{"paper_id":"ede8a5d6-694b-4530-b9a5-682239b6447b","body_text":"Gestational trophoblastic disease (GTD) comprises a group of disorders arising from\nthe anomalous growth of trophoblastic tissue. It presents a benign clinical spectrum\nrepresented by hydatidiform mole, either partial or complete, and by gestational\ntrophoblastic neoplasia (GTN)-invasive mole, choriocarcinoma, placental site\ntrophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT) characterizing\nthe malignant forms ( 1 - 4 ) .\nIn most cases of GTN, cure can be achieved ( 4 ) . To that end, the radiologist should play an important role\nin its early diagnosis, decreasing the morbidity and mortality of molar pregnancy,\nas well as in the staging and follow-up of patients with GTN, guiding the rigorous\nand systematic treatment. The initial test used for the diagnosis of hydatidiform\nmole is ultrasound, in combination with determination of the level of the beta\nsubunit of human chorionic gonadotropin (β-hCG) in serum ( 1 , 3 ) . Although chest X-ray is recommended as an initial means of\nscreening for metastases, computed tomography (CT) and magnetic resonance imaging\n(MRI) have generally been incorporated into the evaluation of metastatic\ndisease ( 2 , 4 ) , especially in more complex clinical\ncases ( 2 ) .\nIn this review, we present clinical and radiological correlations in patients with\nGTD, describing the diagnostic requirements for the use of the various ancillary\nmethods, together with details regarding their radiological aspects and therapeutic\nutility in GTD, as well as summarily updating the information about this important\ncomplication of pregnancy.\n\nAccounting for 80% of all cases of GTD, hydatidiform mole reportedly occurs in\n0.6-1.1/1000 pregnancies in North America ( 5 ) . It is estimated that hydatidiform mole occurs in 1/200-400\npregnancies in Brazil ( 6 ) ,\napproximately 5-10 times more frequently than in North America and Europe ( 7 ) , perhaps reflecting differences in\ndietary or genetic influences.\nAs a cause of GTD, choriocarcinoma is rarer than is hydatidiform mole, the former\noccurring in 1/20,000-40,000 pregnancies  ( 8 ) . Currently, there are few data in the literature on PSTT\nand ETT. A recent study conducted in the United Kingdom suggested that PSTT and ETT\ncollectively account for only 0.2% of cases of GTD ( 9 ) .\nWomen over 45 years of age are at an increased risk of molar pregnancy, as are those\nunder 16 years of age, those with a history of molar pregnancy (a 1% increase after\none such pregnancy and a 15-20% increase after two), and those with a history of\nmiscarriage ( 7 ) .\nHydatidiform mole constitutes an error of fertilization. Complete hydatidiform\nmole originates from the fertilization of an oocyte without maternal chromosomes\nby a haploid sperm with subsequent duplication of paternal DNA, giving rise to\nan egg of exclusively parthenogenetic origin, with a diploid (46,XX) karyotype.\nIn less than 10% of cases, complete hydatidiform mole arises when an oocyte\nwithout genetic material is fertilized by two separate sperm (dispermy),\nresulting in an egg of exclusively androgenetic origin, with a 46,XX or 46,XY\nkaryotype. That aberration does not allow the formation of embryonic tissue or\nits attachments. Partial hydatidiform mole results from the fertilization of a\nnormal egg by two sperm, resulting in a zygote with a triploid (69,XXY or\n69,XXX) diandric karyotype ( 10 ) . In such cases, it is common to identify an embryo, or even a\nfetus, that is malformed and has anomalous attachments.\nPatients with complete hydatidiform mole classically present with specific\nsymptoms-vaginal bleeding (in 84%), increased uterine volume (in 50%), theca\nlutein cysts (in 40%), and high serum levels of β-hCG (in 50%)-whereas\nthose with partial hydatidiform mole present with symptoms that mimic those of a\ncommon abortion ( 11 ) . Certain\nsigns and symptoms of hydatidiform mole have become uncommon because the\nsystematic use of ultrasound has resulted in the early (first-trimester)\ndetection of pregnancy. Such signs and symptoms include anemia, hyperemesis\ngravidarum, hyperthyroidism, respiratory failure, and preeclampsia ( 12 ) .\nThe diagnosis of hydatidiform mole should be based on a combination of clinical\nhistory, physical examination, serum β-hCG determination, and\nultrasound ( 1 , 13 ) . The serum β-hCG level\n(typically > 100,000 mIU/mL) can vary greatly in normal and multiple\npregnancies, as well as in molar pregnancy, and can therefore confound the\ndiagnosis when considered in isolation ( 3 ) . Therefore, ultrasound is considered the principal\nmethod of diagnosing hydatidiform mole ( 1 , 6 , 11 ) .