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Chorio-Epithelioma of Testicle with Report of a Case
THE JOURNAL 01!"' UROLOGY
Vol. 61, No. 6, June 1949 Printed in U.S.A.
CHORIO-EPITHELIOMA OF TESTICLE WITH REPORT OF A CASE ROBERT L. ATKINSON From the Department of Urology, Evanston Hospital, Evanston, Ill.
Chorio-epithelioma is a very rare and highly malignant disease occurring in both sexes. In the female the most frequently involved organ is the uterus, the tumor arising from fetal tissues at the placental site in the uterine fundus. Chorio-epithelioma of the ovary occurs rarely, as shown by Sturley in his ex·cellent review of the literature in 1942. He states that during the 40 year period from 1902, when Kleinhans first described chorio-epithelioma of the ovary, only 41 cases have been reported. Winter, in 1943, reported an incidence of only 3 cases of uterine chorioepithelioma out of 8000 confinement patients, or 0.037 per cent, and Schwalm in the same year reported having observed no cases during a 22 year period among patients at the Berlin Charite' Frauenklinik. Kimbrough reported 7 cases out of 8,335 obstetrical admissions over a 4 year period, an incidence of 0.084 per cent. In the male, chorio-epithelioma is an extremely rare tumor, comprising about 0.016 per cent of all tumors in men. Hellwig, in an analysis of 50 cases of testicular tumors, accumulated over a 20 year period, found 27 "solid carcinomas" (seminoma), 22 adenocarcinomas and only 1 chorio-carcinoma (chorio-epithelioma). Adams reports 1 case out of 21 in the 26 year period from 1913 to 1939· and, in the 142 cases of primary testicular tumor analyzed by Gordon, only 5 were chorio-epithelioma alone and 3 were associated with adenocarcinoma. Belt states that "chorionepithelioma form about 1 per cent of the teratomata." Pathologically chorio-epithelioma growing in the testicle is akin to the comparable uterine growth in that it is a special development of fetal membranes. The etiology and pathogenesis of chorio-epithelioma are not definitely known; however, there are two theories set forth to explain the growth. According to one theory, a parthenogenetic cleavage of the germ cell in the testicle occurs forming the teratoma which in itself is totipotential. The teratoma forms the fetal membranes which form chorionic epithelium. The epithelium then grows abnormally to give rise to the chorio-epithelioma. The other theory, as presented by Petillo, states that the phenomenon of sex reversal is responsible. This phenomenon shows that the sex-determining factor of the sex chromosomes may, in some way, be altered so that differentiated germ cells can transform into cells of the opposite sex. This process of sex reversal, taking place in the testicle, creates the requirements for auto-fertilization, namely, ova and spermatozoa. The embryo resulting from such an auto-fertilization dies off, leaving the chorion to form the chorio-epithelioma. In considering the pathological physiology, one is impressed by the large amount of gonadotropic hormone excreted in the urine giving the strongly positive Aschheim-Zondek test. This hormone is prolan and is liberated by the pituitary probably under the stimulating influence of a hormone from the testicular tumor upon the pituitary. When analyzed quantitatively, the prolan 1068
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concentration in the urine is greatly elevated above the physiological normal of 5 mouse units per liter of urine to as high as 100,000 or more units. This bioassay is of great diagnostic importance when it is positive, but a negative reaction means nothing as certain testicular tumors do not liberate the hormone. The prognosis in all cases of chorio-epithelioma is extremely poor due to the early and distant multiple blood borne metastases which are frequently the cause of the initial signs and symptoms. Very often the testicle containing the neoplasm will not enlarge even after metastatic lesions have prominently manifested themselves. The tumor is quite radio-resistant and so it defies all attempts at radiation therapy. CASE REPORT
A 20 year old white man consulted his family physician because of low back pain for the preceding year and painless swelling of the left testicle for 4 months prior to consultation. The back discomfort had become gradually worse in the
Fm. 1. X-ray of chest, showing metastatic lesions (arrows)
last 5 months. There was no history of injury, strain, or infection. On routine physical examination, the doctor discovered enlarged and tender supraclavicular lymph nodes on the left side and a moderate degree of breast enlargement bilaterally. The left testicle was firm, not tender, but enlarged to about 7 by 6 by 5 cm. The patient was then admitted to the hospital for further study and treatment. Laboratory examination of the urine revealed a strongly positive (quantitative analysis not done) Aschheim-Zondek reaction. Other blood and urine studies were normal. A chest x-ray showed several areas of increased densities suggestive of metastatic lesions (fig. 1). The bony pelvis and spine were normal on x-ray examination. Biopsy done on the left supraclavicular lymph nodes and the cervical nodes revealed much necrosis and cells resembling the anaplastic Langhans type and groups of syncytial cells which suggested the diagnosis of chorio-epithelioma metastatic from the left testicle (fig. 2). Under low spinal anesthesia, the left testicle was removed and hemisected at the operating table. It was found to consist entirely of a solid, moderately firm tumor mass which contained scattered pearly-grey hard nodules measuring 4 to 5 mm. in diameter (fig. 3). Subsequent microscopic examination of the
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ROBERT L. ATKINSON
FIG. 2. Biopsy of left supraclavicular lymph node, showing formation of osteoid tissue,
FIG. 3. A, photograph of testicle, showing increased vascularity. section. Note tumor nodules and hemorrhagic areas.
