0022-534 7/78/1203-0352$02.00/0 Vol. 120, September
THE JOURNAL OF UROLOGY
Printed in U.SA.
Copyright © 1978 by The Williams & Wilkins Co.
PHEOCHROMOCYTOMA PRESENTING AS MIDDELDORPF TUMOR: CASE REPORT J.P. DONOHUE, J.M. PEREZ
AND
M. H. WEINBERGER
From the Department of Urology, Indiana University Medical Center, Indianapolis, Indiana
ABSTRACT
Pheochromocytoma is a tumor that characteristically arises in the adrenal medulla. Extraadrenal tumors make up approximately 10 per cent of all pheochromocytomas, with those occurring in the organ of Zuckerkandl being the most common. Others may occur anywhere along the sympathetic chain, including a number of reported cases in the bladder. A case is reported in which the tumor occurred deep in the presacral pelvic area, retroperitoneal and retrorectal, a socalled Middeldorpf tumor. Its rare presentation and technical demand of its removal underscore the importance of preoperative and intraoperative medical and pharmacologic management. L. B., an 18-year-old black woman, was hospitalized on April 21, 1971 for evaluation of a possible pheochromocytoma. The patient had been in good health until approximately 2 years previously when, during her first pregnancy, she was treated for high blood pressure. Since the early postpartum period the patient had noted intermittent episodes of dizziness with marked diaphoresis occurring about 2 times a month, lasting up to 1 day and associated with low abdominal discomfort. During several of these episodes she was observed by her local physician and was told that her blood pressure was elevated. In March 1971 the patient had been hospitalized elsewhere for hypertension. Vanillyl mandelic acid values on 2 occasions were 3.6 and 3.5 mg. per total volume, with a normal at that laboratory of O to 2 mg. per total volume. Catecholamines were 1,200 mcg./24 hours, some 10 times normal. Serum cortisol levels, 17-ketosteroids and 17-hydroxysteroids, in addition to an excretory urogram (IVP) were within normal limits. Subsequently, the patient was referred to our center for further evaluation. Physical examination was relatively unremarkable except for blood pressures of 130/100 mm. Hg and 130/90 mm. Hg in each arm with the patient in the sitting position. She also had some minimal arteriolar narrowing on funduscopic examination. Chest, cardiovascular, abdominal, pelvic, rectal and neurologic examinations were within normal limits. An IVP and chest x-ray on May 5 were normal. Complete blood count, blood urea nitrogen, creatinine, calcium, blood sugar and electrolytes were within normal limits, as well as 17-hydroxysteroids and 17-ketosteroids. Vanillyl mandelic acid levels were 16.9 mg. per total volume, with a normal of2 to 8 mg. per total volume. Metanephrines were 6.0 mg. per total volume, with a normal of0.3 to 0.9 mg. per total volume. Norepinephrine was 1,674 mcg. per total volume, with a normal of O to 90 mcg. per total volume. Epinephrine was 6 mcg. per total volume, with a normal of Oto 3 mcg. per total volume and homovanillic acid was less than 5 mg. per total volume, with a normal of less than 10 mg. per total volume. On May 7 an abdominal and thoracic aortogram demonstrated an 8 cm. pelvic mass slightly to the left of the midline with the blood supply from the hypogastric, vesical and uterine branches (see figure). The patient was treated for several days preoperatively with phenoxybenzamine, which she tolerated well. On May 12 exploration through a Pfannenstiel incision revealed a retroperitoneal and retrorectal tumor. A circular incision was made around the tumor to include the overlying peritoneum. On further dissection it became evident that the tumor had invaded the left common iliac vein. Despite the ligation of the Accepted for publication December 30, 1977.
