4 King SM, Vogel JHK, Blount GS: Idiopathic muscular subvalvular aortic stenosis with associated congenital cardiovascular lesions. Am J Cardiol 15:837-847, 1965 5 Brock RC: Functional obstruction of the left ventricle. Guys Hosp Rep 106:221-238, 1957 6 Braunwald E, Lambrew CP, Rockoff SB, et al: Idiopathic hypertrophic subaortic stenosis. Description of the disease ba~ed upon an analysis of 64 patients. Circulation 29:IV 3213, 1964 7 Emanuel R: The familial incidence of idiopathic cardiomyopathy. In Hypertrophic Obstructive Cardiomyopathy. Ciha Foundation Study Group (Wolstenholme GEW, O'Connor M, eds) London, Churchill, pp 62, 1971 8 Cockayne EA: The genetics of transposition of the viscera. QJ Med 7:479-493, 1938 !} Torgersen J: Genetic factors in visceral asymmetry and in the development and pathologic changes of lungs, heart and abdominal organs. Arch Pathol47 :566-593, 1949
Primary Mediastinal Choriocarcinoma .1nMa an * Barry A. Cohen, M.D. and Mark A. Needle, M.D.
Choriocarcinoma with a primary site in the chest is rarely found. Characteristically, it is seen in young men presenting with cough, gynecomastia and chest pain. The disease is invariably fatal. The presently accepted therapy (triple therapy), consisting of methotrexate, actinomycin D and chlorambucil, has been unsuccessful to date.
0
nly 22 cases of primary mediastinal choriocarcinoma in a man have been reported. 1 • 6 Fine et al 2 reviewed 109 extragonadal choriocarcinomas including 19 which were primary mediastinal choriocarcinomas. Eight ( 42 percent) were pure choriocarcinoma, six ( 31 percent) were mixed with teratomatous elements and two were with embryonal carcinoma. We report the 23rd case of pure choriocarcinoma and review the literature and current therapy. CASE REPORT
A 25-year-old welder wa~ admitted to St. Joseph's Hospital and Medical Center on Febmary 15, 1973 with the complaints of hemoptysis, cough and expectoration for 15 days. He had a temperature between 37-38•C for five days. He had lost eight pounds over the past month. The history was negative with the exception of an herniorrhaphy-performed in 1968. His mother died of pulmonary tuberculosis several years ago. He stopped smoking five years prior to admission, denied alcohol or dmg use and allergies. On physical examination, he was a well-developed, wellnourished white man. Vital signs: pulse rate 90; blood pressure 124/76 mm Hg, respiration 18, temperature 38.2•C. There were nontender, mobile, firm posterior cervical and right axillary lymph nodes. The lungs were clear, the heart
° From the Department of Obstetrics and Gynecology and Department of Medicine, St. Joseph's Hospital and Medical Center, Paterson, New Jersey.
