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Pheochromocytoma of the Bladder: Case Report and Summary of Literature
\/ oL 98,
THE .JOURNAL OF UROLOGY
Copyright © 1967 by The Williams & Wilkins Co.
Sepr,,
PHEOCHRCHIOCYTOMA OF THE BLADDER: CASE REPOHT AND SUMl\IARY OF LITERATURE RICHARD B. BOURNE
AND
EFSTATHIOS BELTAOS
From the Departm.eni of Surgery, Section of Urology, illarquelle Univers·ity School of Jied?;cir,.c an,l the Department of Pathology, Columbia Hospital, Jl!Iilwaukee, Wisconsin
It has heen 13 years since Zimn1erman reported the first case of pheochromocytoma of the bladder} the case herein reported is number 24. Enough time has elapsed and enough ca~es have been reported to permit a followup analysis of this fascinating disease entity 1-21 Therefore, we
have attempted to update the previously n,ported cases, thus affording a more definitive picture of the treatment and table). CASE H.EPOHT
Accepted for publication October 18, 1966. L Zimmerman, I. J.,Biron, R.E. andMacMahon, Ff. E.: Pheochromocytorna of (.he urinary bladder. NGw Engl. J. Med., 249: 25, 1953. 2 Rosenberg, L. ]\II.: Pheochromocytoma of the minary bladder. New Eng;!. ,f. Med., 257: 1212, 1957. 3 Pugh, R. C. B., Gresham, G. A. and Mullaney, J.: Pheochromocytoma of the bladder. ,T. Path. & Bacteriol., 79: 89, 1960. '1 Lumb, B. R B. and Gresham, G. A.: Phaeochrornocytoma of the urinary bladder. Lancet, 1: 81, HJ58. 5 Varl, B. and Rakovec, S.: Zdrav. vest., 3: 113, 1958. 6 Farley, S. E. and Smith, C. L.: Unnsual location of pheochromocytoma in the urinary bladder. J. Urol., 81: 130, 1959. 7 Scott, W.W. and Eversole, S. L.: Pheochromocytorna of the urinary bladder. J. Urol., 83: 656, 1960. 8 Silver, B.: Cited by Scott and Eversole. 7 9 Micic, R., Kicic, M. and Adanja, S.: Phaeochromocytoma of urinary bladder. Acta Endocr., 39: 1, 1962. 10 Berry, K. W., Jr. and Scott, E. V. Z.: Pheochromocytoma of the bladder. J. Urol., 85: 156, 1961. H Siva.k, G. C.: Pheochromocytoma of bladder. J. Urol., 86: 568, 1961. 12 Tan, T-L. and Young, B. W.: Pheochromocytoma of the bladder; case report. J. Urol., 87: 53, 1962. 13 Poirier, H. and Robinson, J. 0.: Phaeochromocytoma of the urinary bladder in a male patient. Brit. J. Urol., 34: 88, 1962. 14 Blair, D. W. and Branwood, A. W.: Phaeochromocytorna of the ttrinary bladder. Brit. J. Urol., 35: 293, 1963. 15 Milliez, P., Carrez, P., Lagrue, G., Tcherdakoff, P., Samarcq, P., Vigneron, A. and Jacquillat, C.: Pheochromocytome vesical. Bull. Soc. med. Hop. Paris, 114: 1019, 1963. 16 Derom, E., Defoort, IL, Auvert, J., Nicole tis, C. and Couvelaire, R.: Le pheochromocytome vesical interstitiel. J. Urol. Med. Chir., 66: 20, 1960. 17 Van Buskirk, K. E., O'Shaughnessy, E. ,T., Hano, J. and Finder, R. J .. Pheochromocytoma of the bladder. J. A. M. A., 196: 293, 1966. 18 Lathem, J.E. and Hnnt, L. D.: Pheochromocytoma of the minary bladder. J. A. M. A., 197: 588, 1966. '"Higgins, P. NI. and Tresidder, G. C.: Phaeo361
