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Calcified Pheochromocytoma in Von Hippel-lindau Syndrome
0022-5347 /79/1222-0230$02.00/0 Vol. 122, August Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1979 by The Williams & Wilkins Co.
Case Reports CALCIFIED PHEOCHROMOCYTOMA IN VON RIPPEL-LINDAU SYNDROME DAVID L. HARPER, NABIL K. BISSADA,* FRED H. FAAS, WARREN C. BOOP, JOHN C. HOLDER AND CHERYL D. FRIDAY From the Departments of Urology, Medicine (Endocrinology), Neurosurgery, Radiology and Anesthesiology, University of Arkansas for Medical Sciences and The Veterans Administration Hospital, Little Rock, Arkansas
ABSTRACT
Urologic manifestations of the von Rippel-Lindau syndrome include benign and malignant renal tumors and cysts, epididymal cysts and adenomas, adrenal cortical tumors and pheochromocytomas. A rare case of a calcified pheochromocytoma in a patient with the von Rippel-Lindau syndrome is reported. Retinal angiomas were described initially by Collins' and von Hippel. 2 Later, Lindau noted the association ofretinal angiomas with cerebellar and medullary angioblastic tumors, pancreatic cysts and renal tumors. 3 More than 25 distinct lesions have been described to occur in association with the von HippelLindau syndrome, including cysts, adenomas and angiomas of the nervous system, pancreas, liver, kidney, spleen, lung, adrenal, epididymis and ovary. 4 Only retinal angiomas, cerebellar, medullary and spinal hemangioblastomas, pheochromocytomas and renal cell carcinomas commonly produce significant consequences. The association of renal cell carcinoma with the von HippelLindau syndrome has been recognized by urologists for many years. 5•7 Although pheochromocytomas and epididymal lesions are known entities of the disease 8 • 9 the association is less recognized by many urologists. The occurrence of calcification in a pheochromocytoma is rare. ' 0• 11 Herein we report an unusual case of a calcified pheochromocytoma and epididymal cysts in a patient with the von Rippel-Lindau syndrome. /"
.
Accepted for publication November 3, 1978. * Requests for reprints: 4301 W. Markham, Little Rock, Arkansas 72201.
CASE REPORT
P. F., a 42-year-old white man, had had multifocal cerebellar hemangioblastomas requiring 3 craniotomies between 1958 and 1972. In 1976 he was hospitalized for excision of a recurrent cerebellar hemangioblastoma and an abdominal mass was palpated. Abdominal radiography and excretory urography (IVP) revealed a calcified right upper quadrant abdominal mass (fig. 1, A). Further examination showed bilateral epididymal cysts and bilateral hemangiomas of the retina. The patient had no paroxysmal symptoms. Numerous previous blood pressures ranged from 110 to 120 systolic and from 80 to 90 diastolic. He had no hypertensive crises with the previous operations. On physical examination there was no postural decrease in the blood pressure. An electrocardiogram was normal. Family history was significant in that his father had bilateral retinal hemangiomas with hemorrhage, his sister died of a brain tumor and his niece has had recurrent cerebellar hemangioblastomas. Abdominal aortography with bilateral selective renal angiography revealed a large tumor of the right adrenal gland (fig. 1, B). There was no evidence of metastatic disease and no evidence of renal carcinoma in either kidney. The 24-hour urinary catecholamines, metanephrines and van-
FIG. 1. A, IVP demonstrates calcified mass above right kidney. B, selective right renal arteriogram shows inferior adrenal artery supplying
tumor.
230
CALCIFIED PHEOCHROMOCYTOMA IN VON RIPPEL-LINDAU SYNDROME
Measurement of 24-hour urine excretion of catecholamines and metabolites
Date
4/27 /77 5/11/77 5/12/77
Total Catecholamines * (µg./24 hrs.) (norma! 0-140)
Norepinephrinet (µg./24 hrs.) (norma! 0-75)
Epinephrinet (µg. /24 hrs.) (normal 0-
407
0 0
25)
327
Vanillyl Mandelic Acid (mg./ 24 hrs.) (normal 18)
Total Metanephrines* (mg./24 hrs.) (norma! 0.2-1.0)
8.8 111
11.4
2.0
13.0
Pheochromocytoma removed 5/26/77 6/23/77 6/24/77
19 25
14
11
'" Southwest Iviedical Laboratories. t Dr. Nornian Kirshner, Duke University.
231
neuroectodermal origin it is not surprising that neurocutaneous syndromes are associated with a high incidence of pheochromocytoma. 12 • i:i It is interesting that our patient was completely asymptomatic from the pheochromocytoma. The natural history of these tumors is not well understood. However, since the consequences of an untreated pheochromocytoma can be catastrophic excision of the lesion should be done even in the rare instance in which it is found in an asymptomatic individual. Calcification in a pheochromocytoma is also rare, with only 23 cases been reported previously. 10• 11 Urologic investigations are :required in families with the von Hippel-Lindau syndrome, not at the time of the initial examination but at each examination for early detection of renal ,,,.~H"'"·w•~.r Chemical analysis for a pheochromoshould in all with the von
REFERENCES l. Collins, E.
