Hydatidiform Mole Imaging

Gestational trophoblastic neoplasia (GTN) represents a spectrum of premalignant and malignant diseases that occur after abnormal fertilization. GTN includes complete hydatidiform mole (CHM), partial hydatidiform mole (PHM), invasive mole, choriocarcinoma, and placental-site trophoblastic tumor (PSTT). CHM and PHM together account for 80% of all cases of GTN.[1, 2, 3, 4, 5]

Hydatidiform moles should be regarded as premalignant lesions because 15-20% of complete hydatidiform moles (CHMs) and 1% of partial hydatidiform moles (PHMs) undergo malignant transformation into invasive moles, choriocarcinomas, or, in rare cases, placental-site trophoblastic tumors (PSTTs).[2, 6]

Ultrasonography is the imaging investigation of choice (see the images below) to confirm the diagnosis of hydatidiform mole. An experienced operator should perform transabdominal and transvaginal imaging using transducers with the highest frequency possible.[7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18] Clinical examination and beta-human chorionic gonadotropin (beta-hCG) determinations are the recommended initial tests for hydatidiform mole.

In some cases, sonographic examination may be limited because of inadequate equipment or inadequate operator experience. The sonographic appearance of a first-trimester hydatidiform mole can be indistinguishable from that of an anembryonic gestation, specifically blighted ovum. Second-trimester complete hydatidiform mole (CHM) can be confused with retained products of conception.

Clinical features of hydatidiform mole in patients 40 years or older may differ from those in younger patients. For example, older patients may have vaginal bleeding, increased uterine volume, and heremesis.[19]

In a multicenter study, many proven cases of hydatidiform mole were not clinically or sonographically evident. Of 155 cases of hydatidiform mole, only 53 (34%) were correctly diagnosed as hydatidiform mole with ultrasonography.[12]  

MRI has no established role in the initial diagnosis of hydatidiform moles. It is useful in malignant forms of gestational trophoblastic neoplasia (GTN) to characterize the degree of myometrial and/or parametrial invasion and to assess the treatment response.

No reliable plain radiographic findings are reported for hydatidiform mole. The associated risks of ionizing radiation disfavor the use of radiography in pregnant women.

No angiographic studies are clinically useful for assessing hydatidiform mole. Performed by an interventional radiologist, selective embolization of the uterine artery is reported as a well-tolerated and effective treatment option for managing severe bleeding from residual uterine vascular malformations in patients with gestational trophoblastic tumors that have been treated.[20, 21]

CT presents a risk of ionizing radiation, and it has no role in the diagnosis of hydatidiform mole. However, if CT is performed, it may show an enlarged uterus with focal areas of hypoattenuation and unilateral or bilateral ovarian enlargement.

In malignant forms of gestational trophoblastic neoplasia (GTN), CT scanning of the head, chest, abdomen, and pelvis are the recommended investigations for detecting metastatic disease.

Hong et al found that, although chest radiography is ineffective in diagnosing pulmonary micrometastases in patients with hydatidiform mole, the use of chest CT should be considered for the initial evaluation of hydatidiform mole. Of 14 patients who underwent chest CT on initial evaluation, 57% were found to have pulmonary micrometastases.[22]

At present, MRI plays no role in the diagnosis of hydatidiform mole.

MRI is indicated in patients with malignant forms of gestational trophoblastic neoplasia (GTN) for an assessment of tumor vascularity and of myometrial and parametrial extension.

MRI findings may include the following[23, 24, 25, 26] :

• Heterogeneous endometrial enlargement with several hyperintense foci that represent hydropic villi on T2-weighted imaging

• Focal tumor masses in the endometrium and/or myometrium

• Loss of uterine zonal anatomy (indistinctness of the endometrial-myometrial border)

• Pathologic myometrial, endometrial, and parametrial vasculature characterized by dilated and tortuous vessels

In a series of 13 patients with various histologic types of GTN, Preidler et al found the pathologic uterine vasculature to be the most reliable MRI finding for diagnosing hydatidiform mole.[27] They noted no correlation between the severity of MRI findings and serum beta-hCG levels or specific histologic types of GTN.

Ultrasonography is the imaging investigation of choice for hydatidiform mole. The established roles for sonography include the following[13, 28, 29, 30, 31, 32, 33, 34, 35, 36] :

• Initial diagnosis

• Assessment of treatment responses

• Determination of invasion in malignant forms of gestational trophoblastic neoplasia (GTN)

• Determination of recurrent disease in malignant forms of GTN

Ultrasonography should include transabdominal and transvaginal real-time gray-scale imaging by using high-resolution equipment. Early literature described a snowstorm appearance consisting of several echogenic foci, but this finding is no longer seen with new high-resolution ultrasound equipment.

