavity. The patient was admitted to the ICU. Culture of the abdominal fluid showed a Streptococcus viridans and multiresistant E. coli. Despite treatment with meropenem (broad-spectrum carbapenem antibiotic), pain and fever persisted. Imaging showed extensive abscess formation in the abdominal cavity with continuation to the lumen of the small intestine, which required drainage. There was discharge through a defect of the laparotomy wound, which eventually closed spontaneously. In the next following weeks, the patient started to recover. However, this was complicated by a deep venous thrombosis and pulmonary embolisms, treated with nadroparine. In March 2009, 13 weeks after the diagnosis of choriocarcinoma, the condition of the patient was sufficient to restart chemotherapy. After the first course of EMA-CO, she was discharged home (19 weeks after the birth of her son). In total, she received four courses of EMA-CO.
Outcome and follow-up
After receiving the last course of chemotherapy (four courses in total) in April 2009, the hCG was within normal range. The patient remained in follow-up, including regular CT imaging and hCG monitoring. The resulting mass quickly decreased in size and there were no signs of distant metastases. In 2010 and 2011, she underwent surgical corrections of an abdominal incisional hernia. Between 2010 and 2013, several CT scans showed growing cystic lesions of both adnexa, with low hCG levels. Because of discomfort, the patient opted for extirpation of the right adnexa in January 2014. The pathologist reported a benign paratubal cyst. In 2018, after 10 years of follow-up, the patient was still in complete remission and follow-up was ended.
Case 3
Case presentation
A 39-year-old woman (Para 1), with an uneventful medical history, presented with progressive dyspnoea in August 2012. Five days earlier, at 38 weeks of gestation, labour was induced because of vaginal blood loss. Delivery was uncomplicated and she delivered a healthy daughter. After presentation, she rapidly developed a severe acute respiratory insufficiency and she was admitted to the ICU, where she was intubated and ventilated in face-down position because of high oxygen requirements. She started to persistently produce a bloody secretion from the airways.
Investigations
Laboratory investigations showed low infection parameters, anaemia (haemoglobin of 5.3 mmol/L), elevated lactate dehydrogenase (LDH) (2163 U/L), thrombocytopenia (57×109/L) and a highly elevated D-dimer (7963 ng/mL). CT angiography (figure 3) did not confirm pulmonary embolisms but showed a multinodular interstitial lung pattern. Antibiotic treatment for atypical pneumonia was started but did not have any effect. An extensive panel of cultures of blood, urine, throat swabs and bronchoalveolar lavage fluid all yielded negative results. An echocardiogram showed normal cardiac functioning.
CT angiography demonstrating a multinodular interstitial lung pattern (Case 3).
Differential diagnosis
Initially, the differential diagnosis was extensive, although many diagnoses were presumed unlikely. A postpartum cardiomyopathy was excluded because of a low N-terminal pro-brain natriuretic peptide (NT-proBNP), a normal ECG and no circulatory problems. Preeclampsia was not suspected in the absence of proteinuria and kidney involvement. An infectious cause was not demonstrated by any culture and autoimmune disease was not expected because of negative autoimmune serology, no other organ involvement besides the lungs and no response to methyl prednisolone. Because of the rising LDH and decreasing thrombocytes, being disproportionate to the objectified amount of blood loss, the possibility of a malignancy became more suspect. The level of hCG was found to be extremely elevated (300 973 U/L), thereby confirming the diagnosis of a choriocarcinoma. A week after initial presentation, while still intubated, the patient was transferred to our academic hospital. Here, it was decided not to obtain endometrial tissue for pathological purposes since the diagnosis of choriocarcinoma was sufficiently plausible and curettage would yield a risk of massive bleeding.
Treatment
By the time of admission to the ICU of our centre, there were serious respiratory problems: acute respiratory distress syndrome, pulmonary oedema and parenchymatous haemorrhage caused by pulmonary metastases of the choriocarcinoma. It was decided to start with EMA-CO therapy immediately. Subsequently, the patient developed multiorgan failure and needed renal replacement therapy. She also had transient liver failure with synthetic dysfunction, considered as a consequence of chemotherapeutic treatment. Abdominal ultrasound examination showed diffuse hepatic lesions, suspect for metastasis. In addition, haemorrhagic events occurred: major bleedings ex utero after the recent birth—conservatively managed with tranexamic acid and blood products—and a haemothorax that required drainage. Multiple infectious complications (confirmed line sepsis and endometritis with positive blood cultures) were treated with targeted antibiotic and antifungal therapies. Furthermore, there was an episode of Coombs-negative haemolysis, explained as thrombotic thrombocytopenic purpura—haemolytic uremic syndrome, probably luxated by medication. After the second course of EMA-CO (with good response), the patient developed an abdominal sepsis for which a laparotomy was performed at the beginning of October. Two intestinal perforations were found and a subtotal colectomy with terminal ileostomy was needed. In the week after, the patient underwent three relaparotomies for peritoneal lavage and evacuation of abdominal bleeding. Three lesions located proximally from the ileostomy were identified; however, repairing was not possible due to the fragile intestinal tissue. Because of persistent fever, multiple abdominal drains were placed in abdominal fluid collections. The patient developed an enterocutaneous fistula and she was temporary treated with total parenteral nutrition.
