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Multiple primary adenocarcinomas of urogenital tract
MULTIPLE
PRIMARY ADENOCARCINOMAS
UROGENITAL
OF
TRACT
SAKTI DAS, M.D. STANLEY
A. BROSMAN,
M.D.
From the Department of Surgery, Division of Urology, County of Los Angeles/Harbor General Hospital, Torrance, California
ABSTRACT - A case of multiple adenocarcinoma arising from the kidney, bladder, and prostate is presented with a relevant discussion of the possible factors of pathogenesis. A staged approach ofradical extirpative surgery is suggested. .___
Aside from multicentric urothelial transitional cell carcinomas, multiple primary tumors of the urogenital tract are unusual. There have been sporadic reports of two neoplasms of dissimilar histogenesis in the same organ, or multiple synchronous and metachronous appearance of similar or dissimilar neoplasms arising in different organs. The simultaneous occurrence of primary adenocarcinoma of kidney, bladder, and prostate prompted this case report.
(Fig. 1). Venacavography and right renal venography did not show any tumor permeation. Me&static workup with bone survey, chest tomography, bone scan, and liver scan were all unremarkable. Extirpation of the right kidney and bladder carcinoma was planned, but in view of his compromised pulmonary function these procedures
Case Report A sixty-eight-year-old male presented with a two-week history of intermittent total hematuria with mild dysuria. He also had symptoms of progressive lower urinary tract obstruction for the previous year. Hemogram and blood chemistries revealed no abnormalities. His chest x-ray film showed marked emphysematous changes. Intravenous urography revealed a right renal mass distorting the middle calyces. On cystoscopy a large solid tumor, 4 cm. in diameter, was seen on the right lateral wall with another tumor, 2 cm. in diameter, on the dome of the bladder. Transurethral biopsies from the bladder demonstrated an adenocarcinoma arising in the bladder. Ultrasonogram of the right kidney showed a 4-cm. mass in the midlateral portion which was thought to be cystic. Subsequently, a selective renal angiogram with epinephrine infusion delineated a solid tumor mass with neovascularity
UROLOGY
/ SEPTEMBER
1976 / VOLUME
VIII,
NUMBER
FIGURE 1. Renal angiogram with epinephrine infbtion demonstrating solid tumor mass with neooascularity.
3
277
FIGURE 2. (A) Kidney specimen revealed clear cell carcinoma; cells arranged in cords and alveoli with interspersed areas of focal hemorrhage. (B) Bladder specimen demonstrating well-di.erentiated adenocarcinema with papillary formation and superficial muscle involvement. (C) Specimen of prostate revealed benign hyperplasia with areas of well-differentiated adenocarcinoma.
were staged. Initially the patient underwent a radical right nephrectomy with lymph node dissection and a left ureteroileocutaneous diversion. His postoperative course was complicated by pulmonary problems. He had persistent hypoxia and hypercapnia along with marked hypochloremic alkalosis due to large output of gastric drainage. However, with intensive pulmonary care and meticulous electrolyte replacement, the patient recovered fully and was discharged. Six weeks later he was readmitted after receiving a four-day course of radiation (1,600 rads) to the bladder and underwent a radical cystectomy and pelvic lymphadenectomy. His postoperative course this time was uneventful. Histologic examination of the kidney revealed a characteristic clear cell carcinoma without evidence of spread beyond the pseudocapsule. The cells were arranged in cords and alveoli with interspersed areas of focal hemorrhage (Fig. 2A). The bladder specimen showed a moderately well-differentiated adenocarcinoma with papillary formation and superficial muscle involvement (Fig. 2B). The Iymph nodes had active
278
