PULMONARY DISEASE IN GESTATIONAL TROPHOBLASTIC NEOPLASMS Obie M. McNair, Jr, MD, and Octavius D. Polk, Jr, MD Washington, DC
Gestational trophoblastic neoplasms can present as pulmonary nodules without significant disease of the reproductive organs. This article describes a case of metastatic gestational trophoblastic disease to the lungs. This entity must be considered in the differential diagnosis in any female of reproductive age who presents with multiple pulmonary nodules. Thoracotomy has a limited role in the initial evaluation of patients with this disease. However, it may be needed in patients who have evidence of persistent pulmonary disease, despite appropriate therapy. (J Nati Med Assoc. 1992;84:71 3-716.) Key words * gestational trophoblastic neoplasms * pulmonary disease * pulmonary metastasis
Gestational trophoblastic neoplasms are uncommon gynecologic neoplasms that frequently metastasize to the lungs. The manifestations of pulmonary metastasis are varied and can even mimic an inflammatory process. 1 Metastatic disease also can involve the pleura.2 The radiographic picture can be quite confusing in patients who do not have gynecologic symptoms. This article describes a case of gestational trophoblastic neoplasm with pulmonary metastasis. Radiographic changes, including computerized tomographic (CT) scans of the chest, are reviewed. From the Department of Medicine, Division of Pulmonary/ Critical Care Medicine, Howard University Hospital, Washington, DC. Requests for reprints should be addressed to Octavius D. Polk, Jr, MD, Dept of Medicine, Division of Pulmonary/Critical Care Medicine, Howard University Hospital, 2041 Georgia Ave, NW, Washington, DC 20060. JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 84, NO. 8
CASE REPORT A 20-year-old woman from El Salvador was admitted after experiencing nausea, intermittent vaginal bleeding, palpitations, and dyspnea on exertion for 2 weeks. Her last normal menstrual period was 2 months prior to admission. Review of symptoms revealed a weight loss of 15 lb over the last 2 months. The patient had no history of fever, chills, night sweats, hemoptysis, tuberculosis, or tuberculosis exposure. The physical examination revealed a blood pressure of 148/80 mm Hg, a pulse of 120 beats/minute, and respiratory rate of 20/minute. The lungs were clear on auscultation. The cardiovascular examination revealed no murmurs, gallops, or rubs. There was no palpable lymphadenopathy. Breasts were without masses or discharge. Bilateral deep tendon reflexes were 3 +. The remainder of the neurologic examination was normal. Pelvic examination revealed an enlarged uterus with a small amount of blood in the vaginal vault. The cervix was nontender, and the ovaries were not palpable. Laboratory values were as follows: hematocrit, 27%; leukocyte count, 4800/mm3; platelet count, 96 000/mm3; and serum throxine, 37.5 ,ug/dL. A 80 000 ,uU/mL. Arterial blood gases revealed a normal pH of 7.44, decreased PaO2 of 61 mm Hg, and normal PaCO2 of 35 mm Hg on room air. Spirometry was normal. A CT scan of the chest showed multiple rounded nodular densities, approximately 1 cm in diameter, in both lungs (Figure 2). A liver/spleen scan, abdominal CT scan, and brain CT scan were negative for metastatic disease. The patient was then treated with sequential methotrexate chemotherapy with resultant resolution of the lung lesions radiographically (Figure 3).
DIAGNOSIS Metastatic Gestational Trophoblastic Disease This case is an example of gestational trophoblastic neoplasms with pulmonary metastasis. Although this patient presented with gynecologic symptoms, it is not uncommon for patients to present without evidence of disease of the reproductive organs in the presence of metastatic disease.' Pathologists have used the term gestational trophoblastic neoplasms to include three distinct morphologic entities that are readily distinguished histopathologically: hydatidiform mole, chorioadenoma destrusens (invasive mole), and choriocarcinoma. I The distin714
guishing feature of these entities is the degree of retention of recognizable villous structures or simply the degree of differentiation of the neoplastic chorionic tissue.' All of these entities have the potential to metastasize. The reported incidence of molar pregnancy varies significantly in different regions of the world. The incidence of hydatidiform mole is 7 to 10 times higher in Asian countries than in Europe and North America.1 The frequency of molar gestations in the United States is about one per 1500 births and one per 2000 pregnancies.1 The presenting signs and symptoms were reviewed in 306 patients with molar pregnancy who presented to the New England Trophoblastic Disease Center. Vaginal bleeding, anemia, and excessive uterine enlargement were frequently seen. Hyperthyroidism occurred in 7% of the patients and was present in the case described here. Hyperemesis gravidarum occurred in 26% of the cases. ' Chest pain, cough, tachypnea, tachycardia, bilateral rales, and cyanosis were seen in 2% of the patients who presented with trophoblastic embolization.1 Marked elevation of B-HCG has long been regarded as a sign of trophoblastic growth and usually exceeds the levels observed during a normal single pregnancy.' Our patient clearly had a significantly elevated level consistent with a molar pregnancy. JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 84, NO. 8
PULMONARY DISEASE & GESTATIONAL TROPHOBLASTIC NEOPLASMS
Figure 2. CT scan revealing bilateral rounded, well-circumscribed nodules.
