Ultrasonographic and Doppler imaging in the Diagnosis metastasia nodules of Gestation Trophoblastic Tumor in abdominopelvic cavity

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Author: Qin XIE, XiaoYing LEI, GuoZhen YAN

Gestation trophoblastic tumor (GTT) is the group of trophoblastic disease rooting in embryo, which often subdivid into invasive hydatidiforn mole(IHM), choriocarcinoma and placental site trophoblastic tumor. All these show abnormal trophoblastis proliferation histologically1. Gestation trophoblastic tumor is suspected clinically in patients with vaginal bleeding and rapid uterine enlargement who have markedly elevated serum human chorionic gonadotropin(HCG) levels2, especially after hydatidform mole. Typically, Color Doppler ultrasonography shows low-resistance arterial flow extending into the myometrium, it is useful in detection of invasive disease and has replaced angiography of the uterus3-7. At the meantime, indentification of ovarian theca lutein cysts often coincides with a markedly elevated serum HCG level1. So most imaging studies always concentrate on uterus and ovary before, the metastasia nodules of GTT in abdominopelvic cavity is rare reported by ultrasonography. Although the incidence of GTT varies considerably in differenr regions of the world1, Asian populations consistently are affected more often than other ethnic groups. The reason is not fully understood but may have a genetic basis8. We had been studying gestation trophoblastic disease for a long time, and articles about 12-year experience in china had been published9. Because of invasive behavior of GTT, distant metastases always occur. But the report about metastasia nodules of GTT in abdominopelvic cavity detected by abdominopelvic ultrasonography is rare. This study emphasizes to detect metastasia nodules of GTT in abdominopelvic cavity by abdominopelvic ultrasonography.

Materials and Methods

Clinical histories, ultrasonographic images, and Doppler waveform of 13 cases of GTT diagnosed and treated at the 2nd affiliated hospital of Xi,an jiaotong university in China between 2000 and 2006 were evaluated retrospectively. All patients were referred from regional medical facilities in and around the city of Xi,an to the university hospital for finally diagnosis and treatment. Choriocarcinoma was diagnosed in 4 women; An IHM was diagnosed in 9. The age of patients with GTT ranged from 21 to 46 years. The mean age was 34 years (SD, 8.8 years). The parity history at initial referral was recorded The evident symptom was recorded. Serum HCG level were evaluated in all patients too. In addition, all patients were studied by abdominopelvic ultrasonography, which include color and pulsed Doppler interrogation. All examinations were performed with an Acuson Sequoia 512 system (Siemens Medical Solution, Mountain View, CA). Transabdominal imaging alone was performed and was diagnostic in all but 4 patients , who required additional endovaginal supplementation. Various transducers ranging from 2.5 to 5.0 MHz were used for transabdominal imaging. An 6.0~8.0 MHz transducer was used for endovaginal imaging. The ultrasonographic examinations included realtime gray scale evaluation for the presence of solid metastasia nodules or cystic vascular spaces within abdominopelvic cavity besides uterus and ovary. The diameter of metastasia nodules was measured. Color and pulsed Doppler interrogation of the metastasia nodules was performed in all cases. The sample volumes were taken from arteries of the metastasia nodules. The spectral waveforms were analyzed for the presence of high-velocity, low-impedance flow. The resistive indices were recorded. In addition, both maternal ovaries were examined. When present, theca lutein cysts were measured. Color and pulsed Doppler characteristics were used to confirm the diagnosis of GTT, to detect metastasia nodules, and to assess disease recurrence after treatment. Theca lutein cysts were confirmatory of the HCG level elevation. Histologic proof of diagnosis was obtained only in 1 case Choriocarcinoma and 2 cases IHM. The diagnosis was presumed clinically in the other cases of IHM and Choriocarcinoma, with the group differentiated on the basis of the latency of symptom appearance after evacuation of the initial affected gestational1. Patients becoming symptomatic within the subsequent 6 months after curettage of hydatidform molar tissue were stratified into the IHM group. Those who became symptomatic after 12 months after curettage of hydatidform molar tissue or after abortion were placed in the choriocarcinoma group. Once an IHM or choriocarcinoma was diagnosed, all patients were treated with combination chemotherapy protocols using fluorouracil, kengshengmycin, nitrocaphane, methotrexate, and etoposide. Patients follow-up by ultrasonography and serum HCG analysis was attempted in all cases. Similar ultrasonographic criteria were used to diagnose the presence of recurrent disease on patients with persistent or rising serum HCG levels.Treated patients were followed when possible until HCG levels became normal and until the ultrasonographic and Doppler abnormalities disappeared.

Results

Of the 13 cases of GTT, 4 women had the finding of a choriocarcinoma; 9 had an IHM. All patients had vaginal bleeding clinically. Most had abdominal pain and nausea as well. On physical examination, uterine enlargement was the most common finding, and 7 cases could be touched masses in pelvic cavity by gynecologist. Serum HCG levels were universally elevated in all cases of GTT at initial referral, with levels measuring from 500ng/ml to 2000ng/ml. The ultrasonographic and Doppler findings, treatment, and patient outcomes are summarized in Table 1.