106 COHEN, NEEDLE
FIGURE 1. Widening of mediastinum on left side, increase in nodules scattered throughout both lung fields, bilateral basal infiltrates, and small pleural effusion. was clinically normal, the abdomen was soft and no tumor mass or organs were palpated. The genitalia appeared normal on repeated examinations. Laboratory Data: CBC, urinalysis, sput\un culture and smear, and smear and culture for acid-fast bacilli were negative. SMA-12 showed an LDH of 280 and an SGOT of 55. Chest x-ray films showed an anterior mediastinal mass and multiple soft nodules throughout both lung fields. An intravenous pyelogram revealed a double collecting system on the left. A chest x-ray film showed (Fig 1) widening of the mediastinum mainly on the left side with an increase in nodules scattered throughout both lung fields, bilateral basal infiltrates, and a small pleural effusion. The human chorionic gonadotropin titer was 106,496 IUI ml on the 9th hospital day. This rose to 761,856 IU/ml on the 13th hospital day. Normally none is found in the urine. Hospital Cot~rse: The patient ran an intermittent fever ( 3739•C). Shortly after admission he experienced hemoptysis. Lung biopsy was performed on the 7th hospital day revealing choriocarcinoma. His condition deteriorated and on the 42nd hospital day, while on methotrexate, chlorambucil and actinomycin D, he suddenly became dyspneic, anxious, cyanotic and diaphoretic. His condition continued to deteriorate and he expired on the 44th hospital day. Pathology report on biopsy: The pleural surface was irregularly nodular on gross examination. Sections revealed tumor nodules formed by masses of clear cells with vesicular nuclei surrounded by rims of syncytial dark cells presenting irregularly sized nuclei. The lung tissues showed, in addition, evidence of hemorrhage and numerous desquamated cells with foamy cytoplasm within the alveoli. Therapy: On the 8th hospital day, the patient began a course of methotrexate, 50 mg IV q8h x 6 doses; cyclophosphamide, 300 mg IV x 1; vincristine, 0.5 mg IV x 1; leucovorin, 15 mg IM q6h x 16; and actinomycin D, 0.5 mg IV od x 5. Since the HCG titers rose after treatment, another course of chemotherapy including methotrexate, 20 mg IM od x 5; chlorambucil, 2 mg PO od x 5; and actinomycin D, 0.5 mg IV od x 5 were given. The HCG titers remained positive and the patient's condition continued to deteriorate. Methotrexate, chlorambucil and actinomycin D were repeated on the 32nd hospital day and the patient expired on the 44th hospital day.
CHEST, 67: 1, JANUARY, 1975
DISCUSSION
Primary mediastinal choriocarcinoma is characteristically seen in young caucasian men presenting with the symptom triad of cough, gynecomastia and chest pain. a Gynecomastia is present in two-thirds, while cough and chest pain appear to be uniform. Half of the patients are in the third decade and 29 percent over 30 years of age. 1 • 3 Hemoptysis, dyspnea, hoarseness, stridor, Homer's syndrome, dysphagia, malaise, weight loss, anorexia and fever have been described. 1 -a·7 ·" Primary mediastinal choriocarcinoma presents in the anterior mediastinum roentgenographically as a noncavitating well-defined mass 1 with extremely rapid growth. Differential diagnosis includes in order of frequency: teratomas, thymomas, lymphomas and other less common lesions. 1 Grossly the tumor is a rounded, lobulated mass with, at times, a thin capsule. It adheres to the neighboring structures and may compress the superior vena cav3:. The cut surface has a variegated appearance, with or without grey-white solid areas and cystic spaces with hemorrhagic necrosis. Microscopically, syncytial trophoblasts predominate. On occasion, there are clumps of cytotrophoblasts. Much of the surface is necrotic with wide vascular involvement. 9 The diagnosis of primary mediastinal choriocarcinoma requires a meticulous search for testicular involvement. Testicular involvement means scars, cysts or benign tumors found in sections from serially sectioned testes. 