After stopping sedation, initially the patients’ consciousness did not fully recover. Cerebral MRI did not show signs of cerebral metastases. Eventually, awareness recovered spontaneously. Because of a critical illness neuromyopathy, a tracheostoma was placed. At the end of September, weaning from ventilation was started. After staying 3 months in the ICU, the patient was admitted to Medium Care for further recovery at the end of November. At the beginning of December, the trachea cannula was removed and the patient started mobilising. She was discharged from the hospital in January 2013 (20 weeks postpartum) and she was referred to a rehabilitation home until she could be reunited with her family in June 2013.
Outcome and follow-up
Because of poor overall condition of the patient and the risk of (intestinal) complications, the standard three adjuvant courses of chemotherapy were omitted when the hCG decreased to 2.8 U/L. After discharge, hCG was monitored first on a monthly basis and later at larger time intervals. When admitted to the rehabilitation home, the patient had swallowing disorders, restriction of the mouth opening due to muscle weakness, polyneuropathy, a poor nutritional status, contractures in the feet and wrists and significant limitation of shoulder movement. After several months of rehabilitation, her condition improved and she was discharged mid-2013. In the following years, she underwent surgery on both shoulders because of ossification of the joints and in 2016, the ileostomy was discontinued and an ileorectal anastomosis was constructed. In January 2020, more than 7 years after diagnosis, the patient was still in complete remission.
Discussion
This case series illustrate that choriocarcinoma may present with a variety of symptoms. Case 1 started with neurological complaints. These symptoms were not—as earlier described in a case of puerperal choriocarcinoma3—due to brain metastases but caused by a severe hypercalcemia. This hypercalcaemia was thought to be the consequence of a PTHrp-producing tumour. To our knowledge, there are no other cases described in the literature of choriocarcinoma presenting with hypercalcaemia. However, a study in neoplastic placentas did demonstrate PTHrp production by choriocarcinoma.4
Case 2 presented with persistent abdominal pain, first mistaken for an acute appendicitis. Eventually, this abdominal complaints appeared to be associated with a choriocarcinoma originating from the right ovary. Pure ovarian choriocarcinoma is extremely rare. Most occurrences, probably this case including, are ovarian metastases of gestational uterine choriocarcinoma. The primary placental tumour may be regressed or occult.5
Case 3 is characterised by severe respiratory insufficiency and haemoptysis due to pulmonary metastasis. Lesions of choriocarcinoma are usually very vascular and perfused by fragile vessels, posing a high risk of massive haemorrhagic events. Necrosis is often present in the tumour tissue and may lead to fulminant sepsis. It has been described previously that in the presence of extensive pulmonary or hepatic metastases, the administration of multiple agent chemotherapy may catalyse tumour necrosis and massive haemorrhage.6 This was also observed in Case 3.
Choriocarcinoma in coexistence with a normal intrauterine pregnancy is a rare entity and often not considered as a likely diagnosis. Several theories about its origin have been proposed. Choriocarcinoma may, for example, originate from the placenta in the concurrent pregnancy. There have been reported incidental histological findings of placental choriocarcinoma after uncomplicated deliveries.7 The primary tumour may be resolved when the disease presents with metastases, as described in several case reports.8 9 Another possibility is the occurrence of malignant transformation in the chorionic remnants of an antecedent pregnancy.
As GTN can develop months or many years after a prior pregnancy and present with a variety of symptoms, it may be tricky to diagnose, especially in the absence of a previous molar pregnancy. Choriocarcinoma may present with irregular vaginal bleeding, abdominal pain or swelling and various symptoms from metastatic sites. The diagnosis is based on clinical presentation and hCG measurement. It is therefore recommended to measure the hCG in any woman of reproductive age who presents with unexplained metastatic disease.10 11 As biopsy is highly risky in vascular lesions, this is not a prerequisite for setting the diagnosis and starting treatment. Staging investigations as recommended by international guidelines include chest X-ray, pelvic Doppler ultrasound, CT scanning (thorax and abdomen) and brain MRI.11 GTN is classified using the International Federation of Gynecology and Obstetrics (FIGO) 2000 staging system and WHO risk score.12 13 The variables in the prognostic score system include tumour volume (based on hCG level, size and number of metastases), site of involvement, prior chemotherapy resistance and duration of disease from antecedent pregnancy. A FIGO-WHO score of ≥7 indicates high-risk disease.
Patients with high-risk disease are prone to develop resistance against single-agent chemotherapy and therefore the multiagent EMA-CO regimen is recommended.11 14 15 The EMA-CO treatment should be administered every 2 or 3 weeks and after normalisation of the hCG-level, it is recommended to administer three additional courses for consolidation therapy.