352
hypogastric artery and vein, venous blood loss continued from the presacral fascia where a multitude of veins drained directly from the tumor. With use of vascular clips the dissection was continued with reasonable safety. The presacral bleeding was controlled with direct periosteal suture ligature and hemostasis was excellent. Blood loss was estimated at 2,500 cc, with replacement being 3,000 cc whole blood and 200 cc colloid. The blood pressure decreased to 100/60 when the tumor was removed and it remained stable. Several hypertensive spikes during the mobilization were managed with intravenous phentolamine. There was 1 episode of premature ventricular contractions intraoperatively and this was controlled easily with lidocaine. Convalescence was uneventful. The patient became normotensive as soon as the tumor was removed. The pathology report revealed typical pheochromocytoma with no capsular invasion. Despite vascular (venous) invasion grossly the tumor was not considered malignant. This judgment awaits the subsequent clinical course of the patient, who has remained normotensive. Also, it is noteworthy that the menses have returned. DISCUSSION
Pheochromocytoma, although still a relatively rare tumor, has increasingly become the subject of numerous reports in the literature since 1886 when Frankel first postulated the possibility of such a tumor causing malignant hypertension in an 18-year-old woman. In 1927 Mayo reported the first successful surgically treated case. In 1951 Graham reviewed 207 cases, of which 125 were treated surgically with operative deaths occurring in 33. In 1960 Hume reviewed more than 700 cases from the world literature and reported that, because the diagnosis was being made more frequently, the mortality was decreasing steadily. It also has become evident that at least 10 per cent of pheochromocytomas occur in extra-adrenal locations. The most common location of these extra-adrenal tumors is in the organ of Zuckerkandl, that collection of paraganglia at the base of the inferior mesenteric artery. In 1976 Glenn and Gray published a report concerning tumors of the organ of Zuckerkandl. They describe the histologic pattern of para-aortic paragangliomas as being variable, being either a non-chromaffin, paraganglioma (carotid body) type or a chromaffin-pheochromocytoma type, or a mixture of both. The paraganglioma type appears to be the most common. However, the histologic appearance does not seem to be related well to catecholamine secretion, since chromaffin and nonchromaffin tumors may be functional. Malignant versus nonmalignant tumors also are difficult to distinguish histologically and it seems that the only reliable way to determine malignancy is to demonstrate tumor in areas or organs where paraganglionic tissue does not occur normally, that is the
PHEOCHROMOCYTOMA PRESENTING AS MIDDELDORPF TUMOR
Abdominal aortogram demonstrates tissue flush in presacral area.
353
tional cell tumor) and does not appear to be related absolutely to the histologic appearance of chromaffin versus non-chromaffin. Microscopically, this tumor had the typical appearance of a chromaffin paraganglioma (pheochromocytoma). There have been no reported cases of non-functioning chromaffin paragangliomas. It also has become evident that these extra-adrenal tumors most commonly secrete norepinephrine, whereas adrenal pheochromocytomas secrete either norepinephrine or epinephrine. It does apear that although the histologic appearance is not adequate to differentiate between malignant and benign tumors the non-chromaffin paragangliomas have a lower malignant potential than the chromaffin tumors (2 versus 10 per cent). The case described herein is another unusual presentation in this increasing spectrum of paraganglionic tumors. Our case also demonstrates that although we are dealing with a probable benign lesion local invasion and difficult position can make dissection difficult. In such cases some manipulation of the gland is necessary, which requires optimal pharmacologic preparation. There is wide agreement that intraoperative management requires short-acting a-adrenergic blockade (for example phentolamine) for hypertensive episodes and liberal replacement with whole blood and colloid for hypotension. But less widely appreciated is the great importance of preoperative preparation with long-acting oral a blockage. To prevent massive hypotension at the time of tumor removal 10 mg. phenoxybenzamine orally every 6 hours is given for 1 or 2 weeks. By stabilizing the a-adrenergic receptors in the peripheral vascular tree sudden vasodilation and expansion of the intravascular space do not occur after tumor removal, which reduces greatly the need for whole blood transfusions. The added risk of serum hepatitis associated with multiple transfusions also is reduced. In summary, we have reported what may be the most caudad presentation of an extra-adrenal pheochromocytoma. It was located in the low presacral area, retroperitoneal and retrorectal, a so-called Middeldorpf tumor. Constant manipulation was required to remove the tumor from its deep presacral base and iliac venotomy was necessary to remove venous extension of the tumor. Advances in pharmacologic management noted herein were essential to the successful treatment of this case.
