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A Double Primary Carcinoma of the Urinary Bladder
THE JOURNAL OF UROLOGY
Vol. 72, No. 6, December 1954 Printed in U.S.A.
A DOUBLE PRIMARY CARCINOMA OF THE URINARY BLADDER MICHAEL ROHMAN
AND
SHELDON C. SOMMERS
From the Departments of Pathology and Surgery, Massachusetts Memorial Hospitals, Boston 18, Mass.
Aside from papillary tumors, multiple primary carcinomas of the genitourinary tract are less common than multiple malignancies elsewhere in the body. 1 To our knowledge not more than 4 previous cases of adenocarcinoma with epidermoid carcinoma of the urinary bladder appear in the English literature and one such unusual case is presented. CASE REPORT
H. B., a 75-year-old white married man, was admitted to Massachusetts Memorial Hospitals on January 21, 1954, with the chief complaint of gross hematuria of 1 week's duration which increased until the passage of frank blood clots necessitated hospital admission. The family history revealed the patient's father to have died of carcinoma of the prostate. The environmental history demonstrated a prolonged direct and indirect exposure to aniline dyes. From 1912~1916 he worked in the transportation of drums of aniline dyes, frequently staining his hands with the material. For the succeeding 35 years he worked as a shipper in a leather factory handling skins treated with aniline dyes, although he was not directly active in the processing of the hides. The physical examination revealed an elderly white man with deafaess, a grade I aortic systolic murmur and occasional basilar rales. The remainder of the examination was essentially negative. The laboratory examinations on admission confirmed the presence of hematuria. There was no anemia and the nonprotein nitrogen was normal. Roentgen studies presented no evidence of metastatic carcinoma. The flat abdominal film showed both kidneys to be normal in size and shape, and the psoas outlines were clear. Excretory urography showed good dye concentration in the kidneys, with normal filling of the renal pelves and calyces. There was marked irregularity of the bladder consistent with tumor. On January 22, 1954, cystoscopy revealed a large, fungating, ulcerated growth on the right lateral and posterior wall of the bladder extending to the dome. On January 25, 1954, a partial cystectomy was performed by Dr. Samuel N. Vose. The tumor was found to be a hard, fungating growth involving the entire dome of the bladder, extending into both lateral walls toward the trigone. The lesion was most extensive on the right side, although neither ureter was grossly involved. An estimated three-fifths of the bladder was resected with approximately 1.0 cm. of marginal uninvolved tissue. This investigation was aided in part by a research grant (C-1754) from the National Cancer Institute of the ~ational Institutes of Health, U.S. Public Health Service. Accepted for publication May 21, 1954. 1 Kretschmer, H. L.: J. Urol., 40: 421-445, 1938. 1174
DOUBLE PRIMARY CARCINOMA
1175
Fm. 1. A, nodule of adenocarcinoma found in base of bladder ulceration. It is partly surrounded by cpidermoid carcinoma. S54-252. Hematoxylin and eosin stains. B, area of collision of adenocarcinoma and cpidermoid carcinoma. Transitions between two neoplasms were not observed. C, cystitis glandularis area from cystectomy specimen, with atypical epithelial changes, possibly precancerous.