\nAfter being diagnosed, patients with GTD should be evaluated at a referral center\nfor its treatment, where the uterine contents can be evacuated by vacuum\naspiration ( 1 , 2 ) . Because it has a lower risk of\nuterine perforation, vacuum aspiration is preferable to curettage.\nHistopathological examination should be performed in order to confirm the\ndiagnosis and to identify the histological type of the hydatidiform mole.\nThe serum level of β-hCG is expected to decline after uterine evacuation,\nand subsequent measurements are performed weekly. After three normal results,\nserum β-hCG levels are determined on a monthly basis for the next six\nmonths, in order to detect recurrence and malignancy ( 13 ) . Patients should not attempt to conceive\navoided during this period.\n\nAccording to the International Federation of Gynecology and Obstetrics (FIGO), GTN is\nidentified by the following criteria ( 14 ) : a plateau in the serum β-hCG level lasting for more\nthan three weeks (on days 1, 7, 14, and 21) an elevated serum β-hCG level for\nmore than two weeks (days 1, 7, and 14); a histopathological diagnosis of\nchoriocarcinoma; and an elevated serum β-hCG level for six months or more\nafter uterine evacuation. The occurrence of GTN after complete hydatidiform mole\nranges from 18% to 29%, compared with 0.5% to 11% after partial hydatidiform\nmole ( 12 ) .\nThe most common type of GTN is invasive mole, because, in most cases, the diagnosis\nis made when the cancer is still confined to the uterus ( 15 ) . Choriocarcinoma is a rarer type that often\ngenerates distant metastases. Characteristically, choriocarcinoma is associated with\nextensive tissue necrosis and hemorrhage ( 16 ) .\nLess than 1% of cases of GTN are PSTT, which differs from the other types in that it\nproduces low levels of β-hCG, has high human placental lactogen\nimmunoreactivity, and features indolent cell growth, with a tendency to metastasize.\nAnother extremely rare variant is ETT, which is having similar to PSTT in terms of\nits clinical behavior ( 17 ) .\nAfter being diagnosed with GTN, patients should first be screened for metastases. We\nfollowed the guidelines established by the European Society of Medical Oncology,\nwhich recommend an initial assessment by Doppler flow study of the pelvis and chest\nX-ray. In patients showing lung metastases, brain MRI and abdominal CT are\nindicated ( 18 ) .\nThe treatment of GTN essentially consists of chemotherapy, for which the\nhistopathological diagnosis is not a prerequisite ( 1 , 19 ) .\nHowever, the treatment is preceded by anatomical staging ( Table 1 ), which allows the results to be compared among\nvarious referral centers ( 20 ) ,\nas well as allowing the determination of the FIGO risk score for\nchemoresistance ( 7 ) , as\nshown in  Table 2 , which is fundamental to\nchoosing the treatment strategy, except in cases of PSTT or ETT ( 21 ) .\n2000 FIGO staging system for GTN.\n2000 FIGO risk scoring system.\nMetastases are identified in approximately 10-19% of patients with GTN,\nmetastases to the lung accounting for 76-87%), followed by those to the vagina\n(30%), liver (10%), brain (10%), and, to a lesser degree, the kidney,\ngastrointestinal system, and spleen ( 2 ) . Most GTN metastases are hematogenous, except for those to\nthe vagina, which occur by contiguous dissemination ( 22 ) .\nFor low-risk GTN (FIGO score ≤ 6), the treatment of choice is single-agent\nchemotherapy. The first-line drugs are methotrexate and actinomycin-D, both of\nwhich have been shown to induce remission in 50-90% of cases ( 7 ) . Patients with high-risk GTN\n(FIGO score ≥ 7) require treatment with multiple antineoplastic agents,\nas do those with stage IV disease. One of the most common treatment regimens is\nthe combination of etoposide, methotrexate, and actinomycin-D, alternating\nweekly with cyclophosphamide plus vincristine ( 23 ) . Even patients with metastatic disease have a\ngood prognosis, with cure rates greater than 90%, especially if treated at a\nreferral center ( 4 ) .\nSurgery and radiotherapy are necessary in some patients with high-risk GTN,\nespecially in those with chemoresistance. Because PSTT and ETT respond poorly to\nchemotherapy, they should be treated with chemotherapy and hysterectomy,\nsometimes including pelvic lymphadenectomy ( 24 ) . In cases of PSTT and ETT, the five-year survival rate\nranges from 100%, for patients with localized disease, to 50- 60%, for those\nwith metastatic disease ( 4 ) .