liver, lung and lymph nodes. Even this may be misleading, since local extenilion of the tumor to nearby lymph nodes may not actually represent malignancy. Other sites for extra-adrenal pheochromocytomas include the carotid body and glomus jugulare. These tumors also may occur in the larynx, mediastinum, lung, orbit, vagus and bladder. Recently, an increasing number of articles have been reported in the literature concerning pheochromocytomas in the bladder. These tumors are REFERENCES usually, but not always, associated with classic symptoms of BLAIR, D. W. AND BRANWOOD, A. W.: Phaeochromocytoma of the pheochromocytomas, including flushing, sweating, palpitaurinary bladder. Brit. J. Urol., 35: 293, 1963. tions and headaches, sometimes occurring with either mictu- BOURNE, R. B. AND BELTAOS, E.: Pheochromocytoma of the bladder: trition or a full bladder. Some patients also may present with case report and summary ofliterature. J. Urol., 98: 361, 1967. hematuria. Endoscopically, because of their submucosal loca- CABANAS, V. Y., FAULCONER, R. J. AND FEKETE, A. M.: Pheochrotion these tumors are not visualized although ulceration of the mocytoma presenting as a ureterocele. J. Urol., 110: 389, 1973. overlying mucosa may occur. They also may present under DOCTOR, V. M., PHADKE, A.G. AND SIRSAT, M. V.: Phaeochromocytoma of the urinary bladder. Brit. J. Urol., 44: 351, 1972. some unusual circumstances. For example, in 1973 Cabanas and associates reported a case of pheochromocytoma present- GLENN, J. F. AND GRAY, G. F.: Functional tumors of the organ of Zuckerkandl. Ann. Surg., 183: 578, 1976. ing as a ureterocele in a complete ureteral duplication. In 1976 Leong and associates also reported a case of pheochromocy- HIGGINS, P. M. AND TRESIDDER, G. C.: Phaeochromocytoma of the urinary bladder. Brit. Med. J., 5508: 274, 1966. toma occurring in the base of a resected transitional cell JAVAHERI, P. AND RAAFAT, J.: Malignant phaeochromocytoma of the carcinoma. The first tumor appeared to be functioning and the urinary bladder: report of two cases. Brit. J. Urol., 47: 401, 1975. patient remained normotensive since the operation. The sec- LEONG, C. H., WONG, K. K. AND SAW, D.: Asymptomatic phaeoond tumor was apparently non-functional and was an incidenchromocytoma of the bladder co-existing with carcinoma. Brit. J. tal finding. Since chromaffin tissue nests found in the wall of Urol., 48: 123, 1976. the bladder have been discussed previously the occurrence of MIDDELDORPF, K.: Zur Kenntniss der Angebornen Sacralgeschwiilste. Virch. Arch. Path., 101: 37, 1885. a pheochromocytoma in the bladder is possible. Malignant lesions occurring in the bladder are rare but several have been MOLONEY, G. E., CoWDELL, D. M. AND LEWIS, C. L.: Malignant urinary bladder. J. Urol., 83: 656, 1960. reported. The malignant nature of these tumors was based on the findings of metastatic deposits in the bone, liver or lymph ScoTT, W. W. AND EVERSOLE, S. L.: Pheochromocytoma of the urinary bladder. J. Urol., 83: 656, 1960. nodes. Most of these tumors (more than 90 per cent) are SIVER, J., THOMAS, D., YouNG, R. AND DOWLING, R.H.: Phaeochroassociated with symptoms of flushing, diaphoresis, palpitamocytoma of the bladder. Proc. Roy. Soc. Med., 64: 670, 1971. tions, headaches and weakness, which are generally paroxys- ZIMMERMAN, I. J., BIRON, R. E. AND MACMAHON, H. E.: Phaeochromal in nature. The absence of such symptoms is rare (such as mocytoma of the urinary bladder. New Engl. J. Med., 249: 25, the case of the pheochromocytoma occurring with the transi1953.
