Choriocarcinoma

Chest ultrasound and color Doppler flow imaging were used to assess the pulmonary nodule of a 24-year-old pregnant woman with dyspnea and hemoptysis. The ultrasonogram showed multiple hypoechoic subpleural nodules. Color Doppler imaging of the nodules revealed characteristics of high vascularity and high blood flow. A percutaneous needle aspiration under ultrasonic guidance confirmed the diagnosis of choriocarcinoma.

Choriocarcinoma is a relatively rare malignancy and commonly metastasizes to the lung. The tumor grows rapidly, with widespread hematogenous dissemination which may be fatal before the diagnosis of choriocarcinoma is even suspected; however, it is now very amenable to treatment with cytotoxic chemotherapy, with high rates of remission even in patients presenting with metastatic disease. Timely diagnosis of the disease is most important for successful treatment; therefore, aggressive diagnostic procedures may be warranted. To our knowledge, this is the first case report of a pregnancy coexisting with a metastatic choriocarcinoma of the lung diagnosed by Doppler ultrasound. Color Doppler mapping of the metastatic nodules showed very high vascular density and a characteristic high blood flow image. A percutaneous ultrasonically guided needle aspiration confirmed the diagnosis of choriocarcinoma.

Case Report

A 24-year-old woman with a 22-week pregnancy was admitted because of having had dyspnea and cough with blood-tinged sputum for 2 months. During the past 3 years, she had had 2 artificial and 4 spontaneous abortions. In August 1991, she became pregnant again, about 6 months prior to admission. The patient developed dyspnea and cough with blood-tinged sputum 4 months later; this was her 14th week of pregnancy. She was admitted to a local hospital, where a chest roentgenogram showed multiple nodules in both lung fields; bronchoscopy revealed a polypoid lesion, with a blood clot in the bronchus of the lateral segment of the right middle lobe. The results of brushing cytology and biopsy from the polypoid lesion were negative for malignancy The patient was transferred here at the 22nd week of pregnancy, with aggravation of dyspnea and hemoptysis. On admission, she was breathless, but not cyanotic, and had bilateral basilar inspiratory crackles. A chest roentgenogram showed multiple nodular lesions of both lung fields, with a right-sided pleural effusion (Fig 1). Arterial blood gas values were as follows: pH, 7.50; PACO2, 128 mm Hg; Pao2, 95 mm Hg; HCO, , 19 mEq/L; and base excess, 3.5 mEq/L with oxygen of 5 L/min via nasal cannula. There was no vaginal bleeding. The size of the uterus was approximately 22 weeks' gestation; fetal heartbeat was normal. The serum level of human chorionic gonadotropin (HCG) was 418,797 mIU/ml (normal range of second trimester, 10,600 to 30,000 mIU/ML).

Ultrasonography with color Doppler imaging was performed with a unit (Toshiba SSA-270A) with a 3.75-MHz sector-array probe and the pulse repetition frequency maximum up to 15 kHz. The ultrasonogram showed a small amount of effusion in the right hemithorax and multiple hypoechoic subpleural nodules in both lung fields; the size of these nodules was about 1 cm in diameter, with a maximum of 2.0 cm. Color Doppler imaging showed very high vascularity of the nodule, with the characteristics of hue change of a color Doppler signal from red to yellow (or blue to green in the opposite direction of flow) to indicate a high blood flow of these vessels (Fig 2A). The peak V was close to the 0.26-m/s maximum of the chosen scale (the pulse repetition frequency was 1.18 kHz). Tumor vessels in 2 perpendicular cross-sectional planes of the nodule were counted, with a vascularity index of 2.5 vessels per square centimeter. Color Doppler flow in the spectrum was unable to demonstrate the large systolic-diastolic gradient well because of too rapid respiratory movement. An ultrasonically guided needle aspiration with a 22-gauge needle was done, yielding a cytologic diagnosis of choriocarcinoma. Minimal pneumothorax was found after lung aspiration because the patient could not hold back from breathing.

Chemotherapy with a high-risk regimen (1 mg of actinomycin plus 350 mg of etoposide plus 525 mg of methotrexate, alternating with 1.7 mg of vincristine plus 1,050 mg of cyclophosphamide) was given on the third day of hospitalization. Classic hysterectomy was performed and the fetus removed when intrauterine death was found 10 days following chemotherapy. The serum level of HCG fell to 438 mIU/ml, and the chest roentgenogram returned to almost normal after 4 courses of chemotherapy. Follow-up color Doppler

Discussion

Choriocarcinoma is a relatively rare tumor occurring during pregnancy The most common symptom is vaginal bleeding.[1] A third of the patients may present with signs of metastases in the lung (80 percent), vagina (30 percent), pelvis (20 percent), or brain (10 percent). All 3 main types of pulmonary choriocarcinoma are caused by hematogenous metastases: 65 to 95 percent with well-defined round nodular lesions; 5 to 15 percent with a miliary or alveolar pattern; and the remainder with pulmonary emboli. The common clinical mainfestations are dyspnea, cough, and hemoptysis. Histologic studies of the metastatic lesions may show high vascularity and extensive hemorrhage in nodules and adjacent lung parenchyma.[2] Angiography reveals prominent arteriovenous shunting.[3]

