Gestational Trophoblastic Disease

Early in my midwifery career, during my apprenticeship in fact, I learned about gestational trophoblastic disease firsthand. It fascinated me from the start. Here in South Sudan, I have seen several molar pregnancies per month, every month. Each case is unique and some of them are more complicated than others. This post will be a little more clinical/technical than others and may not interest those who are not midwives but I did my best to write in terms most people can understand.

For readers unfamiliar with molar pregnancies, I will give a brief overview. Gestational trophoblastic disease (GTD) is the term given to a group of rare tumors that develop during the early stages of pregnancy. After conception, the body prepares for pregnancy by surrounding the newly fertilized egg with a layer of cells called the trophoblast. The trophoblast helps the embryo implant itself to the uterine wall. These cells also form a large part of the tissue that make up the placenta. In GTD, there are abnormal changes in the trophoblast cells that cause tumors to develop.

Most GTD tumors are benign, but some have the potential to turn malignant. GTD is usually classified into one of two categories:

• Hydatidiform moles
• Gestational trophoblastic neoplasia (GTN)

A hydatidiform mole is also known as a molar pregnancy. In a molar pregnancy, there is a problem with the fertilized egg, and there is an overproduction of trophoblast tissue and the excess tissue grows into abnormal masses that are usually benign but can sometimes turn cancerous. There are two types of hydatidform moles:

• Partial mole: The fertilized egg contains the normal set of maternal DNA but double the number of paternal DNA. Because of this, the embryo only partially develops and does not become a viable fetus.
• Complete mole: The fertilized egg has no maternal DNA and instead has two sets of paternal DNA. A fetus does not form.

There are several types of gestational trophoblastic neoplasia:

• Choriocarcinoma: This cancerous tumor forms inside the uterus. Choriocarcinomas usually occur when growths from molar pregnancies turn cancerous. Rarely, choriocarcinomas form from tissue left in the uterus after a miscarriage, an abortion or the delivery of a healthy baby.
• Invasive mole: Trophoblast cells form an abnormal mass that grows into the muscle layer of the uterus.
• Placental-site trophoblastic tumor: This extremely rare, slow-growing tumor develops where the placenta attaches to the uterine wall. Placental-site trophoblastic tumors are often not discovered until years after a full-term pregnancy.
• Epithelioid trophoblastic tumor: Extremely rare tumor and it’s progression mimics that of a placental-site trophoblastic tumor.

The only way to prevent GTD is to not become pregnant. Risk factors for GTD include, age under 20 or over 35, previous GTD and history of miscarriage. None of these risk factors can account for why we see such a high rate of molar pregnancies here in the camp in South Sudan.

Due to the cystic degeneration of the placenta (abnormal proliferation of the chorionic villi) the mole presents in the form of translucent vesicles, 1-2 cm in diameter, connected by filaments like a cluster of grapes

Here in the field, patients with molar pregnancies will often present with bleeding and then upon exam and ultrasound, the mole is discovered. Other times, when a patient comes in for a prenatal exam, no fetal heartbeat is heard and then upon ultrasound exam, a mole is discovered. Some of them can go to 20 weeks or more undiscovered in places like this because women often do not seek care until their pregnancy is more advanced or they have an issue.

The pregnancy test is always positive. Hydatidform moles are commonly associated with markedly elevated hCG levels often in excess of 100,000 mIU/mL with complete moles. Here in the field, we do not have quantative hCG so we cannot use this as part of our diagnostics and must rely on the other signs for diagnosis. Partial hydatidiform moles do not have the same presenting features as complete moles. Although the main presenting symptom is also vaginal bleeding, which occurs in about 75% of patients. Fewer than 10% of patients with partial moles have hCG levels > 100,000 mIU/mL. More than 90% of patients with partial moles have symptoms and ultrasound findings consistent with an incomplete or missed abortion, and the diagnosis is usually made only after MVA or currettage is done. I have been surprised a couple of times!

With a complete mole, ultrasound will show a heterogenous vesicular placenta filling the entire uterine cavity. The characteristics of molar pregnancies on ultrasound is called snowstorm or grapes in a snowstorm because of it’s grape-like cluster appearance. It’s unmistakable. A partial mole can be a little harder to detect and can be somewhat confusing if one is unsure what they are looking at or isn’t suspecting a mole.

It is helpful to see what a complete mole looks like when it expels on its own. In Bangladesh, we had a patient who came in at 20 weeks gestation in preterm labor with some bleeding. We did not get a heartbeat and we did not have ultrasound. We assume it was a fetal demise. On exam I could feel there were notfetal parts presenting and what felt like placenta through the cervix, which would explain the bleeding. She was not in maternity long before starting to push. Out came a complete mole totally intact. As you can see, the cyst-like features are what show up on ultrasound most often. Not all moles are this classic. Some have more placenta-like qualities to them. On manual vacuum extraction (MVA), the mole comes out in bits so it is rare to see one intact unless they expel spontaneously.