2 Multiple sections of the testes at postmortem were free of tumor in this case. The presumptive diagnosis of choriocarcinoma can be made by the association of gynecomastia, cough, chest pain and a demonstrable titer of urinary chorionic gonadotropin with a positive pregnancy test. In the series of Fine et al, 2 a positive pregnancy test was found in 90 percent of the cases. Gynecomastia is related to the production of chorionic gonadotropin. Circulating gonadotropin stimulates the Leydig cells to produce testosterone and estrogen. This estrogen production may be the determining factor in the mammary gland hypertrophy so often seen. a Leydig cell hyperplasia was found in 30 to 40 cases of extragonadal choriocarcinoma in Fine's series. 1 Pathogenesis: Marchand 10 in 1895, was first to propose that chorioepitheliomas in a female originated in the chorionic villi. Sometime in 1902, Schlagenhanfer11 described the development of chorioepithelioma in the germ cells of testes or of other teratomatous tissues. Many theories have been advanced to explain the growth of such tumors in extragenital sites such as mediastinum, peritoneal organs and retroperitoneum. 12- 15 It is apparent from such studies that abnormal inclusions of germ cells can occur anywhere along the urogenital ridge extending from C6 to L3. 16 In accordance with this, Frank, 17 in 1932, stressed that the mediastinum may very well be the primary site of an extragenital teratomatous lesion. Ewing1 " supported this view, stating that the sex cells may occur anywhere along the entire length of the embryonal endoderm and, therefore,
CHEST, 67: 1, JANUARY, 1975
quite reasonably may be found in the mediastinum.~ Fine and co-workers 2 suggested that anterior mediastinal choriocarcinoma may be secondary to a primary testicular choriocarcinoma; however, testicular tumors rarely metastasize to the anterior mediastinum. Metastases in 19 cases reported by Fine et al were to the lungs (17), liver (18), kidney (10), lymph nodes (8) and brain ( 5). The origin of choriocarcinoma is unknown, but Yurick and Ottoman 1 have handed down their own theory as well as presenting those of others. These are: (a) the included twin theory, (b) the somatic cell rest theory, (c) the primitive germ cell theory, and (d) the included zygote theory. The primitive germ cell theory has received the greatest following 1 • 2 • 7 ·"·19 Primitive germ cells may arise in the covering mesothelium of the primitive gonad or may arise from the yolk sac endoderm, normally migrating along the urogenital ridge coming to rest in the gonad. In cases of primary mediastinal choriocarcinoma, arrest of the germ cell somewhere along the path may have occurred. 9 These cells may remain dormant until puberty or later sex life when some stimulus might cause them to mature and develop into a tumor mass. 1 •19 The suggestion that mediastinal teratomas and choriocarcinomas arise from aberrant germ cells in the thymus anlage has been proposed by Friedman.~" Therapy: No successful protocol has been proposed for this disease. 1 •a, 19 Surgery is of little value due to the rapid growth and invasive nature of the tumor. 3 Deep radiation therapy in the form of cobalt has been disappointing as the choriocarcinoma is a radio-resistant tumor.1 The drug of choice in female choriocarcinoma, methotrexate, has proved unsuccessful in the treatment of the tumor in men. The present treatment of choice is "triple drug therapy" with methotrexate, chlorambucil, and actinomycin D. The choice of combined chemotherapy with an antimetabolite (methotrexate), an oncolytic antibiotic (actinomycin D), and an alkylating agent (cyclophosphamide) as initial treatment is based on past failures to obtain satisfactory response to single agents in the treatment of tumors of germ cell origin, and the effectiveness of triple therapy in certain patients with metastatic gestational trophoblastic tumor resistant to single agents. In a study by Goldstein and Piro, 20 nine men and two women patients with non-gestational trophoblastic tumors containing choriocarcinoma were treated with combination therapy consisting of methotrexate, actinomycin D and cytoxan. Five patients (four men, one woman) are in continued sustained remission without evidence of recurrent disease. Three men and one woman are dead and one man is alive and under treatment with both subjective and objective evidence of response to drug therapy. According to this study, patients with pure choriocarcinoma appear to have a better response rate than those with mixed cell types. However, there are no five-year survivals with any present mode of therapy. ACKNOWLEDGMENT: The authors wish to thank Wolfgang Vogel, M.D. for permission to shtdy his patient.