\nThe rate of recurrence of GTN is approximately 3%, and such recurrence is most\ncommon during the first year of follow-up. Therefore, careful monitoring of hCG\nand contraception are essential. Braga et al. reported that there is increased\nrisk of miscarriage and adverse perinatal outcome during the first 6 months\nafter the end of chemotherapy, stating that affected patients should avoid\nbecoming pregnant for 6 months after the final chemotherapy session ( 25 ) . Thereafter, fertilization is\napparently unaffected, successful pregnancies having been reported in more than\n80% of patients undergoing chemotherapy for the treatment of GTN ( 26 ) .\n\nUltrasound is the initial imaging test employed in the investigation of cases of\nmolar pregnancy. A serum β-hCG level that is abnormally high for early\ngestational age raises suspicion of hydatidiform mole. In such cases, ultrasound\nis mandatory in order to exclude this form of reproductive\ncounterfeiting ( 27 ) .\nThe ultrasound examination can be transabdominal or transvaginal. Due to its\nhigher spatial resolution and anatomical proximity to the study area,\ntransvaginal ultrasound provides a detailed study of uterine lesions, including\nthe morphology and degree of invasion ( 2 ) . Ultrasound of hydatidiform mole can reveal an\nintrauterine mass of variable echogenicity, although most hydatidiform moles are\nechogenic ( 1 , 27 , 28 ) , with multiple, small, diffusely distributed vesicles\nwithin an enlarged uterus ( 1 , 2 , 19 ) . These classic vesicular lesions, the aspect of which\nhas been described as \"snow storm\", \"bunch of grapes\", or \"granular\", range from\n1 mm to 30 mm in size and represent the hyperplastic and hydropic villi seen on\ntransvaginal ultrasound during the first trimester ( Figure 1 ). In the second trimester, the anechoic spaces\nincrease in number and size, thus facilitating the diagnosis, including that\nmade by transabdominal ultrasound ( 27 ) . At some facilities, despite the superiority of\ntransvaginal imaging, pre-chemotherapy molar pregnancy patients often do not\nundergo transvaginal ultrasound due to the chance that a vaginal metastasis,\nwhich has a risk of major bleeding ( 2 ) , will be encountered.\nFigure 1 Transvaginal ultrasound in a patient with bleeding at 14 weeks of\npregnancy, showing an enlarged uterus with an endometrial cavity\nfilled with amorphous material with multiple anechoic areas,\nsuggestive of complete hydatidiform mole. Note the absence of\nembryonic tissue and its attachments. Note that, in the Doppler flow\nstudy, there was no vascular flow among the vesicles, indicating\ntheir avascular nature.\nTransvaginal ultrasound in a patient with bleeding at 14 weeks of\npregnancy, showing an enlarged uterus with an endometrial cavity\nfilled with amorphous material with multiple anechoic areas,\nsuggestive of complete hydatidiform mole. Note the absence of\nembryonic tissue and its attachments. Note that, in the Doppler flow\nstudy, there was no vascular flow among the vesicles, indicating\ntheir avascular nature.\nOn ultrasound imaging, it can be difficult to differentiate between complete and\npartial hydatidiform moles. The sensitivity of ultrasound is higher for the\ndetection of complete hydatidiform mole and increases after 16 weeks of\npregnancy ( 7 ) . The\ndiagnosis should always be confirmed by histopathological examination of tissue\nobtained through uterine evacuation ( 2 ) . Sebire et al. ( 29 )  reviewed 155 histopathological examinations of tissue\nobtained from patients with ultrasound suspicion of molar pregnancy. Only 34% of\nthose had a confirmed diagnosis, the vast majority being defined as abortion.\nThe authors found the positive predictive value of ultrasound to be higher in\ncases of complete hydatidiform mole than in those of partial hydatidiform mole\n(58% vs. 17%).\nIn a study involving the largest sample of patients with suspected hydatidiform\nmole ever studied (> 1000 patients), the role of ultrasound in the diagnosis\nof molar pregnancy was evaluated ( 30 ) . The authors reported that the sensitivity, specificity,\npositive predictive value, and negative predictive value of ultrasound in\nidentifying molar pregnancy were 44%, 74%, 88%, and 23%, respectively.