Gestational trophoblastic disease (GTD)

Overview

Gestational trophoblastic disease (GTD) is a kind of tumor that is distinguished by aberrant trophoblastic growth. Human chorionic gonadotropin is produced by trophoblast cells (hCG). GTD is classified into two types: hydatidiform moles (which contain villi) and other trophoblastic neoplasms.

GTD that is non-molar or malignant is referred to as gestational trophoblastic neoplasia (GTN). Invasive moles, choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor are among them. These cancers can develop weeks or years after a pregnancy, although they are most frequent after a molar pregnancy.

Gestational trophoblastic disease definition

A tumor develops inside the uterus from tissue that originates after conception in gestational trophoblastic disease (GTD) (the joining of sperm and egg). This tissue is composed of trophoblast cells and is generally found in the uterus, surrounding the fertilized egg. Trophoblast cells help attach the fertilized egg to the uterine wall and are a component of the placenta (the organ that transports nutrients from the mother to the child

There are situations when the fertilized egg and trophoblast cells do not work properly. Instead of a healthy fetus, a tumor develops. The pregnancy will appear normal until there are indications or symptoms of the tumor.

The majority of GTD is benign (not cancerous) and does not spread, however other forms develop into malignant (cancerous) and spread to surrounding tissues or distant sections of the body.

Gestational trophoblastic disease (GTD) is a broad term that encompasses several forms of disease:

• Hydatidiform Moles (HM)

1. Complete HM.
2. Partial HM.

• Gestational Trophoblastic Neoplasia (GTN)

1. Invasive moles.
2. Choriocarcinomas.
3. Placental-site trophoblastic tumors (PSTT)
4. Epithelioid trophoblastic tumors (ETT)

Hydatidiform mole (HM) is the most common type of GTD.

Hydatidiform mole (HM)

HMs are slow-growing tumors that resemble fluid sacs. A HM is also known as a molar pregnancy. The exact etiology of hydatidiform moles is unknown.HMs may be complete or partial:

• When sperm fertilizes an egg that does not carry the mother's DNA, a full HM is formed. The egg has father's DNA, and the cells that were supposed to produce the placenta are abnormal.
• When sperm fertilizes a normal egg, a partial HM is formed because the fertilized egg contains two sets of DNA from the father. Only a portion of the fetus develops, and the cells that were supposed to create the placenta are aberrant.

The majority of hydatidiform moles are benign, however they can develop into malignancy. Having one or more of the following risk factors enhances the likelihood of a hydatidiform mole developing into cancer:

• A pregnancy before the age of 20 or after the age of 35.
• A very high amount of beta human chorionic gonadotropin (beta-hCG), a pregnancy hormone produced by the body.
• The presence of a big tumor in the uterus.
• An ovarian cyst that is greater than 6 cm in diameter.
• Pregnancy-related hypertension.
• Thyroid gland hyperactivity (extra thyroid hormone is made).
• During pregnancy, you may have severe nausea and vomiting.
• Trophoblastic cells in the blood can obstruct tiny blood arteries.
• The HM causes serious blood clotting issues.

Epidemiology

Epidemiological studies have revealed a wide range of HM occurrence. The greatest documented incidence has been estimated to be two in 1000 pregnancies in Southeast Asia and Japan. HMs develop in around 1 in 600 therapeutic abortions and 1 in 1500 pregnancies in the United States. After the mole is removed, 20% of these individuals will experience malignant transformation, necessitating treatment.

Choriocarcinoma occurs in roughly 1 in 20,000 to 40,000 pregnancies in the United States; 50% occur after term pregnancies, 25% after molar pregnancies, and 25% after other gestational events. Choriocarcinoma rates are greater in Southeast Asia and Japan, ranging from three to nine per 40,000 pregnancies. In all groups, the incidence of hydatidiform mole and choriocarcinoma has decreased during the last 30 years.

Etiology

A hydatidiform mole (HM) is a kind of mole that has aberrant gametogenesis and/or fertilization. Extremes in age, ethnicity, and a past history of an HM all imply a genetic foundation for its causation. When compared to women aged 21 to 35 years, the chance of a full mole is higher for women over 35 years old and younger than 21 years old, and it is 7.5 times higher for women over 40 years old.

The chance of recurrent molar pregnancy among women with a history of molar pregnancy is about 1%, which is ten to twenty times higher than the risk in the general population. Interestingly, a history of past spontaneous abortion has been linked to a two- to three-fold increase in molar pregnancy compared to a woman with no history of spontaneous abortion.