,V.G., a 71-year-old man, cam.e to our office in ~ ovember 1965 to have his urethra dilated. He stated that he had been dilated during the past 15 years for a strieture and that his strea1n had been intermittently improved passage of "plugs'' which probably were clots. 1 explained that it had been my practice to estaJ:i lish the diagnosis of :otricture by cy;,;toscopy before subjecting a patient to dilatation of the urethrn.. This was agreeable to the patient but he asked to have a heart specialist c:ee him in the hospital because within the last 2 years he had experienced severe palpitations of the heart following micturition. The palpitations were noticed only when he had to strain to void and could be avoided b.v sitting to urinate. A urinalysi, revealed no celb microscopically; the blood pressure was 130 /70. On admission to the hospital the patient's initial blood pressure was 240 /112, although every other pressure was normal. Fmther questioni11g; revealed that this pressure wa:o obtained shortly after he had voided. Urinalysis showed microscopic hematuria. Panendoscopy revealed a wide caliber stricture at the penoscrotal. angle. On cystoscopy there was a 2 by 3 cm. tumor inside the vesical neck at about 2 o'clock. The mucosa overlying the tumor appeared normal, suggesting that the tumor was submucosal, and there were several large tortuom; vessels at its base. Forced distention of the bladder did not alter the patient's blood pressure. The next day a segmental resection of the bladder was performed including a 1 cm. margin around the tumor. Although regitine had been made available in antici-pation that the tumor wa, a pheochromoc:1'toma 1 chromocytoma of the urinary bladder. Brit. Med .
J., 2: 274, 1966.
2° Farley, S. E.: Cited by Higgins and Tresid-der. 19 21 Withycombe, ,L F. R: Cited by Higgins a11d Tresidder . 19
Review of reported cases
Age-Sex
I
I
Postvoiding Symptoms
Hematuria
+
Seen on Cysto.
Blood Pressure
Hypertension
Operation
(preop.)
Followup
I (postop.) 1-----
74-F 1
53-F 3 (case 1) 37-F'
+
48-F 4
+
+
17-F 5 16-F 6 1
68-F 3 (case 2) 36-F' (case 3)
Not stated
+
Yes
Sustained
220/110 170/88
Seg. cyst.
+
Yes
None
130/90
+
Not stated Yes
Transves. diathermy Seg. cyst.
+
Yes
+
Yes No
Not stated
49-M 8 14-M 7
+
19-M 9
+
No
35-FlO
+
Yes
22-M11
+
No
ll-F 12
+
39-M'"
+
6G-M 1'
l8-M 15
+
+
Yes
+ +
Yes
+
Yes
+
Yes
(micro.) Yes
(micro.)
+
34-F 17
+
Yes
14-F 18
+
No
14-Mrn
+
35_p20
+
50-M 21 71-M (our case)
+
+
Yes Yes
+ +
(micro.)