\nIn cases of complete hydatidiform mole, there is no fetus or fetal material,\nexcept in those rare cases (1-2%) in which there is a dizygotic twin pregnancy\nwith a diploid pattern ( Figure 2 ). In such\ncases, partial hydatidiform mole with trisomy is differentiated by identifying a\nseparate, normal, placenta ( 1 , 2 , 27 ) .\nFigure 2 A:  Routine transvaginal ultrasound at 12 weeks of\npregnancy, showing a fetus with normal morphology and a placental\narea suggestive of complete hydatidiform mole.  B:  MRI\nscan at 27 weeks of pregnancy, showing a fetus without morphological\nanomalies and two distinct placental areas: one with a normal\nappearance; and the other characterized by multiple, hyperintense\nvesicular areas, suggesting a twin molar pregnancy. Because of\nsevere preeclampsia-severe hypertension; hemolysis/elevated liver\nenzymes/low platelet count syndrome; and acute pulmonary edema—a\ncesarean section was performed at 28 weeks of pregnancy. The\nextremely premature neonate survived without sequelae. After the\ncesarean section, the patient showed a satisfactory evolution and\nwas discharged from the post-molar pregnancy follow-up after 12\nmonths of treatment with normal-dose â-hCG, without\nchemotherapy.\nA:  Routine transvaginal ultrasound at 12 weeks of\npregnancy, showing a fetus with normal morphology and a placental\narea suggestive of complete hydatidiform mole.  B:  MRI\nscan at 27 weeks of pregnancy, showing a fetus without morphological\nanomalies and two distinct placental areas: one with a normal\nappearance; and the other characterized by multiple, hyperintense\nvesicular areas, suggesting a twin molar pregnancy. Because of\nsevere preeclampsia-severe hypertension; hemolysis/elevated liver\nenzymes/low platelet count syndrome; and acute pulmonary edema—a\ncesarean section was performed at 28 weeks of pregnancy. The\nextremely premature neonate survived without sequelae. After the\ncesarean section, the patient showed a satisfactory evolution and\nwas discharged from the post-molar pregnancy follow-up after 12\nmonths of treatment with normal-dose â-hCG, without\nchemotherapy.\nPartial hydatidiform mole presents as thickened placental tissue containing\nvarious anechoic cystic lesions ( 31 ) , and some cases can present amniotic membranes and a\nfunctional umbilical circulation, as depicted in  Figure 3 ( 32 ) . It\nis usually accompanied by malformation of the gestational sac or of the fetus,\nwhich can have characteristics such as hydrocephalus, syndactyly, cleft lip, and\ngrowth restriction ( 12 ) .\nHydropic degeneration of the placenta, which occurs in some cases of abortion,\nproduces images of the placenta similar to those seen in cases of partial\nhydatidiform mole, thus increasing the difficulty of making the diagnosis with\nultrasound ( 3 ) .\nFigure 3 Transvaginal ultrasound showing an embryo and a deciduous area filled\nwith anechoic images suggestive of partial hydatidiform mole.\nBecause the patient was clinically stable and there was a fetal\nheartbeat, we opted for watchful waiting, until fetal death was\nconfirmed at 14 weeks of pregnancy, indicating the induction of a\nmolar abortion.\nTransvaginal ultrasound showing an embryo and a deciduous area filled\nwith anechoic images suggestive of partial hydatidiform mole.\nBecause the patient was clinically stable and there was a fetal\nheartbeat, we opted for watchful waiting, until fetal death was\nconfirmed at 14 weeks of pregnancy, indicating the induction of a\nmolar abortion.\nIn more than 40% of cases, theca lutein cysts over 6 cm in diameter can be\nvisualized. Characteristically, they are bilateral and multilocular ( Figure 4 ); they typically do not require\ntreatment ( 1 ) . Theca\nlutein cysts, which derive from ovarian hyperstimulation caused by high\ncirculating levels of gonadotropins, generally regress after a few months, in\nparallel with normalization of β-hCG levels. In rare cases, there is\nadnexal torsion with acute vascular abdomen or rupture that results in\nhemoperitoneum, both of which call for immediate treatment ( 24 ) .\nFigure 4 Pelvic ultrasound showing a massive theca lutein cyst in a patient\nwith complete hydatidiform mole.\nPelvic ultrasound showing a massive theca lutein cyst in a patient\nwith complete hydatidiform mole.\nAlthough quite rare, tubal molar pregnancy, as depicted in  Figure 5 , does occur ( 15 ) . The treatment is the same as that used in tubal\nectopic pregnancy, and the follow-up is similar to that required for\nintrauterine hydatidiform mole.