Hydatidiform Mole


Article Author:
Sassan Ghassemzadeh


Article Editor:
Michael Kang


Editors In Chief:
Anne Kennedy


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
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Saad Nazir
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Pritesh Sheth
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Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
6/4/2019 2:34:03 PM

Introduction

Hydatiform mole (also known as molar pregnancy) is a subcategory of diseases under gestational trophoblastic disease (GTD), which originates from the placenta and can metastasize. It is unique because the tumor originates from gestational tissue rather than from maternal tissue. Other forms of gestational trophoblastic disease include gestational choriocarcinoma (which can be extremely malignant and invasive) and placental site trophoblastic tumors. Hydatiform mole (HM) is categorized as a complete and partial mole and are usually considered the noninvasive form of gestational trophoblastic disease. Although hydatiform moles are usually considered benign, they are premalignant and do have the potential to become malignant and invasive.[1][2][3]

Etiology

As described previously, hydatiform moles are divided into complete and partial moles. Complete mole is the more common type and does not contain a fetus, whereas in a partial mole there is a deformed, nonviable fetus present. Complete moles are typically diploid, whereas partial moles are triploid. Complete moles tend to cause higher levels of the human chorionic gonadotropin (hCG), which is one of the main clinical features of this process. In incomplete moles, the karyotype is 46,XX 90% of the time and 46,XY 10% of the time. It arises when an enucleated egg is fertilized either by two sperms or by a haploid sperm that then duplicates and therefore, only paternal DNA is expressed. On the other hand, in partial moles, the karyotype is 90% of the time triploid and either 69,XXX or 69,XXY. This karyotype arises when a normal sperm subsequently fertilizes a haploid ovum duplicates and or when two sperms fertilize a haploid ovum. In partial moles, both maternal and paternal DNA is expressed.[4][5][6]

Epidemiology

There is a very low frequency of hydatiform moles. In North America and Europe, the frequency has been described as 60 to 120/100,000 pregnancies for hydatiform moles. The frequency has been shown to be higher in other countries of the world. Certain risk factors increase the prevalence of molar pregnancies:

  • Extremes of maternal age:

    • Greater than 35 years old carries a  five to ten-fold increased risk risk

    • Early teenage years, usually less than 20 years old

  • Previous molar pregnancy increases the risk 1% to 2% for future pregnancies

  • Women with previous spontaneous abortions or infertilities
  • Dietary factors including patients that have diets deficient in carotene (vitamin A precursor) and animal fats

  • Smoking

Pathophysiology

As described previously, hydatiform moles arise from the gestational tissue. In whole hydatidiform moles, there is no fetal tissue presents whereas, in partial hydatiform moles, there is some nonviable fetal tissue apparent. Both are due to over-proliferation of the chorionic villi and resulted swelling. They result in high levels of hCG to be produced. To review, in complete moles an enucleated egg is fertilized either by two sperm or a haploid sperm that then duplicates, resulting in only paternal DNA being expressed. Conversely, in partial hydatiform mole, a haploid ovum either duplicates and fertilized by normal sperm or a haploid ovum is fertilized by two sperm, resulting in both the expression of both maternal and paternal DNA.[7]

Histopathology

Hydatiform moles are caused by a proliferation of the villous trophoblast accompanied by swelling of the chorionic villi. As described previously, the main difference between complete and partial hydatidiform histologically is the lack of embryonic/fetal tissue in complete moles, and the presence of-of embryonic tissue in partial moles. Furthermore, in a complete mole, the chorionic villi are diffusely hydropic and typically are surrounded by hyperplastic trophoblasts. In a partial mole there normal chorionic villi and embryonic/fetal tissue mixed with hydropic villi. 

History and Physical

The presentation of the hydatiform mole is somewhat different in a complete mole versus a partial mole. In fact, most partial moles are diagnosed as spontaneous abortions that are later discovered after a pathology report is obtained from the fetal tissue.

Since the advent of ultrasonography, the diagnosis of complete molar pregnancies has increased in the early stages of pregnancy, mainly during the first trimester. The most common symptom (in one study as high as 84% of patients) of a complete mole is vaginal bleeding in the first trimester which is normally due to the molar tissue separating from the decidua, resulting in bleeding. The typical buzz word appearance of the vaginal bleeding is described as a "prune juice" appearance. This is secondary to the accumulated blood products in the uterine cavity and resultant oxidation and liquefaction of that blood. Another symptom of a complete molar pregnancy is hyperemesis (severe nausea and vomiting) which is due to the high level of the hCG hormone circulating in the bloodstream. Some patients also endorse passage of vaginal tissue described as grape-like clusters or vesicles. Late findings of the disease (after the first trimester around 14 to 16 weeks of pregnancy) including signs and symptoms of hyperthyroidism, including tachycardia and tremors, again caused by the high levels of circulating hCG. Other late sequelae are pre-eclampsia which is pregnancy-induced hypertension and proteinuria and/or end-organ dysfunction occurring typically after 34 weeks of pregnancy. When a patient less than 20 weeks pregnant presents with signs and symptoms of pre-eclampsia, a complete molar pregnancy should highly be suspected. In very advanced cases, patients present with severe respiratory distress possible from embolism of the trophoblastic tissue into the lungs.

