Case Report Urol Int 1992;48:463-465
Department of Urology, Niigata University School of Medicine, Department o f Neurosurgery, Brain Research Institute, Niigata University and Department of Urology, Niigata Central Hospital, Niigata, Japan
KeyWords
Gynecomastia Human chorionic gonadotropin production, ectopic Transitional cell carcinoma of the bladder
Gynecomastia and Ectopic Human Chorionic Gonadotropin Production by Transitional Cell Carcinoma of the Bladder Abstract
We report a patient with gynecomastia and ectopic production of human cho rionic gonadotropin (HCG) by a transitional cell carcinoma of the bladder. In the present case, serum HCG levels and gynecomastia paralleled the clinical course. On admission, the patient was suffering from invasive transitional cell carcinoma (grade 3) of the bladder with metastasis to the left inguinal lymph nodes, together with gynecomastia. The serum HCG level was also elevated. After anticancer chemotherapy, the apparent bladder lesion and gynecomastia disappeared, and the serum HCG level declined to within normal limits. About 2 months after discharge, when the patient suffered from recurrent invasive tumors of the bladder, gynecomastia reappeared and the serum HCG level again became elevated. P-HCG was demonstrated in biopsy tissue using the immunoperoxidase technique. The presence of p-HCG was always focally dem onstrated and was shown to be localized in the cytoplasm of the tumor cells.
Introduction
Elevated blood levels of human chorionic gonadotro pin (HCG) are rarely seen in patients with urothelial neo plasm [ 1], and among those patients, the presence of gyne comastia has been infrequent [2-6]. We herein report a patient with gynecomastia and ectopic production of HCG by a transitional cell carcinoma of the bladder, in whom the serum HCG levels and gynecomastia paralleled the clinical course.
Case Report Clinical Course A 60-year-old Japanese man was admitted to Niigata Central Hospital in October 1985 with a 1-year history of gross hematuria and difficulty in urination. The patient’s breast showed gynccomas-
Received: March 25,1991 Accepted: May 27, 1991
tia on admission (fig. 1). The lower abdominal region, penis and scro tum showed marked edema. The testes were atrophic in both size and consistency. Cystoscopic examination showed multiple tumors involving the posterior and bilateral wall of the bladder. Urinalysis on admission demonstrated numerous erythrocytes. Blood analysis showed hemoglobin 15.1 g/dl, white blood cells 5,400/mm3, and platelet count 25.9 X 104/m m 3. The blood urea nitrogen was 11.5 mg/dl. and serum creatinine was 1.9 mg/dl. Total protein was 6.9 g/dl. Serum electrolytes were within normal limits. Glutamic oxalo acetic transaminase, glutamic pyruvic transaminase, lactate dehy drogenase and alkaline phosphatase were all within normal limits. Serum carcinoembryonic antigen was 5.1 ng/ml (normal range: 1.26.3 ng/ml). a-Fetoprotein was 4.4 ng/ml (normal range: less than 20 ng/ml). The electrocardiogram showed an almost normal appear ance. X-ray films of the chest showed a calcified tuberculoma, 1.5 cm in diameter, in the right ventral segment of the upper lobe (S3). Com puterized tomography (CT) of the brain revealed no abnormality. Also, an excretory urogram (DIP) demonstrated no abnormality. CT of the pelvic region revealed invasive tumors of the trigon and bilat eral wall of the bladder (fig. 2). The serum HCG level was elevated up
T. Nishiyama, MD Department of Urology Niigata University School of Medicine Asahimachi-1, Niigata 951 (Japan)
© 1992 S. Kargcr AG, Basel 0042-1138/92/0484-0463 $2.75/0
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 1:08:47 AM
Tsutomu Nishiyamaa Kazuo Washiyamah Toshiki Tanikawaa H¡rotada Mineyamac Toru Sasagawaa Hiroshi Susukia Yasuo Kitamuraa Shotaro Satoa
Patient showing apparent gynecomastia. Initial CT of the pelvic region revealing invasive tumors of the trigone and bilateral wall of the bladder. Microscopical view of the tum or tissue, showing invasive transitional cell carcinoma (grade 3). HE. X 425. P-HCG demonstrated in the biopsy tissue using the indirect immunoperoxidase technique. The antibody to P-HCG was donated by the NIAMDD (USA). The presence of P-HCG was always focally demonstrated (arrows) and localized in the cytoplasm (large arrow and insert) of tumor cells. X 425. Insert: X l ,475. Fig. 1. Fig. 2. Fig. 3. Fig. 4.