Well 8 yrs. postop. BP-150/100 Well 8 yrs. postop. I clinical evidence of rec., bladder neg, refused lap. Sustained Died postop. Seg. cyst. 205/140 Sustained 210/120 110/70 Hemicyst. Well 8 yrs. postop. BP-115/70 Died 3 yrs. postop. Sustained 210/110 230/1481 TUR x3 no rec. Paroxysmal 150/90 80/50 Cysto, Died 44 hrs. 210/120 postop., metas. to liver & nodes Paroxysmal 180/120 130/70 TUR Well 6 yrs. postop. Sustained 190/110 120/80 Cystec. Well 6 yrs. postop., recent BP-156/108, being studied Sustained 260/170 140/90 Seg. cyst. + paroxysmal Paroxysmal 112/74 130/90 Seg. cyst. Well G yrs. 180/120 postop., normotensive Paroxysmal 120/80 120/80 Seg. cyst. Well 6 yrs. postop. normotensive 220/120 Paroxysmal 110/95 125/80 TUR+seg. Well 2 mos. cyst. postop. 140/100 Paroxysmal 150/90 130/80 TUR+seg. Well 5 yrs. postop. cyst. BP-140/80 220/105 160/90 Seg. cyst. Sustained 2 CVAs but well 3 yrs. post.op., BP same; I Sustained 180/110 200/120 Seg. cyst. Died 19th postop. + parox- 280/150 day ysmal Paroxysmal 130/70 110/70 Seg. cyst. 290/120 Paroxysmal 110/80 Normal Local exClSlOll 220/130 Paroxysmal 128/80 120/78 Local ex- j cision 208/120 Paroxysmal 130/90 105/70 Seg. cyst. Well 9 mos. postop. 160/120 Paroxysmal 120/80 100/80 Seg. cyst. Well 8 mos. postop. 240/110 Seg. cyst. None Well 2 yrs. postop. Hi0/90 Paroxysmal 130/70 1-10/62 Seg. cyst. Well 11 mos. postop., BP220/110 140/70 Paroxysmal 110/70 120/70 260/150 Sustained 230/110 190/100 Seg. cyst.
1 ·
1
45-M16
Yes Yes
125/70
Died 40 mos. postop., tumor free at autopsy Well 10 yrs. post op.
362
PHEOCHROMOCYTOMA OF THE BLADDER
FIG.
L Gross tumor
Fm. 2. Microphotograph of tumor it was not necessary as there was no change in blood pres.sure during the procedure. Convalescence 1Yas uneventful and the patient has had no further episodes of palpitations after voiding. His postoperative urinary vanilmandelic acid was normal (1.9 mg. per 24 hours) as was a histamine provocative test. His blood pressure in September 1966 was 140/70, The gros~ specimen was a Hubmucosal tumor, 1.6 cm. in its greatest diameter, which was pale grey in appearance (fig. l). c\Jter immersion in formalin both the tumor and 1he formalin turned a deep yellow, a phenomenon previously noted by others anc! believed to be pathognomonic: of chromaffinoma.'l· 4 · 7 The histologic diagnosis was pheochromocytoma of the bladder (fig. 2). DISCUSSION
'IVhile the etiology of pheochromocytoma of the bladder is not kumrn, it ib generally felt that
the tumor arises from paraganglia related to the autonomic: nerves of the bladder wall. This view is substantiated by Coupland who has shown that extra-adrenal JJaraganglia are widely distributed in the human fetu,. 22 He ha, demonstrated that chromaffin bodies may occur in association with the pelvic as well as the abdominal. sympathetic plexus and, although much of thi~ extra-adrenal tissue has disappeared by the time adult life is reached, there is no valid reason why some parts of it niaynot persist as "rests", even i11 such an anomalous place as the bladder wall, and occasionally give rise to a tumm. Evernole has reported a small rest of chromaffin tissue in the submucosa of the bladder which was found incidentally in a routine section of the bladder at autopsy, 7 As Pugh has pointed out, the greater part of the autonomic nervous tissue of the bladder lies in the outer part of its wall. 3 A chrom-affinoma arising there could, subsequent enlargement, extend either inward to the submucosa or outward to the perivesical tissue_ Thus the absence of a tumor on cystoscopic examination does not rule out its presence. Of the ca~e, reported, 80 per cent of the tumors were seen at cystoscopy, although 4 1vere not. vVhile most earlier patients had a history of hematuria or hypertension, 7 of the last 11 easc,s reported gave a classic story of postmicturitional adrenergic symptoms, which probably represents an increased awareness of this disease entity the clinician, Over-all, 77 per cent of the palients gave a classic history of postmicturitional symptoms, although 15 per cent were in retrospect only. Hematuria was present in 56 per cent of the cases (gross, 43 percent; microscopic, 13 per Hypertension was paroxysmal in 18 and sustained in seven. Two patients had 110 hypertension and were later proven to have nonfunctioning tumors. 3 • 21 vVhere followup evaluation was obtainable, results were generally good. 0£ the 6 patients with sustained three have in1proved and two are normotensive, although one of the latter has recently been found to have blood pressure of 156/108 and is currently being studiecl. 23 All 12 patients with paroxysmal hypertension are normotensive and asymptomatic. The most common form of therapy was seg22 Coupland, R. E.: Prenatal development uf abdominal para-aortic bodies in man_ .J. A.na.t., 86: 357, 1952. . _ 23 Scott, VV. Vv.: Personal commumca.t1011.
