PARAGANGLIOMA RECURRENCE RAYMOND WILLIAM
OF BLADDER WITH
TEN YEARS LATER
A. MADDOCKS, T. FAGAN,
From the Department University of Vermont Burlington, Vermont
M.D.
JR., M.D. of Surgery, Division of Urology, College of Medicine,
- A paraganglioma (pheochromocytoma) of the bladder recurred transurethral resection. This case demonstrates principles regarding diagnosis, and treatment of this rare neoplasm.
ABSTRACT
Pheochromocytomas are functionally active chromaffrn tumors which may be located in the adrenal medulla or other sites where sympathetic ganglia or chromaffin tissue are known to exist. About 10 to 15 per cent of tumors are located in ectopic sites, the most common sites being the extra-adrenal paraganglia in the upper abdomen and the organs of Zuckerkandl. Since Zimmerman, Biron, and MacMahon’ first described a case of pheochromocytoma of the urinary bladder in 1953, approximately 60 subsequent cases have been reported. The bladder is the site of origin of about 10 per cent of extra-adrenal tumors of the paraganglion system. The proper terminology for this tumor, abandoning former terms such as pheochromocytoma, chemodectoma, and chromaffinoma, is paraganglioma of the bladder; it can be further described as functional or nonfunctional, depending on its propensity to liberate catecholamines. We herein report a case of nonfunctioning paraganglioma of the bladder which was inadequately resected initially and recurred, producing symptoms ten years later. Case Report A forty-nine-year-old female was seen in July, 1964, with recurrent gross hematuria. She had four similar episodes of painless hematuria over the preceding five years, and cystoscopy in I959 and 1963 revealed changes of hemorrhagic cystitis especially about the trigone. Other prob-
430
ten years after initial malignancy potential,
lems included long-standing obesity and mild combined hypertension since 1961, easily controlled by diuretics. Admission blood pressures averaged 140/85 mm Hg. VMA (vanilmandelic acid) excretion was 3.5 mg. per twenty-four hours (normal 1.8 to 7.1). Intravenous pyelogram was normal. Cystoscopy revealed elevation of the right side of the trigone with overlying mucosal edema and increased vascularity; bimanual examination revealed a 1.5cm. mass located between the vagina and trigone. A biopsy of this mass revealed paraganglioma with overlying mild squamous metaplasia. The patient returned three weeks later with hematuria and clot retention. After clot evacuation, further transurethral resection of the tumor was accomplished but the base of the lesion, involving the deep muscularis of the trigone had to be left in situ for fear of creating a vesicovaginal fistula. The patient refused further therapy and was discharged. The patient did not return for follow-up until ten years later when gross hematuria with clot retention recurred in August, 1974. She denied hematuria or micturition problems in the tenyear interval. A diagnosis of diabetes mellitus, insulin dependent, was made in 1965. Blood pressure during hospitalization averaged 130/75 mm Hg. VMA excretion was 3.4 mg. per twentyfour hours; catecholamine excretion was normal. Intravenous pyelogram revealed a 3 by 4-cm. filling defect on the right side of the bladder. Bimanual examination revealed a 3-cm. mass at the
UROLOGY
/ APRIL 1976: / VOLU\lE
\‘II, NUklRER 4
base of the bladder. Cystoscopy revealed a mass in the same location as the tumor present in 1964 and an additional smaller l-cm. mass on the midtrigone. The more medial mass was resected, but the larger mass, again, could only be partially removed. Again, the patient refused any furthei therapy and was discharged. Over the past year, she has been entirely asymptomatic. No elevation of blood pressure occurred during any of the three manipulations of the tumor. Histologic appearance of the tumor was similar in all specimens (Fig. 1). Small clusters of uniform somewhat polyhedral cells in characteristic acinar formation were surrounded by fibrous tissue septa. The lesion was highly vascular. Stains for chromaffin showed a positive reaction of the specimen from 1964, but several attempts failed to display chroma& staining in the 1974 specimen. The tumor occupied most of the submucosa but invaded the underlying muscularis.
Comment This case illustrates principles regarding the diagnosis and management of this rare neoplasm. First, the initial presenting symptom in our case was gross painless hematuria. In a recent review of the literature, Leestma and Price’ reported hematuria as the most common presenting symptom in patients with paraganglioma of the bladder (60 per cent of cases). These tumors are most commonly located within or near the trigone and ureteral orifices, as our patient displayed. Intermittent or sustained hypertension was noted in 64 per cent of patients while one-half had severe hypertension during or just before micturition. In most cases the tumors are functional. Our patient had normal VR4A excretion studies, signifying a nonfunctional tumor, an d therefore did not become hypertensive when the tumor was manipulated.
