Abstract: Choriocarcinoma is a highly malignant gynecological tumor with early and widespread metastasis. The mortality rate of brain metastasis in choriocarcinoma can be as high as 29.7% [1]. Cerebral edema combined with brain herniation is the most common direct cause of death in patients with brain metastasis from gestational trophoblastic neoplasia (GTN). Currently, there is no consensus on the treatment of brain metastasis in choriocarcinoma. While there are numerous reports on the treatment of brain metastasis in choriocarcinoma, reports on brain metastasis accompanied by brain herniation are relatively rare. This case report describes a 25-year-old female patient who presented with coma upon admission. A CT scan revealed intracranial hemorrhage with brain herniation. After emergency surgery, the clinical diagnosis was brain metastasis from choriocarcinoma. Following chemotherapy and comprehensive treatment, the patient recovered. Therefore, it is recommended that high-risk patients with brain metastasis from choriocarcinoma be transferred to a comprehensive hospital. Timely and necessary surgical and chemotherapy can reduce the mortality rate of patients with brain metastasis from choriocarcinoma.
Keywords: Brain metastasis herniation; Choriocarcinoma; Brain metastasis; Chemotherapy
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Case Summary: The patient is a 25-year-old married woman who was admitted to our neurosurgery department on October 30, 2022, due to sudden loss of consciousness for 3 hours. On admission, her vital signs were as follows: T 36.5°C, P 88 beats/min, R 15 breaths/min, BP 107/74 mmHg. She was in a shallow coma, uncooperative during examination, unresponsive to verbal stimuli, and opened her eyes to pain but did not speak. Both pupils were equal in size and round, approximately 3 mm in diameter, with brisk light reflexes. There was slight neck resistance. The abdomen was soft, and the right limb flexed to pain, while the left limb retracted to pain. Bilateral Babinski signs were positive, and vaginal bleeding was similar to menstrual flow. Ancillary examinations showed: Cranial CT: An irregular high-density shadow measuring about 6.6 × 5.5 cm was visible in the left cerebral hemisphere, indicating intracranial hemorrhage, with some blood extending into the ventricular system (Figure 1). Cranial CTA: Right posterior circulation transitional variant. Chest CT: Abnormal density shadow in the right middle lobe of the lung. Human chorionic gonadotropin (hCG) level was 8806 mIU/mL. Gynecological ultrasound: Endometrial thickness 8 mm, no obvious abnormalities in the uterus or bilateral ovaries. Medical history: Evacuation of hydatidiform mole in 2015, spontaneous delivery in May 2021, denied family history of genetic diseases.
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Treatment Process: The patient developed brain herniation and underwent urgent craniotomy for hematoma evacuation + intracranial mass resection + decompressive craniectomy + bilateral external ventricular drainage. During the operation, the surgeon successfully entered the hematoma cavity along the puncture path and removed a total of 35 ml of mixed blood clots and cerebrospinal fluid. Postoperatively, the patient was transferred to the ICU for monitoring. Her hCG levels gradually decreased, reaching 2021 mIU/mL on November 3rd, but then increased to 2138 mIU/mL on November 5th. By the sixth postoperative day, the patient's consciousness had slightly improved, and she was transferred back to the neurosurgery ward. Based on her medical history, symptoms, physical examination, and ancillary tests, according to the FIGO staging system, the diagnosis was: Stage IV choriocarcinoma (14 points), very high risk; brain metastasis; pulmonary metastasis; postoperative intracranial hemorrhage. From November 7th, the patient received the EP regimen (etoposide 100 mg/m² and cisplatin 20 mg/m² on days 1 and 2, weekly) for three cycles until November 21st. Due to the risk of exacerbating brain herniation, intrathecal methotrexate (MTX) injection was not administered. After three cycles of the EP regimen, the patient's vital signs stabilized, and she could consume small amounts of water. It was suggested to start the EMA-CO regimen one week later, but this was delayed due to cost concerns. On December 1st, the patient began EMA-CO chemotherapy. Symptomatic management included:
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On November 13th, a new bleed was noted in the left occipital lobe on CT (Figure 2). On November 17th, the patient became agitated, and a follow-up CT showed a small amount of fresh bleeding in the left temporal region (Figure 3). Hemostatic and dehydration treatments were administered to reduce intracranial pressure.