germinal centers and sinus histiocytoses but no evidence of metastases. His prostate revealed benign hyperplasia with areas of moderately welldifferentiated adenocarcinoma (Fig. 2C). Twelve months have elapsed since his discharge. He remains well, and there has been no evidence of tumor recurrence. Comment Because of the biologic unpredictability of most malignancies, the criteria for distinguishing between a second primary growth and that of a metastatic lesion are often uncertain. Most authors have agreed with the criteria presented by Warren and Gates in 1932. ’They postulated that in multiple primary neoplasms (1) each of the tumors must present a definite picture of malignancy, (2) each tumor then must have a distinctive histologic pattern, and (3) the possibility of one lesion being metastatic from the other must be excluded. The incidence of multiple primary neoplasms varies between 2.8 to 11.7 per cent. Berg was
UROLOGY
/ SEPTEMBER 1976 / VOLUME
VIII, NUMBER 3
quoted by Hamoudi et al. 2 as reporting the highest incidence of 11.7 per cent in a series of 4,323 patients, 5 of whom had as many as four primary tumors. At the Mayo Clinic, 1,049 of the 37,580 cancer patients in a ten-year period had multiple primaries3 There were 44 patients with transitional cell carcinoma of the bladder with coexisting prostatic adenocarcinoma, 3 patients with renal adenocarcinoma and bladder carcinoma, 15 with renal adenocarcinoma and prostatic adenocarcinoma, and 1 with renal adenocarcinema, transitional cell carcinoma of bladder, and prostatic adenocarcinoma. Villegas’ reported 2 patients with bilateral primary malignant renal tumors of dissimilar histogenesis and cited two more reports by Wagner (1912) and Camerer (1940). One of the patients reported by Villegas had a concurrent adenocarcinema of the prostate. Urothelial transitional cell carcinomas have been reported in association with renal cell carcinoma5 and Wilms’ tumor.6 Adenocarcinomas constitute the rarest variety of bladder carcinomas, but solitary tumor implants from renal adenocarcinomas have been reported.7 In the patient under discussion the characteristic papillary adenocarcinomatous change of the bladder tumor bore no histologic resemblance to the clear cell carcinoma of the kidney. Its localization to the mucosa of the dome of the bladder helped to substantiate the diagnosis of a primary adenocarcinoma perhaps originating in urachal remnant cells. A number of unproved theories have been expressed to explain these unusual occurrences. Prolonged life expectancy coupled with improved survival of certain cancers could increase the incidence of multiple malignancies.8 Suen, Lau, and Yermakovg observed multiple tumors in 10 per cent of their cancer patients in the sixty-six to seventy-five year age group compared with 8.4 per cent in the seventy-five to eighty-six year age group, and 11.6 per cent in those beyond eightysix years in incidence-associated data. These do not show a significant rise in incidence associated with increasing age. However, the number of primaries in these patients increased steadily with advancing age. Thus, it would appear that increasing age per se may not give rise to more patients with multiple neoplasms but might encourage carcinogenesis in a host already susceptible to the cumulative effects of a carcinogenic environment. Other factors have also been implicated. These include immunodeficiency disease, immunosuppression, and radiation therapy. lo McIntyre and Pointon” demonstrated a higher incidence of
UROLOGY
/ SElTEMBER
1976 / VOLUME
VIII.
bladder cancer in women with cervical carcinoma treated with radiation therapy than in a comparable nonirradiated population. Immunodeficiency and immunosuppression have also been incriminated potentiating carcinogenesis. Hamoudi et al. l2 reported multiple primary neoplasms in an adolescent girl with immunoglobulin-A deficiency. The carcinogenic potential of ionizing radiation is well established. Cohen and D’Angio’O reported unusual bone tumors in children after radiation therapy. Because of the multicentric potential of urothelial tumors, a thorough search for additional urinary tract tumors should be undertaken. Treatment plans are based on the nature and extent of the primary malignancies. If clinically warranted, radical extirpative surgery may be the optimum form of therapy. Data on other patients with multiple cancers indicate that the prognosis is usually poor. 1000 West Carson Street Torrance, California 90509 (DR. BROSMAN) References 1. WARREN, S., and GATES,0. :
Multiple primary malignant tumors: a survey of the literature and a statistical study, Am. J. Cancer 16: 1358 (1932).