FIGURE 1. Representative photomicrographs of paraganglioma of bladder (A) 1964specimen; (B) 1974 specimen. iNote greater vascularity ad increased fibrous tissue in earlier specimen, whereby 1974 specimen is more cellular. (Hematoxylin and eosin stain, x 110.)
Second, because total removal of this tumor was impossible transurethrally, the recurrence ten years later was not unexpected and does not represent a malignant transformation of the tumor. The malignant potential of these tumors does not appear to differ from those of adrenal pheochromocytomas, with less than 10 per cent of reported cases being malignant. Metastases have been reported in 5 per cent of cases and recurrences after removal of the tumor in 18 per cent3 Unfortunately, there are no histologic or biochemical characteristics to differentiate benign from malignant paragangliomas. Thus, the only criteria for malignant potential are metastases at the time of diagnosis or extensive recurrences over a short period of time. Third, treatment for this neoplasm usually has been transurethral biopsy followed by bladder wedge resection, partial cystectomy with or without ureteral reimplantation, or total cystectomy. Because of the usual location of these tumors on or near the trigone, wedge resection
432
or partial cystectomy is not always feasible. In our case the patient refused further surgical therapy and only partial transurethral resection was possible; yet the patient remains presently free of symptoms eleven years after initial diagnosis. Certainly, total cystectomy would not have been appropriate therapy for this benign lesion. Urology Associates
of Burlington, Inc. 371 Pearl Street Burlington, Vermont 05401 (DR. FAGAN)
References ZIMMERMAN, I. J., BIRON, R. E., and MACMAHON, H. E.: Pheochromocytoma of the urinary bladder, N. Engl. J. Med. 249: 25 (1953). LEESTMA, J. E., and PRICE, E. J.: Paraganglioma of the urinary bladder, Cancer 28: 1063 (1971). MALONEY, G. E., COWDELL, R. H., and LEWIS, C. L.: Malignant pheochromocytoma of the bladder, Br. J. Ural. 38: 461 (1966).
UROLOGY
I APRIL 1976 / VOLUME VII, NUMBER 4
OF BLADDER WITH
TEN YEARS LATER
A. MADDOCKS, T. FAGAN,
From the Department University of Vermont Burlington, Vermont
M.D.
JR., M.D. of Surgery, Division of Urology, College of Medicine,
- A paraganglioma (pheochromocytoma) of the bladder recurred transurethral resection. This case demonstrates principles regarding diagnosis, and treatment of this rare neoplasm.
ABSTRACT
Pheochromocytomas are functionally active chromaffrn tumors which may be located in the adrenal medulla or other sites where sympathetic ganglia or chromaffin tissue are known to exist. About 10 to 15 per cent of tumors are located in ectopic sites, the most common sites being the extra-adrenal paraganglia in the upper abdomen and the organs of Zuckerkandl. Since Zimmerman, Biron, and MacMahon’ first described a case of pheochromocytoma of the urinary bladder in 1953, approximately 60 subsequent cases have been reported. The bladder is the site of origin of about 10 per cent of extra-adrenal tumors of the paraganglion system. The proper terminology for this tumor, abandoning former terms such as pheochromocytoma, chemodectoma, and chromaffinoma, is paraganglioma of the bladder; it can be further described as functional or nonfunctional, depending on its propensity to liberate catecholamines. We herein report a case of nonfunctioning paraganglioma of the bladder which was inadequately resected initially and recurred, producing symptoms ten years later. Case Report A forty-nine-year-old female was seen in July, 1964, with recurrent gross hematuria. She had four similar episodes of painless hematuria over the preceding five years, and cystoscopy in I959 and 1963 revealed changes of hemorrhagic cystitis especially about the trigone. Other prob-
430
ten years after initial malignancy potential,
lems included long-standing obesity and mild combined hypertension since 1961, easily controlled by diuretics. Admission blood pressures averaged 140/85 mm Hg. VMA (vanilmandelic acid) excretion was 3.5 mg. per twenty-four hours (normal 1.8 to 7.1). Intravenous pyelogram was normal. Cystoscopy revealed elevation of the right side of the trigone with overlying mucosal edema and increased vascularity; bimanual examination revealed a 1.5cm. mass located between the vagina and trigone. A biopsy of this mass revealed paraganglioma with overlying mild squamous metaplasia. The patient returned three weeks later with hematuria and clot retention. After clot evacuation, further transurethral resection of the tumor was accomplished but the base of the