Primary pulmonary choriocarcinoma is an extremely rare tumor in men, with 13 cases reported in the literature. Due to its rarity, primary choriocarcinoma of the lung in men is often incorrectly diagnosed as more common diseases, such as primary or metastatic lung cancer, and therefore potentially curative chemotherapy or surgery may be withheld from the patient. In this report, we present the case of a 23-year-old man with hemoptysis and progressive dyspnea. Airspace consolidation with multiple nodules of varying sizes was found on a chest radiograph. The results of a urine pregnancy test were positive, and the [beta]-human chorionic gonadotropin level was markedly elevated both in the serum and the urine. Subsequently, testing of a bronchoscopic biopsy specimen proved these tumors to be choriocarcinoma. We conclude that the urine pregnancy test, a simple and convenient method, would be very useful in the rapid diagnosis of primary pulmonary choriocarcinoma in men.
Key words: human chorionic gonadotropin; primary pulmonary choriocarcinoma; urine pregnancy test
Abbreviation: HCG = human chorionic gonadotropin
Choriocarcinoma, a representative neoplasm producing human chorionic gonadotropin (HCG), is an extremely malignant tumor originating from anaplastic trophoblastic tissue. It is usually intrauterine and arises most commonly from molar pregnancy, but may also follow a term or ectopic pregnancy and spontaneous abortions. Extragonadal, nongestational choriocarcinoma is uncommon with a striking predominance in young men between 20 and 35 years of age. Most cases arise in midline structures, such as the retroperitoneum, the mediastinum, and the vicinity of the pineal body but also have been reported in other visceral organs such as the stomach, esophagus, small bowel, prostate, and urinary bladder. (1) To our knowledge, there have been only 22 cases of primary pulmonary choriocarcinoma reported in the literature. Of those cases, 13 developed in men. (2) Extragonadal choriocarcinoma arising in the lung is thought to be unresponsive to treatment and is associated with a poor prognosis. We report a young male patient with extragonadal, nongestational choriocarcinoma apparently arising in the lung. A positive urine pregnancy test result and an elevated serum [beta]-HCG level are compatible with the presence of this neoplasm, and the diagnosis was confirmed histologically by bronchoscopy examination.
A 23-year-old man was admitted to the hospital with a 3-week history of hemoptysis and progressive dyspnea. A chest radiograph on hospital admission revealed airspace consolidation in the periphery of the upper portion of both lungs with multiple nodules of variable sizes in both lung fields (Fig 1). A CT scan of the chest confirmed the presence of pulmonary nodules with ground-glass opacities in both lungs, which is consistent with the presence of pulmonary hemorrhage (Fig 2). On physical examination, no gynecomastia was noted. The abdomen was soft with no abnormal findings. A genital examination revealed no evidence of any scrotal masses. The remainder of the physical examination was unremarkable except for diffuse crackles in both lung fields. Under the impression of suspected germ cell tumors, a biological tumor marker study was performed. The result of a urine pregnancy test was positive, and the levels of [beta]-HCG were very high at 1,600,000 IU/L in the serum (normal, < 5 IU/L) and 3,464,000 IU/L in the urine. However, the serum [alpha]-fetoprotein level was within normal limits (ie, 3.8 ng/mL). A transbronchial lung biopsy in the right lower lobe showed intense hemorrhage and fibrinoid deposits in the alveoli with a dimorphic population of malignant cells with hyperchromatic nuclei and multinucleated syncytiotrophoblasts, which is consistent with choriocarcinoma (Fig 3), although a weak positive result of a [beta]-HCG immunohistochemical stain was found to be due to limited lesions (data not shown). Based on the findings, a diagnosis of choriocarcinoma was made. The patient was given chemotherapy, which consisted of actinomycin-D, methotrexate, and cyclophosphamide. Despite aggressive chemotherapy and management in the ICUs, the patient's condition deteriorated rapidly, and he died of acute respiratory failure 8 days after hospital admission. A request for an autopsy was denied.
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Choriocarcinoma is a germ cell tumor containing syncytiotrophoblastic giant cells and often secreting a biological tumor marker ([beta]-HCG). It usually occurs in women, mainly as a gestational trophoblastic neoplasm, and rarely occurs in men as a nonseminomatous testicular tumor. Extragonadal nongestational primary pulmonary choriocarcinoma is exceedingly rare. (1-3) In the case presented, pulmonary choriocarcinoma was diagnosed on the basis of the following findings: obvious lesions were found only in the lung; raised [beta]-HCG levels were found both in the serum and in the urine; and pathologic confirmation of the disease.
