Duke-NUS Graduate Medical School Hydatidiform_Mole

Transcription

1 Duke-NUS Graduate Medical School Hydatidiform_Mole The topic of this presentation is on hydatidiform moles. A hydatidiform mole, also known as a molar pregnancy, is a relatively rare condition whereby there is abnormal proliferation of the placenta in a pregnancy, resulting in a massive cyst in the uterus rather than a viable pregnancy. Today we'll be talking about two types of moles, complete moles and pasture moles, as well as their complications. Some of the risk factors for molar pregnancies include extremes of age. That is below 20 or above 35. A prior history of gestational trophoblastic disease, nulliparity, a diet low in beta carotene, folic acid, and animal fat, smoking, and usage of OCPs. There are two types of molar pregnancies, complete and incomplete. A complete mole is a result of the fertilization of an enucleate ovum. That is an ovum with a missing or nonfunctional nucleus with a normal sperm which then replicates itself. More rarely a complete mole can be formed by the fertilization of an enucleate egg with two normal sperms. In both cases the chromosomes in a complete mole are all paternally derived. Complete moles are the more common molar pregnancy, accounting for 90% of molar pregnancies. Among them the most common karyotype is 46XX. In a complete mole there is noninvasive trophoblastic proliferation, which leads to diffused swelling of the chorionic villi and hydropic degeneration. This gives the mole its characteristic appearance of grape-like vesicles filling the uterus. Notably, in a complete mole there's an absence of fetus, fetal villi, or fetal red blood cells. In addition, there's abnormal proliferation of syncytial trophoblasts which produces high levels of hcg. hcg has both alpha and beta levels, and the alpha sub unit can be found in LH, FSH, and TSH. Because of this, they can act as homologues to LH and FSH and stimulate development of large theca lutein cysts. Likewise, they can also act as homologues to TSH to cause hypothyroidism. The high hcg levels can also cause hyperemesis gravidarum and early pre-eclampsia. 15% to 20% of complete moles progress to malignancy.

2 On the other hand, a partial or incomplete mole is formed when a normal ovum is fertilized by two sperms simultaneously. The most common karyotype associated with it is 69XXY. An incomplete mole results in placenta abnormality characterized by focal hydropic villi, and trophoblastic hyperplasia, primarily of the cytotrophoblasts. In contrast to a complete mole, there's normal or only slightly elevated hcg since cytotrophoblasts do not produce hcg. Uniquely incomplete moles are associated with the presence of a fetus. In fact, amniotic fluid and fetal heart rate may also be present. However, the fetus often has multiple structural abnormalities, and it's likely to be growth restricted. Furthermore, most fetuses survive only several weeks in vitro before being spontaneously aborted in the late first or early second trimester. It is worthy to note that partial moles are almost always benign and have a much lower malignancy potential than a complete mole. Compared to the 15% to 20% who progress to a persistent mole, less than 5% of patients with partial moles will develop persistent malignant disease. A molar pregnancy usually presents with the following symptoms. First vaginal bleeding, which is caused by the separation of the tumor from underlying desidual, leading to disruption of maternal vessels. In cases of prolonged bleeding, signs and symptoms of anemia may be observed. One may also observe passage of molar vesicles, nausea and vomiting caused by hyperemesis gravidarum. On physical examination one may observe hypertension due to pre-eclampsia, and a uterine size which is more than gestational age, which may be caused by tumors, blood clots, or hemorrhage. Partial or incomplete moles present in the same way. However the symptoms are less severe from that of complete moles, as the hcg levels are only slightly elevated. As such, they are diagnosed later than complete moles. 90% of them will present with vaginal bleeding from miscarriage or incomplete abortion in late first or early second trimester. As such incomplete moles are often diagnosed later than complete moles. Unlike complete moles, the abdomen is smaller for its gestational age, due to the presence of complications such as intrauterine growth restriction.