PRIMARY MEDIASTINAL CHORIOCARCINOMA IN A MAN 107
REFERENCES
Yurick BS, Ottoman RE: Primary mediastinal choriocarcinoma. Radiology 75:901-907, 1960 2 Fine G, Smith RW Jr, Pachter MR: Primary extragenital choriocarcinoma in the male subject. Case report and review of the literature. Am J Med 32:776-794, 1962 3 Wenger ME, Dines DE, Ahmann DL, et al: Primary mediastinal choriocarcinoma. Mayo Clin Proc 43:570-575, 1968 4 Fanger H, MacAndrew R: Extragenital chorionepithelioma in female arising from mediastinal teratoma. RI Med J 35:259-260, 1952 5 Lynch MJG, Blewett GL: Choriocarcinoma arising in male mediastinum. Thorax 8:157-161, 1953 6 Erdmann ]F, Brown HA, Shaw HW (Cited by Ottoman and Yurick, 1960). 7 Bennington JL, Haber SL, Schweid A: Primary mediastinal choriocarcinoma. Dis Chest 46:623-626, 1964 8 Holt LP, Melcher DH, Colquhoun J: Extra-gonadal choriocarcinoma in the male. Postgrad Med J 41:134-138, 1965 9 Primary mediastinal choriocarcinoma (lead article). Br Med J 135, 1969 10 Marchand F: Uber die so generation decidualin geschwillste in Anschluss and Normale Geburt, abort, blasen mole and extraule Minschwangerschaft. Monatsch Geburtsh Gynak 1:419, 515, 1895 11 Schlagenhanfer F: Uber das Vorkommen chorionepithliom und trangenmolenartiger Wucherungen in Teratomen. Wien Klin Wschr 15:571, 604, 1902 12 Miller ], Browne FJ: Extragenital chorionepithelioma of congenital origin. J Obstet Gynaec 29:48, 1922 13 Arey LB: Developmental Anatomy: A Textbook and Laboratory Manual of Embryology. Philadelphia, W.B. Saunders, 1946 14 Patten BM: Human Embryology (chap. 8). New York, Blakiston Company, 1946 15 Friedman NB: Comparative morphogenesis of extragenital and gonadal teratoid tumours. Cancer 4:265-276, 1951 16 Prusty S, Bhayana ], Wayak NC, et al: Primary mediastinal choriocarcinoma. Dis Chest 56:543-546, 1969 17 Frank RT: Discussion. Arch Path 13:187, 1932 18 Ewing J: Neoplastic Disease. Philadelphia, W.B. Saunders, 1940, p 1047 19 Magovem GJ, Blades B: Primary extragenital chorioepithelioma in the male mediastinum. J Thorac Cardiovasc Surg 35:378-383, 1958 20 Goldstein DP, Piro AN: Combined chemotherapy in the treatment .of germ cell tumours containing choriocarcinoma in males and females. Surg Gynecol Obstet 134:61, 1972
108 CHILD, ABBASI, PEARCE
Echocardiographic Differentiation of Mediastinal Tumors from Primary Cardiac Disease* John S. Child, M.D., Abdul S. Abbasi, M.D., and Morton Lee Pearce, M.D.
Three cases of mediastinal tumors (thymic cyst, fibrosarcoma, fibrotipoma) mimicking primary cardiac disease were studied by echocardiography. The echocardiographic findings of the thymic cyst are presented and the echocardiograms in the other two patients discussed. Intrinsic cardiac pathology was excluded and discovery of abnormal extracardiac echoes prompted further investigation. In each instance, the echocardiographic interpretation of the nature and position of each extracardiac mass was confirmed by surgery or autopsy. We conclude that echocardiography is a useful noninvasive technique in differentiating between cardiac and extracardiac disease, and should be performed whenever an unusual or enlarged cardiac silhouette is encountered.
E
chocardiography has been useful in the noninvasive diagnosis of a variety of cardiac abnormalities including intracardiac tumors, in particular atrial myxomas.'- 5 A variety of mediastinal tumors presenting as cardiovascular disorders have been reported, 6 - 12 which required various invasive procedures for their diagnosis. We present three patients with mediastinal tumors simulating primary intrinsic cardiac disease in whom echocardiography was useful in excluding cardiac pathology and in suggesting extracardiac pathology in close proximity to the heart. METIIOD
The echocardiograms were recorded with commercially available equipment. A 2.25 MHZ 10 em focussed transducer with 0.5 em diameter, and a repetition rate of 1000 pulses per second was utilized. The echocardiograms were recorded on a strip chart in one, and on polaroid film in the other two patients. By using a conventional technique,la the transducer was placed in the fourth or fifth intercostal space at the left sternal border except in one patient in whom the third intercostal space was more helpful for recording mediastinal echoes. The different cardiac structures were identified by scanning the ultrasound beam from the cardiac base toward the apex. The transducer was first pointed anteroposteriorly and slightly medially to identify the mitral valve. The transducer was then directed laterally and inferiorly to record simultaneously echoes from the posterior left ventricular wall and the interventricular septum. The near gain was reduced in an attempt to record the anterior right ventricular wall. °From the Department of Medicine, UCLA Hospital and Wadsworth Veterans Administration Hospital, Los Angeles. Supported in part by AHA Greater Los Angeles Affiliate Award No. 490-1 G I. Reprint requests: Dr. Child, Division of Cardiology, UC Center for Health Sciences, Los Angeles 90024
CHEST, 67: 1, JANUARY, 1975
Primary Mediastinal Choriocarcinoma .1nMa an * Barry A. Cohen, M.D. and Mark A. Needle, M.D.