464
After the treatment the apparent bladder lesion and gynecomastia disappeared, and the serum HCG level declined to within normal limits. The patient was discharged in March 1986 and was thereafter treated as an outpatient. About 2 months after discharge, the patient was readmitted to Niigata Central Hospital because of difficulties with urination, anasarca and poor appetite. Cystoscopy and CT of the pelvic region revealed recurrent invasive tumors of the bladder. The patient did not respond to further anticancer chemotherapy, and his condition deteriorated progressively. His serum HCG level also rose to 86.3 IU/1 (July 1986) and gynecomastia reappeared. He died on August 6, 1986.
Nishiyama/Washiyama/Tanikawa/ Mineyama/Sasagawa/Susuki/Kitamura/ Sato
Gynecomastia and Ectopic HCG Production by Transitional Cell Carcinoma of the Bladder
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 1:08:47 AM
to 27.8 IU/1 (normal range, under 1 0 IU/1 in man). Bladder washings were positive for malignant cells. The patient underwent biopsy and transurethral resection of the lesions. The specimens from the blad der lesions were revealed to be an invasive transitional cell carci noma (grade 3), invasive to the smooth muscular tissue (fig. 3). Moreover, the cancer was found to have massively metastasized to the left inguinal lymph nodes on biopsy. P-HCG was demonstrated in the biopsy tissue using the immunoperoxidase technique (fig. 4). The presence of P-HCG was always focally demonstrated and was shown to be localized in the cytoplasm of the cancer cells. The patient was subsequently treated with cisplatin, methotrexate and doxorubi cin at Niigata Central Hospital and Niigata University Hospital.
Postmortem Examination Autopsy was performed after death. The major findings were as follows. (1) Multiple transitional cell carcinomas of the bladder (grade 3) infiltrated into the serous membrane. Immunoperoxidase staining with the antibody to (3-HCG was focally positive and local ized in the cytoplasm of the tumor cells. There was no choriocarcinomatous component in the carcinoma tissue. (2) Examination of the atrophic testes failed to disclose any tumor. (3) There was no evi dence of a primary malignancy in any other region.
Discussion
Up to now, several investigators reported an elevation of HCG levels in the blood and/or urine of some patients with bladder carcinoma [1,7]. Most of these patients had high-grade malignancy or an advanced clinical state. In some of these cases, trophoblastic differentiation was rec ognized on routine histology [2, 3, 5, 6, 8], Even in those cases showing elevated serum HCG, however, it is rare to observe gynecomastia in patients with bladder carcinoma [2-6], In the present case, serum HCG levels and gyneco mastia paralleled the clinical course. On admission, the patient had an invasive transitional cell carcinoma (grade 3) of the bladder with metastasis to the left inguinal lymph nodes, together with gynecomastia. The serum HCG level was also elevated. After anticancer chemotherapy, the gynecomastia disappeared and the serum HCG level also declined to within normal limits upon disappearance of
the apparent bladder lesion. When the patient suffered progressive deterioration due to tum or recurrence, the gynecomastia reappeared and the serum HCG level be came again elevated. Several investigators have shown that alterations exist in the structure of the sugar chains of HCG produced in carcinoma cells [9, 10] and that this HCG has an extremely low biological activity in vivo [9], Thus, the appearance or absence of gynecomastia may depend on the strength of the biological activity of HCG produced by the tum or cells. Recently, HCG-producing elements have been identi fied in bladder tumors using immunohistochemical pro cedures [5, 6, 8, 10-12], HCG-producing cells have been reported to occur in tumors that showed severe cytological abnormality. In the present case, the specimens from the bladder lesions were grade 3 transitional cell carcino ma. (3-HCG was demonstrated in the biopsy tissue ob tained from the patient, using the immunoperoxidase technique (fig. 4), the (3-HCG being always focally demon strated and localized in the cytoplasm. However, there was no choriocarcinomatous component in the carci noma tissue from this case. Thus. HCG production, its endocrine manifestation, gynecomastia, and the detection of HCG-producing ele ments in the bladder tumors may provide useful informa tion on tum or progression in patients with urothelial malignancies [13].