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Hemoglobin levels decreased, and blood transfusions were given to correct this. On November 8th, the patient received 2 units of packed red blood cells (PRBCs) and 200 mL of plasma. On November 19th, she received 3 units of PRBCs and 200 mL of plasma. On December 7th, she received 2 units of PRBCs. During the perioperative period, patients with increased intracranial pressure causing headache, vomiting, and other neurological symptoms were treated with intravenous 20% mannitol and glycerol fructose. Steroids were also given if necessary to reduce intracranial pressure. Additionally, appropriate sedation, analgesia, and hemostasis were provided to control bleeding, reduce intracranial pressure, and alleviate the crisis.
| Date | Symptoms | Blood hCG (mIU/mL) | Ancillary Tests | Treatment |
|---|---|---|---|---|
| 10.30 | Coma | 8806 | Cranial CT: Irregular high-density shadow measuring about 6.6 × 5.5 cm in the left cerebral hemisphere, intracranial hemorrhage, some blood extending into the ventricular system, midline structures slightly shifted. Pulmonary CT: Abnormal density shadow in the right middle lobe, approximately 37 mm × 32 mm in axial view. | Emergency craniotomy for hematoma evacuation + intracranial mass resection + decompressive craniectomy + bilateral external ventricular drainage. Postoperative transfer to ICU. |
| 11.7 | Can open eyes spontaneously | 5911 | ALT 69 IU/L, AST 91 IU/L | First cycle of EP chemotherapy; hepatoprotective treatment. |
| 11.13 | Good mental state and sleep, nasogastric feeding, intermittent low fever | 13348 | Hemoglobin (Hb) 79 g/L, CT shows new bleeding in the left occipital lobe. | Transfusion of 2 units of PRBCs and 200 mL of plasma. Hemostasis, neuroprotection, dehydration to reduce intracranial pressure, acid suppression, and liver function improvement. |
| 11.17 | Agitation, rapid breathing | 2676 | CT: Small amount of fresh bleeding in the left temporal region. | Hemostasis, anti-inflammatory treatment. |
| 11.19 | Small sips of water | 1091 | Hemoglobin (Hb) 66 g/L | Transfusion of 3 units of PRBCs and 200 mL of plasma. |
| 11.28 | Intermittent cough, nasogastric feeding, no oral intake, partial motor aphasia, able to respond but speech is slurred and unclear | 58.24 | Complete blood count: White blood cells 2.59 × 10^9/L, neutrophil percentage 67.6%, hemoglobin 90 g/L, C-reactive protein 10.16 mg/L. | Subcutaneous injection of granulocyte colony-stimulating factor (G-CSF) 200 μg. |
| 12.1 | Improved cough, nasogastric feeding, no oral intake, partial motor aphasia, able to respond but speech is slurred and unclear | 22.85 | - | EMA-CO chemotherapy. |
| 12.7 | Good mental state, sleep, and appetite, nasogastric feeding, no nausea or vomiting, partial motor aphasia, able to respond but speech is slurred and unclear | - | Complete blood count: White blood cells 2.83 × 10^9/L (low), hemoglobin 77 g/L (low), platelets 350 × 10^9/L. | Subcutaneous injection of G-CSF 200 μg, transfusion of 2 units of PRBCs. |
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Results:
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Blood hCG levels peaked at 30851 mIU/mL on November 10th and gradually decreased to 6.15 mIU/mL on December 10th.
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On December 13th, the patient requested to return home for continued treatment. At discharge, she could respond to questions, and her left limb could move on command, but her right limb remained unresponsive to pain.
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One year postoperatively, the patient could converse and walk independently.
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Discussion: Choriocarcinoma is a highly malignant gestational trophoblastic neoplasia (GTN). Due to the extensive proliferation and invasion of trophoblasts into the myometrium and blood vessels [2], significant and widespread hemorrhagic necrosis often accompanies the disease. Functionally, trophoblasts exhibit active growth and invasive characteristics, replacing vascular endothelial cells to form an endothelial layer, facilitating their easy entry into the maternal bloodstream. Therefore, choriocarcinoma frequently involves distant metastasis. Metastatic choriocarcinoma often follows non-molar pregnancies, with metastasis occurring early and widely.
According to the International Federation of Gynecology and Obstetrics (FIGO) prognostic scoring system, GTN patients are divided into low-risk and high-risk groups, with scores ≤6 indicating low risk and >6 indicating high risk. The 2015 FIGO cancer report introduced the concept of ultra-high-risk GTN: patients with FIGO prognostic scores ≥12 and liver or brain metastasis or extensive metastasis. The main causes of death in high-risk GTN patients include: (1) widespread drug-resistant lesions; (2) pulmonary infection and respiratory failure due to progression of pulmonary lesions; (3) massive bleeding at the lesion site, including intracranial hemorrhage and rupture of hepatic metastases [3]. Studies have shown that the risk of early death in GTN with FIGO scores ≥13 is significantly higher [4].
