Trophoblast Tumors (GTDs)
What is it?
Gestational trophoblast pathology (GTD) refers to a spectrum of rare tumors originating from the placenta. GTD includes pre-malignant forms, such as partial and complete hydatidiform mole, and malignant forms, defined as gestational trophoblastic neoplasia (GTN) that include invasive mole, choriocarcinoma, placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT). The most common form of GTD is hydatidiform mole (1 in 1000 pregnancies in Europe and North America). Malignant trophoblast tumors can originate from any pregnancy, even months or years after pregnancy.
The frequency of GTD is higher in Asia than in North America and Europe. Trophoblast pathology occurs predominantly in the two extremes of a woman's fertile life: <16 years of age and >45 years of age, as the number of gametogenesis and fertilization defects is higher in these age groups.
Which are the symptoms?
Vesicular grind is usually diagnosed by histologic examination after a miscarriage. It should be suspected in the presence of blood loss (spotting or metrorrhagia), abdominal pain, elevated hCG levels, hyperthyroidism, pre-eclampsia in the second trimester of pregnancy. These symptoms and clinical findings are generally found associated with complete vesicular mole. In the partial form, in fact, the clinical presentation is often vaguer and difficult to distinguish from the threat of abortion.
Invasive mole may be suspected by persistence or recurrence of blood loss even after revision of the uterine cavity. As a complication of invasive mole, very serious sequelae such as uterine rupture may suddenly occur.
Malignant forms of GTD should be suspected in the presence of lung, brain, or abdominal metastases and elevated beta-hCG levels.
- Blood loss (spotting or metrorrhagia)
- Pelvic and lumbosacral pain
- Hyperthyroidism
- Pre-eclampsia
- Tachycardia
- Respiratory difficulties
- Hyperemesis gravidarum
- Increased uterus volume
- Deuterine cysts
How is it diagnosed?
Elevated serum beta-hCG values associated with specific ultrasound findings are highly indicative of trophoblastic pathology. In recent years, thanks to improved ultrasound techniques, in many cases ultrasound routinely performed early in pregnancy allows the diagnosis of vesicular molar to be made before symptoms develop. The diagnosis of mole pathology is most often made in asymptomatic patients undergoing revision of the uterine cavity following ultrasound diagnosis of internal abortion.
Histological and possible cytogenetic examination remains essential for the diagnosis. For correct staging, the following examinations are necessary:
- Gynecological examination
- Pelvic ultrasound
- Chest X-ray to highlight possible pulmonary metastases; in fact, the lung is the most frequent site of distant dissemination
- CT abdomen and chest
- CT or MRI brain to exclude the presence of brain metastases
Suggested exams
How is it treated?
In case of molar pathology the treatment is represented by hysterosuction under ultrasound guidance. Subsequently it is necessary to monitor beta-HCG values to exclude the need for additional treatments. Normally the duration of monitoring is 6 months for a complete mola and 1 month from zero beta-HCG in case of partial mola.
During monitoring, the attempt of a new pregnancy is not recommended.
Indications for chemotherapy treatment after vesicular molar are: plateau of serum hCG levels, increase of serum beta-hCG levels, serum beta-hCG levels > 20000 mIU/ml after 4 weeks from emptying of the uterine cavity, histological diagnosis of chorioncarcinoma, serum beta-hCG levels measurable 6 months after revision of the uterine cavity.
The first-choice therapy in patients with low-risk GTN is chemotherapy with methotrexate.
Patients who develop resistance to methotrexate should be treated with polychemotherapy (EMA-CO regimen) or monotherapy using a different drug such as actinomycin-D.
Overall survival in these patients remains close to 100% and fertility is maintained.
Patients with high-risk metastatic disease should be treated with polychemotherapy.
The first choice regimen is EMA-CO which is based on the use of etoposide, methotrexate, actinomycin-D, cyclophosphamide, and vincristine. To achieve complete eradication of the disease, chemotherapy is continued for 3-4 cycles after serum marker values have been reduced to zero.
In patients who develop chemoresistance during or after treatment with EMA-CO regimen, a salvage scheme based on polychemotherapy is recommended.
In case of chemoresistant localizations, surgical removal of the uterus is necessary when possible.
PSTT/ETT differ from invasive molar and choriocarcinoma in their lower chemosensitivity and low beta-hCG production. In case of non-metastatic disease, the first choice is the removal of the uterus, while, in case of metastatic disease the treatment is chemotherapeutic.
Where do we treat it?
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