References 6 Yamase HT, Wurzer RS, Nieh PT, Gondos B: Immunohistochemical demonstration of hu man chorionic gonadotropin in tumors of the urinary bladder. Ann Clin Lab Sci 1985:15: 414-417. 7 Fukutani K, Libby JM, Panko WB, Scardino PT: Human chorionic gonadotropin detected in urinary concentrates from patients with ma lignant tumors of the testis, prostate, bladder, ureter and kidney. J Urol 1983;129:74-77. 8 Burry AF. Munn SR. Arnold EP, McRae CU: Trophoblastic metaplasia in urothelial carci noma of the bladder. Br J Urol 1986;58:143— 146. 9 Mizuochi T, Nishimura R, Dcrappe C, Taniguchi T, Hamamoto T, Mochizuki M, Kobata A: Structures of the asparagine-linked sugar chains of human chorionic gonadotropin pro duced in choriocarcinoma. J Biol Chem 1983; 258:14126-14129.
10 Rodenberg CJ, Kruscman ACN, de Maaker HA, Freuren GJ, van Oosterom AT: Immuno histochemical localization and chromato graphic characterization of human chorionic gonadotropin in a bladder carcinoma. Arch Pa thol Lab Med 1985;109:1046-1048. 11 Shah VM, Newman J, Crocker J, Chappie CR, Collard MJ, O’Brien JM, Considine J: Ectopic p-human chorionic gonadotropin production by bladder urothelial neoplasia. Arch Pathol Lab Med 1986;110:107-111. 12 Campo EC, Algaba F. Palacin A, Germa R, Sole-galcells FJ, Cardcsa A: Placental proteins in high-grade urothelial neoplasms. An immu nohistochemical study of human chorionic go nadotropin, human placental lactogen, and pregnancy-specific beta-l-glyoprotein. Cancer 1989;63:2497-2504. 13 Martin JE, Jenkins RJ, Zuk RJ, Oliver RTD, Baithum SI: Human chorionic gonadotrophin expression and histological findings as predic tors of response to radiotherapy in carcinoma of the bladder. Virchows Arch 1989:414:273277.
465
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 1:08:47 AM
1 Dexeus F, Logothetis C, Hossan E, Samuels ML: Carcinoembryonic antigen and beta-hu man chorionic gonadotropin as serum markers for advanced urothelial malignancies. J Urol 1986:136:403-407. 2 Hyman A, Leiter HE: Extratesticular chorioepithelioma in a male probably primary in the urinary bladder. J Mt Sinai Hosp 1943; 10:212— 219. 3 Ainsworth RW, Greshman GA: Primary cho riocarcinoma of the urinary bladder in a male. J Pathol Bacteriol 1960;79:185-192. 4 Kawamura J. Machida S. Yoshida O, Oscko F, Imura H. Hattori M: Bladder carcinoma asso ciated with ectopic production of gonadotro pin. Cancer 1978;42:2773-2780. 5 Dennis PM. Turner AG: Primary choriocarci noma of the bladder evolving from a transi tional cell carcinoma. J Clin Pathol I984;37: 503-505.