The presentation of a partial hydatiform mole is usually less dramatic than that of a complete mole. These patients typically present as described before with symptoms similar to a threatened or spontaneous abortion including vaginal bleeding. Since partial hydatiform moles have a fetal tissue, on examination, these patients may have fetal heart tones evident on Doppler. 

On physical exam, more than 50% of cases, uterine size discrepancy and date discrepancy usually takes place. In a complete mole, the uterus is usually larger than the expected gestational date of the pregnancy, whereas, in partial moles, the uterus can be smaller than the suggested date.

Evaluation

In a pregnant patient with vaginal bleeding, one should always obtain a serum quantitative hCG level and patient's blood type. In hydatiform moles, the serum hCG levels are typically much higher than patients of the same gestational date in a normal pregnancy or ectopic pregnancy. Complete moles tend to have very high levels of serum hCG, typically greater than 100,000, whereas partial moles may be within normal range for gestational age or even lower than expected. Blood type is important because most patients with complete or partial hydatiform moles present with vaginal bleeding, and therefore Rh antibody screening needs to be performed to determine whether anti-D immunoglobulin needs to be administered if the patient is Rh(D) negative. Other laboratory tests include:

Complete blood count (CBC) (to evaluate for anemia and thrombocytopenia)

BMP (to evaluate for electrolyte imbalance and renal insufficiency)

Thyroid panel (if signs and symptoms of hyperthyroidism present) 

Liver function tests and urinalysis (if pre-eclampsia is suspected to evaluate for transaminitis and proteinuria)

Coagulation profile including PT/INR to evaluate for disseminated intravascular coagulation in severe cases.

The imaging of choice in a suspected hydatiform mole is a pelvic ultrasound. In a complete mole, the ultrasound findings include a heterogeneous mass in the uterine cavity with multiple anechoic spaces, most commonly referred to as a "snowstorm" appearance. These small cystic areas are typically the hydropic villi described previously in the histopathology section. Furthermore, there is the absence of an embryo or fetus, and no amniotic fluid is present. In a partial mole, there typically is the finding of a fetus which may be viable, the presence of amniotic fluid, and the placenta appears to have enlarged, cystic spaces (often described as "Swiss cheese" appearance). In one study, it was noted that partial moles were diagnosed as a missed or incomplete abortion in 15% to 60% of cases. 

If a molar pregnancy is diagnosed, the next step is typically a chest x-ray to determine metastasis. Furthermore, a chest x-ray should be obtained if patient's initial symptoms include any signs of respiratory distress or increased work of breathing to evaluate for pulmonary edema.[8][9][10]

Treatment / Management

In the emergency department, one must first stabilize the patient. If there is any evidence of respiratory distress and pulmonary edema, one should initiate non-invasive positive pressure ventilation (such as BiPAP) or initiate mechanical ventilation emergently. Furthermore, if there are signs of symptoms of eclampsia (late stage of pre-eclampsia) including seizures, one should initiate appropriate management including benzodiazepines and magnesium sulfate administration. If the patient has signs of pre-eclampsia, urgent blood pressure control is necessary with medications such as hydralazine and labetalol. If there are signs and symptoms of hyperthyroidism, practitioners should initiate proper treatment including beta blockers and monitor for thyroid storm. If severe anemia is present, the clinician should consider a blood transfusion. As discussed earlier, if a patient is Rh(D) negative, the physician should administer the anti-D immunoglobulin.

Once the patient is stabilized, an emergent obstetrics consultation is necessary for the likely need of dilation and curettage (D and C). In patients with advanced maternal age typically greater than 40 years old and those who have completed childbearing, hysterectomy is often performed instead of a D and C. Hysterectomy, however, does not reduce the risk of invasive disease. After the evacuation of the molar pregnancy, if the hCG levels remain elevated, there is evidence of persistent or invasive disease requiring malignancy workup and at times chemotherapy. A gynecology oncology consultation is usually necessary in these cases to guide therapy.

Pearls and Other Issues

 

 

Enhancing Healthcare Team Outcomes

A molar pregnancy is best managed with a multidisciplinary team that also includes the nurses. Once molar pregnancy is diagnosed, and an obstetric/gynecology consultation is obtained, patients are typically admitted to the hospital for surgery. Weekly serum hCG levels are obtained after surgery until an undetectable level of hCG is reached (usually done in an outpatient setting). Patients with previous molar pregnancy are advised to use reliable contraception to avoid a new pregnancy, as it could conflict with weekly serum hCG level testing and make it impossible to determine the occurrence of invasive molar disease. The risk of invasive disease in a complete molar pregnancy is around 15% to 20%, and in a partial molar pregnancy is 1% to 5%.