.1
THE JOURNAL OF UROLOGY
Printed in U.SA.
Copyright © 1978 by The Williams & Wilkins Co.
PHEOCHROMOCYTOMA PRESENTING AS MIDDELDORPF TUMOR: CASE REPORT J.P. DONOHUE, J.M. PEREZ
AND
M. H. WEINBERGER
From the Department of Urology, Indiana University Medical Center, Indianapolis, Indiana
ABSTRACT
Pheochromocytoma is a tumor that characteristically arises in the adrenal medulla. Extraadrenal tumors make up approximately 10 per cent of all pheochromocytomas, with those occurring in the organ of Zuckerkandl being the most common. Others may occur anywhere along the sympathetic chain, including a number of reported cases in the bladder. A case is reported in which the tumor occurred deep in the presacral pelvic area, retroperitoneal and retrorectal, a socalled Middeldorpf tumor. Its rare presentation and technical demand of its removal underscore the importance of preoperative and intraoperative medical and pharmacologic management. L. B., an 18-year-old black woman, was hospitalized on April 21, 1971 for evaluation of a possible pheochromocytoma. The patient had been in good health until approximately 2 years previously when, during her first pregnancy, she was treated for high blood pressure. Since the early postpartum period the patient had noted intermittent episodes of dizziness with marked diaphoresis occurring about 2 times a month, lasting up to 1 day and associated with low abdominal discomfort. During several of these episodes she was observed by her local physician and was told that her blood pressure was elevated. In March 1971 the patient had been hospitalized elsewhere for hypertension. Vanillyl mandelic acid values on 2 occasions were 3.6 and 3.5 mg. per total volume, with a normal at that laboratory of O to 2 mg. per total volume. Catecholamines were 1,200 mcg./24 hours, some 10 times normal. Serum cortisol levels, 17-ketosteroids and 17-hydroxysteroids, in addition to an excretory urogram (IVP) were within normal limits. Subsequently, the patient was referred to our center for further evaluation. Physical examination was relatively unremarkable except for blood pressures of 130/100 mm. Hg and 130/90 mm. Hg in each arm with the patient in the sitting position. She also had some minimal arteriolar narrowing on funduscopic examination. Chest, cardiovascular, abdominal, pelvic, rectal and neurologic examinations were within normal limits. An IVP and chest x-ray on May 5 were normal. Complete blood count, blood urea nitrogen, creatinine, calcium, blood sugar and electrolytes were within normal limits, as well as 17-hydroxysteroids and 17-ketosteroids. Vanillyl mandelic acid levels were 16.9 mg. per total volume, with a normal of2 to 8 mg. per total volume. Metanephrines were 6.0 mg. per total volume, with a normal of0.3 to 0.9 mg. per total volume. Norepinephrine was 1,674 mcg. per total volume, with a normal of O to 90 mcg. per total volume. Epinephrine was 6 mcg. per total volume, with a normal of Oto 3 mcg. per total volume and homovanillic acid was less than 5 mg. per total volume, with a normal of less than 10 mg. per total volume. On May 7 an abdominal and thoracic aortogram demonstrated an 8 cm. pelvic mass slightly to the left of the midline with the blood supply from the hypogastric, vesical and uterine branches (see figure). The patient was treated for several days preoperatively with phenoxybenzamine, which she tolerated well. On May 12 exploration through a Pfannenstiel incision revealed a retroperitoneal and retrorectal tumor. A circular incision was made around the tumor to include the overlying peritoneum. On further dissection it became evident that the tumor had invaded the left common iliac vein. Despite the ligation of the Accepted for publication December 30, 1977.