364
BOURNE AND BELTAOS
mental resection of the bladder. One cystectomy was performed because the biopsy had been interpreted elsewhere as leiomyosarcoma and the slides were not available to the author preoperatively, although they were later re-read as pheochromocytoma. 7 Four patients were treated by transurethral resection, but two of these required subsequent segmental resections and a third required 2 followup transurethral resections. Since the tumors are not mucosa! in origin and may extend deeply into the wall, it seems logical that transurethral resection would not usually be the treatment of choice. Four patients had evidence of metastatic disease. One died of peripheral vascular collapse 44 hours after cystoscopy. No tumor was found at cystoscopy but autopsy revealed a pheochromocytoma between the bladder and symphysis with metastases to the liver and mesenteric lymph nodes. The other 3 patients had a positive iliac lymph node which was resected along with the primary tumor. All three are well and normotensive in 1966, 6 years, 8 years and 9 months postoperatively. One of these is reported to have had a recent blood pressure of 156/108 and is currently being studied. 23 Five patients have died. Three died postoperatively of complications of hypertension and only one of these had evidence of metastatic disease. The fourth died 40 months postoperatively of a cerebral hemorrhage and the fifth died 3 years after operation. Both were free of tumor. As Rosenberg has pointed out: "It is virtually impossible to determine pathologically whether a pheochromocytoma is benign or malignant since both types infiltrate locally and grow into blood vessels. The only sure way to diagnose a malignant pheochromocytoma is to find distant metastases in areas ,vhere pheochromocyt01nas are not expected to develop" .2 The lymph node in Farley's case was at first believed to represent a metastasis from the bladder tumor, but further examination suggested that it was actually a separate pheochromocytoma occurring in another paraganglion at the bifurcation of the hypogastric vessels. 6 Scott likewise could not be certain
whether his lymph node represented a metastasis or a separate paraganglionoma, 7 although his co-author Eversole felt it did represent a metastasis because of lymphoid elements in the specimen. 23 Higgins thought the lymph node enlargement in his case was inflammatory at the time of operation but microscopic examination showed a metastatic deposit of pheochromocytoma. 19 Subsequent lymphangiography revealed possible filling defects in other nodes and the patient received a course of cobalt therapy. Milliez found a satellite nodule 1 cm. from the primary tumor in the bladder but he did not state whether he though this was a separate pheochromocytoma or a metastasis. 15 CONCLUSIONS
A high degree of clinical suspicion is the most important factor in the diagnosis of pheochromocytoma of the bladder, since 77 per cent of patients gave a classical history. The treatment of choice would seem to be segmental cystectomy or local excision. Because the tumor is submucosal or intramural, transurethral resection is often incomplete and may require another operation. Only 4 patients had evidence of metastatic disease and three of these had a positive iliac lymph node and all are well 6 years, 8 years and 9 months postoperatively. The fourth died 44 hours after cystoscopy of peripheral vascular collapse and is the only patient with distant metastases (liver and mesenteric lymph nodes). The prognosis generally is good. All 12 patients with paroxysmal hypertension are now normotensive. Of 6 patients with sustained hypertension, three are improved and two have a normal pressure. Although the tumor was seen at cystoscopy in 80 11er cent of cases, it was not seen in four. Therefore its absence on cvstoscopy does not rule out its presence.