2.
3.
BERG. Quoted by Hamoudi, ,4. B., et al.: Llultiple neoplasms in an adolescent child associated with IGA deficiency, Cancer 33: 1133 (1974). MOERTEL, C. G.: Multiple Primary Malignant Neoplasms. Recent Results in Cancer Research, New York, Springer Verlag, Inc., 1966, vol. 7. p. 4.
4. VILLECAS, A. C.:
5.
6. 7. 8.
Bilateral primary malignant renal tumors of dissimilar histogenesis. Report of 2 cases and review of literature, J. Urol. 98: 450 (1967). GILLIS, D. J., FINNERTY, P., and MAXTED, W. C. : Simultaneous occurrence of hypernephroma and transitional cell carcinoma with development of transitional cell carcinoma in the opposite kidney: case report, ibid. 166: 646 (1971). ORLIN, I.: Association of two contiguous urological tumors with adult Wilms’ tumor, ibid. 109: 362 (1973). BUTLER, M. J.: A solitary metastasis to the bladder from a renaladenocarcinoma, Br. J. Urol. 46: 584 (1974). GEBHART, R. N.: Multiple neoplasms occurring in a single individual, (1974).
Eye
Ear Nose Throat
Mon. 53: 235
SUEN, K. C., LAU, L. L., and YERMABO~,V.: Cancer and old age: an autopsy study of 3,535 patients over 65 years old, Cancer 33: 1164 (1974). IJnusual bone tumors 10. COHEN, J., and D’ANCIO, G. J.: after roentgen therapy of children - two case reports, Am. J. Roentgenol. Radium Ther. Nucl. Med. 86: 502 9.
(1961). 11. MCINTYRE, D., and POINTON,R. C. S.:
NUMBER 3
Vesical neo-
plasm occurring after radiation treatment for carcinoma of the uterine (1971).
cervix.
J. R. Coll.
Surg.
Edinh.
16: 141
279
PRIMARY ADENOCARCINOMAS
UROGENITAL
OF
TRACT
SAKTI DAS, M.D. STANLEY
A. BROSMAN,
M.D.
From the Department of Surgery, Division of Urology, County of Los Angeles/Harbor General Hospital, Torrance, California
ABSTRACT - A case of multiple adenocarcinoma arising from the kidney, bladder, and prostate is presented with a relevant discussion of the possible factors of pathogenesis. A staged approach ofradical extirpative surgery is suggested. .___
Aside from multicentric urothelial transitional cell carcinomas, multiple primary tumors of the urogenital tract are unusual. There have been sporadic reports of two neoplasms of dissimilar histogenesis in the same organ, or multiple synchronous and metachronous appearance of similar or dissimilar neoplasms arising in different organs. The simultaneous occurrence of primary adenocarcinoma of kidney, bladder, and prostate prompted this case report.
(Fig. 1). Venacavography and right renal venography did not show any tumor permeation. Me&static workup with bone survey, chest tomography, bone scan, and liver scan were all unremarkable. Extirpation of the right kidney and bladder carcinoma was planned, but in view of his compromised pulmonary function these procedures
Case Report A sixty-eight-year-old male presented with a two-week history of intermittent total hematuria with mild dysuria. He also had symptoms of progressive lower urinary tract obstruction for the previous year. Hemogram and blood chemistries revealed no abnormalities. His chest x-ray film showed marked emphysematous changes. Intravenous urography revealed a right renal mass distorting the middle calyces. On cystoscopy a large solid tumor, 4 cm. in diameter, was seen on the right lateral wall with another tumor, 2 cm. in diameter, on the dome of the bladder. Transurethral biopsies from the bladder demonstrated an adenocarcinoma arising in the bladder. Ultrasonogram of the right kidney showed a 4-cm. mass in the midlateral portion which was thought to be cystic. Subsequently, a selective renal angiogram with epinephrine infusion delineated a solid tumor mass with neovascularity
UROLOGY
/ SEPTEMBER
1976 / VOLUME
VIII,
NUMBER
FIGURE 1. Renal angiogram with epinephrine infbtion demonstrating solid tumor mass with neooascularity.