Department of Urology, Niigata University School of Medicine, Department o f Neurosurgery, Brain Research Institute, Niigata University and Department of Urology, Niigata Central Hospital, Niigata, Japan
KeyWords
Gynecomastia Human chorionic gonadotropin production, ectopic Transitional cell carcinoma of the bladder
Gynecomastia and Ectopic Human Chorionic Gonadotropin Production by Transitional Cell Carcinoma of the Bladder Abstract
We report a patient with gynecomastia and ectopic production of human cho rionic gonadotropin (HCG) by a transitional cell carcinoma of the bladder. In the present case, serum HCG levels and gynecomastia paralleled the clinical course. On admission, the patient was suffering from invasive transitional cell carcinoma (grade 3) of the bladder with metastasis to the left inguinal lymph nodes, together with gynecomastia. The serum HCG level was also elevated. After anticancer chemotherapy, the apparent bladder lesion and gynecomastia disappeared, and the serum HCG level declined to within normal limits. About 2 months after discharge, when the patient suffered from recurrent invasive tumors of the bladder, gynecomastia reappeared and the serum HCG level again became elevated. P-HCG was demonstrated in biopsy tissue using the immunoperoxidase technique. The presence of p-HCG was always focally dem onstrated and was shown to be localized in the cytoplasm of the tumor cells.
Introduction
Elevated blood levels of human chorionic gonadotro pin (HCG) are rarely seen in patients with urothelial neo plasm [ 1], and among those patients, the presence of gyne comastia has been infrequent [2-6]. We herein report a patient with gynecomastia and ectopic production of HCG by a transitional cell carcinoma of the bladder, in whom the serum HCG levels and gynecomastia paralleled the clinical course.
Case Report Clinical Course A 60-year-old Japanese man was admitted to Niigata Central Hospital in October 1985 with a 1-year history of gross hematuria and difficulty in urination. The patient’s breast showed gynccomas-
Received: March 25,1991 Accepted: May 27, 1991
tia on admission (fig. 1). The lower abdominal region, penis and scro tum showed marked edema. The testes were atrophic in both size and consistency. Cystoscopic examination showed multiple tumors involving the posterior and bilateral wall of the bladder. Urinalysis on admission demonstrated numerous erythrocytes. Blood analysis showed hemoglobin 15.1 g/dl, white blood cells 5,400/mm3, and platelet count 25.9 X 104/m m 3. The blood urea nitrogen was 11.5 mg/dl. and serum creatinine was 1.9 mg/dl. Total protein was 6.9 g/dl. Serum electrolytes were within normal limits. Glutamic oxalo acetic transaminase, glutamic pyruvic transaminase, lactate dehy drogenase and alkaline phosphatase were all within normal limits. Serum carcinoembryonic antigen was 5.1 ng/ml (normal range: 1.26.3 ng/ml). a-Fetoprotein was 4.4 ng/ml (normal range: less than 20 ng/ml). The electrocardiogram showed an almost normal appear ance. X-ray films of the chest showed a calcified tuberculoma, 1.5 cm in diameter, in the right ventral segment of the upper lobe (S3). Com puterized tomography (CT) of the brain revealed no abnormality. Also, an excretory urogram (DIP) demonstrated no abnormality. CT of the pelvic region revealed invasive tumors of the trigon and bilat eral wall of the bladder (fig. 2). The serum HCG level was elevated up
T. Nishiyama, MD Department of Urology Niigata University School of Medicine Asahimachi-1, Niigata 951 (Japan)
© 1992 S. Kargcr AG, Basel 0042-1138/92/0484-0463 $2.75/0
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 1:08:47 AM
Tsutomu Nishiyamaa Kazuo Washiyamah Toshiki Tanikawaa H¡rotada Mineyamac Toru Sasagawaa Hiroshi Susukia Yasuo Kitamuraa Shotaro Satoa
Patient showing apparent gynecomastia. Initial CT of the pelvic region revealing invasive tumors of the trigone and bilateral wall of the bladder. Microscopical view of the tum or tissue, showing invasive transitional cell carcinoma (grade 3). HE. X 425. P-HCG demonstrated in the biopsy tissue using the indirect immunoperoxidase technique. The antibody to P-HCG was donated by the NIAMDD (USA). The presence of P-HCG was always focally demonstrated (arrows) and localized in the cytoplasm (large arrow and insert) of tumor cells. X 425. Insert: X l ,475. Fig. 1. Fig. 2. Fig. 3. Fig. 4.
