Background
Gestational choriocarcinoma is the most common gestational trophoblastic neoplasia; it is often secondary to a hydatidiform mole and to abortion, ectopic pregnancy, premature delivery, or term delivery. This malignant tumor grows rapidly and metastasizes in the lungs, brain, liver, kidneys, intestine, pelvis, and vagina. Approximately 60% of patients with choriocarcinoma develop pulmonary metastases. However, for patients with a respiratory condition, choriocarcinoma with lung metastasis is a relatively rare lung cancer diagnosis. Three cases of choriocarcinoma with pulmonary metastasis who had the primary symptom of hemoptysis are described.
Discussion
Hemoptysis is a common symptom of respiratory disease. However, choriocarcinoma with pulmonary metastasis is not a common cause of hemoptysis. The primary manifestation of the three patients was hemoptysis with cough, with or without dyspnea. Menstruation was significant in making the correct diagnosis. The patient in the first case was at her 36th week of pregnancy. The second had a history of hydatidiform mole, and the third patient had a history of abortion. In general, choriocarcinoma is secondary to a mole and to abortion, ectopic pregnancy, and preterm pregnancy or term pregnancy. The incidence of choriocarcinoma in China is high, approximately one case per 2882 pregnancies [
1]. In Europe and North America, approximately one case per 40,000 pregnancies is reported. In Southeast Asia and Japan, 9.2 cases per 40,000 pregnancies and 3.3 cases per 40,000 pregnancies are reported, respectively. The incidence of choriocarcinoma lung metastasis was 85.1% [
2].
The most common metastatic sites were the lungs (80%), vagina (30%), brain (10%), and liver (10%), whereas lymphatic system metastasis was rare [
3,
4]. The above-mentioned phenomenon is related to the biological characteristics of choriocarcinoma, which are uncontrolled trophoblast stem cells and abnormal hyperplasia. These characteristics cause the loss of the original villi structure, vascular damage owing to invasion capability, the continuous infiltration and dissolution of endometrial stromal cells, and myometrium invasion, which leads to early blood vessel invasion and hematogenous metastasis. Choriocarcinoma cancer embolus sheds in vein reflux to the right side of the heart and then into the pulmonary artery, which embolizes small pulmonary artery branches. Then, the choriocarcinoma cell proliferates and invades the blood vessel wall, destroys lung tissue, and causes pulmonary metastases when mixed with hematoma. Afterward, the choriocarcinoma cell invades through the small pulmonary vein, returns to the left side of the heart, and transfers through systemic artery to the brain, liver, and every organ of the body. The lung is often the first site of hematogenous metastasis, and other organs are rarely affected [
5]. In pathology, the center of lung metastatic lesions often shows clots and necrotic tissue surrounded by two layers of malignant trophoblasts. The inner layer is a mononuclear trophoblastic cell layer. Slight nuclear atypia and atypical mitotic figures may be observed, which are irrelevant to the prognosis. The outer layer is the multinucleated syncytiotrophoblast layer, which characteristically lacks chorionic villi and chorionic gonadal hormone promotion, and is positive for hCG staining. Compressed by transmitted lesions, the lung tissue around the lesion often collapse, and hemorrhage, edema, and inflammatory cell infiltration can be observed. Immunohistochemistry is helpful for the differential diagnosis. In syncytiotrophoblast, hCG is strongly positive, and human placental lactogen prime is weakly positive [
6]. Chorioepithelioma hCG, inhibin and human leukocyte antigen-G, and melanoma cell adhesion molecule (Mel-CAM) are often positive [
7]. The first patient tested positive for hCG. The other two patients did not undergo the test. The lung tissue pathology of the second patient showed necrotic tissue and the lung biopsy of the third patient was negative; immunohistochemical tests are not necessary for the clinical determination of choriocarcinoma. These immunohistochemical tests may play an important role in the differential diagnosis of the disease.
If a woman of childbearing age has a history of choriocarcinoma or irregular vaginal bleeding, postpartum or owing to abortion, which is accompanied by an elevated hCG level in her blood and urine, then choriocarcinoma may be the diagnosis. Combined with appearance of metastasis as shown in lung CT, the clinical diagnosis of choriocarcinoma with lung metastasis could be made. A definitive diagnosis requires a pathological examination of a uterine specimen or metastasis after resection. Choriocarcinoma cells secrete hCG, which can help in the diagnosis, therapeutic evaluation, and follow up of patients with choriocarcinoma. Tests for hCG have considerably high sensitivity and specificity.
The most common sites for metastasis are in the lungs. In the early stage of choriocarcinoma with lung metastasis, patients usually have no obvious clinical manifestations. Hemoptysis, chest distress, and chest pain may present in severe cases with multiple and larger metastases, and even hemothorax or severe respiratory failure can occur in the most serious cases. Currently, patients diagnosed with choriocarcinoma are advised to undergo a chest CT scan to check for lung metastasis, and this approach can often help in the early detection of lung metastasis, particularly in asymptomatic patients. For patients with hemoptysis as the initial symptom, if there are high risk factors, physicians should be aware of the possibility of a choriocarcinoma diagnosis.
The chest imaging manifestations of pulmonary metastatic choriocarcinoma vary. Metastatic lesions may be isolated or multiple. Several miliary lesions and solitary or multiple nodules or masses can be observed and expressed as flaky, patchy, or cotton-like lesions [
8‐
14]. These signs can occur alone or at the same time and can transform into each other in the development of the disease. A cavity lesion, which shows a thick wall cavity, is occasionally observed [
15]. Endobronchial metastasis is unusual. However, this type of metastasis is still reported [
16].
The treatment for choriocarcinoma is chemotherapy, combined with surgery, radiotherapy, and interventional therapy. The low-risk patients who have low resistance for methotrexate (MTX) or actinomycin D (ActD) can be treated with a single therapy, whereas the high-risk patients need a multidrug therapy. Most of the lung metastases can be treated after chemotherapy. Only a small number of patients with lung lesions resistant to chemotherapy or recurrence need surgical treatment.
Acknowledgements
The authors wish to thank Zhiquan Gong, PhD, for his contributions in drafting and revising the manuscript for important intellectual content. We gratefully acknowledge the patients in this report.