22. Gestational Trophoblastic Disease

Question 1

What is Gestational Trophoblastic Disease (GTD)?

Answer 1

GTD is an unusual condition that can be lethal, but thanks to developments in chemotherapy, cure rates are excellent. It is vital for medical students to be aware of GTD, as affected women can often be cured and remain fertile.

Question 2

What is the definition of Gestational Trophoblastic Disease (GTD)?

Answer 2

GTD is a neoplasia of the trophoblastic elements of the placenta, also known as “placental cancer.”

Question 3

How is Gestational Trophoblastic Disease (GTD) classified?

Answer 3

GTD is a spectrum of disease, ranging from benign to malignant. The extremes include:

• Hydatidiform Mole (benign)
• Choriocarcinoma (malignant)

The central part of the spectrum includes persistent GTD, with Placental Site Trophoblastic Tumour (PSTT), a rare type that usually occurs post-term.

Question 4

What are the main types of Gestational Trophoblastic Disease?

Answer 4

The main types include:

1. Hydatidiform Mole (benign)
2. Choriocarcinoma (malignant)
3. Persistent GTD (intermediate stage)
4. Placental Site Trophoblastic Tumour (PSTT) (rare, usually post-term)

Question 5

Why is it important for medical students to know about GTD?

Answer 5

Awareness of GTD is essential because, with proper treatment, women affected by it can often be cured and maintain fertility, making it a significant condition to diagnose and manage early.

Question 6

What is a complete hydatidiform mole?

Answer 6

A complete hydatidiform mole occurs when an empty ovum is fertilized by two sperms (dispermy). It is more common in older women and has a greater risk for persistence and invasion than a partial molar pregnancy. The chorionic villi are oedematous and resemble a bunch of grapes, with extensive trophoblastic proliferation. There are no fetal parts present.

Question 7

What is a partial hydatidiform mole?

Answer 7

A partial hydatidiform mole occurs when an ovum is fertilized by two sperms, resulting in a fetus with triploid genetic material. The fetus is abnormal, with possible growth restriction, mental retardation, and limb anomalies. Partial moles have fewer “grape-like” structures, a mixture of normal-sized and hydropic villi, and focal trophoblastic proliferation.

Question 8

What is persistent gestational trophoblastic disease (GTD)?

Answer 8

Persistent GTD occurs in approximately 15% of post-molar patients, where HCG levels do not regress but either rise or plateau. This is indicative of a persistent mole. It is diagnosed when HCG levels fail to return to normal after a molar pregnancy.

Question 9

What is an invasive mole?

Answer 9

An invasive mole refers to trophoblastic neoplasia that has penetrated the myometrium of the uterus. It is a form of gestational trophoblastic disease (GTD) that occurs after a molar pregnancy.

Question 10

What is choriocarcinoma, and when can it occur?

Answer 10

Choriocarcinoma is a rare, aggressive form of GTD that can occur after any form of pregnancy, whether normal or abnormal (such as after a molar pregnancy). It is characterized by trophoblastic cells invading the uterine wall.

Question 11

What are the rarer forms of gestational trophoblastic tumors?

Answer 11

The rarer forms of gestational trophoblastic tumors include placental site trophoblastic tumors and epithelioid trophoblastic tumors. These are less common and present with unique features compared to invasive mole and choriocarcinoma.

Question 12

Who can be affected by gestational trophoblastic disease (GTD)?

Answer 12

GTD can affect any fertile woman. The true incidence is difficult to determine, but it is more common in certain regions.

Question 13

How does the incidence of GTD vary between Western and Eastern societies?

Answer 13

In Western societies, GTD complicates about 1 in 2000 pregnancies. However, in Eastern countries, such as Indonesia, it can occur much more frequently, with an incidence as high as 1 in 125 pregnancies.

Question 14

What is the risk of recurrence for gestational trophoblastic disease (GTD)?

Answer 14

A previous history of GTD increases the risk of recurrence by six-fold. This highlights the importance of monitoring women with a history of GTD in future pregnancies.

Question 15

What are the common symptoms of a hydatidiform mole?

