| disease | Hydatidiform Mole |
| alias | Hydatidiform Mole |
The disappearance of villous stroma microvessels leads to fluid accumulation in the villous stroma, forming vesicles of varying sizes that resemble grapes, hence the term hydatidiform mole. It is classified into complete and partial types, with the majority being complete hydatidiform moles. Clinical diagnosis of hydatidiform mole typically refers to complete hydatidiform mole; cases with placental tissue and/or a fetus are labeled as partial hydatidiform mole. Among naturally occurring late abortion tissues, 40% of patients exhibit some degree of hydropic degeneration, but these are not diagnosed as hydatidiform mole.
bubble_chart Clinical Manifestations
1. Amenorrhea Since the grape-like growth occurs in the trophoblast of the fertilized egg, there is often amenorrhea for 2-3 months or longer.
2. Vaginal bleeding A severe symptom, which is a manifestation of the natural late abortion of a hydatidiform mole. It usually begins 2-3 months after amenorrhea, mostly as intermittent minor bleeding, but there may be repeated episodes of heavy bleeding during this period. Upon careful examination, vesicle-like structures may sometimes be found in the blood. Vaginal bleeding clearly originates from the uterus; in addition to flowing out through the vagina, some may accumulate inside the uterus. It may also temporarily remain entirely within the uterus, thereby prolonging the period of amenorrhea.
3. Uterine enlargement In most patients, the uterus is larger than the pregnancy uterus corresponding to the months of amenorrhea. Many patients seek medical attention due to a palpable lower abdominal mass (enlarged uterus or luteinized cyst), but a few may have a uterus that matches or is even smaller than the expected size for the amenorrhea period. There are two possible scenarios: ① The villous vesicles degenerate and atrophy, halting development and resulting in a retained hydatidiform mole; ② Some of the vesicular mole has been expelled, reducing the size of the uterus and leading to an incomplete late abortion of the hydatidiform mole.
4. Abdominal pain Due to rapid uterine enlargement causing distending pain or intrauterine bleeding stimulating uterine contractions, the pain may range from mild to severe.5. Pregnancy toxemia symptoms About half of the patients may experience severe vomiting after amenorrhea, and later stages may present with hypertension, edema, and proteinuria.
6. No detectable fetus Around 8 weeks of amenorrhea, B-ultrasound monitoring fails to detect a gestational sac, fetal heartbeat, or fetus. Even by 18 weeks of pregnancy, no fetal movement is felt, and no fetal heartbeat is heard. B-ultrasound scans show a snowflake-like image without any fetal structure.
7. Ovarian luteinized cysts Some patients may develop ovarian luteinized cysts, which can be detected through bimanual examination or more easily via B-ultrasound.
8. Hemoptysis Some patients may experience hemoptysis or blood-streaked sputum. Doctors should proactively inquire about such symptoms.
9. Anemia and infection Repeated bleeding without timely treatment will inevitably lead to anemia and related symptoms, and in rare cases, may even result in death due to hemorrhage. Repeated bleeding also increases the risk of infection, especially if vaginal procedures are unclean or intercourse occurs during bleeding, further promoting infection. Infections may be localized to the uterus and adnexa or lead to sepsis.
bubble_chart Auxiliary Examination
Abdominal ultrasound scanning may reveal hypoechoic areas of varying sizes within the uterus, caused by intrauterine hematoma. Additionally, the presence of a fetus can be detected, showing not only snowflake-like echoes but also fetal and/or placental images. The B-ultrasound diagnostic procedure is non-invasive, highly accurate, and serves as a powerful tool for confirming hydatidiform mole.
If more than 8 weeks after the expulsion of the mole, careful curettage confirms no residual hydatidiform mole in the uterine cavity and no luteinized cysts are present, yet serum hCG remains above 1,000 mIU/ml or continues to rise, subsequent evidence may confirm malignant transformation. If hCG levels are below 1,000 mIU/ml but luteinized cysts are present, a thorough examination for metastatic lesions is necessary, or the possibility of ovarian luteinized cysts should be considered, requiring close follow-up. If the luteinized cysts regress along with declining hCG levels, continued monitoring as a benign hydatidiform mole is appropriate.