\nFigure 5 Transvaginal ultrasound showing an empty endometrial cavity, adjacent\nto a large quantity of amorphous, anechoic, multivesicular material,\nsuggesting tubal molar pregnancy, which was subsequently confirmed\nby histopathology.\nTransvaginal ultrasound showing an empty endometrial cavity, adjacent\nto a large quantity of amorphous, anechoic, multivesicular material,\nsuggesting tubal molar pregnancy, which was subsequently confirmed\nby histopathology.\nSome cases of mole show nonspecific alterations on Doppler flow studies, although\nultrasound is more widely used in the evaluation of cases of GTN ( 2 , 19 ) .\nMyometrial invasion is best defined by transvaginal ultrasound. Invasive moles,\nchoriocarcinoma, and PSTT have a similar appearance-a focal myometrial mass that\ncan be either uniformly echogenic or hypoechoic ( Figure 6 ), as well as being complex or multicystic ( 33 ) . Anechoic spaces within the\nmass are related to hemorrhage, tissue necrosis, cysts, or vascular\nspaces ( 2 , 19 ) . Patients with more advanced\ndisease can present with an enlarged uterus, with lobulated, heterogeneous\ncontours, or a pelvic mass that extends to adjacent organs ( 28 ) . The volume of the uterine\nlesion must be determined because it has an established relationship with the\nsize of the tumor and the risk of chemoresistance ( 34 ) .\nFigure 6 Transvaginal ultrasound, acquired during post-molar pregnancy\nfollowup, when hCG levels were elevated. Note the presence of\nhypoechoic areas in the myometrium, resembling the hypervascular\n“Swiss cheese” aspect, suggestive of an invasive mole, on the\nDoppler flow study.\nTransvaginal ultrasound, acquired during post-molar pregnancy\nfollowup, when hCG levels were elevated. Note the presence of\nhypoechoic areas in the myometrium, resembling the hypervascular\n“Swiss cheese” aspect, suggestive of an invasive mole, on the\nDoppler flow study.\nThe changes seen on ultrasound of GTN are nonspecific, and the differential\ndiagnosis should include other pelvic malignancies, as well as myoma and\nadenomyosis ( 33 ) .\nCorrelating clinical history with β-hCG levels and with Doppler flow\nstudy findings is essential to making the correct diagnosis ( 28 ) .\nBecause GTN subtypes are indistinguishable from each other in imaging studies,\nthe diagnostic hypothesis follows a specific sequence. The initial assumption is\ninvasive mole. However, if metastasis is detected, the focus shifts to\nchoriocarcinoma. Chemotherapy is started even before histological confirmation\nhas been obtained, and both entities are treated with the same chemotherapy\nregimen ( 1 ) . Effective\npost-treatment ultrasound usually identifies a hypoechoic lesion that\nprogressively decreases in size ( 28 ) .\nA diagnosis of PSTT is strongly suggested when there are changes that are\ncharacteristic of GTN in combination with low levels of β-hCG. Unlike\ninvasive mole and choriocarcinoma, PSTT is distinguished by its relative\nchemoresistance and the potential need for surgical treatment ( 2 , 27 ) .\nColor and spectral Doppler flow studies are used together with an ultrasound gray\nscale in the assessment of GTN and in its post-treatment follow-up ( 35 ) . The vasculature has a\nchaotic appearance, with color distortion and vascular changes, due to\narteriovenous communications and neovascularization of the myometrial\nmass ( 19 ) . The uterine\nvessels can be evaluated by determining their wave patterns, peak systolic\nvelocity, resistance index (RI), and pulsatility index (PI).\nIn the evaluation of uterine arteries during the first trimester of a normal\npregnancy, Doppler flow studies show high impedance wave patterns with low\ndiastolic velocities, except at the placental implantation site. Because of\nphysiological vascular invasion by trophoblastic tissue, the placental\nimplantation site has a low-impedance flow ( 2 , 27 ) . In the\nsecond and third trimesters, there is reduced impedance due to the physiological\nadvance of arterial invasion of the trophoblast. However, in the first trimester\nof a molar pregnancy, there is high flow velocity and low-impedance wave\npatterns due to the greater arterial invasion caused by abnormal proliferation\nof the trophoblast ( 27 , 28 ) . Zhou et al. ( 31 )  compared the RIs of the\nuterine arteries in patients with hydatidiform mole (complete or partial) with\nthose of the uterine arteries in patients with GTN, finding that the RIs were\nlower in the latter group. Although there is no consensus on the values, an RI\n< 0.4 and a PI < 1.5 are thought to be indicative of a uterine artery with\nlow resistance, which is typical of GTN ( 31 ) .