1176
MICHAEL ROHMAN AND SHELDON C. SOMMERS
Pathologic study of the resected specimen showed it to consist of a ,go gm. disc-shaped section of urinary bladder and tumor measuring 8.5 by 8.5 cm. in diameter and averaging 3.2 cm. in thickness. The mucosal surface presented a central ulceration measuring 1.6 cm. in cross diameter and 0.3 cm. in depth with tapering margins. The base was granular and a yellowish gray in color. The entire bladder wall was infiltrated and replaced by a yellowish-gray, rubbery, hard tumor which extended to the peritoneal surface and which cut with a granular sensation. Microscopically a specimen taken from the area of gross ulceration showed the base to be composed, in part, of an elliptical nodule of adenoca11cinoma (fig. li, A). The malignant glands were moderately well differentiated and composed of cuboidal and columnar cells with irregular large nuclei. A few mitoses and goblet cells were identified. At its base the adenocarcinoma was surnmnding small blood vessels and along one margin it was in contact with but did not merge with typical epidermoid carcinoma, grade II (fig. 1, B). At this margin the surface was composed of metaplastic glandular epithelium and there were a few glands of the cystitis glandularis type which did not appear carcinomatous. Beneath the adenocarcinoma, irregular strands of epidermoid carcinoma, grade II, were invading the full thickness of the bladder wall. An additional section of bladder wall showed the mucosa to be replaced by metaplastic cystitis glandularis (fig. 1, C). The cells which formed the glands varied in size, polarity, and nuclear structure, suggesting the possibility of a precancerous condition. DISCUSSION
Various authors indicate that primary adenocarcinoma of the urinary bladder represents 0.1 to 2.0 per cent of all primary bladder tumors. Howard and Bergman2 reported 8 cases in 1064 cases of bladder neoplasms, an incidence of 0.75 per cent. Hamm3 reported 17 cases of glandular tumors of the bladder in a group of 902 cases coded by the American Urological Association Registry of Tumors, an incidence of 1.9 per cent. Coppridge et al. 4 found two such cases listed among 2000 bladder neoplasms coded by the Army Institute of Pathology. It is generally believed that adenocarcinoma of the urinary bladder arises from one of three possible sites: 6 • 6 1) the paraprostatic glands situated in the bladder neck; 2) urachal rests in the bladder dome; 3) areas of glandular metaplasia anywhere in the bladder, i.e. cystitis glandularis. The latter lesion is considered to be pre-cancerous by many observers. 2· 4 • 5 • 7 The development of adenocarcinoma in these metaplastic glands is well demonstrated by the presei:i:t case wherein frank adenocarcinoma is seen adjacent to an area of marked cystitis glandularis. Multiple primary bladder tumors of different cell origins have rarely been Howard, A.H. and Bergman, R. T.: J. Urol., 69: 455--460, 1948. Harnrn, F. C.: J. Urol., 44: 227-233, 1944. 4 Coppridge, W. M., Roberts, L. C. and Culp, D. A.: J. Urol., 66: 540-549, 1951. 5 Ash, J.E.: J. Urol., 44: 135-145, 1944. 6 Ruckel, R.: In Handb. d. Spez. Path. Anat. u. Hist.; Lubarsch u. Henke. Berlin: J. Springer, 1934, vol. 6:2, pp. 632-636. 7 Patch, F. S.: J.A.M.A., 136: 824-827, 1948. 2
3
DOUBLE PRIMARY CARCINOMA
1177
mentioned in the literature. W agner 8 reported a case of benign adenoma in association with squamous carcinoma in an exstrophied bladder. Mackles et aP described a case of papillary carcinoma with primary leiomyosarcoma of the bladder. Wheeler and Hi1110 described 2 cases of combined epidermoid and adenocarcinoma of the bladder. Saphir and Kurland 11 reported 2 cases in which carcinoma of the urinary bladder contained glandular and transitional cell types, intermixed. They suggested that such tumors arose from one area in which the two cell types were present rather than from two or more separate regions. Because the epidermoid and glandular cells of the tumor herein reported were so sharply demarcated, and because the glandular cells were so clearly associated with marked cystitis glandularis, we consider this case to represent a true instance of double primary neoplasm arising from different cell types and areas. Ash 5 found a positive history of aniline dye exposure in 75 of 2500 cases of bladder tumor. Hueper12 stated that "aniline tumors" of the bladder are usually of the broad based papillary or nodular infiltrative transitional cell type. Although no cases of adenocarcinoma of the bladder in aniline dye workers are previously reported, Hueper stated that "aniline tumors" may be of the glandular type and that they represent 2 per cent of the tumors, an incidence similar to that found in malignant bladder tumors of unknown etiology. He further noted that while most of the tumors occur in workers involved in the processing of aniline dyes, occasional lesions are reported in workers handling the finished dyes. SUMMARY
A case is reported in which the patient had known exposure to aniline dyes and in whom a separate adenocarcinoma and epidermoid carcinoma of the bladder developed in association ·with cystitis glandularis. No similar case was found in a review of the literature. Wagner, A.: Deutsche Ztschr. Chir., 104: 329-334, 1910. Mackles, A., Immergut, S., Grayzel, D. M. and Cottler, Z. R.: J. Urol., 59: 1121-1126, 1948. 10 Wheeler, J. D. and Hill, W. T Cancer, 7: 119-135, 1954. 11 Saphir, 0. and Kurland, S. K. Urol. & Cutan. Rev., 43: 709-719, 1939. 12 Hueper, W. C.: Arch. Path., 25 856-899, 1938. 8 9
Vol. 72, No. 6, December 1954 Printed in U.S.A.