Pathophysiology

Hydatidiform moles are immature placentas that are very edematous. They are classified as whole and partial moles. When an empty ovum is fertilized by a sperm, a full molar pregnancy occurs. Only placental portions grow as a result of this. A full mole has a karyotype of 46,XX and is 100% paternal in origin. When two sperm fertilize a single ovum, this results in a half mole. As a consequence, some or all of the fetal components develop. A triploid karyotype of 69,XXX, 69,XXY, or 69,XYY is typical for a partial mole; nevertheless, a diploid karyotype may also exist.

GTN classification

Gestational trophoblastic neoplasia (GTN) is a type of gestational trophoblastic disease (GTD) that is almost always malignant.

Gestational trophoblastic neoplasia (GTN) includes the following:

Invasive moles

Invasive moles are made up of trophoblast cells that develop into the uterine muscle layer. Invasive moles are more prone than hydatidiform moles to develop and spread. In rare cases, a full or partial HM might develop into an invasive mole. Without treatment, an invasive mole may vanish.

Choriocarcinomas

A choriocarcinoma is a cancerous tumor that develops from trophoblast cells and spreads to the uterine muscle layer and adjacent blood vessels. It can also spread to the brain, lungs, liver, kidney, spleen, intestines, pelvis, or vagina. Women who have had any of the following are more prone to develop choriocarcinoma:

• Molar pregnancy, especially with a complete hydatidiform mole.
• Normal pregnancy.
• Tubal pregnancy (the fertilized egg implants in the fallopian tube rather than the uterus).
• Miscarriage.

Placental-site trophoblastic tumors

A placental-site trophoblastic tumor (PSTT) is a kind of gestational trophoblastic neoplasia that develops where the placenta connects to the uterus. The tumor develops from trophoblast cells and extends into the uterine muscle and blood vessels. It has the potential to spread to the lungs, pelvis, or lymph nodes. A PSTT develops slowly, and symptoms may show months or years after a normal pregnancy.

Epithelioid trophoblastic tumors

A benign or malignant epithelioid trophoblastic tumor (ETT) is a relatively rare kind of prenatal trophoblastic neoplasia. When a tumor becomes malignant, it has the potential to spread to the lungs.

Gestational trophoblastic disease (GTD) symptoms

Pathological and clinical characteristics of partial and full hydatidiform moles are discussed below.

Karyotype

• Partial: 69,XXX or 69,XXY
• Complete: 46,XX or 46,XY

Fetal tissues

• Partial: present
• Complete: absent 

Villous edema

• Partial: variable, focal
• Complete: diffuse

Trophoblastic proliferation

• Partial: focal
• Complete: Diffuse

Clinical Presentation

• Partial: tiny uterus for gestational age, low presenting hCG level, uncommon medical problems
• Complete: uterus is 50% bigger for gestational age, hCG level is high upon presentation, medical problems occur roughly 25% of the time and include hypertension, hyperthyroidism, anemia, and hyperemesis gravidarum.

Malignant sequelae 

• Partial: less than 5%
• Complete: approximately 20%

Presentation

• Partial: often as missed abortion in absence of symptoms
• Complete: clinical or ultrasonographic diagnosis

These and other signs and symptoms might be the result of gestational trophoblastic illness or another ailment. Consult your doctor if you experience any of the following symptoms:

• Menstruation has nothing to do with vaginal bleeding.
• A uterus that becomes bigger than usual during pregnancy.
• Pelvic discomfort or pressure.
• During pregnancy, you may have severe nausea and vomiting.
• Early in the pregnancy, I had high blood pressure, a headache, and swelling in my feet and wrists.
• Vaginal bleeding that lasts longer than usual after birth.
• Anemia causes fatigue, shortness of breath, dizziness, and a rapid or irregular pulse.

An overactive thyroid is occasionally caused by GTD. The following are signs and symptoms of an overactive thyroid:

• Fast or irregular heartbeat.
• Shakiness.
• Sweating.
• Frequent bowel movements.
• Trouble sleeping.
• Feeling anxious or irritable.
• Weight loss.

Diagnosis

Hydatidiform moles are most commonly detected during the first trimester of pregnancy. Abnormal bleeding is the most prevalent symptom. Other symptoms include uterine enlargement that is higher than expected for pregnant age, fetal heart tones that are missing, cystic ovary enlargement, hyperemesis gravidarum, and an unusually high level of hCG for gestational age.