The lung is the most frequent site of metastatic disease. Eighty percent of patients at the New England Trophoblastic Disease Center had lung lesions at the time of diagnosis.' The patients may have had hemoptysis, cough, chest pain, dyspnea, or may even have been asymptomatic.1 Our patient had dyspnea on exertion and resting hypoxemia. The cause of the hypoxemia may have been the result of extensive arteriovenous shunts, which develop from massive metastatic pulmonary deposits of trophoblastic tissue and have been reported in several patients.2 There are four basic types of pulmonary metastasis in gestational trophoblastic neoplasms: discrete, rounded nodular densities; alveolar or "snowstorm" pattern; embolic pattern, which produces changes resulting from embolic occlusion of pulmonary arteries without evidence of masses in the lungs; and pleural effusions, which are often serasanguinous.' The discrete, rounded nodules are the most common radiographic presentation; this was the pattern seen in our patient. Bagshawe and Garnett3 reported discrete, rounded nodular densities in 16 of 23 patients (70%), and Libshitz and associates4 found this pattern in 33 of 35 patients (94%). The nodules are often bilateral and are usually 1 cm to 3 cm in diameter. A solitary pulmonary lesion may be seen in rare cases and may even suggest a primary tumor. Large lesions may cavitate, and the radiographic pattern may mimic a pyogenic or tuberculous abscess.' The alveolar pattern occurs less often in patients with pulmonary metastasis. It was seen in 4 of 23 patients (6%) by Libshitz.4 Alveolar metastases have the appearance of multiple, small, ill-defined opacities. These tumors are very vascular, and hemorrhage around small metastatic nodules may be responsible for this appearance. This pattern may simulate an inflammatory process. ' JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 84, NO. 8
Figure 3. Chest roentgenogram taken after 2 months of treatment with chemotherapy, showing almost complete resolution of lesions.
Trophoblastic emboli may occasionally produce radiographic findings of focal oligemia, right ventricular enlargement, and prominence of the pulmonary arteries. Focal infiltrates and "Hampton's hump" may be seen if pulmonary infarction occurs. Patients can even develop pulmonary hypertension with repeated episodes of emboli.5 Pleural effusion or hemothorax can be seen in patients with metastatic disease involving the pleura.6 Evans and associates7 noted pleural effusions in 11 of 45 patients with metastatic disease involving the lung. These effusions can become loculated because they are often hemorrhagic. ' In October 1979, at a meeting of the International Society for the Study of Trophoblastic Neoplasms, a revised anatomic staging system was adopted.' The stages are: * Stage 0-molar pregnancy (both low risk and high risk), * Stage I-disease confined to uterine corpus, * Stage II-metastasis to pelvis and/or vagina, * Stage III-metastasis to lung, and * Stage IV-distant metastasis (liver, brain, etc). Stage 0 represents either low-risk or high-risk molar pregnancy. Low or high risk was based on the potential for proliferative trophoblastic sequelae in patients treated with evacuation alone. The criteria for a high-risk molar pregnancy is: 1) uterus size greater than appropriate for dates, 2) B-HCG > 100 000 IU/mL, 3) theca lutein cysts >6 cm in diameter, and 4) associated medical factors such as the presence of toxemia, previous trophoblastic tumor, maternal age of ¢40 715
PULMONARY DISEASE & GESTATIONAL TROPHOBLASTIC NEOPLASMS
years, coagulopathy, hyperthyroidism, and trophoblastic embolization. Stage I is defined as disease confined to the uterus corpus, Stage II disease has metastasized to the pelvis and/or vagina, and Stage III disease includes all patients with pulmonary metastasis with or without uterine, pelvic, or vaginal lesions. Precise morphologic diagnosis is not easily obtained in the Stage III group without open thoracotomy. However, thoracotomy is not advocated in these patients merely to provide information regarding the histologic pattern because the majority (92%) of patients with Stage III disease can achieve complete remission with chemotherapy, regardless