March 29, 2024

Introduction

Gestational trophoblastic disease (GTD) is a group of rare tumors that develop in the cells that form the placenta during pregnancy. It is also known as gestational trophoblastic neoplasia. GTD originates from abnormal growth of the cells that would typically develop into the placenta.

There are different types of GTD, including:

  • Hydatidiform mole (Complete and Partial): This is the most common form of GTD. It occurs when there is an abnormal fertilization of an egg, resulting in the growth of a non-viable pregnancy. In a complete mole, the placental tissue becomes a mass of cysts without a fetus. In a partial mole, there may be some fetal tissue present along with the abnormal placental tissue.
  • Invasive mole: In rare cases, a hydatidiform mole can invade the wall of the uterus or spread to nearby tissues.
  • Choriocarcinoma: This is a malignant form of GTD that can occur after a hydatidiform mole, miscarriage, ectopic pregnancy, or normal pregnancy. Choriocarcinoma can spread to other organs, such as the lungs, liver, and brain.
  • Placental-site trophoblastic tumor: This is an extremely rare form of GTD that develops from the cells at the site where the placenta was attached to the uterus.

The exact cause of GTD is not well understood, but certain risk factors may increase the likelihood of developing the condition. These risk factors include a previous molar pregnancy, a history of GTD, maternal age (under 20 or over 35), and certain genetic factors.

Symptoms of GTD can vary depending on the specific type but may include vaginal bleeding (often in the first trimester), unusually high levels of human chorionic gonadotropin (hCG) hormone, enlarged uterus, severe nausea and vomiting (hyperemesis gravidarum), and high blood pressure.

GTD is typically diagnosed through a combination of physical exams, ultrasound imaging, and blood tests to measure hCG levels. Treatment for GTD depends on the type and stage of the disease. It may involve the surgical removal of the abnormal tissue (dilation and curettage or hysterectomy), chemotherapy, or a combination of both.

With early detection and appropriate treatment, the prognosis for GTD is generally excellent. Most women with GTD can be cured, and the chances of a successful subsequent pregnancy are usually good. Regular follow-up care and monitoring of hCG levels are important to detect any recurrence or complications.

 

GTD Epidemiology

Epidemiological data on GTD varies across different regions of the world, but it is generally considered a relatively rare condition. Here are some key points regarding the epidemiology of GTD:

Incidence:

  • Globally, the incidence of GTD varies widely, ranging from approximately 0.4 to 2.7 cases per 1,000 pregnancies.
  • The highest incidence rates are reported in Southeast Asia, particularly in Indonesia, the Philippines, and certain regions of China, where rates can exceed 10 cases per 1,000 pregnancies.
  • In Western countries, the incidence is generally lower, ranging from 0.5 to 1.0 cases per 1,000 pregnancies.

Risk Factors:

  • GTD is more common in women of Asian descent compared to women of European or African descent.
  • A prior history of GTD significantly increases the risk of recurrence in subsequent pregnancies.
  • The risk of developing GTD is also increased in women who are older than 40 or younger than 20 at the time of pregnancy.
  • Other risk factors include a history of infertility, previous miscarriage, and certain blood types (e.g., A, AB).

Hydatidiform Mole:

  • Hydatidiform mole (HM) is the most common form of GTD, accounting for the majority of cases.
  • Complete hydatidiform mole (CHM) occurs when there is fertilization of an empty egg, resulting in the absence of fetal tissue. Partial hydatidiform mole (PHM) occurs when there is fertilization of an egg with two sperm or when an abnormal fetus is present.
  • The incidence of HM varies across populations, with higher rates reported in Asian countries.

Choriocarcinoma and Invasive Mole:

  • Choriocarcinoma is a rare malignant form of GTD that can develop after a molar pregnancy, ectopic pregnancy, miscarriage, or a normal pregnancy. It is characterized by the presence of abnormal trophoblastic cells that can spread to other parts of the body.
  • Invasive mole is an intermediate form between a hydatidiform mole and choriocarcinoma, where the trophoblastic cells invade the uterine wall but do not metastasize like choriocarcinoma.
  • Choriocarcinoma and invasive mole are less common than hydatidiform mole, but they have a higher potential for malignancy.

Overall, while gestational trophoblastic disease is a rare condition, its incidence can vary geographically. Early detection, proper management, and close follow-up are crucial for ensuring favorable outcomes for affected individuals.

 

GTD Classifications

The main classifications of GTD include:

1) Hydatidiform mole (HM): This is the most common type of GTD, accounting for about 80% of cases. It is further divided into two subtypes:

  • Complete hydatidiform mole (CHM): In this subtype, the sperm fertilizes an empty egg, resulting in the absence of fetal tissue and the proliferation of abnormal placental tissue.
  • Partial hydatidiform mole (PHM): In PHM, there is a normal egg fertilized by two sperm or an abnormal sperm, resulting in an abnormal embryo and some fetal tissue.

2) Invasive mole: This is a rare form of GTD in which the abnormal placental tissue grows into the muscle layer of the uterus. It can invade nearby tissues but does not spread to distant organs.