Answer 15

Symptoms of a hydatidiform mole include:

• Vaginal bleeding in early pregnancy
• Passing “grape-like structures” vaginally (more common in complete moles)
• An incidental finding on ultrasound
• Uterine size larger than expected for gestational age (more common in complete moles)
• Pre-eclampsia
• Thyrotoxicosis due to cross-reactivity between B-HCG and TSH
• Bilateral theca lutein cysts of the ovaries, presenting with lower abdominal discomfort and pelvic masses
• Excessive vomiting in pregnancy (hyperemesis)

These symptoms are often due to abnormally high B-HCG levels in molar pregnancies, although early detection with ultrasound has led to earlier diagnoses.

Question 16

How does uterine size and pre-eclampsia relate to hydatidiform moles?

Answer 16

In hydatidiform moles, particularly complete moles, the uterine size is often larger than expected for the gestational age due to extensive trophoblastic proliferation and oedematous villi. Pre-eclampsia can also develop early in the pregnancy, which is another common complication of molar pregnancies.

Question 17

What causes thyrotoxicosis and bilateral theca lutein cysts in hydatidiform mole?

Answer 17

Thyrotoxicosis can occur due to the homology between the B subunit of B-HCG and TSH, leading to cross-reactivity and hyperthyroidism. Bilateral theca lutein cysts of the ovaries may develop, leading to lower abdominal discomfort and pelvic masses.

Question 18

What findings on pelvic ultrasound are characteristic of a hydatidiform mole?

Answer 18

Complete mole: A “snow-storm” pattern is often seen on ultrasound due to the presence of oedematous, cystic villi.

Partial mole: May show a fetus with a focally abnormal placenta, and fetal anomalies may be detected at the 13 or 20-week ultrasound if the pregnancy is discovered later.

Question 19

How are HCG levels used in managing hydatidiform mole, and what other investigations are important?

Answer 19

Measuring HCG levels is not a diagnostic test for hydatidiform mole, but it is useful in evaluating the regression or progression of the disease.
Other important investigations include:

• Full blood count, renal function, and electrolytes
• Serum quantitative B-HCG levels
• Thyroid function tests (to assess for thyrotoxicosis)
• Chest x-ray (to check for metastasis, especially in choriocarcinoma)
• HIV counselling and testing (good practice)
• Group and save / cross-matched blood as appropriate in case of bleeding

Question 20

What are the initial treatment steps for a patient with hydatidiform mole?

Answer 20

Initial treatment involves:

Resuscitation if necessary, including correction of fluid loss and blood transfusion

Suction curettage under ultrasound guidance to evacuate the molar tissue.

The products of conception should be sent for histological evaluation to confirm the diagnosis.

Question 21

What should be considered regarding blood and Rh status during treatment for hydatidiform mole?

Answer 21

• Molar pregnancies are highly vascular, and there is a risk of bleeding, so it is prudent to have group and save blood available.
• After evacuation, blood tests should be checked before discharge, including offering Rhogam for Rh-negative patients to prevent Rh sensitization in future pregnancies.
• Additionally, it is important to test for syphilis and provide treatment if needed.

Question 22

What is the importance of centralized care and histology confirmation in the management of GTD?

Answer 22

The management of all GTD should be centralized at a tertiary level of care for specialized monitoring and treatment.

It is important to confirm the histology of the molar pregnancy before referral to ensure accurate diagnosis and appropriate management.

A repeat B-HCG test should be done to monitor the disease’s progression.

Question 23

What is the follow-up process for a woman who has had a hydatidiform mole?

Answer 23

• The patient should be adequately counselled about the diagnosis and the importance of follow-up.
• Follow-up visits are scheduled every two weeks until B-HCG results become negative.
• Once B-HCG is negative, visits are reduced to once a month for 6 months.
• Effective contraception is mandatory during this period to prevent a new pregnancy, which could interfere with surveillance due to the new source of beta-HCG.

Question 24

Can a woman who has had a molar pregnancy safely conceive again, and what should be considered in her next pregnancy?

Answer 24

There is no contraindication to a subsequent pregnancy once a patient has been discharged from follow-up and surveillance.

However, women who have had a molar pregnancy are at a higher risk of recurrence.