• Physical exam and history: An examination of the body to examine general indicators of health, including the appearance of lumps or anything else that appears strange. A history of the patient's health habits, as well as previous diseases and treatments, will be collected.
• Ultrasound: The gold standard in non-invasive procedures is ultrasound. The "snowstorm" or "bunches of grapes" pattern of the uterus is the most typically described look of a molar pregnancy on ultrasonography. However, because of early detection, frequently in the first trimester, this is less prevalent nowadays. The majority of full moles in the first trimester exhibit the sonographic appearance of a complicated, echogenic intrauterine mass with many tiny cystic gaps.
• On gross pathology, these areas correlate to the hydropic villi. Despite the effectiveness of ultrasonography in making this diagnosis, a molar pregnancy is found only after pathology investigation of a uterine curettage sample in patients who are assumed to have had a spontaneous abortion. This is especially common in those who have a partial mole.
• Blood chemistry studies: A method in which a blood sample is examined to determine the levels of specific compounds produced into the blood by the body's organs and tissues. A chemical in an unusual (higher or lower than normal) concentration might be a symptom of sickness. Blood is also tested to determine the health of the liver, kidneys, and bone marrow.
• Serum tumor marker test: A method in which a blood sample is examined to determine the levels of particular compounds produced by organs, tissues, or tumor cells in the body. When some compounds are discovered in high concentrations in the body, they are associated to particular forms of cancer. These are known as tumor markers. The amount of beta human chorionic gonadotropin (beta-hCG), a hormone produced by the body during pregnancy, is measured in the blood for GTD. The presence of beta-hCG in the blood of a woman who is not pregnant might be a symptom of GTD.
• Urinalysis: A test to determine the color of urine as well as its contents, such as sugar, protein, blood, bacteria, and beta-hCG levels.

Management

• There are different types of treatment for patients with gestational trophoblastic disease.

Patients with gestational trophoblastic illness might get a variety of treatments. Some therapies are mainstream (already used), while others are being investigated in clinical studies. Patients may wish to consider participating in a clinical study before beginning therapy. A treatment clinical trial is a research study designed to enhance current medicines or gather information on novel treatments for cancer patients. When clinical studies demonstrate that a new therapy is superior to the standard treatment, the new treatment may be adopted as the standard treatment.

• Three types of standard treatment are used:

1. Sutgery
2. Chemotherapy
3. Radiation therapy

• Clinical trials are being conducted to explore new forms of therapy.
• Treatment for gestational trophoblastic illness may have unintended consequences.
• Patients may choose to consider participating in a clinical study.
• Patients can enroll in clinical trials before, during, or after beginning cancer therapy.
• It is possible that more testing will be required.

The cornerstone of treatment for total or partial moles is surgical uterine evacuation (dilation and evacuation, suction curettage).

Patients who have finished having children have the option of having a hysterectomy. Medical treatment is contentious and understudied. There is considerable worry that using uterotonics to induce uterine contractions may raise the risk of metastatic illness.

After evacuation, all patients with HM should be observed with successive serum hCG testing results to exclude out post-molar gestational trophoblastic neoplasia (GTN). The American College of Obstetricians and Gynecologists recommends the following protocol:

• Every week until non-detectable for 3 weeks, then
• Every month for 6 months: If the hCG remains undetectable for six months, then the patient may resume trying to become pregnant.

If hCG levels rise or stay elevated for several weeks after the evacuation of a whole or partial molar pregnancy, the patient is diagnosed with GTN.

• Hysterectomy: The uterus and, in certain cases, the cervix are removed during surgery. A vaginal hysterectomy is performed when the uterus and cervix are removed through the vagina. A total abdominal hysterectomy is performed when the uterus and cervix are removed through a major incision (cut) in the abdomen. A complete laparoscopic hysterectomy is performed when the uterus and cervix are removed through a tiny incision (cut) in the abdomen using a laparoscope.

• Chemotherapy is a cancer treatment that employs medications to halt the proliferation of cancer cells, either by killing them or preventing them from growing. Chemotherapy medications enter the circulation and can reach cancer cells throughout the body whether administered orally or injected into a vein or muscle (systemic chemotherapy). Chemotherapy medications primarily target cancer cells in the cerebrospinal fluid, an organ, or a bodily cavity such as the abdomen when administered directly into those locations (regional chemotherapy). The method of administration of chemotherapy is determined by the kind and stage of the cancer being treated, as well as whether the tumor is low-risk or high-risk.