352
hypogastric artery and vein, venous blood loss continued from the presacral fascia where a multitude of veins drained directly from the tumor. With use of vascular clips the dissection was continued with reasonable safety. The presacral bleeding was controlled with direct periosteal suture ligature and hemostasis was excellent. Blood loss was estimated at 2,500 cc, with replacement being 3,000 cc whole blood and 200 cc colloid. The blood pressure decreased to 100/60 when the tumor was removed and it remained stable. Several hypertensive spikes during the mobilization were managed with intravenous phentolamine. There was 1 episode of premature ventricular contractions intraoperatively and this was controlled easily with lidocaine. Convalescence was uneventful. The patient became normotensive as soon as the tumor was removed. The pathology report revealed typical pheochromocytoma with no capsular invasion. Despite vascular (venous) invasion grossly the tumor was not considered malignant. This judgment awaits the subsequent clinical course of the patient, who has remained normotensive. Also, it is noteworthy that the menses have returned. DISCUSSION
Pheochromocytoma, although still a relatively rare tumor, has increasingly become the subject of numerous reports in the literature since 1886 when Frankel first postulated the possibility of such a tumor causing malignant hypertension in an 18-year-old woman. In 1927 Mayo reported the first successful surgically treated case. In 1951 Graham reviewed 207 cases, of which 125 were treated surgically with operative deaths occurring in 33. In 1960 Hume reviewed more than 700 cases from the world literature and reported that, because the diagnosis was being made more frequently, the mortality was decreasing steadily. It also has become evident that at least 10 per cent of pheochromocytomas occur in extra-adrenal locations. The most common location of these extra-adrenal tumors is in the organ of Zuckerkandl, that collection of paraganglia at the base of the inferior mesenteric artery. In 1976 Glenn and Gray published a report concerning tumors of the organ of Zuckerkandl. They describe the histologic pattern of para-aortic paragangliomas as being variable, being either a non-chromaffin, paraganglioma (carotid body) type or a chromaffin-pheochromocytoma type, or a mixture of both. The paraganglioma type appears to be the most common. However, the histologic appearance does not seem to be related well to catecholamine secretion, since chromaffin and nonchromaffin tumors may be functional. Malignant versus nonmalignant tumors also are difficult to distinguish histologically and it seems that the only reliable way to determine malignancy is to demonstrate tumor in areas or organs where paraganglionic tissue does not occur normally, that is the
PHEOCHROMOCYTOMA PRESENTING AS MIDDELDORPF TUMOR
Abdominal aortogram demonstrates tissue flush in presacral area.
353
tional cell tumor) and does not appear to be related absolutely to the histologic appearance of chromaffin versus non-chromaffin. Microscopically, this tumor had the typical appearance of a chromaffin paraganglioma (pheochromocytoma). There have been no reported cases of non-functioning chromaffin paragangliomas. It also has become evident that these extra-adrenal tumors most commonly secrete norepinephrine, whereas adrenal pheochromocytomas secrete either norepinephrine or epinephrine. It does apear that although the histologic appearance is not adequate to differentiate between malignant and benign tumors the non-chromaffin paragangliomas have a lower malignant potential than the chromaffin tumors (2 versus 10 per cent). The case described herein is another unusual presentation in this increasing spectrum of paraganglionic tumors. Our case also demonstrates that although we are dealing with a probable benign lesion local invasion and difficult position can make dissection difficult. In such cases some manipulation of the gland is necessary, which requires optimal pharmacologic preparation. There is wide agreement that intraoperative management requires short-acting a-adrenergic blockade (for example phentolamine) for hypertensive episodes and liberal replacement with whole blood and colloid for hypotension. But less widely appreciated is the great importance of preoperative preparation with long-acting oral a blockage. To prevent massive hypotension at the time of tumor removal 10 mg. phenoxybenzamine orally every 6 hours is given for 1 or 2 weeks. By stabilizing the a-adrenergic receptors in the peripheral vascular tree sudden vasodilation and expansion of the intravascular space do not occur after tumor removal, which reduces greatly the need for whole blood transfusions. The added risk of serum hepatitis associated with multiple transfusions also is reduced. In summary, we have reported what may be the most caudad presentation of an extra-adrenal pheochromocytoma. It was located in the low presacral area, retroperitoneal and retrorectal, a so-called Middeldorpf tumor. Constant manipulation was required to remove the tumor from its deep presacral base and iliac venotomy was necessary to remove venous extension of the tumor. Advances in pharmacologic management noted herein were essential to the successful treatment of this case.
