John I. Brewer Trophoblastic Disease Center
The John I. Brewer Trophoblastic Disease Center of Northwestern University's Feinberg School of Medicine (Brewer Center) was established within the Department of Obstetrics and Gynecology in 1962.
The center studies and treats gestational trophoblastic diseases. These include rare growth disturbances of the placenta such as hydatidiform mole, invasive mole, choriocarcinoma, and placental site trophoblastic tumor.
The center serves as a treatment facility for patients with trophoblastic diseases, a consultation service for physicians and patients, and a clinical and laboratory research unit. More than 6,000 patients have been referred to the Brewer Center from 42 states and seven foreign countries, including approximately 850 who have received treatment for trophoblastic tumors at the center.
The center studies and treats gestational trophoblastic diseases. These include rare growth disturbances of the placenta such as hydatidiform mole, invasive mole, choriocarcinoma, and placental site trophoblastic tumor.
The center serves as a treatment facility for patients with trophoblastic diseases, a consultation service for physicians and patients, and a clinical and laboratory research unit. More than 6,000 patients have been referred to the Brewer Center from 42 states and seven foreign countries, including approximately 850 who have received treatment for trophoblastic tumors at the center.
About Gestational Trophoblastic Disease
Gestational trophoblastic disease (GTD) is a spectrum of rare growth disturbances of the trophoblasts of the placenta, the structure through which the developing embryo or fetus receives nourishment during pregnancy.
Types of GTD
There are four main forms of GTD:
The term gestational trophoblastic neoplasia (GTN) has been applied collectively to the latter conditions, which can progress, invade, metastasize, and lead to death if left untreated.
GTD was historically associated with significant morbidity and mortality. Hydatidiform mole was often accompanied by serious bleeding and other medical complications prior to the development of early detection and effective uterine evacuation means. The outcomes for gestational trophoblastic neoplasms were likewise poor before the introduction of chemotherapy into their management.
The mortality rate for invasive mole approached 15 percent, most often because of hemorrhage, infection, embolic phenomena, or complications from surgery. Choriocarcinoma had a mortality rate of almost 60 percent even when hysterectomy was done for apparent localized disease, and almost all women died who had a disease that spread beyond the uterus.
Gestational trophoblastic neoplasms are now some of the most curable of all tumors, with cure rates exceeding 90 percent, even in the presence of widespread metastatic disease. This success is the result of:
- Hydatidiform mole (also known as molar pregnancy). There are two types, including: Complete (without a fetus) and Partial (with an abnormal fetus)
- Persistent postmolar gestational trophoblastic neoplasia (also known as invasive mole)
- Choriocarcinoma (cancer of the placental trophoblast)
- Placental site trophoblastic tumor (PSTT) and its related epithelioid trophoblastic tumor (ETT) ( extremely rare variants)
The term gestational trophoblastic neoplasia (GTN) has been applied collectively to the latter conditions, which can progress, invade, metastasize, and lead to death if left untreated.
GTD was historically associated with significant morbidity and mortality. Hydatidiform mole was often accompanied by serious bleeding and other medical complications prior to the development of early detection and effective uterine evacuation means. The outcomes for gestational trophoblastic neoplasms were likewise poor before the introduction of chemotherapy into their management.
The mortality rate for invasive mole approached 15 percent, most often because of hemorrhage, infection, embolic phenomena, or complications from surgery. Choriocarcinoma had a mortality rate of almost 60 percent even when hysterectomy was done for apparent localized disease, and almost all women died who had a disease that spread beyond the uterus.
Gestational trophoblastic neoplasms are now some of the most curable of all tumors, with cure rates exceeding 90 percent, even in the presence of widespread metastatic disease. This success is the result of:
- The inherent sensitivity of trophoblastic neoplasms to chemotherapy
- The effective use of the pregnancy hormone tumor marker human chorionic gonadotropin (hCG) for diagnosing disease and monitoring therapy
- The referral of patients to or consultation with clinicians who have special expertise in management of these diseases
- The identification of prognostic factors that predicts treatment response and enhances individualization of therapy
- The use of combined modality treatment with chemotherapy, radiation, and surgery in the highest risk patients
Hydatidiform Mole (Molar Pregnancy)
What is Molar Pregnancy?
Hydatidiform mole or molar pregnancy refers to an abnormal pregnancy that arises as a result of a problem at the time of fertilization/conception, when the egg and sperm join together.