B, testicle on cut.
testicle revealed a jumble of embryonic tissues in which mesodermal elements predominated (fig. 4).
CHORIO-EPITHELIOMA. OF TESTICLE
1071
Fm. 4. Photomicrograph of testicle removed antomortem. Placental villi can bo seen, one in longitudinal section, others in cross section. Diagnosis: chorio-epithelioma.
Fm. 5. A, photomicrograph of brain. Brain tissue in upper left corner. Cords of tumor cells and blood cells are invading brain tissue. B, photomicrograph of lung, showing thickened alveolar wall and mass of tumor cells below, and blood cells above wall.
The patient was discharged on January 1, 1947, t,crelve days after the admission and 5 days after orchidectomy. He was re-admitted on April 4, 1947
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ROBERT L. ATKINSON
having lost 50 pounds during the intervening 10 weeks. He was quite restless, extremely emaciated and dyspneic and had a left facial paralysis and left eyelid ptosis. Both breasts -were markedly enlarged and tender. The left supraclavicular nodes were fixed and discrete and larger than when seen on the first admission 4 months previously. There was no inguinal adenopathy. The course was rapidly downhill and the patient died on April 10, 1947. The essential postmortem findings were those of widespread metastases with masses of confluent and discrete enlarged lymph nodes in the entire mesentery of the small bowel superimposed on a similar retroperitoneal mass which extended from the level of the pancreas to the aortic bifurcation. Other lesions were found in both lungs, liver, pancreas, spleen, peri-aortic nodes, adrenals, and brain (fig. 5). SUMMARY
The rarity of chorio-epithelioma is shown by statistical data of various observers, the incidence ranging from 0.03 per cent to 0.084 per cent for women. In the male, chorio-epithelioma forms 1 per cent to 4.7 per cent of testicular tumors and about 0.06 per cent of all tumors in men. A case history of testr-eular chorio-epithelioma in a 20 year old ex-service man is presented.
824 Ji~dson Ave., Evanston, Ill. REFERENCES ADAMS, J. E.: A study of malignant testicular tumor including case reports of chorion- epithelioma accompanied by hypertension and teratoma testis with single tridermal metastases. J. Urol., 47: 491, 1942. -BELT, E.: Tumors of the testicle. Am. J. Surg., 38: 201, 1937. GORDON, W. E.: Tumors of the testis; a study of pathology of 142 cases of primary neoplasms of testis in man. J. Urol., 43: 851, 1940. HELLWIG, C. A.: Tumors of the testis; analysis-of 50 cases. Urol. & Cutan. Rev., 48: 538, 1944. KIMBROUGH, R. A., JR.: Value of hormonal study in diagnosis of chorionepithelioma. Am. J. Obst. & Gynec., 28: 12, 1934. PETILLO, D.: A critical review of the pathogenesis of chorioma testis and a new theory. Urol. & Cutan. Rev., 48: 53, 1944. SCHWALM, H.: Zentralbl. f. Gynak., 58: 1212, 1934. STURLEY, R. F.: Teratomatous chorionepithelioma of the ovary. Minn. Med., 25: 629, 1942. WINTER, E.W.: Ztschr. f. Gebursch. u. Gynak., 107: 243, 1934.