\nIt should be borne in mind that the color Doppler ultrasound features of GTN are\nnonspecific. Other conditions can have a similar appearance, such conditions\nincluding the presence of residual trophoblastic tissue from a miscarriage or\nectopic pregnancy, pelvic inflammatory disease, other uterine malignancies,\ndiverticulitis or appendicitis with uterine abscesses, and uterine arteriovenous\nmalformations ( 19 ) .\nThe PI of the uterine artery is an indirect measure of functional vasculature of\nthe tumor, being considered a predictor of resistance to chemotherapy,\nespecially to methotrexate, regardless of the FIGO score ( 35 ) . It is known that a low PI\nindicates a higher number of arteriovenous communications and greater\nneovascularization. Sita-Lumsden et al. ( 36 )  showed that patients with a PI ≤ 1 for the\nuterine artery have an absolute risk of methotrexate resistance of 67%, compared\nwith 42% for those with a uterine artery PI > 1.\nDoppler flow studies can also be used to evaluate the response to chemotherapy.\n Pari passu  to the drop in the serum levels of β-hCG,\nregression of the vascular cystic spaces of the intramyometrial mass is also\nseen. During the post treatment follow-up, ultrasound can also serve to diagnose\ndisease complications such as uterine arteriovenous malformations ( 2 , 27 ) .\nChest X-ray is the examination of choice for the initial evaluation of metastatic\nlung cancer. There are three basic forms of radiological presentation of\nmetastatic pulmonary GTN: typical, alveolar, and embolic. The typical image is\nthat of dense nodules with well-defined contours, usually multiple and bilateral\n( Figure 7 ). When there is cellular\ninvolvement, a chest X-ray can show multiple nodules and small, poorly defined\nopacities, similar to the images produced by inflammatory processes.\nRadiographic images showing pulmonary hypertension and cardiovascular changes\nsuggest the occurrence of thromboembolic phenomena ( 37 ) . Other, rarer, radiographic changes have also\nbeen associated with GTN, including pleural effusion, interlobular septal\nthickening, cavitations, and air bronchogram ( 38 ) .\nFigure 7 Posteroanterior chest X-ray, acquired during follow-up, showing\nnumerous, dense, bilateral metastatic nodules, of varying sizes.\nPosteroanterior chest X-ray, acquired during follow-up, showing\nnumerous, dense, bilateral metastatic nodules, of varying sizes.\nEven after effective chemotherapy treatment, lung nodules can still be seen on\nchest X-rays. If there is no growth of the tumor mass during the radiological\nfollow-up and β-hCG levels remain in the normal range, such nodules\nshould be considered residual, probably related to tissue necrosis and not to\nactive neoplasia ( 39 ) .\nIn cases of GTN, the use of CT is fundamental for the investigation of sites of\nmetastasis, except for those in the vagina or the brain ( 2 ) . It is noteworthy that the lung\nis the most common site of GTN ( 40 )  and that choriocarcinoma is the GTN subtype most often\nidentified ( 41 ) .\nOn CT, GTN confined to the uterus can be described as a low-attenuation lesion\nwithin an enlarged uterus ( 42 ) .\nMetastases derived from choriocarcinoma are characteristically hypervascular,\nwith a tendency to bleed ( 2 ) .\nThe pulmonary lesions of GTN seen on CT are typically rounded and larger than 3\ncm in diameter. Such lesions rarely form cavities ( Figure 8 ). They can be single lesions (otherwise usually\nfound in numbers of less than 10), and they have a miliary aspect ( 40 ) . Pleural, endovascular, and\nendobronchial lesions have also been described ( 2 ) .\nFigure 8 Contrast-enhanced CT of the chest, acquired during follow-up, showing\nnumerous metastatic lung lesions. Although of limited clinical\nsignificance, micrometastases can be seen scattered diffusely\nthroughout the lung parenchyma.\nContrast-enhanced CT of the chest, acquired during follow-up, showing\nnumerous metastatic lung lesions. Although of limited clinical\nsignificance, micrometastases can be seen scattered diffusely\nthroughout the lung parenchyma.\nDespite the increased sensitivity of CT in detecting micrometastases of GTN, the\nFIGO recommends chest Xray as the initial test for pulmonary evaluation. Studies\nhave shown that nodules can persist after effective chemotherapy, without\naffecting the prognosis ( 39 ) .