Gestational Trophoblastic Disease

Gestational trophoblastic diseases are a spectrum of placental disorders resulting from abnormal placental trophoblastic growth. These disorders range from benign molar pregnancies (complete and partial moles) to neoplastic conditions such as invasive moles and choriocarcinoma. Diagnosis is confirmed by elevated serum beta human chorionic gonadotropin (hCG) and ultrasound findings, which are dependent on the disorder. Treatment is primarily through dilation and curettage and/or methotrexate.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Overview

Epidemiology

  • Occurs in about 1 pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care in 1,200 pregnancies in the United States, with hydatidiform mole representing 80 percent of the cases. Higher incidence in Southeast Asia and Japan 
  • Risk factors:
    • History of gestational trophoblastic disease (GTD)
    • History of prior spontaneous abortion Spontaneous abortion Spontaneous abortion, also known as miscarriage, is the loss of a pregnancy before 20 weeks' gestation. However, the layperson use of the term "abortion" is often intended to refer to induced termination of a pregnancy, whereas "miscarriage" is preferred for spontaneous loss. Spontaneous Abortion and/or infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility
    • Protein, folic acid, and carotene deficiency

Classification

  • Hydatidiform moles: considered premalignant because of their potential for malignancy
    • Complete mole
    • Partial mole
  • Invasive moles
  • Choriocarcinoma: incidence USA 1/40,000

Hydatidiform Mole

Hydatidiform moles are characterized by cystic swelling of the chorionic villi and proliferation of the chorionic epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium. There are 2 types: complete mole and partial mole.

Complete mole Partial mole
Karyotype 46,XX or 46,XY Triploid (69,XXX, 69,XXY, or 69,XYY)
Formed from Enucleated egg and a single sperm 2 sperm and 1 egg
Fetal parts Absent Present
Human chorionic gonadotropin (HCG) level ↑↑↑
Ultrasound findings
  • Honeycomb uterus
  • “Clusters of grapes”
  • “Snowstorm” uterus
Reveals fetal parts
Malignancy risk Higher risk for choriocarcinoma Rare

Clinical presentation

  • Vaginal bleeding
  • Uterine enlargement (more than expected for given gestational age)
  • Pelvic pressure or pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
  • May be associated with 
    • Early (before 20 weeks) preeclampsia
    • Theca-lutein cysts
    • Hyperemesis gravidarum
    • Hyperthyroidism Hyperthyroidism Thyrotoxicosis refers to the classic physiologic manifestations of excess thyroid hormones and is not synonymous with hyperthyroidism, which is caused by sustained overproduction and release of T3 and/or T4. Graves' disease is the most common cause of primary hyperthyroidism, followed by toxic multinodular goiter and toxic adenoma. Thyrotoxicosis and Hyperthyroidism

Diagnosis

  • HCG levels: ↑ serum beta-hCG 
  • Ultrasound:
    • Reveals an irregular distribution of hypoechoic (cystic) and hyperechoic (solid) areas within the uterus
    • Characteristically referred to as a “snowstorm pattern

Treatment

  • Dilation and curettage with methotrexate
  • HCG levels are monitored (expected to downtrend after treatment)
  • Hysterectomy (last resort)
Blasenmole ct axial

Hydatid in axial computed tomography (CT) image

Image: “Blasenmole Computertomographie axial” by Hellerhoff. License: CC BY-SA 3.0

Related videos

Choriocarcinoma

Choriocarcinoma is a highly aggressive malignant neoplasm of trophoblastic cells that can develop during or after pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care in the mother or baby.

Etiology

Can be preceded by:

  • Hydatidiform mole (50%)
  • Abortion of an ectopic pregnancy Ectopic pregnancy Ectopic pregnancy refers to the implantation of a fertilized egg (embryo) outside the uterine cavity. The main cause is disruption of the normal anatomy of the fallopian tube. Ectopic Pregnancy (20%)
  • Normal-term pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care (30%)

Clinical presentation

  • Abnormal uterine bleeding Abnormal Uterine Bleeding Abnormal uterine bleeding is the medical term for abnormalities in the frequency, volume, duration, and regularity of the menstrual cycle. Abnormal uterine bleeding is classified using the acronym PALM-COEIN, with PALM representing the structural causes and COEIN indicating the non-structural causes. Abnormal Uterine Bleeding or amenorrhea
  • If hematogenous spread to the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: shortness of breath and/or hemoptysis Hemoptysis Hemoptysis is defined as the expectoration of blood originating in the lower respiratory tract. Hemoptysis is a consequence of another disease process and can be classified as either life threatening or non-life threatening. Hemoptysis can result in significant morbidity and mortality due to both drowning (reduced gas exchange as the lungs fill with blood) and hemorrhagic shock. Hemoptysis

Diagnosis

  • HCG levels: ↑ serum beta-hCG
  • Pelvic ultrasound: hypervascularity
  • Chest X-ray: pulmonary metastases with “cannonball” shape

Treatment

  • Depends on stage and risk classification
  • Low risk: methotrexate monotherapy or combination with actinomycin D
  • High risk: multi-agent regimen
    • Etoposide
    • Methotrexate (MTX)
    • Actinomycin D
    • Leucovorin calcium
    • Cyclophosphamide
    • Vincristine
Interface between choriocarcinoma with central necrosis and normal placenta

Choriocarcinoma with central necrosis

Image: “Interface between choriocarcinoma with central necrosis and normal placenta Placenta The placenta consists of a fetal side and a maternal side, and it provides a vascular communication between the mother and the fetus. This communication allows the mother to provide nutrients to the fetus and allows for removal of waste products from fetal blood. Placenta, Umbilical Cord, and Amniotic Cavity” by Department of Obstetrics and Gynecology, St. Louis University, Missouri, USA. License: CC BY 2.0

Clinical Relevance

Ectopic pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care: Eccyesis or ectopic pregnancy Ectopic pregnancy Ectopic pregnancy refers to the implantation of a fertilized egg (embryo) outside the uterine cavity. The main cause is disruption of the normal anatomy of the fallopian tube. Ectopic Pregnancy refers to the implantation of the blastocyst outside the uterine cavity. The most common site is the fallopian tube. Affected patients suffer from acute abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain. Diagnosis is by ultrasound and laboratory analysis, which confirms pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care with implantation outside the uterus.

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