Gestational trophoblastic disease (GTD)

What is it?

Gestational trophoblast disease (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 mole is usually diagnosed by histologic examination after a spontaneous abortio. It should be suspected in the presence of blood loss (spotting or metrorrhagia), abdominal pain, elevated hCG levels, hyperthyroidism, and pre-eclampsia in the second trimester of pregnancy. These symptoms and clinical findings are generally associated with complete vesicular mole. In the partial form, in fact, the clinical presentation is often more vague and difficult to distinguish from the threat of abortion. 

Invasive grinding may be suspected because of persistence or recurrence of blood loss even after revision of the uterine cavity. As a complication of invasive grinding, very serious sequelae such as uterine rupture can suddenly occur. 

Malignant forms of GTD should be suspected in the presence of lung, brain, or abdominal metastases and elevated beta-hCG levels.

  • bleeding (spotting or metrorrhagia)
  • pelvic and lumbosacral pain
  • hyperthyroidism
  • pre-eclampsia
  • tachycardia
  • difficulty breathing
  • 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 the improvement of ultrasound techniques, in many cases the ultrasound performed routinely at the beginning of pregnancy allows to make the diagnosis of vesicular mole before the development of symptoms. The diagnosis of molar pathology is most often made in asymptomatic patients undergoing uterine cavity revision following ultrasound diagnosis of internal abortion.

Histologic and possible cytogenetic examination remains essential for diagnosis. For correct staging, the following examinations are necessary:

  • Gynaecological examination
  • Pelvic ultrasound
  • Rx thorax to highlight possible pulmonary metastases; the lung is in fact the most frequent site of distant dissemination
  • CT abdomen and chest
  • CT or MRI brain to exclude the presence of brain metastases

How is it treated?

In case of molar pathology, the treatment is represented by hysterosuction under ultrasound guidance. Subsequently, monitoring of beta-HCG values should be performed to rule out the need for additional treatment.  Normally, the duration of monitoring is 6 months for complete grinding and 1 month from zero beta-hCG in case of partial grinding.

Durante il monitoraggio è controindicata la ricerca di una nuova gravidanza.

Le indicazioni al trattamento chemioterapico dopo mola vescicolare sono: plateau dei livelli sierici dellehcg, aumento dei livelli sierici di beta-hCG, livelli sierici di beta-hCG > 20000 mIU/ml dopo 4 settimane dallo svuotamento della cavità uterina, diagnosi istologica di corioncarcinoma, livelli sierici di beta-hCG dosabili dopo 6 mesi dalla revisione della cavità uterina.

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 scheme is EMA-CO based on the use of etoposide, methotrexate, actinomycin-D, cyclophosphamide, and vincristine. In order to achieve complete eradication of the disease, chemotherapy is continued for 3-4 cycles after the serum values of the marker are zero. For patients who develop chemoresistance during the treatment with an EMA-CO regimen or relapse after it, salvage regimen based on polychemotherapy is indicated. 
In case of chemoresistant localizations, when possible, surgical removal of the uterus is necessary.

PSTT/ETT differ from invasive mole and choriocarcinoma by having 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 chemotherapy. 

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Where do we treat it?

Within the San Donato Group, you can find Gestational trophoblastic disease (GTD) specialists at these departments:

Are you interested in receiving the treatment?

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