Most malignant tumors can stimulate the growth of new blood vessels by secreting an angiogenesis factor.[4] The neovascularization and arteriovenous shunts of these tumor vessels give rise to flow that can be detected as high-velocity signals with a distinctive rasping sound on continuous-wave or pulsed Doppler studies. These "tumor flow signals" have been detected in carcinoma of the breast,[5,6] hepatocellular carcinoma,[7] and renal cell carcinoma.[8] Two types of Doppler signals have been identified in tumors:[9] the first was a high-frequency signal with a large systolic-diastolic gradient and originating from arteriovenous shunts; and the second type was a relatively high-frequency, almost continuous signal with little systolic-diastolic fluctuation. These low-impedence signals are related to sinusoid space, which lacks muscular walls, a characteristic also commonly found in tumors. Doppler ultrasound study in our case demonstrated high vascularity and high blood flow in color Doppler imaging. These findings are comparable to the pathologic characteristies of choriocarcinoma with highly vascular lesions and arteriovenous shunts. In addition, the findings explain the clinical manifestation of hemoptysis, which is otherwise unusual in pulmonary metastases. According to the quantitation of color Doppler imaging of tumor flow by Cosgrove et al,[6] metastatic pulmonary choriocarcinoma has higher vascularity than malignant breast cancers (2.5 vessels vs 0.5 vessels per square centimeter). This also confirms that the choriocarcinoma has high-vascularity lesions. Although it has been suggested that hyperechoic or hypoechoic patterns are associated with hypervascular or hypovascular lesions, respectively,[10] this has not been confirmed. In this case the ultrasonogram showed hypoechoic nodular lesions, whereas Doppler blood flow showed hypervascularity This provided information to assess the risk of bleeding when an ultrasonically guided needle biopsy was used to establish the diagnosis. Our preliminary study of color Doppler ultrasonography of lung cancers found only few color Doppler flow signals as the same size of primary lung cancer (data not shown). Detection of high Doppler shift seems to be a promising tool for the differential diagnosis of pulmonary metastatic hypervascular lesions such as choriocarcinoma, thyroid carcinoma, and renal cell carcinoma from primary lung cancer. Further study is necessary to confirm this point.

Color Doppler flow imaging, developed by Namekawa et al,[11] was originally used to evaluate the dynamics of blood flow in the heart and large blood vessels. Since then, it has been widely applied to evaluate tumor blood flow in breast tumors, hepatocellular carcinoma, and renal masses; however, to our knowledge, there have been no reports in the literature on the use of color Doppler flow imaging in lung cancers. Here the high blood flow by Doppler ultrasound in metastatic pulmonary choriocarcinoma was demonstrated as useful to distinguish it from primary lung cancer and to provide information about the risk of ultrasonically guided lung aspiration.

References

[1] Kuhn RJP, Long SR, Forune DW Choriocarcinoma with intrauterine pregnancy Aust NZ J Obstet Gynaec 1980; 20:94-8 [2] Neurhauseer EBD. Pulmonary hypertension in infancy and childhood: the Gordon Richards Memorial Lecture. J Can Assoc Radiol 1961; 12:64 [3] Green DJ, Carden TS Jr, Hammond CB, Johnsrude IS. Angiographic demonstration of arteriovenous shunts in pulmonary metastatic choriocarcinoma. Radiology 1973; 108:67-70 [4] Schor AM, Schor SL. Tumour angiogenesis. i Pathol 1983; 141:385-413 [5] Schoenberger SG, Sutherland CM, Robinson AE. Breast neoplasms: duplex sonographic imaging as an adjunct in diagnosis. Radiology 1988; 168:665-68 [6] Cosgrove DO, Bamber JC, Davey JB, McKinna JA, Sinnet HD. Color Doppler signals from breast tumors. Radiology 1990; 176:175-80 [7] Tanaka S, Kitamura T, Fujita M, Nakanishi K, Okuda S. Color Doppler flow imaging of liver tumors. AJR 1990; 154:509-14 [8] Kuijpers D, Jasper R. Renal mass: differential diagnosis with pulsed Doppler US. Radiology 1989; 170:59-60 [9] Taylor KJW, Ramos I, Carter D, Morse SS, Snower D, Fortune K. Correlation of Doppler US tumor signals with neovascular morphologic features. Radiology 1988; 166:57-62 [10] Juul N, Torp-Pedersen S, Sronovall A, Holm HH, Koch F, Larsen S. Ultrasonically guided fine needle aspiration biopsy of renal mass. J Urol 1985; 133:579-81 [11] Namekawa K, Kasai C, Tsukamoto M. Imaging of blood flow using autocorrelation. Ultrasound Med Biol 1982; 8(suppl 1):138

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