A DOUBLE PRIMARY CARCINOMA OF THE URINARY BLADDER MICHAEL ROHMAN
AND
SHELDON C. SOMMERS
From the Departments of Pathology and Surgery, Massachusetts Memorial Hospitals, Boston 18, Mass.
Aside from papillary tumors, multiple primary carcinomas of the genitourinary tract are less common than multiple malignancies elsewhere in the body. 1 To our knowledge not more than 4 previous cases of adenocarcinoma with epidermoid carcinoma of the urinary bladder appear in the English literature and one such unusual case is presented. CASE REPORT
H. B., a 75-year-old white married man, was admitted to Massachusetts Memorial Hospitals on January 21, 1954, with the chief complaint of gross hematuria of 1 week's duration which increased until the passage of frank blood clots necessitated hospital admission. The family history revealed the patient's father to have died of carcinoma of the prostate. The environmental history demonstrated a prolonged direct and indirect exposure to aniline dyes. From 1912~1916 he worked in the transportation of drums of aniline dyes, frequently staining his hands with the material. For the succeeding 35 years he worked as a shipper in a leather factory handling skins treated with aniline dyes, although he was not directly active in the processing of the hides. The physical examination revealed an elderly white man with deafaess, a grade I aortic systolic murmur and occasional basilar rales. The remainder of the examination was essentially negative. The laboratory examinations on admission confirmed the presence of hematuria. There was no anemia and the nonprotein nitrogen was normal. Roentgen studies presented no evidence of metastatic carcinoma. The flat abdominal film showed both kidneys to be normal in size and shape, and the psoas outlines were clear. Excretory urography showed good dye concentration in the kidneys, with normal filling of the renal pelves and calyces. There was marked irregularity of the bladder consistent with tumor. On January 22, 1954, cystoscopy revealed a large, fungating, ulcerated growth on the right lateral and posterior wall of the bladder extending to the dome. On January 25, 1954, a partial cystectomy was performed by Dr. Samuel N. Vose. The tumor was found to be a hard, fungating growth involving the entire dome of the bladder, extending into both lateral walls toward the trigone. The lesion was most extensive on the right side, although neither ureter was grossly involved. An estimated three-fifths of the bladder was resected with approximately 1.0 cm. of marginal uninvolved tissue. This investigation was aided in part by a research grant (C-1754) from the National Cancer Institute of the ~ational Institutes of Health, U.S. Public Health Service. Accepted for publication May 21, 1954. 1 Kretschmer, H. L.: J. Urol., 40: 421-445, 1938. 1174
DOUBLE PRIMARY CARCINOMA
1175
Fm. 1. A, nodule of adenocarcinoma found in base of bladder ulceration. It is partly surrounded by cpidermoid carcinoma. S54-252. Hematoxylin and eosin stains. B, area of collision of adenocarcinoma and cpidermoid carcinoma. Transitions between two neoplasms were not observed. C, cystitis glandularis area from cystectomy specimen, with atypical epithelial changes, possibly precancerous.