 


  • Image 1729 Not availableImage 1729 Not available
    Contributed by Scott Dulebohn, MD
Attributed To: Contributed by Scott Dulebohn, MD

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Hydatidiform Mole - Questions

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A 3-month pregnant female presents with an unusually distended abdomen and vomiting. What should be the next step?



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Once a diagnosis of a hydatidiform mole has been made, the next step is a dilatation and curettage. The patient may need to be warned of which of the following?



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Which is true of human chorionic gonadotropin (hCG) levels after treatment of a molar pregnancy?



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Why should patients with an evacuated molar pregnancy be followed?



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Which of the following statements about molar pregnancies is TRUE?



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A patient has a suction curettage for an incomplete abortion. The pathology indicates trophoblastic proliferation and hydropic degeneration. There is no fetal tissue and absence of vasculature. What is the next best step in management?



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A patient was found to have a hydatidiform mole. In which case would treatment with single agent chemotherapy be indicated?



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Which of the following describes a benign tumor that develops in the uterus?



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Select the true statement about molar pregnancy.



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Which of the following regarding hydatidiform mole is true?



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Which of the following regarding hydatidiform mole is not true?



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Which is true regarding the treatment of hydatidiform mole?



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A 24-year-old G1P0 female at 15 weeks gestational age has vaginal bleeding and passes a small amount of tissue and watery fluid. The uterus is large for dates and an ultrasound-guided dilation and curettage yields grapelike, avascular, cystic structures that do not invade the uterine wall. No fetal tissue is identified. The villi mesenchyme and cytotrophoblasts do not immunostain for p57. What is the diagnosis?



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Which finding is least characteristic of complete hydatidiform moles?



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This endovaginal coronal view of a uterus was taken of a woman who presented at approximately 7 weeks gestational age. What is the diagnosis?

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    Contributed by Dr. Michael Lambert
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A 29-year old G1P0 female who is 16 weeks pregnant undergoes a blood test, which reveals an hCG of 350,000 IU. She undergoes an abdominal ultrasound, which shows bilateral enlarged thin-walled multicystic structures in the lower pelvis at the adnexa and complex intrauterine mass containing many small cysts. What is the likely diagnosis?



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You are performing an ultrasound on a 40-year old female who claims to be about seven weeks pregnant. The ultrasound reveals an enlarged uterus with numerous anechoic spaces (granular appearance) and no identifiable gestational sac. What symptom will this patient most likely have presented within this setting?



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Hydatidiform Mole - References

References

Mittal S,Menon S, Interstitial pregnancy mimicking an invasive hydatidiform mole. American journal of obstetrics and gynecology. 2019 May;     [PubMed]
Sarmadi S,Izadi-Mood N,Sanii S,Motevalli D, Inter-observer variability in the histologic criteria of diagnosis of hydatidiform moles. The Malaysian journal of pathology. 2019 Apr;     [PubMed]
Ning F,Hou H,Morse AN,Lash GE, Understanding and management of gestational trophoblastic disease. F1000Research. 2019;     [PubMed]
Braga A,Mora P,de Melo AC,Nogueira-Rodrigues A,Amim-Junior J,Rezende-Filho J,Seckl MJ, Challenges in the diagnosis and treatment of gestational trophoblastic neoplasia worldwide. World journal of clinical oncology. 2019 Feb 24;     [PubMed]
Yuk JS,Baek JC,Park JE,Jo HC,Park JK,Cho IA, Incidence of gestational trophoblastic disease in South Korea: a longitudinal, population-based study. PeerJ. 2019;     [PubMed]
Li X,Xu Y,Liu Y,Cheng X,Wang X,Lu W,Xie X, The management of hydatidiform mole with lung nodule: a retrospective analysis in 53 patients. Journal of gynecologic oncology. 2019 Mar;     [PubMed]
Kar A,Mishra C,Biswal P,Kar T,Panda S,Naik S, Differential expression of cyclin E, p63, and Ki-67 in gestational trophoblastic disease and its role in diagnosis and management: A prospective case-control study. Indian journal of pathology     [PubMed]
Ross JA,Unipan A,Clarke J,Magee C,Johns J, Ultrasound diagnosis of molar pregnancy. Ultrasound (Leeds, England). 2018 Aug;     [PubMed]
Heller DS, Update on the pathology of gestational trophoblastic disease. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. 2018 Jul;     [PubMed]
Ling C,Zhao J,Qi X, Partial molar pregnancy in the cesarean scar: A case report and literature review. Medicine. 2018 Jun;     [PubMed]

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