lesion, involving the deep muscularis of the trigone had to be left in situ for fear of creating a vesicovaginal fistula. The patient refused further therapy and was discharged. The patient did not return for follow-up until ten years later when gross hematuria with clot retention recurred in August, 1974. She denied hematuria or micturition problems in the tenyear interval. A diagnosis of diabetes mellitus, insulin dependent, was made in 1965. Blood pressure during hospitalization averaged 130/75 mm Hg. VMA excretion was 3.4 mg. per twentyfour hours; catecholamine excretion was normal. Intravenous pyelogram revealed a 3 by 4-cm. filling defect on the right side of the bladder. Bimanual examination revealed a 3-cm. mass at the
UROLOGY
/ APRIL 1976: / VOLU\lE
\‘II, NUklRER 4
base of the bladder. Cystoscopy revealed a mass in the same location as the tumor present in 1964 and an additional smaller l-cm. mass on the midtrigone. The more medial mass was resected, but the larger mass, again, could only be partially removed. Again, the patient refused any furthei therapy and was discharged. Over the past year, she has been entirely asymptomatic. No elevation of blood pressure occurred during any of the three manipulations of the tumor. Histologic appearance of the tumor was similar in all specimens (Fig. 1). Small clusters of uniform somewhat polyhedral cells in characteristic acinar formation were surrounded by fibrous tissue septa. The lesion was highly vascular. Stains for chromaffin showed a positive reaction of the specimen from 1964, but several attempts failed to display chroma& staining in the 1974 specimen. The tumor occupied most of the submucosa but invaded the underlying muscularis.
Comment This case illustrates principles regarding the diagnosis and management of this rare neoplasm. First, the initial presenting symptom in our case was gross painless hematuria. In a recent review of the literature, Leestma and Price’ reported hematuria as the most common presenting symptom in patients with paraganglioma of the bladder (60 per cent of cases). These tumors are most commonly located within or near the trigone and ureteral orifices, as our patient displayed. Intermittent or sustained hypertension was noted in 64 per cent of patients while one-half had severe hypertension during or just before micturition. In most cases the tumors are functional. Our patient had normal VR4A excretion studies, signifying a nonfunctional tumor, an d therefore did not become hypertensive when the tumor was manipulated.
FIGURE 1. Representative photomicrographs of paraganglioma of bladder (A) 1964specimen; (B) 1974 specimen. iNote greater vascularity ad increased fibrous tissue in earlier specimen, whereby 1974 specimen is more cellular. (Hematoxylin and eosin stain, x 110.)
Second, because total removal of this tumor was impossible transurethrally, the recurrence ten years later was not unexpected and does not represent a malignant transformation of the tumor. The malignant potential of these tumors does not appear to differ from those of adrenal pheochromocytomas, with less than 10 per cent of reported cases being malignant. Metastases have been reported in 5 per cent of cases and recurrences after removal of the tumor in 18 per cent3 Unfortunately, there are no histologic or biochemical characteristics to differentiate benign from malignant paragangliomas. Thus, the only criteria for malignant potential are metastases at the time of diagnosis or extensive recurrences over a short period of time. Third, treatment for this neoplasm usually has been transurethral biopsy followed by bladder wedge resection, partial cystectomy with or without ureteral reimplantation, or total cystectomy. Because of the usual location of these tumors on or near the trigone, wedge resection
432
or partial cystectomy is not always feasible. In our case the patient refused further surgical therapy and only partial transurethral resection was possible; yet the patient remains presently free of symptoms eleven years after initial diagnosis. Certainly, total cystectomy would not have been appropriate therapy for this benign lesion. Urology Associates
of Burlington, Inc. 371 Pearl Street Burlington, Vermont 05401 (DR. FAGAN)
References ZIMMERMAN, I. J., BIRON, R. E., and MACMAHON, H. E.: Pheochromocytoma of the urinary bladder, N. Engl. J. Med. 249: 25 (1953). LEESTMA, J. E., and PRICE, E. J.: Paraganglioma of the urinary bladder, Cancer 28: 1063 (1971). MALONEY, G. E., COWDELL, R. H., and LEWIS, C. L.: Malignant pheochromocytoma of the bladder, Br. J. Ural. 38: 461 (1966).
UROLOGY
I APRIL 1976 / VOLUME VII, NUMBER 4