Because the lung is a frequent site of metastatic choriocarcinoma, the diagnosis of the primary tumor should be made carefully. In this case, although multiple nodules were found in both lungs, we considered the patient to have primary choriocarcinoma because there was no apparent evidence of a primary genital tumor, and no lesions were found in midline structures or in other visceral organs by CT scan, abdominal echography, and gastroendoscopy. Nevertheless, the possibility of a metastasis from invisible lesions in other locations could not be ruled out completely because the request for an autopsy was denied.
There are several possible theories explaining the development of primary pulmonary choriocarcinoma. Some authors (4) believe that the tumors arise from retained primordial germ cells that migrate abnormally during embryonic development. Others believe that the tumors represent metastasis from a primary gonadal (ie, testicular or ovarian) tumor that regressed spontaneously (1) or arose from a trophoblastic emboli related to molar pregnancy after long periods of latency. (5) In other reports, (6,7) the hypothesis of dedifferentiation or metaplasia to the trophoblast from a nongonadal tissue such as primary lung cancer is supported. This theory may help to resolve a semantic problem, namely, whether primary pulmonary choriocarcinoma is identical to HCG-producing giant cell carcinoma of the lung because the histopathologic similarity of choriocarcinoma with giant cell lung cancer has been reported. (2,3)
Among the patients with primary pulmonary choriocarcinoma whose cases have been reported in the literature, most demonstrated solitary pulmonary nodules in the lung field. (3,5-7) However, in our patient, multiple nodular lesions were found on a chest radiograph. The presenting radiologic features in our patient would support the assertion that the tumors may metastasize from a primary gonadal tumor undergoing spontaneous regression. However, as in the debate in the literature concerning the origin of the diffuse or multinodular form of bronchioloalveolar carcinoma of the lung, the tumors in our patient could be multicentric in origin or may merely represent a mode of extension within the lung of a tumor arising in the small foci of primordial germ cells.
In contrast to gestational choriocarcinoma, the natural course of primary pulmonary choriocarcinoma is rapidly fatal in the great majority of cases. Prompt recognition of this unique disease is crucial because rapid intervention may be life-saving. However, treatment modalities such as chemotherapy, radiation, or surgical resection in patients with widespread, far-advanced malignant tumors have usually proven to be ineffective in providing better long-term survival, (3,8,9) as has been shown in this case. There have been only three reported cases (2 (Table 3)) of survival for > 1 year in male patients with primary pulmonary choriocarcinoma. The reason that nongestational choriocarcinoma behaves so differently from gestational cancers is unknown.
A positive result of a [beta]-HCG test in patients with hemoptysis and progressive dyspnea should arouse suspicions of the presence of pulmonary choriocarcinoma, thus leading to an early diagnosis. In most of the reported cases, however, the patients had sought medical attention too late. In addition, because the radiologic findings of pulmonary hemorrhage may obscure the nodular lesions of choriocarcinoma, and because the [beta]-HCG test and the histologic processing of tissue specimens may take several days, the diagnosis may be delayed, particularly, in male patients. In the presented case, the patient was thought initially to have an infectious disease, germ cell tumors, or metastatic lung cancer, based on the findings of clinical entities, a chest radiograph, and CT scan. A positive urine pregnancy test result, which only takes a couple of minutes, rapidly gave us a very clear direction in the differential diagnosis of the lung lesions.
In conclusion, the diagnosis of primary pulmonary choriocarcinoma must be considered in young male patients with hemoptysis, progressive dyspnea, and radiologic findings of airspace consolidation with solitary/multiple pulmonary nodules. The serum [beta]-HCG level should be examined as early as possible. Before this is done, the performance of a urine pregnancy test, a simple and convenient method, would be very useful in the rapid diagnosis of primary pulmonary choriocarcinoma.
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* From the Departments of Internal Medicine (Drs. Tsai, Chong, and Hung) and Pathology (Dr. Tsai), Kaohsiung Medical University Kaohsiung, Taiwan.
Manuscript received March 15, 2001; revision accepted August 20, 2001.
Correspondence to: Inn-Wen Chong, MD, FCCP, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; e-mail: firstname.lastname@example.org
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