\nIn patients classified as high risk and showing metastasis to the lung or vagina,\nabdominal CT is recommended ( 20 ) . If there is liver involvement, the lesions are usually\nmultiple, heterogeneous, and hypointense, with a high avidity for intravenous\ncontrast in the arterial phase ( Figure 9 ),\nand hemorrhagic transformation is common. These metastatic liver lesions are not\neasily distinguished from other hypervascular liver tumors. In order to make\nthat distinction, it should be borne in mind that these neoplasms develop a\nhypervascular mass with aneurysmal dilatation in the peripheral hepatic\narteries, which are best visualized in the arterial phase, whereas persistent\nvascular lakes are observed in the venous phase. These lesions appear late in\nthe course of the disease and are related to poor prognosis. Although biopsy is\ncontraindicated because of the risk of fatal bleeding ( 43 ) , these lesions can respond to selective\nchemoembolization.\nFigure 9 CT of the abdomen showing three hypointense, hypovascular lesions\nwith peripheral enhancement in a patient with GTN. The patient\nevolved to liver rupture, hemoperitoneum, and death. The autopsy\nrevealed metastatic choriocarcinoma of the liver.\nCT of the abdomen showing three hypointense, hypovascular lesions\nwith peripheral enhancement in a patient with GTN. The patient\nevolved to liver rupture, hemoperitoneum, and death. The autopsy\nrevealed metastatic choriocarcinoma of the liver.\nOther sites are reported to be affected, including the spleen, kidneys,\ngastrointestinal tract, and skin. In cases of PSTT, lymph node involvement is\ncommon ( 4 , 44 ) .\nIn patients with GTN, studies involving positron emission tomography coupled with\nCT (PET/CT), using  18 Ffluorodeoxyglucose, have shown potential not\nonly to determine the extent of the tumor and to identify metastases but also to\nevaluate the response of high-risk tumors to treatment ( Figure 10 ). The detection of metabolically active disease\ncan reveal occult injuries, confirm a complete response to treatment, and allow\nGTN recurrence to be evaluated ( 44 ) . In a study conducted in the United Kingdom, nine patients\nunderwent diagnostic PET/CT during the staging of recurrent GTN. The PET/CT\nhelped locate active disease sites in six of those patients, and one patient\nshowed no abnormalities on ultrasound, MRI, or CT ( 2 ) .\nFigure 10 PET scan, using  18 F-fluorodeoxyglucose, showing intense\nmetabolic tumor activity in the liver, featuring metastatic\nchoriocarcinoma nodules, in a patient under follow-up treatment.\nPET scan, using  18 F-fluorodeoxyglucose, showing intense\nmetabolic tumor activity in the liver, featuring metastatic\nchoriocarcinoma nodules, in a patient under follow-up treatment.\nThe routine evaluation of GTN does not include MRI, which is reserved for use in\ncomplicated and inconclusive cases, such as suspected PSTT, advanced disease,\nand recurrent disease ( 45 ) .\nThrough the use of MRI, the location, vasculature, and extent of the tumor can\nbe evaluated with greater accuracy. However, the imaging findings are\nnonspecific and can be difficult to distinguish from those of, for example,\nretained products of conception or an ectopic pregnancy with GTN ( 46 ) .\nAn MRI scan of a hydatidiform mole obtained during the first trimester shows\nlittle or no abnormality. Such abnormalities are best viewed in the second\ntrimester. Contrast-enhanced T1-weighted images can show a mass with a signal\nequal to or slightly more intense than that of the adjacent myometrium,\ncontaining small, distributed diffusely cystic spaces, reflecting the vesicular\nnature of the tumor ( 46 ) . The\npresence of foci with hyperintense signals is probably due to hemorrhagic foci\nwithin the lesion. On T2-weighted images, the tumor presents a heterogeneous,\nhyperintense mass, with a \"bunch of grapes\" appearance, that distends the uterus\nand endometrial cavity ( 47 ) .\nMyometrial invasion can be suspected when the lesion crosses the myoendometrial\nborder and the transitional zone becomes undefined. These changes have also been\nidentified in routine cases of miscarriage and in patients who have recently\nundergone curettage. Some studies have shown a direct correlation between such\narchitectural deregulation and circulating levels of β-hCG, levels >\n1500 mIU/mL being accompanied by a greater change in uterine architecture and a\ngreater tumor burden, whereas levels < 500 mIU/mL are usually accompanied by\nno changes on MRI scans ( 46 ) .