The clinical manifestations include amenorrhea, with most cases experiencing vaginal bleeding two to three months after amenorrhea, or occasionally later. The bleeding can vary in amount and is often intermittent. In many cases, the uterus may be larger than expected for the gestational age. When the uterus reaches the size of a four- to five-month pregnancy, the pregnant woman may not feel fetal movements, palpate fetal masses, or detect fetal heart sounds. A definitive diagnosis can be made if vesicular molar tissue is found during a careful examination of vaginal bleeding.
hCG measurement: Accurate quantitative testing of hCG is crucial for the diagnosis and follow-up of hydatidiform mole. In normal pregnancy, hCG levels are low initially, peak at 8–10 weeks of gestation, and then gradually decline. After 100 days of gestation, hCG levels drop significantly. In twin (or multiple) pregnancies, hCG levels are higher than in singleton pregnancies. In hydatidiform mole, hCG levels are significantly higher than normal and remain persistently elevated. In non-pregnant women, serum hCG levels are <75 mIU/ml, and β-hCG levels are <20 mIU/ml. The median peak serum hCG level in normal pregnancy is below 100,000 mIU/ml, with a maximum of 210,000 mIU/ml, whereas in hydatidiform mole, serum hCG levels far exceed 200,000 mIU/ml. Therefore, combining clinical findings and B-ultrasound results, a single elevated hCG value can confirm the diagnosis of hydatidiform mole. If serial quantitative hCG tests are performed and levels remain high after 14 weeks of gestation, the diagnosis becomes even more definitive.
If more than eight weeks after the expulsion of the mole, careful curettage confirms no residual hydatidiform mole in the uterine cavity and no luteinized cysts, yet serum hCG remains above 1,000 mIU/ml or continues to rise, subsequent evidence may confirm malignant transformation. If hCG levels are below 1,000 mIU/ml but luteinized cysts are present, a thorough examination for metastatic lesions is necessary, or the elevated hCG may be due to ovarian luteinized cysts, requiring close follow-up. If the luteinized cysts regress along with declining hCG levels, the case should continue to be monitored as benign hydatidiform mole.
In recent years, significant progress has been made in understanding the molecular structure and significance of various forms of hCG. Cole et al. noted that in normal pregnancy and trophoblastic diseases, there are at least seven immunologically active hCG molecules: ① native hCG; ② nicked hCG (missing peptide linkages at β44-45, β47-48, or β48-49); ③ acidic hCG; ④ native free β-subunit; ⑤ nicked free β-subunit; ⑥ β-core fragment; and ⑦ serum β-core fragment–protein complex. Abnormalities in the quantity and quality of hCG and its related molecules have been observed in trophoblastic diseases. Kardana et al. reported that specific immunoassays for free β-subunit showed that in normal pregnancy, hydatidiform mole, and choriocarcinoma, the proportion of free β-subunit to total β-subunit (hCG + free β) was 1.3%, 0.2%, and 25%, respectively. The clinical applications of different hCG forms are under ongoing research.
Immunoassays (e.g., sheep red blood cell agglutination inhibition test) for hCG in morning urine of normal pregnancies typically show peak concentrations below 160,000 IU/L, occasionally reaching 640,000 IU/L. For hydatidiform mole, hCG levels usually range between 500,000 and 600,000 IU/L and remain persistently elevated.