Choriocarcinoma with a primary site in the chest is rarely found. Characteristically, it is seen in young men presenting with cough, gynecomastia and chest pain. The disease is invariably fatal. The presently accepted therapy (triple therapy), consisting of methotrexate, actinomycin D and chlorambucil, has been unsuccessful to date.
0
nly 22 cases of primary mediastinal choriocarcinoma in a man have been reported. 1 • 6 Fine et al 2 reviewed 109 extragonadal choriocarcinomas including 19 which were primary mediastinal choriocarcinomas. Eight ( 42 percent) were pure choriocarcinoma, six ( 31 percent) were mixed with teratomatous elements and two were with embryonal carcinoma. We report the 23rd case of pure choriocarcinoma and review the literature and current therapy. CASE REPORT
A 25-year-old welder wa~ admitted to St. Joseph's Hospital and Medical Center on Febmary 15, 1973 with the complaints of hemoptysis, cough and expectoration for 15 days. He had a temperature between 37-38•C for five days. He had lost eight pounds over the past month. The history was negative with the exception of an herniorrhaphy-performed in 1968. His mother died of pulmonary tuberculosis several years ago. He stopped smoking five years prior to admission, denied alcohol or dmg use and allergies. On physical examination, he was a well-developed, wellnourished white man. Vital signs: pulse rate 90; blood pressure 124/76 mm Hg, respiration 18, temperature 38.2•C. There were nontender, mobile, firm posterior cervical and right axillary lymph nodes. The lungs were clear, the heart
° From the Department of Obstetrics and Gynecology and Department of Medicine, St. Joseph's Hospital and Medical Center, Paterson, New Jersey.
106 COHEN, NEEDLE
FIGURE 1. Widening of mediastinum on left side, increase in nodules scattered throughout both lung fields, bilateral basal infiltrates, and small pleural effusion. was clinically normal, the abdomen was soft and no tumor mass or organs were palpated. The genitalia appeared normal on repeated examinations. Laboratory Data: CBC, urinalysis, sput\un culture and smear, and smear and culture for acid-fast bacilli were negative. SMA-12 showed an LDH of 280 and an SGOT of 55. Chest x-ray films showed an anterior mediastinal mass and multiple soft nodules throughout both lung fields. An intravenous pyelogram revealed a double collecting system on the left. A chest x-ray film showed (Fig 1) widening of the mediastinum mainly on the left side with an increase in nodules scattered throughout both lung fields, bilateral basal infiltrates, and a small pleural effusion. The human chorionic gonadotropin titer was 106,496 IUI ml on the 9th hospital day. This rose to 761,856 IU/ml on the 13th hospital day. Normally none is found in the urine. Hospital Cot~rse: The patient ran an intermittent fever ( 3739•C). Shortly after admission he experienced hemoptysis. Lung biopsy was performed on the 7th hospital day revealing choriocarcinoma. His condition deteriorated and on the 42nd hospital day, while on methotrexate, chlorambucil and actinomycin D, he suddenly became dyspneic, anxious, cyanotic and diaphoretic. His condition continued to deteriorate and he expired on the 44th hospital day. Pathology report on biopsy: The pleural surface was irregularly nodular on gross examination. Sections revealed tumor nodules formed by masses of clear cells with vesicular nuclei surrounded by rims of syncytial dark cells presenting irregularly sized nuclei. The lung tissues showed, in addition, evidence of hemorrhage and numerous desquamated cells with foamy cytoplasm within the alveoli. Therapy: On the 8th hospital day, the patient began a course of methotrexate, 50 mg IV q8h x 6 doses; cyclophosphamide, 300 mg IV x 1; vincristine, 0.5 mg IV x 1; leucovorin, 15 mg IM q6h x 16; and actinomycin D, 0.5 mg IV od x 5. Since the HCG titers rose after treatment, another course of chemotherapy including methotrexate, 20 mg IM od x 5; chlorambucil, 2 mg PO od x 5; and actinomycin D, 0.5 mg IV od x 5 were given. The HCG titers remained positive and the patient's condition continued to deteriorate. Methotrexate, chlorambucil and actinomycin D were repeated on the 32nd hospital day and the patient expired on the 44th hospital day.