The standard treatment for GTN is chemotherapy, with the choice of regimen primarily based on the FIGO prognostic score. Low-risk patients typically receive single-agent chemotherapy, such as methotrexate, actinomycin-D, or fluorouracil. After β-hCG levels normalize, consolidation chemotherapy for 2-3 cycles is continued to reduce the risk of recurrence, achieving a complete remission rate close to 100%. High-risk patients are initially treated with multi-agent combination chemotherapy, with the most common regimen being EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine), achieving a complete remission rate of 85% and a 5-year survival rate of 75%-90% [5]. Other chemotherapy options include the TE/TP, MBE, ICE, BEP, or FAEV regimens. Beijing Union Medical College Hospital pioneered a combination chemotherapy regimen based on 5-fluorouracil (5-FU), with the FAEV regimen achieving a remission rate of 80% in newly diagnosed high-risk stage IV patients [6]. For ultra-high-risk GTN patients, the primary treatment principle remains systemic chemotherapy, supplemented by surgery, radiation therapy, or interventional therapy. For patients with high tumor burden and poor overall condition, standard chemotherapy may cause severe bone marrow suppression, leading to bleeding, infection, and even multi-organ failure. Low-dose EP (etoposide and cisplatin) induction therapy for 1-3 cycles before standard chemotherapy can be considered. Studies have shown that low-dose EP (etoposide 100 mg/m²/day, cisplatin 20 mg/m²/day for 2 days, repeated weekly) before starting EMA-CO can reduce the early mortality rate from 7.2% to 0.7% [7]. In cases of brain metastasis, the dose of methotrexate in the EMA regimen can be increased to 1 g/m² to help the drug penetrate the blood-brain barrier. Since 2017, Charing Cross Hospital has reported the use of immunotherapy in chemotherapy-resistant GTN patients [8], with programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors gradually being applied in the treatment of these tumors, opening new avenues for GTN therapy.
The incidence of brain metastasis in malignant trophoblastic tumors ranges from 6.4% to 21.4% [1,9], with a poor prognosis and high mortality rate. A distinctive feature of GTN brain metastasis is sudden and extensive intracranial hemorrhage due to the inherent ability of trophoblasts to penetrate and erode blood vessels. Intracranial hemorrhage associated with brain metastasis may be related to aneurysmal dilation, with 30 cases of aneurysmal dilation secondary to brain metastases (BMs) reported in the literature, most involving the middle cerebral artery, and multiple aneurysms detected in 17% of cases. The mechanism of aneurysmal dilation is due to distal cerebral vascular occlusion or infiltration caused by tumor emboli, followed by local destruction of the intima, internal elastic lamina, and media, leading to aneurysm formation. Cerebral angiography can be used to study the characteristics of aneurysmal dilation, although identification of aneurysms is challenging in the context of intracranial hemorrhage [10,11]. Brain metastasis can be divided into three stages: the first stage is the thrombotic phase; the second stage is the brain tumor phase, characterized by headaches, dizziness, projectile vomiting, hemiplegia, seizures, and even coma; the third stage is the brain herniation phase, where increased intracranial pressure due to tumor compression, surrounding tissue edema, and hemorrhage leads to brain herniation, compressing vital centers and causing death. Currently, there is no consensus on the optimal treatment for brain metastasis in GTN. Neubauer et al. [12] recommend whole-brain irradiation combined with multi-agent combination chemotherapy for treating brain metastasis patients, but long-term survivors of whole-brain radiotherapy may develop late-onset neurological sequelae in up to one-third of cases. Medical centers like Charing Cross Hospital advocate for intrathecal methotrexate administration alongside systemic chemotherapy [13], which significantly increases intracranial chemotherapy drug concentrations and is an effective method for treating brain metastases, but should only be administered after reducing intracranial pressure to prevent brain herniation. Emergency craniotomy with decompressive craniectomy and tumor resection is an important treatment for patients with intracranial hemorrhage and edema leading to a rapid increase in intracranial pressure, especially when conservative medical treatments fail [14,15,16].
The early mortality rate in GTN brain metastasis patients is high, but excluding early deaths, the 5-year survival rate can reach 81.5%-90% [18,19]. Therefore, safely navigating the early critical phase is crucial for treatment. In this case, the patient presented with coma upon admission, indicative of the third stage of brain metastasis with brain herniation, severely threatening her life. Key aspects of the treatment included: 1. Immediate emergency craniotomy for decompression to facilitate timely chemotherapy. 2. Early initiation of combination chemotherapy after the patient's consciousness slightly improved, along with supportive treatments such as hemostasis, blood transfusions, and dehydration to reduce intracranial pressure. 3. Initial chemotherapy using a low-dose EP regimen for three weeks, followed by standard chemotherapy for high-risk patients once the tumor burden decreased and the patient's overall condition improved. After the EP regimen, the patient's hCG levels continued to rise, likely due to the release of hCG into the bloodstream following tumor cell breakdown.
Conclusion: Brain metastasis in choriocarcinoma generally indicates a poor prognosis and high mortality rate. For patients with significant intracranial masses, elevated intracranial pressure, and even brain herniation, emergency craniotomy combined with chemotherapy is a critical approach to saving lives. The surgery should aim for adequate decompression, and combination chemotherapy should be initiated promptly. The choice of chemotherapy regimen should be based on the FIGO staging and scoring, age, and fertility requirements, implementing stratified and individualized treatment. Correct surgical techniques and chemotherapy can help reduce early mortality and significantly improve patient outcomes. Timely and thorough communication during treatment is also essential.