208 E. Wisconsin A.venue, Jiilwaukee, Wisconsin 53202 (R.B.B.).
THE .JOURNAL OF UROLOGY
Copyright © 1967 by The Williams & Wilkins Co.
Sepr,,
PHEOCHRCHIOCYTOMA OF THE BLADDER: CASE REPOHT AND SUMl\IARY OF LITERATURE RICHARD B. BOURNE
AND
EFSTATHIOS BELTAOS
From the Departm.eni of Surgery, Section of Urology, illarquelle Univers·ity School of Jied?;cir,.c an,l the Department of Pathology, Columbia Hospital, Jl!Iilwaukee, Wisconsin
It has heen 13 years since Zimn1erman reported the first case of pheochromocytoma of the bladder} the case herein reported is number 24. Enough time has elapsed and enough ca~es have been reported to permit a followup analysis of this fascinating disease entity 1-21 Therefore, we
have attempted to update the previously n,ported cases, thus affording a more definitive picture of the treatment and table). CASE H.EPOHT
Accepted for publication October 18, 1966. L Zimmerman, I. J.,Biron, R.E. andMacMahon, Ff. E.: Pheochromocytorna of (.he urinary bladder. NGw Engl. J. Med., 249: 25, 1953. 2 Rosenberg, L. ]\II.: Pheochromocytoma of the minary bladder. New Eng;!. ,f. Med., 257: 1212, 1957. 3 Pugh, R. C. B., Gresham, G. A. and Mullaney, J.: Pheochromocytoma of the bladder. ,T. Path. & Bacteriol., 79: 89, 1960. '1 Lumb, B. R B. and Gresham, G. A.: Phaeochrornocytoma of the urinary bladder. Lancet, 1: 81, HJ58. 5 Varl, B. and Rakovec, S.: Zdrav. vest., 3: 113, 1958. 6 Farley, S. E. and Smith, C. L.: Unnsual location of pheochromocytoma in the urinary bladder. J. Urol., 81: 130, 1959. 7 Scott, W.W. and Eversole, S. L.: Pheochromocytorna of the urinary bladder. J. Urol., 83: 656, 1960. 8 Silver, B.: Cited by Scott and Eversole. 7 9 Micic, R., Kicic, M. and Adanja, S.: Phaeochromocytoma of urinary bladder. Acta Endocr., 39: 1, 1962. 10 Berry, K. W., Jr. and Scott, E. V. Z.: Pheochromocytoma of the bladder. J. Urol., 85: 156, 1961. H Siva.k, G. C.: Pheochromocytoma of bladder. J. Urol., 86: 568, 1961. 12 Tan, T-L. and Young, B. W.: Pheochromocytoma of the bladder; case report. J. Urol., 87: 53, 1962. 13 Poirier, H. and Robinson, J. 0.: Phaeochromocytoma of the urinary bladder in a male patient. Brit. J. Urol., 34: 88, 1962. 14 Blair, D. W. and Branwood, A. W.: Phaeochromocytorna of the ttrinary bladder. Brit. J. Urol., 35: 293, 1963. 15 Milliez, P., Carrez, P., Lagrue, G., Tcherdakoff, P., Samarcq, P., Vigneron, A. and Jacquillat, C.: Pheochromocytome vesical. Bull. Soc. med. Hop. Paris, 114: 1019, 1963. 16 Derom, E., Defoort, IL, Auvert, J., Nicole tis, C. and Couvelaire, R.: Le pheochromocytome vesical interstitiel. J. Urol. Med. Chir., 66: 20, 1960. 17 Van Buskirk, K. E., O'Shaughnessy, E. ,T., Hano, J. and Finder, R. J .. Pheochromocytoma of the bladder. J. A. M. A., 196: 293, 1966. 18 Lathem, J.E. and Hnnt, L. D.: Pheochromocytoma of the minary bladder. J. A. M. A., 197: 588, 1966. '"Higgins, P. NI. and Tresidder, G. C.: Phaeo361