of the histopathology. If death does occur, the most frequent causes are respiratory failure, cerebral hemorrhage, hepatic hemorrhage, sepsis, or gastrointestinal bleeding.' Patients with Stage IV disease have distant metastasis (liver, brain, kidneys, spleen, or gastrointestinal tract). All patients with Stage IV disease have choriocarcinoma. These patients are likely to be resistant to chemotherapy and are therefore considered in the highest risk category.' The primary treatment for Stage III disease consists of chemotherapy. Pulmonary lesions usually diminish in size concentrically after chemotherapy and eventually disappear without residual scar tissue.1 Large pulmonary lesions occasionally can undergo cavitation as the result of tumor necrosis.1 It has been noted that during chemotherapy, some lesions may transiently enlarge, radiographically, as the result of swelling and hemorrhage of the metastatic foci. Pulmonary lesions may even persist after complete remission. Tow8 reported three patients with persistent pulmonary nodules after chemotherapy who underwent thoracotomy. Pathologic examination of the excised specimens revealed extensive pulmonary fibrosis with no evidence of trophoblastic tissue. These findings clearly demonstrate that the measurement of B-HCG remains the primary criterion for remission, not the disappearance of radiographic or clinical signs.' One must keep in mind that radiographic changes may develop as a result of therapy with methotrexate. Everts et a19 described pulmonary findings in patients receiving methotrexate as being predominantly interstitial at the onset. Later, the lesions develop an alveolar appearance with areas of confluence and air bronchograms. The role of thoracotomy in the management of Stage III disease, as mentioned previously, is limited. How-
716
ever, a thoracotomy may be needed to excise a persistent viable pulmonary metastasis despite intensive chemotherapy.'0 Thoracotomy also may be necessary in a patient who has repeated hemorrhages in the pleural space from pleural metastases.11 Prior to surgical intervention, it is essential that other sites of persistent disease be excluded by performing an extensive metastatic work-up.'
CONCLUSION Gestational trophoblastic neoplasms can present as pulmonary nodules without significant disease of the reproductive organs. It must, therefore, be considered in the differential diagnosis in any female of reproductive age who presents with multiple pulmonary nodules. It is clear that thoracotomy has a limited role in the initial evaluation of patients with this disease. However, it may be needed in patients who have evidence of persistent pulmonary disease despite appropriate therapy. Literature Cited 1. Goldstein DP, Berkowitz RS. Gestational trophoblastic neoplasms. In: Clinical Principles of Diagnosis and Management. Philadelphia, Pa: WB Saunders Co; 1982. 2. Deligdisch L, Waxman J. Metastatic gestational trophoblastic neoplasm. A study of two cases in unusual clinical settings and review of the literature. Gynecol Oncol. 1 984; 19:323-328. 3. Bagshawe KD, Garnett ES. Radiological changes in the lungs of patients with trophoblastic tumors. Br J Radiol. 1 963;36:673-679. 4. Libshitz H, Baber C, Hammond C. The pulmonary metastases of choriocarcinoma. Obstet Gynecol. 1977;49:412416. 5. Bagshaw KD, Noble Ml. Cardiorespiratory aspects of trophoblastic tumors. Q J Med. 1966;35:39-54. 6. Hammon CB, Lewis JL. Gestational trophoblastic neoplasms. In: Sciarra JJ, ed. Gynecology and Obstetrics. Vol 4: Gynecologic Oncology. Philadelphia, Pa: Harper & Row Inc; 1983. 7. Evans KT, Cockshott WD, Hendrickse JR Pulmonary changes in malignant trophoblastic disease. Br J Radiol. 1965;38:161 -1 71. 8. Tow SH. The pulmonary lesion in choriocarcinoma. Proc R Soc Med. 1967;60:239-240. 9. Everts CS, Westcott JL, Bragg D. Methotrexate therapy and pulmonary disease. Radiology. 1973;1 07:539-543. 10. Shirley RL, Goldstein DP, Collins JJ Jr. The role of thoracotomy in the management of patients with chest metastasis from gestational trophoblastic disease. J Thorac Cardiovasc Surg. 1972;63:545-550. 11. Defrance JH, Blewett JH Jr, Ricci JA, Patterson LT. Massive hemothorax: two unusual cases. Chest. 1974;66:8284.