It is important to advise women to book early for their next pregnancy to ensure access to an early ultrasound for monitoring and early detection of any issues

Question 25

What is included under Gestational Trophoblastic Neoplasia (GTD)?

Answer 25

Gestational Trophoblastic Neoplasia (GTD) includes:

• Persistent gestational trophoblastic disease (GTD)
• Invasive GTD
• Choriocarcinoma
• Rarer forms like placental site trophoblastic disease (PSTT).

All of these conditions should be managed in specialized tertiary units, with chemotherapy as the primary treatment, except for placental site trophoblastic disease, where surgery is the cornerstone of management.

Question 26

What is the main treatment for Gestational Trophoblastic Neoplasia (GTD)?

Answer 26

The main treatment for GTD is chemotherapy. The type of chemotherapy depends on the patient’s risk according to the WHO/FIGO scoring system.

• Low-risk patients (score 0-6) are treated with single-agent chemotherapy (methotrexate or actinomycin-D).
• High-risk patients (score 7 or greater) receive multi-agent chemotherapy, typically EMA-CO (Etoposide, Methotrexate, Actinomycin-D, Cyclophosphamide, and Vincristine).

Question 27

How is persistent GTD or choriocarcinoma staged?

Answer 27

Persistent GTD and choriocarcinoma are staged using the WHO/FIGO scoring system, which determines the likelihood of chemotherapy resistance. The score is based on factors such as:

• Age (patients >39 years have a worse prognosis)
• Nature of the antecedent pregnancy (term delivery carries a worse prognosis compared to mole or miscarriage)
• Interval between the prior pregnancy and diagnosis (longer intervals have a worse prognosis)
• Initial beta-HCG level (higher levels indicate worse prognosis)
• Size of the largest tumor
• Site of metastases (liver/brain metastases carry a worse prognosis than lung/spleen/kidney/GIT metastases)
• Number of metastases
• Previous chemotherapy failure

Question 28

What is the clinical presentation of Persistent Gestational Trophoblastic Disease (GTD)?

Answer 28

• Most women with persistent GTD are asymptomatic.
• The diagnosis is suspected when B-HCG levels plateau or increase during post-uterine evacuation surveillance.
• Vaginal bleeding may occur, along with symptoms related to metastases (e.g., shortness of breath in lung metastases).
• Further investigations are required once the diagnosis is suspected.

Question 29

What are the common clinical presentations of choriocarcinoma?

Answer 29

Choriocarcinoma often presents with metastatic symptoms. In fact, 75% of patients present to non-gynecological specialties with the following:

• Cerebral: Convulsions or cerebrovascular accidents
• Pulmonary: Hemoptysis (coughing up blood) and dyspnoea (difficulty breathing)
• Vaginal: Bleeding or a vaginal lesion (violet/blue in color)
• Gastrointestinal: Rectal bleeding
• Renal: Hematuria (blood in the urine)
• Liver: Abdominal distension and hepatomegaly (enlarged liver)

Liver metastases carry a poor prognosis as they can rupture, leading to exsanguination (severe blood loss) and death. Bone and lymph node metastases are rare.

Question 30

Why is it important to consider choriocarcinoma in young women with specific symptoms?

Answer 30

It is mandatory to consider choriocarcinoma in any young woman presenting with acute and dramatic symptoms such as those listed above.

Failure to diagnose choriocarcinoma promptly can have devastating consequences due to its potential for rapid metastasis and life-threatening complications.

Question 31

How is choriocarcinoma diagnosed?

Answer 31

HCG confirmation: A positive urinary pregnancy test or serum HCG confirms the presence of HCG, which is essential for diagnosis.

Ultrasound: Primarily used to exclude an intra-uterine pregnancy.

Clinical presentation: If the clinical presentation does not fit with an ectopic pregnancy and HCG is positive, choriocarcinoma is the likely diagnosis.

Question 32

What special investigations should be done for gestational trophoblastic neoplasia (GTD)?

Answer 32

Clinical assessment: Includes a pelvic examination to check for vaginal metastases.
- Note: If vaginal metastases are found, do not biopsy them, as they can bleed profusely.

HCG levels: Measure serum B-HCG levels to track disease progression.

Blood tests: Full blood count, renal function, liver function, and thyroid function tests.