\nDue to the high degree of vascularization, T1-weighted and T2-weighted images\nboth show various spaces with tortuous flows, consistent with vessels that pass\nthrough the tumor mass, myometrium, parametrium, or attachments, as well as with\nengorgement of the iliac vessels ( 48 ) . The hemorrhagic foci usually have a high signal intensity\non T1-weighted images and can best be distinguished from active disease by\ndynamic contrast-enhanced MRI, as shown in  Figure\n11 ( 47 ) .\nFigure 11 Gadolinium contrast-enhanced MRI scan of the pelvis, showing,\nhypointense lesions with avid uptake and vascular dilation in the\nmyometrium, sometimes in close contact with the uterine effusion, in\npatients treated for GTN.\nGadolinium contrast-enhanced MRI scan of the pelvis, showing,\nhypointense lesions with avid uptake and vascular dilation in the\nmyometrium, sometimes in close contact with the uterine effusion, in\npatients treated for GTN.\nChemotherapy reduces the volume and vascularization of the tumor, and MRI scans\nusually show normal images by 6-9 months after the end of treatment ( 48 ) . Vascular malformations can\nbe detected years after treatment ( 2 ) .\nOn MRI scans, PSTT can present in a hypervascular form or a hypovascular form. In\nthe hypervascular form, the tumor has an isointense signal on T1-weighted\nimages, a slightly hyperintense signal on T2-weighted images, and avid uptake\nafter the administration of contrast (gadolinium). Many vessels are visualized\nin all MRI scans. In the hypovascular form, the tumor has less volume, as well\nas a higher signal intensity on T1- and T2-weighted images, and a lower rate of\nuptake of contrast. There is no evident vascularization ( 49 ) .\nIn the metastatic evaluation of GTN, MRI also plays a role. It is superior to\nultrasound in identifying parametrial and vaginal invasion ( 2 ) . On T2-weighted images, a\nhyperintense mass can be seen in the parametrial tissue, whereas vaginal\ninvolvement presents as a bulging into the fornix with a hyperintense signal and\nill-defined borders ( 48 ) .\nPatients with pulmonary metastases of GTN are also submitted to evaluation of the\nbrain tissue. In the brain, there are typically multiple lesions, primarily\nlocated in the parietal lobe at the junction between the white and gray matter.\nThe images seen on an MRI scan have varying characteristics ( Figure 12 ), depending on the duration of the\nassociated bleeding ( 20 , 50 ) . The image is improved by\ncontrast administration ( 2 , 20 , 50 ) .\nFigure 12 MRI scan of the brain, showing a mass suggestive of metastatic\nchoriocarcinoma, in a 32 year-old patient presenting with headache,\nspeech articulation disorder, and dysphagia.\nMRI scan of the brain, showing a mass suggestive of metastatic\nchoriocarcinoma, in a 32 year-old patient presenting with headache,\nspeech articulation disorder, and dysphagia.\nConventional angiography can be used for the embolization of vaginal and liver\nmetastases. Another use of conventional angiography is in the management of\ncases of uterine arteriovenous malformations after GTN in patients who are\nsymptomatic and wish to conceive, given that selective embolization of such\nmalformations, via the uterine artery, has provided auspicious results.\nTraditionally, such patients have undergone hysterectomy and ligation of the\nuterine arteries, making subsequent reproduction impossible ( 2 , 27 ) .\n\nAlbeit a relatively uncommon disease with malignant potential, GTD is almost always\ncurable. Although the β-hCG level is an excellent biomarker, it cannot be\nused in isolation to make the diagnosis of GTD. Ultrasound is the firstline\nexamination in the diagnosis of molar pregnancy. When combined with Doppler flow\nstudies, it is useful not only in the evaluation of GTN but also in the evaluation\nof the response to treatment and in the detection of GTN recurrence. Screening for\nmetastatic GTN should include chest X-ray and CT. In complicated cases, MRI is used\nas an ancillary method to assess the extent of the tumor. To date, there have been\nfew studies involving the use of PET/CT in cases of GTN. However, PET/CT has proven\nefficient in identifying occult neoplasia. It is evident that the radiologist plays\na fundamental role throughout the course of the treatment of patients with GTD, from\ndiagnosis to follow-up after cure.","source_license":"CC-BY-4.0","license_restricted":false}