Vol. 61, No. 6, June 1949 Printed in U.S.A.
CHORIO-EPITHELIOMA OF TESTICLE WITH REPORT OF A CASE ROBERT L. ATKINSON From the Department of Urology, Evanston Hospital, Evanston, Ill.
Chorio-epithelioma is a very rare and highly malignant disease occurring in both sexes. In the female the most frequently involved organ is the uterus, the tumor arising from fetal tissues at the placental site in the uterine fundus. Chorio-epithelioma of the ovary occurs rarely, as shown by Sturley in his ex·cellent review of the literature in 1942. He states that during the 40 year period from 1902, when Kleinhans first described chorio-epithelioma of the ovary, only 41 cases have been reported. Winter, in 1943, reported an incidence of only 3 cases of uterine chorioepithelioma out of 8000 confinement patients, or 0.037 per cent, and Schwalm in the same year reported having observed no cases during a 22 year period among patients at the Berlin Charite' Frauenklinik. Kimbrough reported 7 cases out of 8,335 obstetrical admissions over a 4 year period, an incidence of 0.084 per cent. In the male, chorio-epithelioma is an extremely rare tumor, comprising about 0.016 per cent of all tumors in men. Hellwig, in an analysis of 50 cases of testicular tumors, accumulated over a 20 year period, found 27 "solid carcinomas" (seminoma), 22 adenocarcinomas and only 1 chorio-carcinoma (chorio-epithelioma). Adams reports 1 case out of 21 in the 26 year period from 1913 to 1939· and, in the 142 cases of primary testicular tumor analyzed by Gordon, only 5 were chorio-epithelioma alone and 3 were associated with adenocarcinoma. Belt states that "chorionepithelioma form about 1 per cent of the teratomata." Pathologically chorio-epithelioma growing in the testicle is akin to the comparable uterine growth in that it is a special development of fetal membranes. The etiology and pathogenesis of chorio-epithelioma are not definitely known; however, there are two theories set forth to explain the growth. According to one theory, a parthenogenetic cleavage of the germ cell in the testicle occurs forming the teratoma which in itself is totipotential. The teratoma forms the fetal membranes which form chorionic epithelium. The epithelium then grows abnormally to give rise to the chorio-epithelioma. The other theory, as presented by Petillo, states that the phenomenon of sex reversal is responsible. This phenomenon shows that the sex-determining factor of the sex chromosomes may, in some way, be altered so that differentiated germ cells can transform into cells of the opposite sex. This process of sex reversal, taking place in the testicle, creates the requirements for auto-fertilization, namely, ova and spermatozoa. The embryo resulting from such an auto-fertilization dies off, leaving the chorion to form the chorio-epithelioma. In considering the pathological physiology, one is impressed by the large amount of gonadotropic hormone excreted in the urine giving the strongly positive Aschheim-Zondek test. This hormone is prolan and is liberated by the pituitary probably under the stimulating influence of a hormone from the testicular tumor upon the pituitary. When analyzed quantitatively, the prolan 1068
CH ORIO-EPITHELIOMA OF TESTICLE
1069
concentration in the urine is greatly elevated above the physiological normal of 5 mouse units per liter of urine to as high as 100,000 or more units. This bioassay is of great diagnostic importance when it is positive, but a negative reaction means nothing as certain testicular tumors do not liberate the hormone. The prognosis in all cases of chorio-epithelioma is extremely poor due to the early and distant multiple blood borne metastases which are frequently the cause of the initial signs and symptoms. Very often the testicle containing the neoplasm will not enlarge even after metastatic lesions have prominently manifested themselves. The tumor is quite radio-resistant and so it defies all attempts at radiation therapy. CASE REPORT
A 20 year old white man consulted his family physician because of low back pain for the preceding year and painless swelling of the left testicle for 4 months prior to consultation. The back discomfort had become gradually worse in the
Fm. 1. X-ray of chest, showing metastatic lesions (arrows)
last 5 months. There was no history of injury, strain, or infection. On routine physical examination, the doctor discovered enlarged and tender supraclavicular lymph nodes on the left side and a moderate degree of breast enlargement bilaterally. The left testicle was firm, not tender, but enlarged to about 7 by 6 by 5 cm. The patient was then admitted to the hospital for further study and treatment. Laboratory examination of the urine revealed a strongly positive (quantitative analysis not done) Aschheim-Zondek reaction. Other blood and urine studies were normal. A chest x-ray showed several areas of increased densities suggestive of metastatic lesions (fig. 1). The bony pelvis and spine were normal on x-ray examination. Biopsy done on the left supraclavicular lymph nodes and the cervical nodes revealed much necrosis and cells resembling the anaplastic Langhans type and groups of syncytial cells which suggested the diagnosis of chorio-epithelioma metastatic from the left testicle (fig. 2). Under low spinal anesthesia, the left testicle was removed and hemisected at the operating table. It was found to consist entirely of a solid, moderately firm tumor mass which contained scattered pearly-grey hard nodules measuring 4 to 5 mm. in diameter (fig. 3). Subsequent microscopic examination of the
1070
ROBERT L. ATKINSON
FIG. 2. Biopsy of left supraclavicular lymph node, showing formation of osteoid tissue,
FIG. 3. A, photograph of testicle, showing increased vascularity. section. Note tumor nodules and hemorrhagic areas.