CHEST, 67: 1, JANUARY, 1975
DISCUSSION
Primary mediastinal choriocarcinoma is characteristically seen in young caucasian men presenting with the symptom triad of cough, gynecomastia and chest pain. a Gynecomastia is present in two-thirds, while cough and chest pain appear to be uniform. Half of the patients are in the third decade and 29 percent over 30 years of age. 1 • 3 Hemoptysis, dyspnea, hoarseness, stridor, Homer's syndrome, dysphagia, malaise, weight loss, anorexia and fever have been described. 1 -a·7 ·" Primary mediastinal choriocarcinoma presents in the anterior mediastinum roentgenographically as a noncavitating well-defined mass 1 with extremely rapid growth. Differential diagnosis includes in order of frequency: teratomas, thymomas, lymphomas and other less common lesions. 1 Grossly the tumor is a rounded, lobulated mass with, at times, a thin capsule. It adheres to the neighboring structures and may compress the superior vena cav3:. The cut surface has a variegated appearance, with or without grey-white solid areas and cystic spaces with hemorrhagic necrosis. Microscopically, syncytial trophoblasts predominate. On occasion, there are clumps of cytotrophoblasts. Much of the surface is necrotic with wide vascular involvement. 9 The diagnosis of primary mediastinal choriocarcinoma requires a meticulous search for testicular involvement. Testicular involvement means scars, cysts or benign tumors found in sections from serially sectioned testes. 2 Multiple sections of the testes at postmortem were free of tumor in this case. The presumptive diagnosis of choriocarcinoma can be made by the association of gynecomastia, cough, chest pain and a demonstrable titer of urinary chorionic gonadotropin with a positive pregnancy test. In the series of Fine et al, 2 a positive pregnancy test was found in 90 percent of the cases. Gynecomastia is related to the production of chorionic gonadotropin. Circulating gonadotropin stimulates the Leydig cells to produce testosterone and estrogen. This estrogen production may be the determining factor in the mammary gland hypertrophy so often seen. a Leydig cell hyperplasia was found in 30 to 40 cases of extragonadal choriocarcinoma in Fine's series. 1 Pathogenesis: Marchand 10 in 1895, was first to propose that chorioepitheliomas in a female originated in the chorionic villi. Sometime in 1902, Schlagenhanfer11 described the development of chorioepithelioma in the germ cells of testes or of other teratomatous tissues. Many theories have been advanced to explain the growth of such tumors in extragenital sites such as mediastinum, peritoneal organs and retroperitoneum. 12- 15 It is apparent from such studies that abnormal inclusions of germ cells can occur anywhere along the urogenital ridge extending from C6 to L3. 16 In accordance with this, Frank, 17 in 1932, stressed that the mediastinum may very well be the primary site of an extragenital teratomatous lesion. Ewing1 " supported this view, stating that the sex cells may occur anywhere along the entire length of the embryonal endoderm and, therefore,
CHEST, 67: 1, JANUARY, 1975
quite reasonably may be found in the mediastinum.~ Fine and co-workers 2 suggested that anterior mediastinal choriocarcinoma may be secondary to a primary testicular choriocarcinoma; however, testicular tumors rarely metastasize to the anterior mediastinum. Metastases in 19 cases reported by Fine et al were to the lungs (17), liver (18), kidney (10), lymph nodes (8) and brain ( 5). The origin of choriocarcinoma is unknown, but Yurick and Ottoman 1 have handed down their own theory as well as presenting those of others. These are: (a) the included twin theory, (b) the somatic cell rest theory, (c) the primitive germ cell theory, and (d) the included zygote theory. The primitive germ cell theory has received the greatest following 1 • 2 • 7 ·"·19 Primitive germ cells may arise in the covering mesothelium of the primitive gonad or may arise from the yolk sac endoderm, normally migrating along the urogenital ridge coming to rest in the gonad. In cases of primary mediastinal choriocarcinoma, arrest of the germ cell somewhere along the path may have occurred. 