3
277
FIGURE 2. (A) Kidney specimen revealed clear cell carcinoma; cells arranged in cords and alveoli with interspersed areas of focal hemorrhage. (B) Bladder specimen demonstrating well-di.erentiated adenocarcinema with papillary formation and superficial muscle involvement. (C) Specimen of prostate revealed benign hyperplasia with areas of well-differentiated adenocarcinoma.
were staged. Initially the patient underwent a radical right nephrectomy with lymph node dissection and a left ureteroileocutaneous diversion. His postoperative course was complicated by pulmonary problems. He had persistent hypoxia and hypercapnia along with marked hypochloremic alkalosis due to large output of gastric drainage. However, with intensive pulmonary care and meticulous electrolyte replacement, the patient recovered fully and was discharged. Six weeks later he was readmitted after receiving a four-day course of radiation (1,600 rads) to the bladder and underwent a radical cystectomy and pelvic lymphadenectomy. His postoperative course this time was uneventful. Histologic examination of the kidney revealed a characteristic clear cell carcinoma without evidence of spread beyond the pseudocapsule. The cells were arranged in cords and alveoli with interspersed areas of focal hemorrhage (Fig. 2A). The bladder specimen showed a moderately well-differentiated adenocarcinoma with papillary formation and superficial muscle involvement (Fig. 2B). The Iymph nodes had active
278
germinal centers and sinus histiocytoses but no evidence of metastases. His prostate revealed benign hyperplasia with areas of moderately welldifferentiated adenocarcinoma (Fig. 2C). Twelve months have elapsed since his discharge. He remains well, and there has been no evidence of tumor recurrence. Comment Because of the biologic unpredictability of most malignancies, the criteria for distinguishing between a second primary growth and that of a metastatic lesion are often uncertain. Most authors have agreed with the criteria presented by Warren and Gates in 1932. ’They postulated that in multiple primary neoplasms (1) each of the tumors must present a definite picture of malignancy, (2) each tumor then must have a distinctive histologic pattern, and (3) the possibility of one lesion being metastatic from the other must be excluded. The incidence of multiple primary neoplasms varies between 2.8 to 11.7 per cent. Berg was
UROLOGY
/ SEPTEMBER 1976 / VOLUME
VIII, NUMBER 3
quoted by Hamoudi et al. 2 as reporting the highest incidence of 11.7 per cent in a series of 4,323 patients, 5 of whom had as many as four primary tumors. At the Mayo Clinic, 1,049 of the 37,580 cancer patients in a ten-year period had multiple primaries3 There were 44 patients with transitional cell carcinoma of the bladder with coexisting prostatic adenocarcinoma, 3 patients with renal adenocarcinoma and bladder carcinoma, 15 with renal adenocarcinoma and prostatic adenocarcinoma, and 1 with renal adenocarcinema, transitional cell carcinoma of bladder, and prostatic adenocarcinoma. Villegas’ reported 2 patients with bilateral primary malignant renal tumors of dissimilar histogenesis and cited two more reports by Wagner (1912) and Camerer (1940). One of the patients reported by Villegas had a concurrent adenocarcinema of the prostate. Urothelial transitional cell carcinomas have been reported in association with renal cell carcinoma5 and Wilms’ tumor.6 Adenocarcinomas constitute the rarest variety of bladder carcinomas, but solitary tumor implants from renal adenocarcinomas have been reported.7 In the patient under discussion the characteristic papillary adenocarcinomatous change of the bladder tumor bore no histologic resemblance to the clear cell carcinoma of the kidney. Its localization to the mucosa of the dome of the bladder helped to substantiate the diagnosis of a primary adenocarcinoma perhaps originating in urachal remnant cells. A number of unproved theories have been expressed to explain these unusual occurrences. Prolonged life expectancy coupled with improved survival of certain cancers could increase the incidence of multiple malignancies.8 Suen, Lau, and Yermakovg observed multiple tumors in 10 per cent of their cancer patients in the sixty-six to seventy-five year age group compared with 8.4 per cent in the seventy-five to eighty-six year age group, and 11.6 per cent in those beyond eightysix years in incidence-associated data. These do not show a significant rise in incidence associated with increasing age. However, the number of primaries in these patients increased steadily with advancing age. Thus, it would appear that increasing age per se may not give rise to more patients with multiple neoplasms but might encourage carcinogenesis in a host already susceptible to the cumulative effects of a carcinogenic environment. Other factors have also been implicated. These include immunodeficiency disease, immunosuppression, and radiation therapy. lo McIntyre and Pointon” demonstrated a higher incidence of
UROLOGY
/ SElTEMBER
1976 / VOLUME
VIII.