In Case 1, the diagnosis of choriocarcinoma was not considered, given the normalised hCG levels after the previous molar pregnancy and the radiological findings that pointed in the direction of a sarcoma. In retrospect, hCG should have been assessed in an earlier stage as part of the diagnostic workup. If choriocarcinoma would have been diagnosed earlier, resection of the tumour would not have been performed, but chemotherapy would have been administered instead. Given the poor clinical condition and contraindication of chemotherapeutic therapy for choriocarcinoma in pregnancy, delay in caesarean section would not have been an option. In Case 2, the diagnosis was delayed as well; the first symptoms of abdominal pain started during pregnancy and choriocarcinoma was confirmed 20 weeks later, just after delivery. This case shows that coexistence of a viable pregnancy even further complicates the diagnosis of choriocarcinoma. In Case 3, until presentation with acute respiratory insufficiency, there were no signs of choriocarcinoma. This case shows that one could consider the measurement of hCG in postpartum women with respiratory insufficiency with atypical presentation and radiological findings.
Furthermore, in all three cases, there were reasons not to adhere to the existing guidelines. In Case 1, it was decided not to initiate chemotherapeutic treatment and closely monitor the hCG-level, because of complete surgical excision of the tumour and absence of metastatic disease. The patient in Case 2 developed acute tubular necrosis and EMA-CO therapy was initially contraindicated because of renal failure. Paclitaxel monotherapy was started instead. Approximately 10 weeks later, the patient had sufficiently recovered to start with the first of four courses of EMA-CO therapy. In Case 3, the patient received two courses of EMA-CO. Thereafter, chemotherapy had to be discontinued because of the patient’s poor condition.
The cases we presented here emphasise the difficulties in diagnosing choriocarcinoma and the life-threatening complications that can be caused by this destructive disease. At the same time, the cases illustrate that even in presence of widespread metastatic disease and a very complicated clinical course, choriocarcinoma is completely curable by chemotherapy. Therefore, adequate and prompt diagnosis is vital and choriocarcinoma should be part of the differential diagnosis when women in the reproductive age present with haemorrhagic events, unexplained systemic symptoms and particularly with metastases of an unknown primary malignancy.
Patient’s perspective
Case 1
Initially, I thought my symptoms were part of normal pregnancy complaints. During my previous pregnancies, I had also been tired and nauseous. But this time, it got worse and worse. After a few weeks, my GP referred me to hospital. I got an iron infusion and had to come back for a check-up after 2 weeks. When my mother came to visit and saw me lying in bed, she was very worried and took me to hospital immediately. I appeared confused and started to see things that were not there.
In hospital, I remember the doctor asking me what year it was. I could not answer. That moment I realised that something was wrong. First, they talked about a blood clot in the brain or meningitis. I also heard about a fibroid that was seen on ultrasound. It did not really struck me, I was so tired that I sometimes suddenly fell asleep. I was transferred to the academic hospital. All kinds of examinations and scans were done.
I remember the doctors coming in with a serious face. They sat down in a circle around me. They told me I had a tumour. I also had way too much calcium in my blood for which I received medication. I felt very bad during that time and I had negative thoughts. I just wanted it to stop and there were moments that I did not want to be pregnant anymore. I had the feeling that my illness was related to the pregnancy.
The doctors decided that I would have a caesarean section and that the tumour would be surgically removed. I did not really realise at that time that this meant that I would have a baby at 26 weeks. Shortly after the caesarean, I saw my daughter for the first time. I was still completely drowsy and the situation was unreal to me. We had to wait for the results of the origin of the tumour. I was afraid of what we were going to hear and the treatments I might have to endure. When we heard it was choriocarcinoma and that the tumour had been well removed, it was quite a relief. I did not need to get any chemotherapy, only regular blood monitoring was indicated.
A week after the caesarean, I was discharged from hospital. The time that followed was tough. The combination of my own physical and mental recovery, visiting our premature daughter in hospital and taking care of our two elder children at home, was not easy. Fortunately, we had a lot of support from family and friends.
I appreciated the compassionate care that I received during the hospital admission. It was beyond the medical perspective—people really asked how I felt and also noticed when I did not feel well. I only think it is regrettable that my midwife did not realise that perhaps more was going on than usual pregnancy ailments. After my recovery, I felt very guilty about the thoughts that I had during my illness of not wanting the pregnancy anymore. I had EMDR therapy which helped a lot. Our daughter almost turns four and develops well.
Learning points
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Choriocarcinoma is mostly associated with molar pregnancy; however, it may follow any type of pregnancy and may even occur in coexistence with a viable uterine pregnancy.
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Although choriocarcinoma is highly responsive to chemotherapy, accurate and timely diagnosis is crucial because of the aggressive nature of the disease.
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Choriocarcinoma may present with hypercalcaemia, most probably due to parathyroid hormone-related protein-production of the tumour.
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Radiological findings of choriocarcinoma may be atypical.
Ethics statements
Footnotes
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Contributors MLH and CdK were involved in clinical care of the patients reviewed in this case series. NdF collected clinical data from the electronic patients records. All authors contributed to the interpretation of the data. NdF drafted the manuscript and MLH and CdK revised it critically. All authors gave final approval of the version to be published. All authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.
References
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