GTD is oftentimes accompanied by bleeding and this is most often what brings a patient into maternity if the mole had not been previously diagnosed on early ultrasound. I have not personally experienced much hemorrhaging but we carefully manage these patients as soon as they present with the express purpose of preventing hemorrhage.

The aftercare of a patient with GTD is very important. In about 10 to 15% of patients with a complete mole,will develop post-molar trophoblastic neoplasia (choriocarcinoma). Between 1 and 5% of patients with a partial mole will develop choriocarcinoma. In light of this, we have very specific guidelines in the field appropriate for low-resource settings such as ours. Note, they are much different in resource rich settings.

The patient is counseled on family planning and we explain it is best to avoid another pregnancy for at least a year. Two weeks after MVA, the patient is asked to return for a repeat ultrasound to make sure the uterus is empty. Even when MVA is done correctly, retention of molar debris is not uncommon. When we do not have ultrasound at our disposal, we rely on clinical signs like persistent or recurring bleeding after MVA.

Eight weeks after MVA, we perform a pregnancy test. It should be negative by that time. If it is, then we ask the patient to come back at intervals of 4 to 8 weeks for 1 year. If the test is positive or becomes positive at any time during that year, persistent trophoblastic disease or choriocarcinoma is suspected. Often in the field, there is no place to refer the patient even if we detect the hCG or she becomes symptomatic. This is very disheartening. Without very aggressive, specific treatment, choriocarcinoma is 100%. It is the fastest growing cancer there is and the patient usually dies within a year.

Most recently, a patient presented with bleeding at 16 weeks gestation and no fetal heartbeat, incomplete abortion was diagnosed. she was 35 and had 9 children. She had been referred to me because the midwife in the other project was unable to penetrate further than the inner os while attempting MVA. She suspected it may be a molar pregnancy but was not sure on ultrasound.

The patient was flown to our project and I repeated everything the first midwife had done. On ultrasound exam it did look like a hydatidaform mole to me and I attempted MVA as well, how hard could it be? Well, I experienced exactly what the first midwife described. I could not get the cannula to advance beyond the inner os of the cervix. Okay then! I presented this case to the surgeon. I believed the patient needed to go to OT because there would be no way to get the uterine contents out otherwise. We did an ultrasound together. He saw what I saw and thought it may be a fibroid. I disagreed. It should be noted, he is a general surgeon and not a gyn. I told him either way, the contents could not be evacuated through the os and I doubted whether even a D&C would be successful, which was his first suggestion to me. He did not know how to do them but wanted to learn so he suggested we try that first and I could teach him. When I explained that my working theory was that this was an invasive mole and was similar to a placenta accreta in that it had likely grown into the endometrium, he understood the issue.

We discussed how to proceed. I explained that I thought the mole was taking up the entire uterine cavity because that is how it looked on ultrasound and this is what hydatidiform moles did. So if this was the case, it would not be possible to do a laparotomy and myomectomy because I did not think the contents would come out. Due to the fact that the surgeon had never done any gyn surgeries aside from c-section, he wasn’t keen on changing course mid-surgery if the myomectomy proved fruitless. Planning on hysterectomy from the start was likely a better option.

We don’t routinely do planned hysterectomies because they are generally not lifesaving. We needed to get permission from the hospital coordinator before scheduling the surgery and then counsel the patient and get her consent as well. Since without the surgery, the patient would continue to have pain and bleeding and then potentially start to hemorrhage, I was certain the hospital coordinator would okay it and she did. I told her I could be wrong with the diagnosis but I really did not think so. Or if I was wrong, there was still something large in her uterus that needed to come out and likely could not come any other way. The patient also agreed. She said 9 children were enough for her and would do the surgery, so we schedule for the next morning.

The surgery took about 3 hours. There were bladder and bowel adhesions but everything went well and the patient did not lose much blood, something we are always concerned about because it is difficult to get family donors and we don’t have a blood bank per se, usually just a few units left over from someone who ended not needing blood after it had been donated. The surgeon removed a very unhealthy looking uterus. Even from the outside, you could tell it was diseased. Once dissected, it was obvious the trophoblasts had completely invaded the myometrium. There would have been no possible way to get this out of her uterus because it had completely taken it over. I was quite relieved. And curiously enough, it looked exactly as I imagined it would.

As I mentioned in the beginning of this blog post, my first encounter with choriocarcinoma was during my apprenticeship. It was a very profound experience and had a huge impact on me personally and professionally. My client died but she had refused treatment. I wrote the whole story several years ago and it can be accessed here: http://www.naturaltransitions.org/wp-content/uploads/2011/10/NTM-Sampler-April-24-20121.pdf

Here is South Sudan, the patient recovered well and had a very uncomplicated post-op. She was flown home a week later. She will continue to be followed by the other project where she had come from. She is aware of what we found and what it could possibly mean, although without further pathology, it is difficult to know anything for sure. I am not very hopeful from what I saw that her prognosis will be very good, however, I have seen some of the most miraculous things happen over the years and I would never pretend to know someone’s fate nor am I an expert on this subject. I do hope the odds are in her favor.

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