1176
MICHAEL ROHMAN AND SHELDON C. SOMMERS
Pathologic study of the resected specimen showed it to consist of a ,go gm. disc-shaped section of urinary bladder and tumor measuring 8.5 by 8.5 cm. in diameter and averaging 3.2 cm. in thickness. The mucosal surface presented a central ulceration measuring 1.6 cm. in cross diameter and 0.3 cm. in depth with tapering margins. The base was granular and a yellowish gray in color. The entire bladder wall was infiltrated and replaced by a yellowish-gray, rubbery, hard tumor which extended to the peritoneal surface and which cut with a granular sensation. Microscopically a specimen taken from the area of gross ulceration showed the base to be composed, in part, of an elliptical nodule of adenoca11cinoma (fig. li, A). The malignant glands were moderately well differentiated and composed of cuboidal and columnar cells with irregular large nuclei. A few mitoses and goblet cells were identified. At its base the adenocarcinoma was surnmnding small blood vessels and along one margin it was in contact with but did not merge with typical epidermoid carcinoma, grade II (fig. 1, B). At this margin the surface was composed of metaplastic glandular epithelium and there were a few glands of the cystitis glandularis type which did not appear carcinomatous. Beneath the adenocarcinoma, irregular strands of epidermoid carcinoma, grade II, were invading the full thickness of the bladder wall. An additional section of bladder wall showed the mucosa to be replaced by metaplastic cystitis glandularis (fig. 1, C). The cells which formed the glands varied in size, polarity, and nuclear structure, suggesting the possibility of a precancerous condition. DISCUSSION
Various authors indicate that primary adenocarcinoma of the urinary bladder represents 0.1 to 2.0 per cent of all primary bladder tumors. Howard and Bergman2 reported 8 cases in 1064 cases of bladder neoplasms, an incidence of 0.75 per cent. Hamm3 reported 17 cases of glandular tumors of the bladder in a group of 902 cases coded by the American Urological Association Registry of Tumors, an incidence of 1.9 per cent. Coppridge et al. 4 found two such cases listed among 2000 bladder neoplasms coded by the Army Institute of Pathology. It is generally believed that adenocarcinoma of the urinary bladder arises from one of three possible sites: 6 • 6 1) the paraprostatic glands situated in the bladder neck; 2) urachal rests in the bladder dome; 3) areas of glandular metaplasia anywhere in the bladder, i.e. cystitis glandularis. The latter lesion is considered to be pre-cancerous by many observers. 2· 4 • 5 • 7 The development of adenocarcinoma in these metaplastic glands is well demonstrated by the presei:i:t case wherein frank adenocarcinoma is seen adjacent to an area of marked cystitis glandularis. Multiple primary bladder tumors of different cell origins have rarely been Howard, A.H. and Bergman, R. T.: J. Urol., 69: 455--460, 1948. Harnrn, F. C.: J. Urol., 44: 227-233, 1944. 4 Coppridge, W. M., Roberts, L. C. and Culp, D. A.: J. Urol., 66: 540-549, 1951. 5 Ash, J.E.: J. Urol., 44: 135-145, 1944. 6 Ruckel, R.: In Handb. d. Spez. Path. Anat. u. Hist.; Lubarsch u. Henke. Berlin: J. Springer, 1934, vol. 6:2, pp. 632-636. 7 Patch, F. S.: J.A.M.A., 136: 824-827, 1948. 2
3
DOUBLE PRIMARY CARCINOMA
1177
mentioned in the literature. W agner 8 reported a case of benign adenoma in association with squamous carcinoma in an exstrophied bladder. Mackles et aP described a case of papillary carcinoma with primary leiomyosarcoma of the bladder. Wheeler and Hi1110 described 2 cases of combined epidermoid and adenocarcinoma of the bladder. Saphir and Kurland 11 reported 2 cases in which carcinoma of the urinary bladder contained glandular and transitional cell types, intermixed. They suggested that such tumors arose from one area in which the two cell types were present rather than from two or more separate regions. Because the epidermoid and glandular cells of the tumor herein reported were so sharply demarcated, and because the glandular cells were so clearly associated with marked cystitis glandularis, we consider this case to represent a true instance of double primary neoplasm arising from different cell types and areas. Ash 5 found a positive history of aniline dye exposure in 75 of 2500 cases of bladder tumor. Hueper12 stated that "aniline tumors" of the bladder are usually of the broad based papillary or nodular infiltrative transitional cell type. Although no cases of adenocarcinoma of the bladder in aniline dye workers are previously reported, Hueper stated that "aniline tumors" may be of the glandular type and that they represent 2 per cent of the tumors, an incidence similar to that found in malignant bladder tumors of unknown etiology. He further noted that while most of the tumors occur in workers involved in the processing of aniline dyes, occasional lesions are reported in workers handling the finished dyes. SUMMARY
A case is reported in which the patient had known exposure to aniline dyes and in whom a separate adenocarcinoma and epidermoid carcinoma of the bladder developed in association ·with cystitis glandularis. No similar case was found in a review of the literature. Wagner, A.: Deutsche Ztschr. Chir., 104: 329-334, 1910. Mackles, A., Immergut, S., Grayzel, D. M. and Cottler, Z. R.: J. Urol., 59: 1121-1126, 1948. 10 Wheeler, J. D. and Hill, W. T Cancer, 7: 119-135, 1954. 11 Saphir, 0. and Kurland, S. K. Urol. & Cutan. Rev., 43: 709-719, 1939. 12 Hueper, W. C.: Arch. Path., 25 856-899, 1938. 8 9