In the 12 patients with GTT, 5 cases occurred during the first pregnancy ; 4 occurred during the second; 3 occurred during the third; and 1 occurred during the fourth. In the 4 patients with choriocarcinoam, 1 initially had a hydatidform mole and were treated by dilation and suction evacuation; and 3 cases occurred after an elective therapeutic abortion. These cases were diagnosed because having invasive disease within the myometrium, as well as metastasia nodules by follow-up ultrasonographic and Doppler examination, (Figure 1, 2, 3 and 4). Doppler interrogation showed a mean arterial resistive index of 0.31(SD, 0.08) in metastasia nodules. In addition to vaginal bleeding and abdominal pain, 1 women with choriocarcinoam had a headache. Distant brain metastasia nodules were diagnosed with the aid of computed tomography. All 9 patients with an IHM initially had a hydatidform mole and were treated by dilation and suction evacuation. These cases were diagnosed as having invasive disease soon after the dilation and suction evacuation for the hydatidform mole because the HCG levels failed to normalized. Metastasia nodules were detected by follow-up ultrasonographic and Doppler examination, (Figure 5, 6 ). Doppler interrogation showed a mean arterial resistive index of 0.35(SD, 0.05) in metastasia nodules. An IHM with renal metastasia node, (Figure 7), color and pulsed Doppler sonogram showed a arterial resistive index of 0.41 in metastasia nodules, and markedly increased uterine vascularity. Myometrial invasion by cystic vascular space ever appeared. Following-up sonogram after 6 courses of combination chemotherapy showed the renal metastasia node did not disappear. Form then, the patient has been observing. In addition to vaginal bleeding and abdominal pain, 5 women with an IHM had a cough, and 2 had a headache. Distant pulmonary metastasia nodules and brain metastasia nodules were diagnosed with the aid of computed tomography and chest radiography as well as by ultrasonography. Except an IHM with the renal metastasia node, abnormal ultrasonographic and Doppler findings in other metastasia disease disappeared when chemotherapy was successful(Figure 2D).

Discussion

Even though an IHM is nonmalignant process, it has invasive behavior. And a choriocarcinoma is great malignant tumor, so distant metastases of GTT can always occur. The trophoblastic tissue invades the maternal vascular system and can be transported to local site such as pelvis but also be transported to distant sites such as kidney, colon, lung, brain, and so on. Rare sites of metastases to the spinal cord and paraspinous tissues have also been reported1. In our group, cases with an IHM were all found to have metastsatic disease, three with cystic vascular space occured near the uterus, 1 with solid mass occurred in colon, two in side wall of pelvic cavity, 1 with solid mass in right renal, 1 in abdominal cavity, and 1 with solid mass near the uterus. Cases with a choriocarcinoma were found to have metastsatic disease too, One with cystic vascular space occured near the uterus, 1 with solid mass occurred in colon, and 2 with solid mass near the uterus. So color Doppler ultrasonography has become the standard in comfirming the diagnosis, not only in evaluating for myometeial invasion, but also in finding distant metastasia nodules. But color Doppler ultrasonography could not find pulmonary or brain metastasia nodules, with the aid of computed tomography and chest radiography, the other metastasia nodules may be detected. In this study, Doppler ultrasonography showed low-impedance flow in cases of distant metastasia nodules, with resistive indices of less than 0.5. Presumably, as well as myometeial invasion, this indicted a greater degree of vascular invasion by trophoblastic tissue at the time of diagnosis by the invasive entities9. The causation of low-impedance flow is the form of arteriovenous fistula. Venous blood can flow backwards without any blocking because of the veins around uterus with no venous valve, abnormal trophoblastic tissueof GTT could keep on invading from veins to arteries. So, the characteristic high-flow, low-impedance arterial blood flow pattern is formed. That is why distant metastases of GTT is so common. In addition to serum HCG levels, Doppler sonogram is helpful in detecting disease recurrence, and in evaluating the efficacy of treatment. The characteristic high-flow, low-impedance arterial blood flow pattern of distant metastasia nodules of GTT allows Doppler studies to aid in this evaluation, often adding valuable information, as well as myometeial invasion. As we have seen, except an IHM with renal metastasia node, abnormal sultrasonographicand Doppler findings in other metastasia disease disappeared when chemotherapy was successful. The greatest utility of the Doppler flow studies was in their ability to show the presence of disease response to chemotherapy. In china, nearly all pelvic ultrasonography is performed by the transabdominal approach. Endovaginal supplementation is used only in occasional cases when the transabdominal approach proved confusing or nondiagnostic. In this group, endovaginal ultrasonography was performed in only 4 patients. Even then, the sultrasonographicand Doppler imaging were thought to be adequate for diagnosis. In this study, the diagnosis of an IHM or a choriocarcinoma was proved histologically in three cases. In the other cases, the diagnosis was presumed on the basis of clinical appearance and the latency of symptom onset. According to criterion referred, of the 12 patients with GTT, nine had an invasive hydatidiforn mole(IHM), Five had choriocarcinoma. Although the assigned diagnosis is the most likely, the accuracy is not perfect. Specifically no cases of placental site trophoblastic tumor were reported in this study and in the articles about 12-year experience in china had been published9. A placental site trophoblastic tumor is derived from extravillous trophoblastic cells of the placental bed. Patients generally have either heavy irregular bleeding or amenorrhea10. A placental site trophoblastic tumor tends to be resistant to chemotherapy and often needs hysterectomy for treatment.

