Gestational Trophoblastic Disease
Claire Hoppenot
Celestine Tung
GENERAL PRINCIPLES
Gestational trophoblastic disease (GTD) is usually curable with appropriate diagnosis and surgical/medical management.
Preoperative evaluation for GTD can stratify patients in terms of risk for a medical complication at the time of surgery.
Prepare for the possibility of high blood loss with uterotonics and a balloon for tamponade.
Definition
Partial hydatidiform mole: Triploid pregnancy (69XXY, 69XYY, and 69XXX) from two sperm fertilizing an ovum with maternal chromosomes
Complete hydatidiform mole: Diploid pregnancy (46XX and 46XY) from two sperm fertilizing an empty ovum
Invasive mole: Benign hydatidiform mole with evidence of myometrial invasion
Choriocarcinoma: Malignant disease with absence of villi, anaplasia, and trophoblastic hyperplasia
Placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT): Malignancy arising from intermediate cells at the placental implantation site, characterized by lymphovascular invasion
Gestational trophoblastic neoplasia (GTN): Malignant form of trophoblastic disease that encompasses postmolar GTN (based on human chorionic gonadotropin [hCG] after the evacuation of a complete or partial mole), metastatic disease, or histopathologic evidence of choriocarcinoma, PSTT, or ETT.
Physical Examination
Presentation (1)
Complete hydatidiform moles present with vaginal bleeding, uterine enlargement greater than dates, hyperemesis, pregnancy-induced hypertension, hyperthyroidism
Partial hydatidiform mole frequently has abnormal vaginal bleeding, but most frequently (>90%) is diagnosed on incomplete or missed abortions.
GTN presents with irregular bleeding, uterine enlargement, persistent ovarian cysts, metastatic vaginal lesions, and pulmonary symptoms.
General: Check vitals to assess for tachycardia and hypotension, check for bruising or other evidence of disseminated intravascular coagulation (DIC).
Listen to the heart to assess for tachycardia and heart murmurs.
Listen to the lungs to assess for effusions (dullness to auscultation and percussion) and volume overload (crackles, particularly in the lung bases).
Perform an abdominal examination to determine the size of the uterine fundus and whether there is abdominal tenderness.
Assess the lower extremities for edema, erythema, and tenderness.
Pelvic examination: Perform a thorough vulvar and vaginal examination to assess for metastases. Visualize the cervix to determine whether there is vaginal and external cervical involvement with GTN, assess the amount of bleeding, and evaluate for the potential need for laminaria for cervical ripening (although rare).
Differential Diagnosis
Complete hydatidiform mole
Partial hydatidiform mole
GTN
Ovarian choriocarcinoma, dysgerminoma, embryonal carcinoma, or mixed germ cell tumor
Normal pregnancy
Abnormal pregnancy including incomplete abortion or missed abortion
Heterophile antibodies
Nonoperative Management
Induction of labor (IOL)
Not recommended owing to an increased risk of hemorrhage and postmolar GTN. Uterine contractions against a closed cervix may increase the risk of trophoblastic disease embolization, allowing the spread of the disease.
In most case series, a majority of women undergoing an IOL subsequently need a dilation and evacuation (D&E) for uterine evacuation.
Twin pregnancy
1/22,000 to 100,000 pregnancies will have a twin molar/normal pregnancy. With nonoperative management, 40% can have a normal viable fetus, but with a high risk of complications (medical complications of elevated hCG, hemorrhage) and persistent GTN. Dilation and curettage (D&C) with pregnancy termination is generally recommended.
IMAGING AND OTHER DIAGNOSTICS
Imaging
Ultrasound is the mainstay of diagnosis.
Incidental first-trimester ultrasound finding of absence of fetal parts, “snowstorm” appearance (complete moles), or abnormal pregnancies (partial moles) (Figure 3.3.1)
71% of GTD were accurately diagnosed on ultrasound.
15% of complete moles have theca lutein cysts on the ovaries.
CT scans evaluate for distant disease.
Blood tests
hCG is a reliable tumor marker.
Can be >100,000 mIU/mL for complete moles, lower for partial moles, and only slightly increased for PSTT and ETT.
GTD is associated with more heterogeneous hCG than a normal pregnancy, including hyperglycosylated hCG.
Postmolar GTN: Diagnosed with a rise (>10% across three values over a 2-week period) or plateau (stable within 10% across four values over a 3-week period) in hCG after a hydatidiform mole.
Rarely, hcg can be elevated outside of pregnancy or GTN (phantom hCG or quiescent GTD).
Figure 3.3.1. “Snowstorm” ultrasound appearance of complete hydatidiform molar pregnancy.
Pathology (1)
Complete mole
Diffuse swelling of villi and trophoblastic hyperplasia
Absent fetus/embryo
Diploid on flow cytometry
Characterized by absent p57 staining (paternally imprinted, maternally expressed gene)
Partial mole
Focal swelling of villi and trophoblastic hyperplasia
Abnormal fetus/embryo or fetal parts
Triploid on flow cytometry
Invasive mole
Swollen villi, hyperplastic trophoblast
Myometrial invasion
Choriocarcinoma
Abnormal trophoblastic hyperplasia, absent villi, anaplasia, hemorrhage, and necrosis
PSTT
Tumor cells infiltrate myometrium with vascular/lymphatic invasion, intermediate cells, absent villi, less hemorrhage, and necrosis
Positive staining for human placental lactogen (hPL)
PREOPERATIVE PLANNING
Check a complete blood count, clotting function, renal and liver function studies, thyroid levels, blood type, antibody screen, hCG levels, and a preoperative chest x-ray to evaluate for metastases.
Send a type and screen and ensure the blood bank can handle massive transfusion of blood, platelets, and coagulation factors.
Crossmatch 2U packed red blood cells (pRBC) for patients with a uterine size >16 weeks.
Operative setup for D&C
Perform D&C in the operating room (OR) under general or regional anesthesia—consider ultrasound guidance in OR to decrease the risk of uterine perforation.
Place large-bore intravenous (IV) access, consider central access based on uterine size and preoperative bleeding.
Ensure availability of general endotracheal intubation in case of heavy bleeding and need for conversion to laparoscopy or laparotomy.
Ensure availability of equipment and surgeons comfortable with laparotomy or laparoscopy.
Rh-negative patients should receive Rh immune globulin at the time of evacuation.
Consider laminaria placement to dilate the cervix before D&C for patients with a larger uterus.
Staging of GTN
The staging of GTN involves an International Federation of Gynecology and Obstetrics (FIGO) stage and a risk score.
FIGO staging
Stage I: Disease confined to the uterus
Stage II: Disease outside the uterus, confined to the gynecologic structures (vagina, adnexa, broad ligament, and parametrium)
Stage III: Disease extends to lungs.
Stage IV: Disease extends to other metastatic sites.
Risk score
Low-risk GTN: Risk score ≤ 7. High-risk GTN: Risk score > 7.
Based on age, antecedent pregnancy, time from pregnancy to treatment, pretreatment hCG, largest tumor mass size, site of metastases, number of metastases, and previous treatments
SURGICAL MANAGEMENT
For most patients, a D&C will be the only necessary treatment.
For patients with metastatic disease, D&C may decrease the amount of chemotherapy needed.
For patients with persistent GTD, repeated D&C can avoid chemotherapy for 20% to 60% of patients but has an increased risk of complications (8% uterine perforation and 5% estimated blood loss [EBL] > 1 L).