Currently, X-ray techniques are rarely used for diagnosing hydatidiform mole.
bubble_chart Treatment Measures
1. Clearing the Uterine Cavity Due to the risk of massive hemorrhage at any time with a hydatidiform mole, the uterine contents should be promptly removed after diagnosis is confirmed. Suction curettage is generally used. During the procedure, the uterine body gradually shrinks and hardens. Although the aspirate contains a significant amount of blood, most of it is pre-existing intrauterine blood, so the patient's pulse and blood pressure usually remain stable. Many advocate that if the uterus extends above the umbilicus, an abdominal hysterotomy should be performed to remove the hydatidiform mole, as this allows thorough clearance under direct vision and better hemostasis. However, in practice, even when the uterus is enlarged to the size of a 7-8 month pregnancy, suction curettage can still effectively clear the contents. If a hysterectomy is needed, it can be performed immediately after suction. Hysterotomy for hydatidiform mole removal may inadvertently increase the risk of implantation or metastasis. In the absence of suction equipment, the cervix can be dilated, and the hydatidiform mole can be removed with forceps.
The first uterine evacuation need not be overly aggressive to avoid injuring the softer uterine wall. A second curettage can be performed about a week later.
Patients who continue to experience uterine bleeding after uterine evacuation should be managed based on their condition. If incomplete evacuation or new vesicular growth is suspected (incomplete molar abortion), a thorough curettage should be carefully performed. Persistent bleeding may indicate invasive disease into the uterine wall, as seen in malignant hydatidiform mole or choriocarcinoma.
Even in cases of spontaneous late abortion of a hydatidiform mole, uterine evacuation is necessary. There are differing opinions on whether intravenous uterotonics should be administered during evacuation. Opponents argue that strong uterine contractions could force large amounts of molar villi into the bloodstream, causing embolism or metastasis. Therefore, if uterine contractions are adequate during the procedure, routine use of uterotonics is unnecessary and should only be considered if bleeding is excessive and uterine tone is poor.
2. Hysterectomy For women over 40 or multiparous women with rapid uterine enlargement, hysterectomy is advised. Younger women may retain their ovaries. If the uterus is larger than a 5-month pregnancy, most of the vesicular tissue should be removed vaginally before hysterectomy to facilitate the procedure.
3. Blood Transfusion Severely anemic patients should receive small, repeated, slow transfusions while closely monitored for active bleeding. Uterine evacuation should be delayed until the patient's condition improves. If active bleeding occurs, transfusion should accompany evacuation.
4. Correcting Electrolyte Imbalance Prolonged bleeding and poor appetite often lead to dehydration and electrolyte imbalances, which should be assessed and corrected.
5. Infection Control Long-term uterine bleeding or repeated unclean procedures can lead to infection, manifesting as local (uterine or adnexal) infection or sepsis. Adequate antibiotics should be administered, and anemia and electrolyte imbalances should be actively corrected.
6. Chemotherapy There is no consensus on prophylactic chemotherapy for benign hydatidiform mole. Literature suggests that prophylactic chemotherapy does not significantly reduce the malignant transformation rate compared to controls, or any reduction is not statistically significant due to insufficient cases. Some researchers have attempted to identify high-risk factors for malignant transformation through clinical and pathological examination, such as: ① Age over 40; ② Uterus significantly larger than expected for gestational age; ③ Urine hCG immunoassay >107 IU/L; ④ History of hemoptysis; ⑤ Pathological hyperplasia is no longer considered a risk factor. Thus, DNA and RNA FCM analysis of evacuated tissue is a reliable objective indicator for predicting malignant transformation, guiding targeted prophylactic treatment.
bubble_chart Follow-up Consultation
All patients with hydatidiform mole should be advised to undergo regular follow-ups and maintain long-term contact with the hospital. It is particularly important to schedule regular re-examinations within 2 years to detect malignant changes early, though residual vesicular mole may sometimes persist. Patients should be advised to use effective contraception for at least 2 years. During the first six months, re-examinations should be conducted monthly. If irregular vaginal bleeding, hemoptysis, headache, or other discomfort occurs, immediate hospital examination is necessary.
During follow-ups, in addition to inquiring whether menstruation is normal, attention should also be paid to the presence of the aforementioned symptoms. Examinations should assess whether the uterus has recovered well, check for purplish-blue nodules in the vagina or vulva, and confirm the presence of shadows on chest X-rays (preferably chest films).