Complete hydatidiform mole

With modern equipment, the typical sonographic appearance of complete hydatidiform mole (CHM) in the second and third trimesters is an enlarged uterine endometrial cavity containing innumerable anechoic cysts sized 1-30 mm (see the images below). On pathologic examination, these cysts represent grossly swollen (hydropic) chorionic villi that have a bunch-of-grapes appearance.[17]

In the first trimester, the sonographic appearance of CHM is relatively nonspecific. The classic finding of multiple, tiny, anechoic cystic spaces is rarely seen. The most common sonographic appearance of CHM in the first trimester is a homogeneously hyperechoic endometrial mass. An anembryonic gestation (empty gestational sac) may be the only sonographic finding (see images below); if it is, its distinction from blighted ovum is difficult or impossible.

Partial hydatidiform mole

Sonograms of partial hydatidiform mole (PHM) may show cystic changes similar to those of CHM but in a more focal distribution. The major distinguishing feature of PHM is embryonic tissue (see the image below). In practice, PHM can be difficult to distinguish from CHM on sonograms, and this distinction is usually made pathologically. This limitation is insignificant because the management approaches are similar for CHM and for PHM.

Theca lutein ovarian cysts

Theca lutein ovarian cysts are present in 50% of hydatidiform moles. They result from ovarian hyperstimulation secondary to high circulating levels of beta-human chorionic gonadotropin (hCG). On sonograms, theca lutein cysts appear as large, septate cystic ovarian lesions. They may be unilateral or bilateral, and they may be extremely large. If the lesions are large, transabdominal scanning is needed to completely visualize them. The presence of bilateral and/or large theca luteins is well correlated with serum beta-hCG levels >100,000 mIU/mL.

Theca lutein cysts usually resolve within 8-12 weeks after hydatidiform moles are evacuated.[37] Cysts that persist after beta-hCG levels return to normal should prompt further workup to exclude a neoplastic process. In rare cases, theca lutein cysts rupture, hemorrhage, or cause ovarian torsion.

When theca lutein cysts are present, the radiologist must recommend appropriate imaging follow-up to exclude the small possibility of a preexisting or concomitant cystic ovarian neoplasm. This follow-up should include sonographic evaluation after serum beta-hCG levels are normalized. In most patients, theca lutein cysts regress within 8-12 weeks after the hydatidiform mole is evacuated.

Doppler

Doppler ultrasonography has no clearly defined role in the evaluation of hydatidiform mole. However, it is useful in diagnosing invasive forms of GTN, in which cystic vascular spaces with high-velocity, low-impedance flow are almost always demonstrated. Doppler ultrasonography also plays a role in monitoring the response of the disease after chemotherapy. Regression of cystic vascular masses is observed after successful treatment.[13, 36, 38, 16]

hCG normalization

According to Kerkmeijer et al, earlier serum hCG regression in patients with complete hydatidiform moles is likely the result of first-trimester ultrasonography that leads to detection and evacuation of complete moles at younger gestational ages, thereby resulting in lower hCG levels at the time of evacuation. The investigators found that 99% of a recent cohort achieved hCG normalization within 19 weeks after uterine evacuation as compared with 25 weeks in a historic group.[14]

Degree of confidence

Sebire et al reviewed findings in 155 women in histologically proven complete hydatidiform moles (CHMs) or partial hydatidiform moles (PHMs) who had previous sonograms.[12] In only 34% was a molar pregnancy diagnosed. In the remainder, the condition was misdiagnosed as a miscarriage.[39] Accuracy was higher with CHMs (37 [58%] of 64 patients) than with PHMs (16 [18%] of 91 patients).

In a single-center study of first-trimester CHM, initial sonographic diagnoses were made in 17 (71%) of 24 cases.[15] Early pregnancy failure was the most common alternative diagnosis in the cases that were missed.

In a Swedish study, ultrasound predicted a molar diagnosis in 73% of cases of CHM but only 35% of cases of PHM.[40]

False positives/negatives

The radiologist must recognize that a first-trimester hydatidiform mole can be pathologically and sonographically indistinguishable from an early pregnancy failure[3]  . Sonograms may simply show an empty gestational sac without other findings to suggest a hydatidiform mole. In a single-center study of first-trimester CHM, an initial sonographic diagnosis was made in 17 (71%) of 24 cases.[15] Early pregnancy failure was the most common alternative diagnosis in the cases that were missed.

The radiologist must maintain a high index of suspicion for hydatidiform mole in the first trimester, even when it is not suspected based on clinical findings. The serum beta-hCG level may be normal, and clinical findings may be absent or minimal. The classic clinical findings of vaginal bleeding, anemia, hyperemesis gravidarum, preeclampsia, and hyperthyroidism are usually absent until the second trimester.

No nuclear medicine studies are clinically useful for evaluating hydatidiform mole. Positron emission tomography (PET) and PET CT show promise as problem-solving tools in malignant forms of gestational trophoblastic neoplasia (GTN). Selected case reports and case series demonstrated the usefulness of PET for identifying lesions in patients with GTN and with negative or equivocal ultrasonographic, CT, and MRI findings.[41, 42]

Data about the effectiveness of PET in evaluating GTN are limited. Grisaru et al reported that PET CT had a sensitivity of 97% and a specificity of 94% for gynecologic malignancy.[41] However, of their 53 patients, only 1 had GTN. The rest had various other types of cancer, including ovarian, uterine, vaginal and cervical.