Gestational trophoblastic diseases (GTD) include hydatidiform moles (both complete and partial), invasive moles, and choriocarcinoma. They typically arise from the abnormal fertilization of the ovum. Hydatidiform moles are benign, whereas invasive moles and choriocarcinoma are malignant lesions with a tendency to metastasize to other organs, especially the lungs. Patients with GTD frequently present with vaginal bleeding and pelvic tenderness. Complete hydatidiform moles are associated with several additional clinical features (e.g., enlarged uterus, hyperemesis gravidarum, preeclampsia). Diagnosis is established based on a significantly elevated serum β-HCG and ultrasound findings (e.g., a mass that resembles a bunch of grapes in complete hydatidiform moles). If malignancy is suspected, workup must include an x-ray of the chest to screen for lung metastases. Hydatidiform moles are normally treated via dilation and curettage, whereas choriocarcinoma typically requires chemotherapy.
|Overview of gestational trophoblastic disease|
|Partial mole||Complete mole||Choriocarcinoma|
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|Clinical features|| |
|Histopathological exam||Microscopy|| || |
|P57 staining|| || || |
- Classified as complete or partial moles (see “Etiology” below)
- Benign trophoblastic disease
- Proliferates within the uterus without myometrial infiltration or hematogenic dissemination
- May develop malignant traits and become an invasive mole
- Risk factors
- Does not contain any fetal or embryonic parts
- Caused by fertilization of an empty egg that does not carry any chromosomes. The (physiological) haploid chromosome set contributed by the sperm is subsequently duplicated.
- In rare cases, the formation of a complete mole may also result from simultaneous fertilization of an empty egg by two sperms.
- 46XX: more common (∼ 90% of cases)
- 46XY: less common (∼ 10% of cases)
- 46YY: has never been observed because it is nonviable.
- Partial mole
- Hydropic degeneration of chorionic villi with concomitant proliferation of cytotrophoblasts and syncytiotrophoblasts → death of the embryo
- Invasive mole: trophoblasts invade the myometrium → increased risk of bleeding and hematogenous spread
- Vaginal bleeding during the first trimester
- Uterus size greater than normal for gestational age
- Pelvic pressure or pain
- Passage of vesicles that may resemble a bunch of grapes
- Endocrine symptoms (due to ↑ β-hCG level)
- Partial mole
- Laboratory tests: β-hCG level measurement (initial test of choice) ; 
- Complete hydatidiform mole
- Partial hydatidiform mole
- Uterine evacuation (for definite diagnosis and treatment): histopathological examination of evacuated uterine specimen (also see “Treatment” below)
- Chest x-ray: in case of dyspnea or chest pain 
Fetal parts may be present in partial moles.
Some moles may not produce HCG at all.
- Uterine evacuation by dilation and suction curettage: Complete moles have a 20% risk of becoming invasive and a 2% risk of developing into choriocarcinoma. Therefore, complete evacuation of the uterine cavity is the mainstay of treatment.
- Monitor β-HCG levels until in reference range (usually 8–12 weeks)
- Chemotherapy (usually methotrexate; ) if unresolved, as indicated by any of the following:
- Most patients achieve normal reproductive function after recovery. 
- Risk of gestational trophoblastic neoplasia (includes choriocarcinoma and invasive moles)
- Highly aggressive, malignant tumor consisting of trophoblastic tissue
- Exhibits histological signs of malignancy and a tendency to metastasize early
- Choriocarcinoma only develops after fertilization and implantation of the egg.
- Most cases of choriocarcinoma are preceded by
- Malignant transformation of cytotrophoblastic and syncytiotrophoblastic tissue
- Destructive growth into myometrium without chorionic villi → risk of hemorrhage and early metastasis (lung, vagina, brain, liver)
- Postpartum vaginal bleeding and inadequate uterine regression after delivery
- Multiple theca lutein cysts
- Additional symptoms depend on the site of metastasis (e.g., seizures from metastases in the brain, dyspnea or hemoptysis from metastases in the lungs)
- Laboratory tests: : very high β-HCG (initial test of choice)
Pelvic ultrasound 
- Mass of varying appearance (suggestive of hemorrhage and necrosis)
- Hypervascular on color Doppler
- Uterine dilation and curettage (D&C)
- Treatment of choice: methotrexate or dactinomycin 
- Surgical treatment (e.g., hysterectomy); : may be indicated to stop bleeding; from cancerous lesions or to excise distant metastases
- Monitor β-HCG levels for at least 12 months.
- Cure rate of 95–100%
- Worse prognosis in the case of advanced-stage disease