References

1. Fox H. Female reproductive system . In :Anderson MC (ed). Systemic Pathology. Vol 6 . 3rd ed .New York, NY: Churchill Livingstone; 1991:435-445. 2. Green CL, Angtuaco TL, Shah HR, Parmley TH. Gestational trophoblastic disease: a spectrum of radiologic diagnosis. Radiographics 1996; 16:1371-1384 3. Chan FY, Chau MT, Pun TC, Lam C, Ngan HP, Wong RL. A comparison of color Doppler ultrasonography and the pelvis arteriogram in assessment of patients with gestational trophoblastic disease. Br J Obstet Gynacecol 1995; 102:702-725. 4. Xiang Y, Yang X, Yang N, Song H. A comparative study of transvaginal ultrasonograhy and pelvic arteriogram in assessment of patients with gestational trophoblastic tumour. Chin Med Sci J 1998;13:45-48. 5. Taylor KJ, Schwartz PE, Kohorn EI. Gestational trophoblastic neoplasia: diagnosis with Doppler US. Radiology 1987;165:445-448. 6. Carter J, Fowler J, Carlson J, et al. Transvaginal color flow Doppler ultrasonography in the assessment of gestational trophoblastic disease. J Ultrasultraultrasonography993; 12:595-599. 7. Flam F. Colour flow Doppler for gestational trophoblastic neoplasia. Eur J Gynaecol Oncol 1994; 15:443-448. 8. Ho HN, Gill TJ lll, Klionsky B, et al. Differences between white and Chinese populations in human leukocyte antigen sharing and gestational trophoblastic tumors. Am J Obstet Gynecol 1989; 161:942-948 9. Zhou Q, Lei XY, Xie Q, Cardoza JD. ultrasonographic and Doppler imaging in the diagnosis and treatment of gestational trophoblastic disease: a 12-year experience. J Ultrasultraultrasonography2005�C24(1):15-24. 10. Jauniaux E. Diagnosis and follow-up of gestational trophoblastic disorders. In: Rumak CM, Wilson SR, Charboneau JW(eds). Diagnostic Ultrasultraultrasonographyed. St Lous, Mosby Co; 1997:847-856 Table 1. Summary of ultrasonographic and Doppler Findings, Treatment, and Outcome of GTT Cases Parameter Choriocarcinoma IHM No. of cases 4 9 Metastasia Nodules 4 total1 cystic vascular space near the uterus 1 colon 2 near uterus 9 total3 cystic vascular space near the uterus1 colon2 side wall of pelvic cavity1 right renal1 abdominal cavity1 near uterus Diameter of Metastasia Nodules(SD) 3.99cm(1.33) 5.21cm(1.28) Doppler RI(SD) of Metastasia Nodules 0.31( 0.08) 0.35( 0.05) Theca lutein cysts 2 5 Treatment Chemotherapy Hysterectomy 3(drug combination)1 7(drug combination)2 Known death None None RI, resistive index.

Figure 1. A metastasia node near the uterus with a choriocarcinoma(up��down: A��B) A,Transverse sonogram showing a solid metastasia node near the uterus. B,Doppler waveform showing arteries flow of the metastasia node with a resistive index of 0.20. Figure 2. A metastasia node near the uterus with a choriocarcinoma(up��down: A��D) A,Sagittal sonogram showing a solid metastasia node near the uterus. B,Color Doppler imaging in the same patient showing blood flow of the metastasia node. C,Doppler waveform showing arteries flow of in the metastasia node with a resistive index of 0.29. D,Following-up sonogram after 6 courses of combination chemotherapy showing the uterine blood flow became normal ,with a resistive index of 0.53.Now the woman had a baby. Figure 3. Colonic metastasia node with a choriocarcinoma A, Transverse sonogram showing colonic metastasia node , hysterectomy. Figure 4. Cystic vascular space near the uterus with choriocarcinoma Color Doppler imaging showing abundant blood flow in the cystic vascular space. Figure 5. A metastasia node near the uterus with an IHM(up��down: A��B) A,Transverse sonogram showing a metastasia node near the uterus. B, Doppler waveform showing arteries flow of the metastasia node with a resistive index of 0.42 Figure6. Side wall metastasia node of pelvic cavity with an IHM (up��down: A��C) A,Doppler waveform showing arteries flow of invasive disease in the myometrium with a resistive index of 0.33. B, Color Doppler imaging in the same patient showing side wall metastasia node of pelvic cavity. C, Doppler waveform showing venous flow in the side wall metastasia node.

Figure 7. Right renal metastasia node with an IHM (up��down: A��C)

A, Doppler waveform showing arteries flow of invasive disease in the myometrium with a resistive index of 0.28. B, Color Doppler imaging in the same patient showing right renal metastasia node C, in the same patient showing right renal metastasia node after treatment, color Doppler imaging nearly disappear.