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 84, NO. 8
Gestational trophoblastic neoplasms can present as pulmonary nodules without significant disease of the reproductive organs. This article describes a case of metastatic gestational trophoblastic disease to the lungs. This entity must be considered in the differential diagnosis in any female of reproductive age who presents with multiple pulmonary nodules. Thoracotomy has a limited role in the initial evaluation of patients with this disease. However, it may be needed in patients who have evidence of persistent pulmonary disease, despite appropriate therapy. (J Nati Med Assoc. 1992;84:71 3-716.) Key words * gestational trophoblastic neoplasms * pulmonary disease * pulmonary metastasis
Gestational trophoblastic neoplasms are uncommon gynecologic neoplasms that frequently metastasize to the lungs. The manifestations of pulmonary metastasis are varied and can even mimic an inflammatory process. 1 Metastatic disease also can involve the pleura.2 The radiographic picture can be quite confusing in patients who do not have gynecologic symptoms. This article describes a case of gestational trophoblastic neoplasm with pulmonary metastasis. Radiographic changes, including computerized tomographic (CT) scans of the chest, are reviewed. From the Department of Medicine, Division of Pulmonary/ Critical Care Medicine, Howard University Hospital, Washington, DC. Requests for reprints should be addressed to Octavius D. Polk, Jr, MD, Dept of Medicine, Division of Pulmonary/Critical Care Medicine, Howard University Hospital, 2041 Georgia Ave, NW, Washington, DC 20060. JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 84, NO. 8
CASE REPORT A 20-year-old woman from El Salvador was admitted after experiencing nausea, intermittent vaginal bleeding, palpitations, and dyspnea on exertion for 2 weeks. Her last normal menstrual period was 2 months prior to admission. Review of symptoms revealed a weight loss of 15 lb over the last 2 months. The patient had no history of fever, chills, night sweats, hemoptysis, tuberculosis, or tuberculosis exposure. The physical examination revealed a blood pressure of 148/80 mm Hg, a pulse of 120 beats/minute, and respiratory rate of 20/minute. The lungs were clear on auscultation. The cardiovascular examination revealed no murmurs, gallops, or rubs. There was no palpable lymphadenopathy. Breasts were without masses or discharge. Bilateral deep tendon reflexes were 3 +. The remainder of the neurologic examination was normal. Pelvic examination revealed an enlarged uterus with a small amount of blood in the vaginal vault. The cervix was nontender, and the ovaries were not palpable. Laboratory values were as follows: hematocrit, 27%; leukocyte count, 4800/mm3; platelet count, 96 000/mm3; and serum throxine, 37.5 ,ug/dL. A 80 000 ,uU/mL. Arterial blood gases revealed a normal pH of 7.44, decreased PaO2 of 61 mm Hg, and normal PaCO2 of 35 mm Hg on room air. Spirometry was normal. A CT scan of the chest showed multiple rounded nodular densities, approximately 1 cm in diameter, in both lungs (Figure 2). A liver/spleen scan, abdominal CT scan, and brain CT scan were negative for metastatic disease. The patient was then treated with sequential methotrexate chemotherapy with resultant resolution of the lung lesions radiographically (Figure 3).
DIAGNOSIS Metastatic Gestational Trophoblastic Disease This case is an example of gestational trophoblastic neoplasms with pulmonary metastasis. Although this patient presented with gynecologic symptoms, it is not uncommon for patients to present without evidence of disease of the reproductive organs in the presence of metastatic disease.' Pathologists have used the term gestational trophoblastic neoplasms to include three distinct morphologic entities that are readily distinguished histopathologically: hydatidiform mole, chorioadenoma destrusens (invasive mole), and choriocarcinoma. I The distin714
guishing feature of these entities is the degree of retention of recognizable villous structures or simply the degree of differentiation of the neoplastic chorionic tissue.' All of these entities have the potential to metastasize. The reported incidence of molar pregnancy varies significantly in different regions of the world. The incidence of hydatidiform mole is 7 to 10 times higher in Asian countries than in Europe and North America.1 The frequency of molar gestations in the United States is about one per 1500 births and one per 2000 pregnancies.1 The presenting signs and symptoms were reviewed in 306 patients with molar pregnancy who presented to the New England Trophoblastic Disease Center. Vaginal bleeding, anemia, and excessive uterine enlargement were frequently seen. Hyperthyroidism occurred in 7% of the patients and was present in the case described here. Hyperemesis gravidarum occurred in 26% of the cases. ' Chest pain, cough, tachypnea, tachycardia, bilateral rales, and cyanosis were seen in 2% of the patients who presented with trophoblastic embolization.1 Marked elevation of B-HCG has long been regarded as a sign of trophoblastic growth and usually exceeds the levels observed during a normal single pregnancy.' Our patient clearly had a significantly elevated level consistent with a molar pregnancy. JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 84, NO. 8
PULMONARY DISEASE & GESTATIONAL TROPHOBLASTIC NEOPLASMS
Figure 2. CT scan revealing bilateral rounded, well-circumscribed nodules.