464
After the treatment the apparent bladder lesion and gynecomastia disappeared, and the serum HCG level declined to within normal limits. The patient was discharged in March 1986 and was thereafter treated as an outpatient. About 2 months after discharge, the patient was readmitted to Niigata Central Hospital because of difficulties with urination, anasarca and poor appetite. Cystoscopy and CT of the pelvic region revealed recurrent invasive tumors of the bladder. The patient did not respond to further anticancer chemotherapy, and his condition deteriorated progressively. His serum HCG level also rose to 86.3 IU/1 (July 1986) and gynecomastia reappeared. He died on August 6, 1986.
Nishiyama/Washiyama/Tanikawa/ Mineyama/Sasagawa/Susuki/Kitamura/ Sato
Gynecomastia and Ectopic HCG Production by Transitional Cell Carcinoma of the Bladder
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 1:08:47 AM
to 27.8 IU/1 (normal range, under 1 0 IU/1 in man). Bladder washings were positive for malignant cells. The patient underwent biopsy and transurethral resection of the lesions. The specimens from the blad der lesions were revealed to be an invasive transitional cell carci noma (grade 3), invasive to the smooth muscular tissue (fig. 3). Moreover, the cancer was found to have massively metastasized to the left inguinal lymph nodes on biopsy. P-HCG was demonstrated in the biopsy tissue using the immunoperoxidase technique (fig. 4). The presence of P-HCG was always focally demonstrated and was shown to be localized in the cytoplasm of the cancer cells. The patient was subsequently treated with cisplatin, methotrexate and doxorubi cin at Niigata Central Hospital and Niigata University Hospital.
Postmortem Examination Autopsy was performed after death. The major findings were as follows. (1) Multiple transitional cell carcinomas of the bladder (grade 3) infiltrated into the serous membrane. Immunoperoxidase staining with the antibody to (3-HCG was focally positive and local ized in the cytoplasm of the tumor cells. There was no choriocarcinomatous component in the carcinoma tissue. (2) Examination of the atrophic testes failed to disclose any tumor. (3) There was no evi dence of a primary malignancy in any other region.
Discussion
Up to now, several investigators reported an elevation of HCG levels in the blood and/or urine of some patients with bladder carcinoma [1,7]. Most of these patients had high-grade malignancy or an advanced clinical state. In some of these cases, trophoblastic differentiation was rec ognized on routine histology [2, 3, 5, 6, 8], Even in those cases showing elevated serum HCG, however, it is rare to observe gynecomastia in patients with bladder carcinoma [2-6], In the present case, serum HCG levels and gyneco mastia paralleled the clinical course. On admission, the patient had an invasive transitional cell carcinoma (grade 3) of the bladder with metastasis to the left inguinal lymph nodes, together with gynecomastia. The serum HCG level was also elevated. After anticancer chemotherapy, the gynecomastia disappeared and the serum HCG level also declined to within normal limits upon disappearance of
the apparent bladder lesion. When the patient suffered progressive deterioration due to tum or recurrence, the gynecomastia reappeared and the serum HCG level be came again elevated. Several investigators have shown that alterations exist in the structure of the sugar chains of HCG produced in carcinoma cells [9, 10] and that this HCG has an extremely low biological activity in vivo [9], Thus, the appearance or absence of gynecomastia may depend on the strength of the biological activity of HCG produced by the tum or cells. Recently, HCG-producing elements have been identi fied in bladder tumors using immunohistochemical pro cedures [5, 6, 8, 10-12], HCG-producing cells have been reported to occur in tumors that showed severe cytological abnormality. In the present case, the specimens from the bladder lesions were grade 3 transitional cell carcino ma. (3-HCG was demonstrated in the biopsy tissue ob tained from the patient, using the immunoperoxidase technique (fig. 4), the (3-HCG being always focally demon strated and localized in the cytoplasm. However, there was no choriocarcinomatous component in the carci noma tissue from this case. Thus. HCG production, its endocrine manifestation, gynecomastia, and the detection of HCG-producing ele ments in the bladder tumors may provide useful informa tion on tum or progression in patients with urothelial malignancies [13].