Pregnancy tests are crucial during follow-up. After complete removal of the hydatidiform mole, approximately 60% or more of patients test negative for pregnancy within 30 days. If the test remains positive beyond 40 days, malignant changes or residual vesicular mole should be highly suspected.
If a pregnancy test turns positive again during follow-up after previously turning negative, and pregnancy is ruled out, malignant changes should be highly suspected. Similarly, if the original urine test was positive but the dilution test turned negative, and the dilution test later becomes positive again during follow-up—especially if the dilution titer increases—malignant changes should also be highly suspected.
1. Massive hemorrhage: If a hydatidiform mole is not diagnosed and treated promptly, it can lead to recurrent bleeding and intrauterine hematoma, resulting in loss of blood. It may also cause severe bleeding during spontaneous expulsion. On the basis of existing anemia, hemorrhagic shock or even death can occur. Therefore, hydatidiform mole should be treated as an emergency, as even a short delay could result in further loss of blood and endanger the patient.
2. Incomplete hydatidiform mole or late abortion: After spontaneous late abortion or suction-induced late abortion, residual vesicular mole tissue may remain. For hydatidiform mole patients who experienced spontaneous late abortion shortly before hospitalization and can tolerate a clearing pericardium procedure, immediate clearing pericardium should be performed. For cases with prolonged expulsion time or signs of infection, antibiotics should be administered for several days before performing clearing pericardium.
3. Hydatidiform mole embolism: Vesicular mole tissue may migrate through the bloodstream to other parts of the body, most commonly the lungs and vagina, where it can form localized hemorrhagic lesions. Small emboli or undetected cases may resolve spontaneously. Yu Peiliang et al. reported a case where oxytocin-induced labor led to widespread pulmonary metastasis of hydatidiform mole, resulting in pulmonary micro-stirred pulse spasm syndrome and death due to pulmonary edema and heart failure. Unlike malignant tumor metastasis, hydatidiform mole embolism can be suppressed by the immune system and disappear. Cases have been documented by Lin Qiaozhi and Su Yingkuan. However, chemotherapy is currently recommended upon detection.
4. Malignant transformation: Progression to invasive hydatidiform mole or choriocarcinoma. The malignant transformation rate is approximately 10–20%. Details follow.
5. Torsion of theca-lutein ovarian cysts: This often occurs after the expulsion of a hydatidiform mole. In cases of torsion, surgical removal of the twisted uterine adnexa should be performed immediately.
1. Late abortion and hydatidiform mole: Although hydatidiform mole patients often exhibit symptoms of late abortion, their uterus is usually larger than that of a normal pregnancy at the same stage. Additionally, the pregnancy test is positive with a higher titer, making differentiation relatively straightforward. However, in some hydatidiform mole cases, the uterus may not be significantly enlarged, especially in the early stages, which can easily be confused with threatened late abortion. Nevertheless, the pregnancy test titer in hydatidiform mole is generally higher than in threatened late abortion. Ultrasound examination can distinguish between the two.
2. Polyhydramnios: This condition mostly occurs in the late stages of pregnancy, though acute polyhydramnios may develop in the mid-trimester, presenting with dyspnea and no vaginal bleeding. In contrast, hydatidiform mole rarely causes dyspnea but is often accompanied by recurrent vaginal bleeding. Ultrasound can reveal the distinct features of each condition, facilitating differentiation.
3. Uterine fibroids complicating pregnancy: If uterine fibroids are detected before pregnancy, differentiation is straightforward. Fibroids combined with pregnancy typically do not cause vaginal bleeding. During bimanual examination, fibroids may be palpated in certain parts of the uterine body. Ultrasound can aid in differentiation.
4. Twin pregnancy: Differentiating between monozygotic twins with polyhydramnios and threatened late abortion versus hydatidiform mole is particularly challenging. Not only are the clinical manifestations highly similar, but the pregnancy test titer is also higher than normal, often leading to misdiagnosis. Twin pregnancy generally does not involve vaginal bleeding, whereas hydatidiform mole often does. Ultrasound examination can confirm the diagnosis.
