bubble_chart Overview

Choriocarcinoma is a highly malignant tumor that occurs after hydatidiform mole, late abortion, or full-term childbirth. Its incidence rate is approximately 0.0001% to 0.36%, with a few cases occurring after ectopic pregnancy, mostly in women of childbearing age. Occasionally, it occurs in the ovaries of unmarried women and is referred to as primary choriocarcinoma. In the 1950s, the mortality rate was very high. In recent years, the application of chemotherapy has significantly improved the prognosis of choriocarcinoma.

bubble_chart Pathological Changes

The uterus is irregularly enlarged, with one or more purplish-blue nodules visible on the surface. The cut surface appears dark red, often accompanied by hemorrhage, necrosis, and infection. The lesions are soft and fragile, may protrude into the uterine cavity, or infiltrate and destroy the serosal layer to reach the parametrial tissues. They can also spread through the bloodstream and metastasize to any organ or tissue. Microscopically, there is marked hyperplasia of trophoblastic cells, arranged in a disorderly pattern without villous structures, with clusters of syncytiotrophoblasts and cytotrophoblasts (Langhans cells).

Characteristics of metastasis: See the section on characteristics of metastasis in malignant hydatidiform mole.

bubble_chart Clinical Manifestations

1. Vaginal bleeding: After childbirth, late abortion, especially after hydatidiform mole clearing the pericardium, there may be irregular bleeding of varying amounts. If the chorionic membrane cancer has invaded the uterine muscle wall while the endometrial lesions are mild, there may be no vaginal bleeding.

2. Abdominal mass: Due to an enlarged uterus, hematoma formation in the broad ligament, or enlarged luteal cysts, patients often complain of a lower abdominal mass.

3. Abdominal pain: Caused by cancerous tissue eroding the uterine wall or blood accumulation in the uterine cavity, or due to cancerous tissue perforating the uterus or visceral metastasis.

4. Metastatic symptoms: The trophoblastic cells of chorionic membrane cancer first invade the veins of the parauterine tissue, then retrograde metastasis to the vagina, ascend through the right heart to the lungs, and subsequently spread to major organs such as the brain, liver, kidneys, and gastrointestinal tract.

(1) Pulmonary metastasis: Chorionic carcinoma mainly metastasizes via the bloodstream, with pulmonary metastasis being the most common. Hemoptysis is an early symptom, and chest pain, dyspnea, or even pleural effusion may also occur. Metastatic lesions invading the bronchial mucosa can cause hemoptysis; invasion of the pleura may lead to chest pain, pleural effusion, or hemothorax. Widespread microvascular tumor cell embolism can cause dyspnea.

(2) Vaginal metastasis: Second only to pulmonary metastasis. Characterized by purplish-blue nodules protruding from the vaginal mucosa, forming solid masses. If the surface ruptures, it can cause severe bleeding and is prone to infection.

(3) Brain metastasis: Often secondary to pulmonary metastasis, it is one of the common causes of death in chorionic carcinoma patients. In the earliest stage, tumor emboli in the cerebral arteries cause transient ischemic symptoms, such as sudden falls, aphasia, or blindness, which resolve within seconds or minutes. Later, tumor cells grow and spread in blood vessels, leading to destructive symptoms, such as subarachnoid hemorrhage and adjacent brain tissue damage. Main symptoms include headache, hemiplegia, vomiting, imbalance, visual disturbances, aphasia, high fever, spasms, and even unconsciousness. If cerebral herniation occurs, the patient may die suddenly.

(4) Liver metastasis: Tenderness in the liver area, hepatomegaly, and rupture may cause internal bleeding.

(5) Gastrointestinal metastasis: Hematemesis or tarry stools may occur.

(6) Urinary tract metastasis: Hematuria, etc. {|109|}

bubble_chart Diagnosis

The correct diagnosis can be obtained based on medical history, signs, metastatic symptoms, and various auxiliary examinations.

1. Clinical features: For hydatidiform mole, postpartum or late abortion with irregular vaginal bleeding, uterus failing to return to normal size as expected, being larger and softer, the possibility of choriocarcinoma should be considered.

2. Blood or urine HCG measurement: Elevated titers or reappearance of positive HCG in blood or urine after being negative.

3. X-ray lung film: Spherical shadows may be seen in the lungs, distributed in both lung fields, sometimes only a single metastatic lesion. Or several nodules may fuse into cotton-like or mass-like lesions.

4. Pathological diagnosis: Large areas of necrotic tissue and blood clots can be seen in the uterine muscle layer or other resected organs, surrounded by a large number of active, long, single trophoblastic cells, with no villous structure present.

bubble_chart Treatment Measures

1. The treatment principle is primarily chemotherapy, supplemented by surgery. For young, childless patients, every effort should be made to avoid hysterectomy to preserve fertility. If hysterectomy is unavoidable, the ovaries can still be preserved.

2. Chemotherapy

(1) Drug selection: For general early-stage cases, a single drug can be used, with 5-Fu as the first choice. If the condition is urgent or has reached an advanced stage, two or more drugs should be combined. Commonly used combinations include 5-fluorouracil (5-Fu) plus actinomycin D (ksm). 5-Fu and ksm have the best efficacy, minimal side effects, and are effective against metastases in the lungs, digestive tract, urinary tract, and reproductive system. They can be administered intravenously, via stirred pulse infusion, intracavitary or intratumoral injection, or orally.

(2) Common treatment regimens:

① Single-drug therapy: The dose used is larger than in multi-drug therapy, e.g., 5-Fu 28–30 mg/kg/day.