3 Because hcg levels are extremely high in complete moles relative to values for normal pregnancy and correlate with tumor size, they can be used to diagnose and assess treatment effectiveness. A serum hcg level above 100,000 is indicative of a molar pregnancy. Under pelvic ultrasound no fetus or amniotic fluid is seen. Instead the intrauterine tissue has a snowstorm appearance due to the swelling of chorionic villi. In the figure on the left we see the classically described snowstorm appearance of a complete mole in the region label M. In addition the skin may also reveal [INAUDIBLE] bilateral theca lutein cysts. However, the definitive diagnosis of molar pregnancy is made on pathological examination of intrauterine tissue after the uterus has been evacuated. In diagnosing an incomplete molar pregnancy serum hcg levels are likely to be relatively normal. Pelvic ultrasound may reveal a fetus with a heartbeat. In addition, intrauterine tissue has a Swiss cheese appearance. Similar to complete moles, a definite diagnosis can only be made on pathological examination of the intrauterine tissue after evacuation. The management of complete and partial moles are similar. The definitive treatment involves the immediate removal of uterine contents by suction curettage. In older women who have completed their family a hysterectomy may be performed instead. Following evacuation or hysterectomy patients have to be followed up closely for persistent disease, which occurs in 15% to 25% of patients with a complete mole. Serial hcg titers are measured within 48 hours of evacuation. And then weekly until negative for three consecutive weeks. hcg levels are then followed monthly for six months. Any plateau or rise in hcg levels during this period is indicative of a persistent or invasive mole. Because it is critical to monitor hcg levels, pregnancy must be avoided in the follow up period with reliable contraception such as oral contraceptive pills. Subsequent pregnancies should be closely monitored with early ultrasound and hcg monitoring to exclude recurrent disease. In 20% of patients with a molar pregnancy, the hydatitiform mole undergoes malignant transformation to cause persistent or invasive disease. Some of the risk factors for malignant transformation include a maternal age above 40 years old, extremely high beta hcg levels, and the presence of theca lutein cysts larger than 6 cm in diameter. Invasive moles are therefore

4 more commonly associated with complete molar pregnancies. Invasive moles occur when there is local uterine invasion of a complete or incomplete mole, and make up 75% of gestational trophoblastic neoplasia. They are characterized by penetration of large swollen villi and trophoblasts into the myometrium via direct extension through tissue or venous channels. Most of the invasive moles are nonmetastatic, with about 15% metastasizing to the lungs or vagina. Patients with invasive moles are usually asymptomatic at the time of diagnosis. However, they may sometimes present with abnormal uterine bleeding. Another form of malignant trophoblastic disease is choriocarcinoma. It is a highly malignant tumor, where the trophoblastic tumors travel via the blood stream to achieve extra uterine spread to distant organs. 50% of choriocarcinoma is preceded by hydatitiform moles, and 25% from normal pregnancy, and 25% from miscarriage, abortion, or ectopic pregnancies. Histologically choriocarcinomas are characterized by sheets of trophoblastic cells formed from both the inner cyto and outer syncytial layers of the trophoblastic cells without apparent villi formation. Necrosis and severe hemorrhage may be seen as the cancer cells destroy the uterine wall and vasculature. Metastatic disease is also common with potential metastasis to organs such as the lungs, vagina, pelvis, brain, liver, intestines, and kidneys. Patients with choriocarcinoma commonly present with post partum bleeding or irregular uterine bleeding years after pregnancy. It is also known as the great imitator, because patients can present with signs and symptoms of many disease entities. The diagnosis of choriocarcinoma of the placenta is similar to invasive moles. And metastasis should be assessed with a full blood count, coagulation profiles, renal panel, and liver function tests. Imaging studies are also helpful in determining the metastatic sites. If vagina or lung metastasis are present, a CT or MRI brain should be obtained. The treatment mortalities for choriocarcinoma of the placenta is similar to that of invasive moles, with low risk patients treated with single agent chemotherapy, and high risk patients treated with multi agent chemotherapy. With that we have come to the end of our presentation. Below are the references used for this topic. And we hope

5 this has been informative. Thank you.