9 These cells may remain dormant until puberty or later sex life when some stimulus might cause them to mature and develop into a tumor mass. 1 •19 The suggestion that mediastinal teratomas and choriocarcinomas arise from aberrant germ cells in the thymus anlage has been proposed by Friedman.~" Therapy: No successful protocol has been proposed for this disease. 1 •a, 19 Surgery is of little value due to the rapid growth and invasive nature of the tumor. 3 Deep radiation therapy in the form of cobalt has been disappointing as the choriocarcinoma is a radio-resistant tumor.1 The drug of choice in female choriocarcinoma, methotrexate, has proved unsuccessful in the treatment of the tumor in men. The present treatment of choice is "triple drug therapy" with methotrexate, chlorambucil, and actinomycin D. The choice of combined chemotherapy with an antimetabolite (methotrexate), an oncolytic antibiotic (actinomycin D), and an alkylating agent (cyclophosphamide) as initial treatment is based on past failures to obtain satisfactory response to single agents in the treatment of tumors of germ cell origin, and the effectiveness of triple therapy in certain patients with metastatic gestational trophoblastic tumor resistant to single agents. In a study by Goldstein and Piro, 20 nine men and two women patients with non-gestational trophoblastic tumors containing choriocarcinoma were treated with combination therapy consisting of methotrexate, actinomycin D and cytoxan. Five patients (four men, one woman) are in continued sustained remission without evidence of recurrent disease. Three men and one woman are dead and one man is alive and under treatment with both subjective and objective evidence of response to drug therapy. According to this study, patients with pure choriocarcinoma appear to have a better response rate than those with mixed cell types. However, there are no five-year survivals with any present mode of therapy. ACKNOWLEDGMENT: The authors wish to thank Wolfgang Vogel, M.D. for permission to shtdy his patient.
PRIMARY MEDIASTINAL CHORIOCARCINOMA IN A MAN 107
REFERENCES
Yurick BS, Ottoman RE: Primary mediastinal choriocarcinoma. Radiology 75:901-907, 1960 2 Fine G, Smith RW Jr, Pachter MR: Primary extragenital choriocarcinoma in the male subject. Case report and review of the literature. Am J Med 32:776-794, 1962 3 Wenger ME, Dines DE, Ahmann DL, et al: Primary mediastinal choriocarcinoma. Mayo Clin Proc 43:570-575, 1968 4 Fanger H, MacAndrew R: Extragenital chorionepithelioma in female arising from mediastinal teratoma. RI Med J 35:259-260, 1952 5 Lynch MJG, Blewett GL: Choriocarcinoma arising in male mediastinum. Thorax 8:157-161, 1953 6 Erdmann ]F, Brown HA, Shaw HW (Cited by Ottoman and Yurick, 1960). 7 Bennington JL, Haber SL, Schweid A: Primary mediastinal choriocarcinoma. Dis Chest 46:623-626, 1964 8 Holt LP, Melcher DH, Colquhoun J: Extra-gonadal choriocarcinoma in the male. Postgrad Med J 41:134-138, 1965 9 Primary mediastinal choriocarcinoma (lead article). Br Med J 135, 1969 10 Marchand F: Uber die so generation decidualin geschwillste in Anschluss and Normale Geburt, abort, blasen mole and extraule Minschwangerschaft. Monatsch Geburtsh Gynak 1:419, 515, 1895 11 Schlagenhanfer F: Uber das Vorkommen chorionepithliom und trangenmolenartiger Wucherungen in Teratomen. Wien Klin Wschr 15:571, 604, 