References 6 Yamase HT, Wurzer RS, Nieh PT, Gondos B: Immunohistochemical demonstration of hu man chorionic gonadotropin in tumors of the urinary bladder. Ann Clin Lab Sci 1985:15: 414-417. 7 Fukutani K, Libby JM, Panko WB, Scardino PT: Human chorionic gonadotropin detected in urinary concentrates from patients with ma lignant tumors of the testis, prostate, bladder, ureter and kidney. J Urol 1983;129:74-77. 8 Burry AF. Munn SR. Arnold EP, McRae CU: Trophoblastic metaplasia in urothelial carci noma of the bladder. Br J Urol 1986;58:143— 146. 9 Mizuochi T, Nishimura R, Dcrappe C, Taniguchi T, Hamamoto T, Mochizuki M, Kobata A: Structures of the asparagine-linked sugar chains of human chorionic gonadotropin pro duced in choriocarcinoma. J Biol Chem 1983; 258:14126-14129.
10 Rodenberg CJ, Kruscman ACN, de Maaker HA, Freuren GJ, van Oosterom AT: Immuno histochemical localization and chromato graphic characterization of human chorionic gonadotropin in a bladder carcinoma. Arch Pa thol Lab Med 1985;109:1046-1048. 11 Shah VM, Newman J, Crocker J, Chappie CR, Collard MJ, O’Brien JM, Considine J: Ectopic p-human chorionic gonadotropin production by bladder urothelial neoplasia. Arch Pathol Lab Med 1986;110:107-111. 12 Campo EC, Algaba F. Palacin A, Germa R, Sole-galcells FJ, Cardcsa A: Placental proteins in high-grade urothelial neoplasms. An immu nohistochemical study of human chorionic go nadotropin, human placental lactogen, and pregnancy-specific beta-l-glyoprotein. Cancer 1989;63:2497-2504. 13 Martin JE, Jenkins RJ, Zuk RJ, Oliver RTD, Baithum SI: Human chorionic gonadotrophin expression and histological findings as predic tors of response to radiotherapy in carcinoma of the bladder. Virchows Arch 1989:414:273277.
465
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 1:08:47 AM
1 Dexeus F, Logothetis C, Hossan E, Samuels ML: Carcinoembryonic antigen and beta-hu man chorionic gonadotropin as serum markers for advanced urothelial malignancies. J Urol 1986:136:403-407. 2 Hyman A, Leiter HE: Extratesticular chorioepithelioma in a male probably primary in the urinary bladder. J Mt Sinai Hosp 1943; 10:212— 219. 3 Ainsworth RW, Greshman GA: Primary cho riocarcinoma of the urinary bladder in a male. J Pathol Bacteriol 1960;79:185-192. 4 Kawamura J. Machida S. Yoshida O, Oscko F, Imura H. Hattori M: Bladder carcinoma asso ciated with ectopic production of gonadotro pin. Cancer 1978;42:2773-2780. 5 Dennis PM. Turner AG: Primary choriocarci noma of the bladder evolving from a transi tional cell carcinoma. J Clin Pathol I984;37: 503-505.