3) Choriocarcinoma: This is an aggressive and malignant form of GTD. It occurs when the abnormal placental tissue becomes cancerous and spreads to other parts of the body, such as the lungs, liver, or brain.

4) Placental site trophoblastic tumor (PSTT): This is a rare form of GTD that originates from the placental implantation site after a normal pregnancy or an abortion. It tends to be less aggressive than choriocarcinoma but can still metastasize.

5) Epithelioid trophoblastic tumor (ETT): ETT is also a rare form of GTD, usually occurring after a previous molar pregnancy. It arises from the chorionic epithelium and can metastasize to distant sites.

It’s important to note that GTD is a complex condition that requires specialized medical care for diagnosis, treatment, and monitoring. Treatment approaches vary depending on the type and extent of the disease, but they often involve a combination of surgery, chemotherapy, and close monitoring of tumor markers.

 

Molar Pregnancy Symptoms & Complications

A molar pregnancy, also known as a hydatidiform mole, is a rare abnormality of pregnancy where there is an overgrowth of abnormal cells in the uterus. It can present with various symptoms and signs, and if left untreated, it can lead to complications. Here are the symptoms, signs, and complications associated with molar pregnancy:

1) Symptoms and Signs:

  • Vaginal bleeding: It may range from light spotting to heavy bleeding, resembling a miscarriage or menstruation.
  • Severe nausea and vomiting (hyperemesis gravidarum): Persistent and severe morning sickness beyond the normal range.
  • Rapid enlargement of the uterus: The uterus may grow larger than expected for the gestational age.
  • Passage of grape-like clusters through the vagina: These are grape-like cysts composed of the abnormal placental tissue.
  • High blood pressure (hypertension): This can occur in some cases.
  • Hyperthyroidism: Overactive thyroid gland resulting in symptoms such as weight loss, palpitations, and anxiety.
  • Absence of fetal heartbeat or movement: Molar pregnancies usually do not develop into a normal fetus.

2) Complications:

  • Invasive mole: In some cases, the abnormal placental tissue can grow into the muscle layer of the uterus, leading to a condition called an invasive mole. This can cause persistent bleeding and require surgical removal.
  • Choriocarcinoma: In rare cases, the abnormal cells can become cancerous and spread to other parts of the body, leading to a condition known as choriocarcinoma. Symptoms may include persistent bleeding, pelvic pain, and the development of tumors in other organs.
  • Uterine rupture: Invasive moles or choriocarcinomas can weaken the uterine wall and increase the risk of uterine rupture, which is a medical emergency.

It’s important to note that while these symptoms and signs may suggest a molar pregnancy, they can also occur in other conditions. If you experience any of these signs, it’s crucial to seek medical attention promptly for a proper diagnosis and appropriate management.

 

GTD Investigations & Treatment

The basic principles of investigations and treatment for GTD are as follows:

  1. Medical history and physical examination: The first step in the investigation of GTD involves obtaining a detailed medical history, including any previous pregnancies and pregnancies with complications. A thorough physical examination, including pelvic examination, is performed to assess for any signs of GTD.
  2. Imaging studies: Transvaginal ultrasound is commonly used to evaluate the uterus and ovaries for the presence of abnormal masses or lesions. It helps in diagnosing and staging GTD.
  3. Beta-human chorionic gonadotropin (β-hCG) measurement: β-hCG is a hormone produced during pregnancy, and its levels are significantly elevated in GTD. Serial measurements of β-hCG are used to monitor the response to treatment and detect any disease recurrence.
  4. Histopathological examination: If GTD is suspected, a suction curettage or biopsy is performed to obtain tissue samples from the uterus. These samples are sent for histopathological examination to confirm the diagnosis and determine the specific type of GTD.
  5. Staging: Staging is essential to determine the extent of GTD and guide appropriate treatment. It involves assessing the tumor size, invasion of nearby structures, and the spread to distant organs.

Treatment of GTD depends on the specific type and stage of the disease:

  1. Hydatidiform mole (complete or partial):
    • Complete mole: A dilation and curettage (D&C) procedure is performed to remove the abnormal tissue. Follow-up monitoring of β-hCG levels is necessary to ensure complete resolution.
    • Partial mole: D&C is also performed, followed by close monitoring of β-hCG levels. In some cases, chemotherapy may be required if there are persistent or rising β-hCG levels.
  2. Invasive mole:
    • Treatment typically involves a D&C procedure followed by chemotherapy to eliminate any remaining tumor cells.
  3. Choriocarcinoma:
    • Chemotherapy is the primary treatment for choriocarcinoma, often using a combination of chemotherapy drugs. The specific regimen and duration depend on the stage and risk category.
  4. Placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT):
    • These rare types of GTD may require surgical intervention, such as hysterectomy or removal of metastatic lesions. Chemotherapy may also be employed, especially in cases of metastatic disease or high-risk tumors.

Throughout the treatment process, close monitoring of β-hCG levels is crucial to assess treatment response and detect any recurrence or persistence of the disease. Regular follow-up visits and imaging studies are conducted to ensure complete remission and long-term surveillance. Individualized treatment plans are developed based on the specific characteristics of each case of GTD. It is important to consult with a specialist in gynecologic oncology for the management of GTD.

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