Molar pregnancies occur once in every 1000 to 1500 pregnancies in the United States and are more common in women under 20 years of age and in women above age 40. Women who have had a previous molar pregnancy are more likely to have a recurrence. It is rare to have a genetic mutation that results in repeated molar pregnancies.
Hydatidiform mole or molar pregnancy refers to an abnormal pregnancy that arises as a result of a problem at the time of fertilization/conception, when the egg and sperm join together.
Molar pregnancies occur once in every 1000 to 1500 pregnancies in the United States and are more common in women under 20 years of age and in women above age 40. Women who have had a previous molar pregnancy are more likely to have a recurrence. It is rare to have a genetic mutation that results in repeated molar pregnancies.
Types of Molar Pregnancy
Complete Molar Pregnancy
In a complete molar pregnancy, genetic material from the egg is lost and the only genetic material present is that of the sperm. No fetus is formed and the placenta grows rapidly.
Signs and Symptoms
Testing and Diagnosis
After evaluation of symptoms, physical examination, and hCG level testing, pelvic ultrasonography is then obtained. Pelvic ultrasound is the best method to diagnose a molar pregnancy, because it is able to capture the characteristic pattern of multiple holes within the placenta and no fetus.
Partial Molar Pregnancy
In a partial molar pregnancy, there is fertilization of an egg by two sperm, resulting in three sets of chromosomal genetic material (triploidy). An abnormal fetus forms and the placenta shows some of the same features as a complete mole.
Signs and Symptoms
Testing and Diagnosis
After evaluation of symptoms, physical examination, hCG level testing, and pelvic ultrasonography, the differential diagnosis may be a miscarriage versus partial mole. The diagnosis of a partial mole is most often confirmed on dilation and curettage.
Treatment of Molar Pregnancy
After the diagnosis of a molar pregnancy (complete or partial), the abnormal pregnancy should be evacuated from the uterus. Suction curettage is the preferred method. An alternative is a hysterectomy (removal of the uterus), if future fertility is not desired.
In a complete molar pregnancy, genetic material from the egg is lost and the only genetic material present is that of the sperm. No fetus is formed and the placenta grows rapidly.
Signs and Symptoms
- Vaginal bleeding between 6 to 16 weeks of gestation
- Larger than normal uterus
- Prolonged vomiting
- High blood pressure
- Hyperthyroidism
- Elevated hCG (pregnancy hormone) levels
Testing and Diagnosis
After evaluation of symptoms, physical examination, and hCG level testing, pelvic ultrasonography is then obtained. Pelvic ultrasound is the best method to diagnose a molar pregnancy, because it is able to capture the characteristic pattern of multiple holes within the placenta and no fetus.
Partial Molar Pregnancy
In a partial molar pregnancy, there is fertilization of an egg by two sperm, resulting in three sets of chromosomal genetic material (triploidy). An abnormal fetus forms and the placenta shows some of the same features as a complete mole.
Signs and Symptoms
- Vaginal bleeding
- Abnormal hCG (pregnancy hormone) levels
Testing and Diagnosis
After evaluation of symptoms, physical examination, hCG level testing, and pelvic ultrasonography, the differential diagnosis may be a miscarriage versus partial mole. The diagnosis of a partial mole is most often confirmed on dilation and curettage.
Treatment of Molar Pregnancy
After the diagnosis of a molar pregnancy (complete or partial), the abnormal pregnancy should be evacuated from the uterus. Suction curettage is the preferred method. An alternative is a hysterectomy (removal of the uterus), if future fertility is not desired.
Gestational Trophoblastic Neoplasia
What is gestational trophoblastic neoplasia?
Gestational trophoblastic neoplasia (GTN) includes persistent postmolar gestational trophoblastic neoplasia, choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. The overall cure rate in treating these tumors at our center currently exceeds 90 percent.
Gestational trophoblastic neoplasia (GTN) includes persistent postmolar gestational trophoblastic neoplasia, choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. The overall cure rate in treating these tumors at our center currently exceeds 90 percent.
Types of GTN
Postmolar GTN
Postmolar GTN is diagnosed most commonly by a plateau or rise in hCG levels following a molar pregnancy removal. There is a 15 to 20 percent chance that women with molar pregnancy will develop postmolar GTN which will then be treated with chemotherapy and/or surgery.
Signs and Symptoms
Invasive Mole
An invasive mole arises when the wall of the uterus is invaded by a molar pregnancy which continues after a molar pregnancy removal. Invasive mole is most often diagnosed as postmolar GTN because of persistent elevation of hCG levels after molar removal.