The lung is the most frequent site of metastatic disease. Eighty percent of patients at the New England Trophoblastic Disease Center had lung lesions at the time of diagnosis.' The patients may have had hemoptysis, cough, chest pain, dyspnea, or may even have been asymptomatic.1 Our patient had dyspnea on exertion and resting hypoxemia. The cause of the hypoxemia may have been the result of extensive arteriovenous shunts, which develop from massive metastatic pulmonary deposits of trophoblastic tissue and have been reported in several patients.2 There are four basic types of pulmonary metastasis in gestational trophoblastic neoplasms: discrete, rounded nodular densities; alveolar or "snowstorm" pattern; embolic pattern, which produces changes resulting from embolic occlusion of pulmonary arteries without evidence of masses in the lungs; and pleural effusions, which are often serasanguinous.' The discrete, rounded nodules are the most common radiographic presentation; this was the pattern seen in our patient. Bagshawe and Garnett3 reported discrete, rounded nodular densities in 16 of 23 patients (70%), and Libshitz and associates4 found this pattern in 33 of 35 patients (94%). The nodules are often bilateral and are usually 1 cm to 3 cm in diameter. A solitary pulmonary lesion may be seen in rare cases and may even suggest a primary tumor. Large lesions may cavitate, and the radiographic pattern may mimic a pyogenic or tuberculous abscess.' The alveolar pattern occurs less often in patients with pulmonary metastasis. It was seen in 4 of 23 patients (6%) by Libshitz.4 Alveolar metastases have the appearance of multiple, small, ill-defined opacities. These tumors are very vascular, and hemorrhage around small metastatic nodules may be responsible for this appearance. This pattern may simulate an inflammatory process. ' JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 84, NO. 8
Figure 3. Chest roentgenogram taken after 2 months of treatment with chemotherapy, showing almost complete resolution of lesions.
Trophoblastic emboli may occasionally produce radiographic findings of focal oligemia, right ventricular enlargement, and prominence of the pulmonary arteries. Focal infiltrates and "Hampton's hump" may be seen if pulmonary infarction occurs. Patients can even develop pulmonary hypertension with repeated episodes of emboli.5 Pleural effusion or hemothorax can be seen in patients with metastatic disease involving the pleura.6 Evans and associates7 noted pleural effusions in 11 of 45 patients with metastatic disease involving the lung. These effusions can become loculated because they are often hemorrhagic. ' In October 1979, at a meeting of the International Society for the Study of Trophoblastic Neoplasms, a revised anatomic staging system was adopted.' The stages are: * Stage 0-molar pregnancy (both low risk and high risk), * Stage I-disease confined to uterine corpus, * Stage II-metastasis to pelvis and/or vagina, * Stage III-metastasis to lung, and * Stage IV-distant metastasis (liver, brain, etc). Stage 0 represents either low-risk or high-risk molar pregnancy. Low or high risk was based on the potential for proliferative trophoblastic sequelae in patients treated with evacuation alone. The criteria for a high-risk molar pregnancy is: 1) uterus size greater than appropriate for dates, 2) B-HCG > 100 000 IU/mL, 3) theca lutein cysts >6 cm in diameter, and 4) associated medical factors such as the presence of toxemia, previous trophoblastic tumor, maternal age of ¢40 715
PULMONARY DISEASE & GESTATIONAL TROPHOBLASTIC NEOPLASMS
years, coagulopathy, hyperthyroidism, and trophoblastic embolization. Stage I is defined as disease confined to the uterus corpus, Stage II disease has metastasized to the pelvis and/or vagina, and Stage III disease includes all patients with pulmonary metastasis with or without uterine, pelvic, or vaginal lesions. Precise morphologic diagnosis is not easily obtained in the Stage III group without open thoracotomy. However, thoracotomy is not advocated in these patients merely to provide information regarding the histologic pattern because the majority (92%) of patients with Stage III disease can achieve complete remission with chemotherapy, regardless of the histopathology. If