,V.G., a 71-year-old man, cam.e to our office in ~ ovember 1965 to have his urethra dilated. He stated that he had been dilated during the past 15 years for a strieture and that his strea1n had been intermittently improved passage of "plugs'' which probably were clots. 1 explained that it had been my practice to estaJ:i lish the diagnosis of :otricture by cy;,;toscopy before subjecting a patient to dilatation of the urethrn.. This was agreeable to the patient but he asked to have a heart specialist c:ee him in the hospital because within the last 2 years he had experienced severe palpitations of the heart following micturition. The palpitations were noticed only when he had to strain to void and could be avoided b.v sitting to urinate. A urinalysi, revealed no celb microscopically; the blood pressure was 130 /70. On admission to the hospital the patient's initial blood pressure was 240 /112, although every other pressure was normal. Fmther questioni11g; revealed that this pressure wa:o obtained shortly after he had voided. Urinalysis showed microscopic hematuria. Panendoscopy revealed a wide caliber stricture at the penoscrotal. angle. On cystoscopy there was a 2 by 3 cm. tumor inside the vesical neck at about 2 o'clock. The mucosa overlying the tumor appeared normal, suggesting that the tumor was submucosal, and there were several large tortuom; vessels at its base. Forced distention of the bladder did not alter the patient's blood pressure. The next day a segmental resection of the bladder was performed including a 1 cm. margin around the tumor. Although regitine had been made available in antici-pation that the tumor wa, a pheochromoc:1'toma 1 chromocytoma of the urinary bladder. Brit. Med .
J., 2: 274, 1966.
2° Farley, S. E.: Cited by Higgins and Tresid-der. 19 21 Withycombe, ,L F. R: Cited by Higgins a11d Tresidder . 19
Review of reported cases
Age-Sex
I
I
Postvoiding Symptoms
Hematuria
+
Seen on Cysto.
Blood Pressure
Hypertension
Operation
(preop.)
Followup
I (postop.) 1-----
74-F 1
53-F 3 (case 1) 37-F'
+
48-F 4
+
+
17-F 5 16-F 6 1
68-F 3 (case 2) 36-F' (case 3)
Not stated
+
Yes
Sustained
220/110 170/88
Seg. cyst.
+
Yes
None
130/90
+
Not stated Yes
Transves. diathermy Seg. cyst.
+
Yes
+
Yes No
Not stated
49-M 8 14-M 7
+
19-M 9
+
No
35-FlO
+
Yes
22-M11
+
No
ll-F 12
+
39-M'"
+
6G-M 1'
l8-M 15
+
+
Yes
+ +
Yes
+
Yes
+
Yes
(micro.) Yes
(micro.)
+
34-F 17
+
Yes
14-F 18
+
No
14-Mrn
+
35_p20
+
50-M 21 71-M (our case)
+
+
Yes Yes
+ +
(micro.)