• Radiation therapy is a form of cancer treatment that employs high-energy x-rays or other types of radiation to kill or prevent cancer cells from developing. Radiation treatment is classified into two types:

1. External radiation therapy uses a machine outside the body to send radiation toward the cancer.
2. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer.

Follow-up tests may be needed

Some of the tests used to identify the cancer or determine the stage of the disease may need to be repeated. Some tests will be repeated to see how effective the therapy is. The findings of these tests may be used to make decisions on whether to continue, adjust, or discontinue therapy.

Some of the tests will continue to be performed after the therapy has concluded. The findings of these tests might indicate whether or not your condition has altered or whether the cancer has returned (come back). These exams are often known as follow-up testing or check-ups.

Beta human chorionic gonadotropin (beta-hCG) levels in the blood will be monitored for up to 6 months after therapy has finished. This is due to the fact that a beta-hCG level that is greater than normal may indicate that the tumor has not responded to therapy or that it has progressed to malignancy.

Differential Diagnosis

• Biliary obstruction
• Bladder cancer
• Brain tumours
• Cerebrovascular accidents
• Haemorrhage cystitis: non-infectious
• HCG secreting germ cell tumours
• Nephrolithiasis
• Ovarian choriocarcinoma
• Pregnancy diagnosis
• Quiescent GTN
• Urothelial tumours of renal pelvis and ureters

Stages

• After prenatal trophoblastic neoplasia is detected, tests are performed to determine whether the cancer has spread to other regions of the body.
• Cancer spreads in three ways throughout the body.
• Cancer can spread from its original site to other sections of the body.
• For hydatidiform moles, there is no stage scheme.
• GTN employs the following stages:

1. Stage I
2. Stage II
3. Stage III
4. Stage IV

• The treatment of gestational trophoblastic neoplasia is based on the type of disease, stage, or risk group.

There are three ways that cancer spreads in the body.

Cancer can spread through tissue, the lymph system, and the blood:

• Tissue. The cancer spreads from where it started into neighboring places.
• The lymphatic system: The malignancy spreads from the site of origin by infiltrating the lymphatic system. The cancer spreads to other regions of the body via the lymph vessels.
• Blood. The cancer spreads from the site of origin by entering the bloodstream. The cancer spreads to other parts of the body via the blood vessels.

Cancer may spread from where it began to other parts of the body.

Metastasis occurs when cancer spreads to another section of the body. Cancer cells break out from the original tumor and migrate via the lymph system or bloodstream.

• The lymphatic system: The cancer enters the lymphatic system, moves via the lymph vessels, and eventually develops a tumor (metastatic tumor) in another portion of the body.
• Blood. The cancer enters the bloodstream, travels through the blood vessels, and eventually develops a tumor (metastatic tumor) in another portion of the body.

The initial tumor and the metastatic tumor are both cancers. If choriocarcinoma spreads to the lung, the cancer cells in the lung are choriocarcinoma cells. It's metastatic choriocarcinoma, not lung cancer.

Prognosis

Certain factors affect prognosis (chance of recovery) and treatment options.

Gestational trophoblastic disease usually can be cured. Treatment and prognosis depend on the following:

• Exactly the sort GTD.
• The extent to which the tumor has progressed to the uterus, lymph nodes, or other regions of the body.
• The number of tumors and their location in the body.
• The greatest tumor's size.
• The concentration of beta-hCG in the blood.
• When the tumor was discovered after the pregnancy began.
• Whether the GTD happened as a result of a molar pregnancy, a miscarriage, or a normal pregnancy.
• Treatment for pregnant trophoblastic neoplasia in the past.

Treatment options also depend on whether the woman wishes to become pregnant in the future.

Conclusion 

An interprofessional team, including nurses and pharmacists, is ideally suited to managing GTD. Patients with molar pregnancies should be closely watched for problems such as hyperthyroidism, pre-eclampsia, and ovarian theca lutein cysts.

Although uterine hyperthyroidism should disappear after uterine evacuation, patients may require beta-adrenergic blocking drugs before to anesthesia to counteract the effects of thyroid storm. Pre-eclampsia also resolves swiftly once the uterus is evacuated. Theca lutein cysts will regress on their own when beta-HCG levels diminish. Patients must, however, be informed about the signs and symptoms of ovarian torsion and burst ovarian cysts.