death does occur, the most frequent causes are respiratory failure, cerebral hemorrhage, hepatic hemorrhage, sepsis, or gastrointestinal bleeding.' Patients with Stage IV disease have distant metastasis (liver, brain, kidneys, spleen, or gastrointestinal tract). All patients with Stage IV disease have choriocarcinoma. These patients are likely to be resistant to chemotherapy and are therefore considered in the highest risk category.' The primary treatment for Stage III disease consists of chemotherapy. Pulmonary lesions usually diminish in size concentrically after chemotherapy and eventually disappear without residual scar tissue.1 Large pulmonary lesions occasionally can undergo cavitation as the result of tumor necrosis.1 It has been noted that during chemotherapy, some lesions may transiently enlarge, radiographically, as the result of swelling and hemorrhage of the metastatic foci. Pulmonary lesions may even persist after complete remission. Tow8 reported three patients with persistent pulmonary nodules after chemotherapy who underwent thoracotomy. Pathologic examination of the excised specimens revealed extensive pulmonary fibrosis with no evidence of trophoblastic tissue. These findings clearly demonstrate that the measurement of B-HCG remains the primary criterion for remission, not the disappearance of radiographic or clinical signs.' One must keep in mind that radiographic changes may develop as a result of therapy with methotrexate. Everts et a19 described pulmonary findings in patients receiving methotrexate as being predominantly interstitial at the onset. Later, the lesions develop an alveolar appearance with areas of confluence and air bronchograms. The role of thoracotomy in the management of Stage III disease, as mentioned previously, is limited. How-
716
ever, a thoracotomy may be needed to excise a persistent viable pulmonary metastasis despite intensive chemotherapy.'0 Thoracotomy also may be necessary in a patient who has repeated hemorrhages in the pleural space from pleural metastases.11 Prior to surgical intervention, it is essential that other sites of persistent disease be excluded by performing an extensive metastatic work-up.'
CONCLUSION Gestational trophoblastic neoplasms can present as pulmonary nodules without significant disease of the reproductive organs. It must, therefore, be considered in the differential diagnosis in any female of reproductive age who presents with multiple pulmonary nodules. It is clear that thoracotomy has a limited role in the initial evaluation of patients with this disease. However, it may be needed in patients who have evidence of persistent pulmonary disease despite appropriate therapy. Literature Cited 1. Goldstein DP, Berkowitz RS. Gestational trophoblastic neoplasms. In: Clinical Principles of Diagnosis and Management. Philadelphia, Pa: WB Saunders Co; 1982. 2. Deligdisch L, Waxman J. Metastatic gestational trophoblastic neoplasm. A study of two cases in unusual clinical settings and review of the literature. Gynecol Oncol. 1 984; 19:323-328. 3. Bagshawe KD, Garnett ES. Radiological changes in the lungs of patients with trophoblastic tumors. Br J Radiol. 1 963;36:673-679. 4. Libshitz H, Baber C, Hammond C. The pulmonary metastases of choriocarcinoma. Obstet Gynecol. 1977;49:412416. 5. Bagshaw KD, Noble Ml. Cardiorespiratory aspects of trophoblastic tumors. Q J Med. 1966;35:39-54. 6. Hammon CB, Lewis JL. Gestational trophoblastic neoplasms. In: Sciarra JJ, ed. Gynecology and Obstetrics. Vol 4: Gynecologic Oncology. Philadelphia, Pa: Harper & Row Inc; 1983. 7. Evans KT, Cockshott WD, Hendrickse JR Pulmonary changes in malignant trophoblastic disease. Br J Radiol. 1965;38:161 -1 71. 8. Tow SH. The pulmonary lesion in choriocarcinoma. Proc R Soc Med. 1967;60:239-240. 9. Everts CS, Westcott JL, Bragg D. Methotrexate therapy and pulmonary disease. Radiology. 1973;1 07:539-543. 10. Shirley RL, Goldstein DP, Collins JJ Jr. The role of thoracotomy in the management of patients with chest metastasis from gestational trophoblastic disease. J Thorac Cardiovasc Surg. 1972;63:545-550. 11. Defrance JH, Blewett JH Jr, Ricci JA, Patterson LT. Massive hemothorax: two unusual cases. Chest. 1974;66:8284.
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 84, NO. 8