Well 8 yrs. postop. BP-150/100 Well 8 yrs. postop. I clinical evidence of rec., bladder neg, refused lap. Sustained Died postop. Seg. cyst. 205/140 Sustained 210/120 110/70 Hemicyst. Well 8 yrs. postop. BP-115/70 Died 3 yrs. postop. Sustained 210/110 230/1481 TUR x3 no rec. Paroxysmal 150/90 80/50 Cysto, Died 44 hrs. 210/120 postop., metas. to liver & nodes Paroxysmal 180/120 130/70 TUR Well 6 yrs. postop. Sustained 190/110 120/80 Cystec. Well 6 yrs. postop., recent BP-156/108, being studied Sustained 260/170 140/90 Seg. cyst. + paroxysmal Paroxysmal 112/74 130/90 Seg. cyst. Well G yrs. 180/120 postop., normotensive Paroxysmal 120/80 120/80 Seg. cyst. Well 6 yrs. postop. normotensive 220/120 Paroxysmal 110/95 125/80 TUR+seg. Well 2 mos. cyst. postop. 140/100 Paroxysmal 150/90 130/80 TUR+seg. Well 5 yrs. postop. cyst. BP-140/80 220/105 160/90 Seg. cyst. Sustained 2 CVAs but well 3 yrs. post.op., BP same; I Sustained 180/110 200/120 Seg. cyst. Died 19th postop. + parox- 280/150 day ysmal Paroxysmal 130/70 110/70 Seg. cyst. 290/120 Paroxysmal 110/80 Normal Local exClSlOll 220/130 Paroxysmal 128/80 120/78 Local ex- j cision 208/120 Paroxysmal 130/90 105/70 Seg. cyst. Well 9 mos. postop. 160/120 Paroxysmal 120/80 100/80 Seg. cyst. Well 8 mos. postop. 240/110 Seg. cyst. None Well 2 yrs. postop. Hi0/90 Paroxysmal 130/70 1-10/62 Seg. cyst. Well 11 mos. postop., BP220/110 140/70 Paroxysmal 110/70 120/70 260/150 Sustained 230/110 190/100 Seg. cyst.
1 ·
1
45-M16
Yes Yes
125/70
Died 40 mos. postop., tumor free at autopsy Well 10 yrs. post op.
362
PHEOCHROMOCYTOMA OF THE BLADDER
FIG.
L Gross tumor
Fm. 2. Microphotograph of tumor it was not necessary as there was no change in blood pres.sure during the procedure. Convalescence 1Yas uneventful and the patient has had no further episodes of palpitations after voiding. His postoperative urinary vanilmandelic acid was normal (1.9 mg. per 24 hours) as was a histamine provocative test. His blood pressure in September 1966 was 140/70, The gros~ specimen was a Hubmucosal tumor, 1.6 cm. in its greatest diameter, which was pale grey in appearance (fig. l). c\Jter immersion in formalin both the tumor and 1he formalin turned a deep yellow, a phenomenon previously noted by others anc! believed to be pathognomonic: of chromaffinoma.'l· 4 · 7 The histologic diagnosis was pheochromocytoma of the bladder (fig. 2). DISCUSSION
'IVhile the etiology of pheochromocytoma of the bladder is not kumrn, it ib generally felt that
the tumor arises from paraganglia related to the autonomic: nerves of the bladder wall. This view is substantiated by Coupland who has shown that extra-adrenal JJaraganglia are widely distributed in the human fetu,. 22 He ha, demonstrated that chromaffin bodies may occur in association with the pelvic as well as the abdominal. sympathetic plexus and, although much of thi~ extra-adrenal tissue has disappeared by the time adult life is reached, there is no valid reason why some parts of it niaynot persist as "rests", even i11 such an anomalous place as the bladder wall, and occasionally give rise to a tumm. Evernole has reported a small rest of chromaffin tissue in the submucosa of the bladder which was found incidentally in a routine section of the bladder at autopsy, 7 As Pugh has pointed out, the greater part of the autonomic nervous tissue of the bladder lies in the outer part of its wall. 3 A chrom-affinoma arising there could, subsequent enlargement, extend either inward to the submucosa or outward to the perivesical tissue_ Thus the absence of a tumor on cystoscopic examination does not rule out its presence. Of the ca~e, reported, 80 per cent of the tumors were seen at cystoscopy, although 4 1vere not. vVhile most earlier patients had a history of hematuria or hypertension, 7 of the last 11 easc,s reported gave a classic story of postmicturitional adrenergic symptoms, which probably represents an increased awareness of this disease entity the clinician, Over-all, 77 per cent of the palients gave a classic history of postmicturitional symptoms, although 15 per cent were in retrospect only. Hematuria was present in 56 per cent of the cases (gross, 43 percent; microscopic, 13 per Hypertension was paroxysmal in 18 and sustained in seven. Two patients had 110 hypertension and were later proven to have nonfunctioning tumors. 3 • 21 vVhere followup evaluation was obtainable, results were generally good. 0£ the 6 patients with sustained three have in1proved and two are normotensive, although one of the latter has recently been found to have blood pressure of 156/108 and is currently being studiecl. 23 All 12 patients with paroxysmal hypertension are normotensive and asymptomatic. The most common form of therapy was seg22 Coupland, R. E.: Prenatal development uf abdominal para-aortic bodies in man_ .J. A.na.t., 86: 357, 1952. . _ 23 Scott, VV. Vv.: Personal commumca.t1011.