Choriocarcinoma
Choriocarcinoma is a malignant disease that can invade into the uterine walls and blood vessels resulting in spread to distant sites, such as the lungs, brain, liver, kidneys, intestines, spleen, and vagina. Choriocarcinoma affects about 1 in 40,000 pregnancies. Although choriocarcinoma can arise in association with any pregnancy, 50 percent arise from molar pregnancy. There are no characteristic signs or symptoms.
Placental Site Trophoblastic Tumor (PSTT) and Epithelioid Trophoblastic Tumor (ETT)
PSTT and ETT are extremely rare forms of GTN. They usually cause irregular bleeding and are associated with an enlarged uterus or cervical tumor. Diagnosis of PSTT and ETT requires expert review of biopsy or hysterectomy specimens. These tumors require different treatment from other GTNs.
Evaluation and Staging
When GTN is diagnosed, evaluation and staging (including blood work, laboratory tests, X-rays, MRI and/or CT scans) is the next step to determine risk factors and treatment. Treatment is then based on classification into risk groups defined by a combination of stage (where the disease is located) and score (prognostic factors).
Use of this staging system is essential for determining the most appropriate initial therapy to assure the best possible outcomes with the least toxicity.
Postmolar GTN is diagnosed most commonly by a plateau or rise in hCG levels following a molar pregnancy removal. There is a 15 to 20 percent chance that women with molar pregnancy will develop postmolar GTN which will then be treated with chemotherapy and/or surgery.
Signs and Symptoms
- Persistent irregular vaginal bleeding
- Persistently enlarged uterus
Invasive Mole
An invasive mole arises when the wall of the uterus is invaded by a molar pregnancy which continues after a molar pregnancy removal. Invasive mole is most often diagnosed as postmolar GTN because of persistent elevation of hCG levels after molar removal.
Choriocarcinoma
Choriocarcinoma is a malignant disease that can invade into the uterine walls and blood vessels resulting in spread to distant sites, such as the lungs, brain, liver, kidneys, intestines, spleen, and vagina. Choriocarcinoma affects about 1 in 40,000 pregnancies. Although choriocarcinoma can arise in association with any pregnancy, 50 percent arise from molar pregnancy. There are no characteristic signs or symptoms.
Placental Site Trophoblastic Tumor (PSTT) and Epithelioid Trophoblastic Tumor (ETT)
PSTT and ETT are extremely rare forms of GTN. They usually cause irregular bleeding and are associated with an enlarged uterus or cervical tumor. Diagnosis of PSTT and ETT requires expert review of biopsy or hysterectomy specimens. These tumors require different treatment from other GTNs.
Evaluation and Staging
When GTN is diagnosed, evaluation and staging (including blood work, laboratory tests, X-rays, MRI and/or CT scans) is the next step to determine risk factors and treatment. Treatment is then based on classification into risk groups defined by a combination of stage (where the disease is located) and score (prognostic factors).
Use of this staging system is essential for determining the most appropriate initial therapy to assure the best possible outcomes with the least toxicity.
Treatment of GTN
Low-risk disease
Women with nonmetastatic (stage I) and low-risk metastatic (stages II & III, score <7) GTN can be treated with low-toxicity, single-agent chemotherapy with resulting survival rates approaching 100 percent.
At the Brewer Center, the overall survival rate for low-risk GTN is 100 percent.
High-risk disease
Women classified as having high-risk metastatic disease (stages II-III, score ≥7 and stage IV) need to be treated in a more aggressive manner with multi-agent chemotherapy +/- adjuvant radiation or surgery to achieve cure rates of 80 to 90 percent.
At our Center, overall survival rates for high-risk GTN are up to 93 percent.
Women with nonmetastatic (stage I) and low-risk metastatic (stages II & III, score <7) GTN can be treated with low-toxicity, single-agent chemotherapy with resulting survival rates approaching 100 percent.
At the Brewer Center, the overall survival rate for low-risk GTN is 100 percent.
High-risk disease
Women classified as having high-risk metastatic disease (stages II-III, score ≥7 and stage IV) need to be treated in a more aggressive manner with multi-agent chemotherapy +/- adjuvant radiation or surgery to achieve cure rates of 80 to 90 percent.
At our Center, overall survival rates for high-risk GTN are up to 93 percent.
Follow Up
Successful treatment of GTN with chemotherapy has resulted in a large number of women who maintain their reproductive function. Most women resume normal ovarian function, exhibit no increase in infertility, and can anticipate successful pregnancy if desired.
To make an appointment with one of our experts, call 312.695.0990.
To make an appointment with one of our experts, call 312.695.0990.