② Dual-drug therapy: The dose is slightly smaller than in single-drug therapy, and the treatment duration is shorter, e.g., 5-Fu at 26 mg/kg/day and actinomycin D at 6 μg/kg/day.

③ Drug dosage: To achieve satisfactory results, the dosage of each drug must reach the patient's maximum tolerance level, especially in the first and second treatment cycles. With appropriate drug selection and sufficient dosage, most cases can show rapid improvement. Specific dosages and administration methods are listed in the table below (Table 20-1).

(4) Administration speed: The speed of administration for each drug has specific requirements. For example, 5-Fu, after being added to 500ml of 5% glucose, must be dripped within 2～8 hours; too fast increases toxicity, while too slow may affect efficacy.

(5) Course duration: A longer course increases toxicity, while a shorter course reduces efficacy. Therefore, a course generally lasts 8～10 days.

(6) Administration route: The same drug may have different effects depending on the administration route. For instance, intravenous administration is best for lung metastasis, oral administration for digestive system metastasis, and portal vein administration for liver metastasis, yielding better therapeutic effects.

(7) Interval between courses: This depends mainly on the condition and the subsidence of drug toxicity. If toxicity is mild and blood counts recover quickly after stopping the drug, the interval can be shorter. If toxicity is severe and blood counts recover slowly, the interval should be longer. The toxicity of 5-Fu or KSM is relatively mild, with an interval of about two weeks, while that of 6-MP and MTX is more severe, with an interval of about 4 weeks.

(8) Efficacy observation: The effects of the drugs are not immediately visible after administration. A significant decrease in blood and urine HCG levels usually appears about 2 weeks after completing a course. The absorption of lung metastasis shadows also becomes apparent about 3 weeks after stopping the medication. Therefore, auxiliary examinations to observe efficacy should not be conducted too early, as this may easily lead to the misconception that the treatment is ineffective.

(9) Criteria for discontinuing medication: To achieve a cure and reduce recurrence, treatment must meet the complete recovery criteria:

① Clinically asymptomatic.

② Pulmonary metastatic lesions completely disappeared.

③ After HCG levels remain consistently normal, consolidate with 1–2 additional treatment courses before stopping medication for observation. For more severe cases, several additional consolidation courses may be administered to prevent recurrence.

3. Surgical Treatment: Since chemotherapy has proven highly effective, surgical intervention is no longer as critical as before. However, in certain situations—such as large lesions unlikely to be fully controlled by chemotherapy, slow HCG decline during treatment, uterine perforation, or hemorrhage from liver metastases—surgery remains a vital method to save lives. Typically, a subtotal hysterectomy is performed, along with resection of bilateral adnexa, the greater omentum, parametrial venous plexus, and ovarian venous plexus.

4. Radiation Therapy: Choriocarcinoma and malignant hydatidiform mole are sensitive to radiotherapy. For isolated metastatic lesions in the lungs, pelvis, or abdomen that are difficult to remove surgically or show poor response to multiple chemotherapy courses, radiation therapy may be considered. Options include cobalt-60 or deep X-ray irradiation. Whole-brain irradiation is used for brain metastases, and unresectable vaginal metastatic nodules may be treated locally with radium. The recommended dose for choriocarcinoma is 3000–4000 cGy over 3–4 weeks, and for malignant hydatidiform mole, 2000–3000 cGy over 2–3 weeks.

5. Treatment of Metastases

(1) Management of Vulvar and Vaginal Bleeding: For unruptured metastatic tumors, intravenous 5-Fu may be supplemented with intralesional injections of 250–500 mg 5-Fu every 2–3 days until significant tumor shrinkage occurs. For ruptured or bleeding tumors, hemostasis can be achieved with gauze packing or gauze coated with sterile hemostatic agents like Yunnan Baiyao. If bleeding persists, surgical resection or suturing may be necessary.

(2) Management of Intraperitoneal Hemorrhage: In cases of acute, significant intraperitoneal bleeding, immediate laparotomy with uterine resection is required, followed by systemic chemotherapy.

(3) Management of Brain Metastases: ① Systemic chemotherapy, preferably with a combination of 5-Fu and KSM. ② Symptomatic treatment to enhance chemotherapy efficacy and reduce intracranial pressure—administer 250 ml of mannitol or sorbitol every 4–6 hours, infused over 30 minutes. ③ Sedation and spasm control with diazepam, barbiturates, or pethidine. ④ Prevent complications such as unconsciousness, spasms, falls, bites, or aspiration pneumonia through meticulous nursing care, while promptly correcting electrolyte imbalances and acid-base disturbances.

(4) Management of Hemoptysis: Massive hemoptysis is challenging to manage, with no ideal solution currently available. ① Administer 20 units of posterior pituitary hormone in 500 ml of 5% glucose intravenously. ② Hemostatic agents like aminomethylbenzoic acid or para-aminomethylbenzoic acid may be used. ③ Surgery: If the bleeding site is identifiable and conditions permit, emergency lobectomy may be considered. Concurrently, manage shock, correct anemia, prevent infection, and guard against asphyxia due to hemoptysis.

bubble_chart Prognosis

The prognosis is related to many factors, such as early diagnosis and timely treatment, which lead to a better prognosis. Choriocarcinoma following childbirth or late abortion has a poorer prognosis compared to choriocarcinoma after benign hydatidiform mole. The longer the interval between the discovery of choriocarcinoma and the initial event, known as the latent period, the worse the prognosis. Cases where the concentration of human chorionic gonadotropin (hCG) drops rapidly after surgery and remains negative generally have a better prognosis. Conversely, if the hCG level in grade I cases declines but fails to reach negative and remains unchanged, the prognosis is poor.