bladder cancer in women with cervical carcinoma treated with radiation therapy than in a comparable nonirradiated population. Immunodeficiency and immunosuppression have also been incriminated potentiating carcinogenesis. Hamoudi et al. l2 reported multiple primary neoplasms in an adolescent girl with immunoglobulin-A deficiency. The carcinogenic potential of ionizing radiation is well established. Cohen and D’Angio’O reported unusual bone tumors in children after radiation therapy. Because of the multicentric potential of urothelial tumors, a thorough search for additional urinary tract tumors should be undertaken. Treatment plans are based on the nature and extent of the primary malignancies. If clinically warranted, radical extirpative surgery may be the optimum form of therapy. Data on other patients with multiple cancers indicate that the prognosis is usually poor. 1000 West Carson Street Torrance, California 90509 (DR. BROSMAN) References 1. WARREN, S., and GATES,0. :
Multiple primary malignant tumors: a survey of the literature and a statistical study, Am. J. Cancer 16: 1358 (1932).
2.
3.
BERG. Quoted by Hamoudi, ,4. B., et al.: Llultiple neoplasms in an adolescent child associated with IGA deficiency, Cancer 33: 1133 (1974). MOERTEL, C. G.: Multiple Primary Malignant Neoplasms. Recent Results in Cancer Research, New York, Springer Verlag, Inc., 1966, vol. 7. p. 4.
4. VILLECAS, A. C.:
5.
6. 7. 8.
Bilateral primary malignant renal tumors of dissimilar histogenesis. Report of 2 cases and review of literature, J. Urol. 98: 450 (1967). GILLIS, D. J., FINNERTY, P., and MAXTED, W. C. : Simultaneous occurrence of hypernephroma and transitional cell carcinoma with development of transitional cell carcinoma in the opposite kidney: case report, ibid. 166: 646 (1971). ORLIN, I.: Association of two contiguous urological tumors with adult Wilms’ tumor, ibid. 109: 362 (1973). BUTLER, M. J.: A solitary metastasis to the bladder from a renaladenocarcinoma, Br. J. Urol. 46: 584 (1974). GEBHART, R. N.: Multiple neoplasms occurring in a single individual, (1974).
Eye
Ear Nose Throat
Mon. 53: 235
SUEN, K. C., LAU, L. L., and YERMABO~,V.: Cancer and old age: an autopsy study of 3,535 patients over 65 years old, Cancer 33: 1164 (1974). IJnusual bone tumors 10. COHEN, J., and D’ANCIO, G. J.: after roentgen therapy of children - two case reports, Am. J. Roentgenol. Radium Ther. Nucl. Med. 86: 502 9.
(1961). 11. MCINTYRE, D., and POINTON,R. C. S.:
NUMBER 3
Vesical neo-
plasm occurring after radiation treatment for carcinoma of the uterine (1971).
cervix.
J. R. Coll.
Surg.
Edinh.
16: 141
279