Consider HIV testing: HIV counselling and testing are essential because chemotherapy is immunosuppressive. HIV-positive patients with low CD4 counts and no antiretroviral therapy may not tolerate chemotherapy well.

Question 33

What imaging is required for gestational trophoblastic neoplasia (GTD)?

Answer 33

Chest x-ray: To assess for lung metastases. If negative, a CT chest is required.

Abdomen and pelvis imaging: At a minimum, patients require abdominal and pelvic imaging.
- In low-resource settings, an ultrasound may be used, but CT abdomen and pelvis provides better sensitivity.

CT brain: If lung metastases are found, a CT brain is also necessary to check for brain metastases.

Question 34

Why is histology not required for diagnosing choriocarcinoma?

Answer 34

Choriocarcinoma is the only gynecological malignancy where histology is not required for diagnosis.

If a woman presents with the symptoms and clinical signs of choriocarcinoma (as previously described), a positive urine pregnancy test with no intra-uterine pregnancy is sufficient for diagnosis, even without histological confirmation.

Question 35

What is the treatment for low-risk Gestational Trophoblastic Neoplasia (GTD)?

Answer 35

Women with low-risk GTD receive single-agent chemotherapy, which can either be:
- Methotrexate
- Actinomycin-D

These agents are effective for managing low-risk cases and are typically less intensive than the treatment for high-risk disease.

Question 36

What is the treatment for high-risk Gestational Trophoblastic Neoplasia (GTD)?

Answer 36

Women with high-risk GTD receive multi-agent chemotherapy, specifically the EMA-CO regimen, which includes:
- Etoposide
- Methotrexate
- Actinomycin-D
- Vincristine
- Cyclophosphamide

This regimen is more intensive and used for patients with a higher risk of progression or metastasis.

Question 37

How long is chemotherapy given for Gestational Trophoblastic Neoplasia (GTD)?

Answer 37

Chemotherapy is administered until B-HCG levels drop below 10 IU.

After achieving this, an additional 2-6 cycles of chemotherapy are given as “insurance” to ensure complete resolution of the disease

Question 38

What contraception advice is given to women undergoing treatment for Gestational Trophoblastic Neoplasia (GTD)?

Answer 38

Adequate contraception must be used during chemotherapy treatment to prevent pregnancy.

Women are advised not to conceive for one year after completing treatment, as pregnancy could interfere with monitoring the success of treatment and raise concerns about recurrence.

Question 39

What is the role of surgery in the management of Gestational Trophoblastic Disease (GTD)?

Answer 39

Surgery has a limited role, as chemotherapy is effective in most patients. However, surgery is important for certain indications, including:
- Suction curettage for a non-invasive molar pregnancy (preserves fertility).
- Hysterectomy for disease confined to the uterus in women who have completed child-bearing.
- Placental site trophoblastic tumor (PSTT): Surgery is required for tumor removal.
- Resection of isolated chemotherapy-resistant nodules (e.g., thoracotomy for lung metastases, craniotomy for brain metastases).

Question 40

What are the indications for emergency surgery in Gestational Trophoblastic Disease (GTD)?

Answer 40

Emergency surgery may be required in the following cases:

• Hysterectomy: For uncontrolled bleeding after evacuation or in cases of sepsis.
• Oophorectomy: For torsion of ovarian cysts.
• Craniotomy: If intracerebral metastases cause bleeding.
• Laparotomy: For bowel or urinary tract obstruction or other complications requiring surgical intervention.

Question 41

What is the role of radiation therapy in the treatment of Gestational Trophoblastic Disease (GTD)?

Answer 41

• Radiotherapy is rarely used in the treatment of GTD.
• It may be considered for brain and liver metastases, where it is sometimes used in combination with chemotherapy to treat resistant or isolated metastatic lesions.
• Radiation therapy is generally not a primary treatment option for most patients with GTD.

Question 42

Where should Gestational Trophoblastic Disease (GTD) be managed, and why?

Answer 42

GTD should be managed in specialized regional or tertiary centres, as these centers have the expertise and resources to provide optimal care.

Although the diagnosis of GTD is often made at the primary care level, urgent referral to a tertiary institution is necessary for appropriate management and treatment.