B, testicle on cut.
testicle revealed a jumble of embryonic tissues in which mesodermal elements predominated (fig. 4).
CHORIO-EPITHELIOMA. OF TESTICLE
1071
Fm. 4. Photomicrograph of testicle removed antomortem. Placental villi can bo seen, one in longitudinal section, others in cross section. Diagnosis: chorio-epithelioma.
Fm. 5. A, photomicrograph of brain. Brain tissue in upper left corner. Cords of tumor cells and blood cells are invading brain tissue. B, photomicrograph of lung, showing thickened alveolar wall and mass of tumor cells below, and blood cells above wall.
The patient was discharged on January 1, 1947, t,crelve days after the admission and 5 days after orchidectomy. He was re-admitted on April 4, 1947
1072
ROBERT L. ATKINSON
having lost 50 pounds during the intervening 10 weeks. He was quite restless, extremely emaciated and dyspneic and had a left facial paralysis and left eyelid ptosis. Both breasts -were markedly enlarged and tender. The left supraclavicular nodes were fixed and discrete and larger than when seen on the first admission 4 months previously. There was no inguinal adenopathy. The course was rapidly downhill and the patient died on April 10, 1947. The essential postmortem findings were those of widespread metastases with masses of confluent and discrete enlarged lymph nodes in the entire mesentery of the small bowel superimposed on a similar retroperitoneal mass which extended from the level of the pancreas to the aortic bifurcation. Other lesions were found in both lungs, liver, pancreas, spleen, peri-aortic nodes, adrenals, and brain (fig. 5). SUMMARY
The rarity of chorio-epithelioma is shown by statistical data of various observers, the incidence ranging from 0.03 per cent to 0.084 per cent for women. In the male, chorio-epithelioma forms 1 per cent to 4.7 per cent of testicular tumors and about 0.06 per cent of all tumors in men. A case history of testr-eular chorio-epithelioma in a 20 year old ex-service man is presented.
824 Ji~dson Ave., Evanston, Ill. REFERENCES ADAMS, J. E.: A study of malignant testicular tumor including case reports of chorion- epithelioma accompanied by hypertension and teratoma testis with single tridermal metastases. J. Urol., 47: 491, 1942. -BELT, E.: Tumors of the testicle. Am. J. Surg., 38: 201, 1937. GORDON, W. E.: Tumors of the testis; a study of pathology of 142 cases of primary neoplasms of testis in man. J. Urol., 43: 851, 1940. HELLWIG, C. A.: Tumors of the testis; analysis-of 50 cases. Urol. & Cutan. Rev., 48: 538, 1944. KIMBROUGH, R. A., JR.: Value of hormonal study in diagnosis of chorionepithelioma. Am. J. Obst. & Gynec., 28: 12, 1934. PETILLO, D.: A critical review of the pathogenesis of chorioma testis and a new theory. Urol. & Cutan. Rev., 48: 53, 1944. SCHWALM, H.: Zentralbl. f. Gynak., 58: 1212, 1934. STURLEY, R. F.: Teratomatous chorionepithelioma of the ovary. Minn. Med., 25: 629, 1942. WINTER, E.W.: Ztschr. f. Gebursch. u. Gynak., 107: 243, 1934.