364
BOURNE AND BELTAOS
mental resection of the bladder. One cystectomy was performed because the biopsy had been interpreted elsewhere as leiomyosarcoma and the slides were not available to the author preoperatively, although they were later re-read as pheochromocytoma. 7 Four patients were treated by transurethral resection, but two of these required subsequent segmental resections and a third required 2 followup transurethral resections. Since the tumors are not mucosa! in origin and may extend deeply into the wall, it seems logical that transurethral resection would not usually be the treatment of choice. Four patients had evidence of metastatic disease. One died of peripheral vascular collapse 44 hours after cystoscopy. No tumor was found at cystoscopy but autopsy revealed a pheochromocytoma between the bladder and symphysis with metastases to the liver and mesenteric lymph nodes. The other 3 patients had a positive iliac lymph node which was resected along with the primary tumor. All three are well and normotensive in 1966, 6 years, 8 years and 9 months postoperatively. One of these is reported to have had a recent blood pressure of 156/108 and is currently being studied. 23 Five patients have died. Three died postoperatively of complications of hypertension and only one of these had evidence of metastatic disease. The fourth died 40 months postoperatively of a cerebral hemorrhage and the fifth died 3 years after operation. Both were free of tumor. As Rosenberg has pointed out: "It is virtually impossible to determine pathologically whether a pheochromocytoma is benign or malignant since both types infiltrate locally and grow into blood vessels. The only sure way to diagnose a malignant pheochromocytoma is to find distant metastases in areas ,vhere pheochromocyt01nas are not expected to develop" .2 The lymph node in Farley's case was at first believed to represent a metastasis from the bladder tumor, but further examination suggested that it was actually a separate pheochromocytoma occurring in another paraganglion at the bifurcation of the hypogastric vessels. 6 Scott likewise could not be certain
whether his lymph node represented a metastasis or a separate paraganglionoma, 7 although his co-author Eversole felt it did represent a metastasis because of lymphoid elements in the specimen. 23 Higgins thought the lymph node enlargement in his case was inflammatory at the time of operation but microscopic examination showed a metastatic deposit of pheochromocytoma. 19 Subsequent lymphangiography revealed possible filling defects in other nodes and the patient received a course of cobalt therapy. Milliez found a satellite nodule 1 cm. from the primary tumor in the bladder but he did not state whether he though this was a separate pheochromocytoma or a metastasis. 15 CONCLUSIONS
A high degree of clinical suspicion is the most important factor in the diagnosis of pheochromocytoma of the bladder, since 77 per cent of patients gave a classical history. The treatment of choice would seem to be segmental cystectomy or local excision. Because the tumor is submucosal or intramural, transurethral resection is often incomplete and may require another operation. Only 4 patients had evidence of metastatic disease and three of these had a positive iliac lymph node and all are well 6 years, 8 years and 9 months postoperatively. The fourth died 44 hours after cystoscopy of peripheral vascular collapse and is the only patient with distant metastases (liver and mesenteric lymph nodes). The prognosis generally is good. All 12 patients with paroxysmal hypertension are now normotensive. Of 6 patients with sustained hypertension, three are improved and two have a normal pressure. Although the tumor was seen at cystoscopy in 80 11er cent of cases, it was not seen in four. Therefore its absence on cvstoscopy does not rule out its presence.
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