1902 12 Miller ], Browne FJ: Extragenital chorionepithelioma of congenital origin. J Obstet Gynaec 29:48, 1922 13 Arey LB: Developmental Anatomy: A Textbook and Laboratory Manual of Embryology. Philadelphia, W.B. Saunders, 1946 14 Patten BM: Human Embryology (chap. 8). New York, Blakiston Company, 1946 15 Friedman NB: Comparative morphogenesis of extragenital and gonadal teratoid tumours. Cancer 4:265-276, 1951 16 Prusty S, Bhayana ], Wayak NC, et al: Primary mediastinal choriocarcinoma. Dis Chest 56:543-546, 1969 17 Frank RT: Discussion. Arch Path 13:187, 1932 18 Ewing J: Neoplastic Disease. Philadelphia, W.B. Saunders, 1940, p 1047 19 Magovem GJ, Blades B: Primary extragenital chorioepithelioma in the male mediastinum. J Thorac Cardiovasc Surg 35:378-383, 1958 20 Goldstein DP, Piro AN: Combined chemotherapy in the treatment .of germ cell tumours containing choriocarcinoma in males and females. Surg Gynecol Obstet 134:61, 1972
108 CHILD, ABBASI, PEARCE
Echocardiographic Differentiation of Mediastinal Tumors from Primary Cardiac Disease* John S. Child, M.D., Abdul S. Abbasi, M.D., and Morton Lee Pearce, M.D.
Three cases of mediastinal tumors (thymic cyst, fibrosarcoma, fibrotipoma) mimicking primary cardiac disease were studied by echocardiography. The echocardiographic findings of the thymic cyst are presented and the echocardiograms in the other two patients discussed. Intrinsic cardiac pathology was excluded and discovery of abnormal extracardiac echoes prompted further investigation. In each instance, the echocardiographic interpretation of the nature and position of each extracardiac mass was confirmed by surgery or autopsy. We conclude that echocardiography is a useful noninvasive technique in differentiating between cardiac and extracardiac disease, and should be performed whenever an unusual or enlarged cardiac silhouette is encountered.
E
chocardiography has been useful in the noninvasive diagnosis of a variety of cardiac abnormalities including intracardiac tumors, in particular atrial myxomas.'- 5 A variety of mediastinal tumors presenting as cardiovascular disorders have been reported, 6 - 12 which required various invasive procedures for their diagnosis. We present three patients with mediastinal tumors simulating primary intrinsic cardiac disease in whom echocardiography was useful in excluding cardiac pathology and in suggesting extracardiac pathology in close proximity to the heart. METIIOD
The echocardiograms were recorded with commercially available equipment. A 2.25 MHZ 10 em focussed transducer with 0.5 em diameter, and a repetition rate of 1000 pulses per second was utilized. The echocardiograms were recorded on a strip chart in one, and on polaroid film in the other two patients. By using a conventional technique,la the transducer was placed in the fourth or fifth intercostal space at the left sternal border except in one patient in whom the third intercostal space was more helpful for recording mediastinal echoes. The different cardiac structures were identified by scanning the ultrasound beam from the cardiac base toward the apex. The transducer was first pointed anteroposteriorly and slightly medially to identify the mitral valve. The transducer was then directed laterally and inferiorly to record simultaneously echoes from the posterior left ventricular wall and the interventricular septum. The near gain was reduced in an attempt to record the anterior right ventricular wall. °From the Department of Medicine, UCLA Hospital and Wadsworth Veterans Administration Hospital, Los Angeles. Supported in part by AHA Greater Los Angeles Affiliate Award No. 490-1 G I. Reprint requests: Dr. Child, Division of Cardiology, UC Center for Health Sciences, Los Angeles 90024
CHEST, 67: 1, JANUARY, 1975