liver, lung and lymph nodes. Even this may be misleading, since local extenilion of the tumor to nearby lymph nodes may not actually represent malignancy. Other sites for extra-adrenal pheochromocytomas include the carotid body and glomus jugulare. These tumors also may occur in the larynx, mediastinum, lung, orbit, vagus and bladder. Recently, an increasing number of articles have been reported in the literature concerning pheochromocytomas in the bladder. These tumors are REFERENCES usually, but not always, associated with classic symptoms of BLAIR, D. W. AND BRANWOOD, A. W.: Phaeochromocytoma of the pheochromocytomas, including flushing, sweating, palpitaurinary bladder. Brit. J. Urol., 35: 293, 1963. tions and headaches, sometimes occurring with either mictu- BOURNE, R. B. AND BELTAOS, E.: Pheochromocytoma of the bladder: trition or a full bladder. Some patients also may present with case report and summary ofliterature. J. Urol., 98: 361, 1967. hematuria. Endoscopically, because of their submucosal loca- CABANAS, V. Y., FAULCONER, R. J. AND FEKETE, A. M.: Pheochrotion these tumors are not visualized although ulceration of the mocytoma presenting as a ureterocele. J. Urol., 110: 389, 1973. overlying mucosa may occur. They also may present under DOCTOR, V. M., PHADKE, A.G. AND SIRSAT, M. V.: Phaeochromocytoma of the urinary bladder. Brit. J. Urol., 44: 351, 1972. some unusual circumstances. For example, in 1973 Cabanas and associates reported a case of pheochromocytoma present- GLENN, J. F. AND GRAY, G. F.: Functional tumors of the organ of Zuckerkandl. Ann. Surg., 183: 578, 1976. ing as a ureterocele in a complete ureteral duplication. In 1976 Leong and associates also reported a case of pheochromocy- HIGGINS, P. M. AND TRESIDDER, G. C.: Phaeochromocytoma of the urinary bladder. Brit. Med. J., 5508: 274, 1966. toma occurring in the base of a resected transitional cell JAVAHERI, P. AND RAAFAT, J.: Malignant phaeochromocytoma of the carcinoma. The first tumor appeared to be functioning and the urinary bladder: report of two cases. Brit. J. Urol., 47: 401, 1975. patient remained normotensive since the operation. The sec- LEONG, C. H., WONG, K. K. AND SAW, D.: Asymptomatic phaeoond tumor was apparently non-functional and was an incidenchromocytoma of the bladder co-existing with carcinoma. Brit. J. tal finding. Since chromaffin tissue nests found in the wall of Urol., 48: 123, 1976. the bladder have been discussed previously the occurrence of MIDDELDORPF, K.: Zur Kenntniss der Angebornen Sacralgeschwiilste. Virch. Arch. Path., 101: 37, 1885. a pheochromocytoma in the bladder is possible. Malignant lesions occurring in the bladder are rare but several have been MOLONEY, G. E., CoWDELL, D. M. AND LEWIS, C. L.: Malignant urinary bladder. J. Urol., 83: 656, 1960. reported. The malignant nature of these tumors was based on the findings of metastatic deposits in the bone, liver or lymph ScoTT, W. W. AND EVERSOLE, S. L.: Pheochromocytoma of the urinary bladder. J. Urol., 83: 656, 1960. nodes. Most of these tumors (more than 90 per cent) are SIVER, J., THOMAS, D., YouNG, R. AND DOWLING, R.H.: Phaeochroassociated with symptoms of flushing, diaphoresis, palpitamocytoma of the bladder. Proc. Roy. Soc. Med., 64: 670, 1971. tions, headaches and weakness, which are generally paroxys- ZIMMERMAN, I. J., BIRON, R. E. AND MACMAHON, H. E.: Phaeochromal in nature. The absence of such symptoms is rare (such as mocytoma of the urinary bladder. New Engl. J. Med., 249: 25, the case of the pheochromocytoma occurring with the transi1953.
.1