2. 3.
4.
5.
FJG. 2. Microphotograph of excised adrenal pheochromocytoma 6.
7. 8.
Convalescence was uneventful. determinations were uc,uua,, as shown in the table. Arrangements have been made to evaluate the relatives of the patient regarding manifestations of the von Hippel-Lindau syndrome.
9. 10. 11.
DISCUSSION
12.
von Hippel-Lindau disease and other neurocutaneous syndromes are considered related dysplasias of tissues arising from neuroectodermal Since the adrenal medulla is also of
13.
X. Intra-ocular growths. Trans. Ophth. Soc. U.K., 14: 141, 1894. von Hippe!, E.: Ueber eine sehr seltene Erkrankung der Netzhaut: Klinische Beobachtungen. Arch. F. Ophth., 59: 83, 1904. Lindau, A.: Studien i.iber Kleinhimcysten: Bau, Pathogenese und Beziehungen zur Angiomatosis Retinae. Acta Path. Microbiol. 1: 1, 1926. Horton, Wong, V. and Eldridge, R.: von Rippel-Lindau disease: clinical and pathological manifestations in nine families with 50 affected members. Arch. Intern. Med., 136: 769, 1976. Malek, R. S. and Greene, L. F.: Urologic aspects of Hippel-Lindau syndrome. J. Urol., 106: 800, 1971. Fetner, C. D., Barilla, D. E., Scott, T., Ballard, J. and Peters, P.: Bilateral renal cell carcinoma in von Hippel-Lindau syndrome: treatment with staged bilateral nephrectomy and hemodialysis. J. Urol., 117: 534, 1977. DeTure, F. A.: Uro!ogic implications of von Rippel-Lindau syndrome. Urology, 11: 612, 1978. Chapman, R. C., Kemp, V. E. and Taliaferro, I.: Pheochromocytoma associated with multiple neurofibromatosis and intracranial hemangioma. Amer. J. Med., 26: 883, 1959. Lowden, B. A. and Harris, G. S.: Pheochromocytoma and von Hippe!-Lindau's disease. Canad. J. Ophth., 11: 282, 1976. fv'.!eyers, M. A. and King, M. C.: Unusual radiologic features of pheochromocytoma. Clin. Radio!., 20: 52, 1969. Mori, Y., Kiyohara, H., Miki, T. and Kotake, T.: Pheochromocytoma with prominent calcification and associated pancreatic islet cell tumor. J. Urol., 118: 843, 1977. G!ushien, A. S., Mansuy, M. M. and Littman, D. S.: Pheochromocytoma; its relationship to neurocutaneous syndromes. Amer. J. Med., 14: 318, 1953. Chapman, R. C. and Diaz-Perez, R.: Pheochromocytoma associated with cerebellar hemangioblastoma. J.A.M.A., 182: 1014, 1962.
THE JOURNAL OF UROLOGY
Copyright© 1979 by The Williams & Wilkins Co.
Case Reports CALCIFIED PHEOCHROMOCYTOMA IN VON RIPPEL-LINDAU SYNDROME DAVID L. HARPER, NABIL K. BISSADA,* FRED H. FAAS, WARREN C. BOOP, JOHN C. HOLDER AND CHERYL D. FRIDAY From the Departments of Urology, Medicine (Endocrinology), Neurosurgery, Radiology and Anesthesiology, University of Arkansas for Medical Sciences and The Veterans Administration Hospital, Little Rock, Arkansas
ABSTRACT
Urologic manifestations of the von Rippel-Lindau syndrome include benign and malignant renal tumors and cysts, epididymal cysts and adenomas, adrenal cortical tumors and pheochromocytomas. A rare case of a calcified pheochromocytoma in a patient with the von Rippel-Lindau syndrome is reported. Retinal angiomas were described initially by Collins' and von Hippel. 2 Later, Lindau noted the association ofretinal angiomas with cerebellar and medullary angioblastic tumors, pancreatic cysts and renal tumors. 3 More than 25 distinct lesions have been described to occur in association with the von HippelLindau syndrome, including cysts, adenomas and angiomas of the nervous system, pancreas, liver, kidney, spleen, lung, adrenal, epididymis and ovary. 4 Only retinal angiomas, cerebellar, medullary and spinal hemangioblastomas, pheochromocytomas and renal cell carcinomas commonly produce significant consequences. The association of renal cell carcinoma with the von HippelLindau syndrome has been recognized by urologists for many years. 5•7 Although pheochromocytomas and epididymal lesions are known entities of the disease 8 • 9 the association is less recognized by many urologists. The occurrence of calcification in a pheochromocytoma is rare. ' 0• 11 Herein we report an unusual case of a calcified pheochromocytoma and epididymal cysts in a patient with the von Rippel-Lindau syndrome. /"
.
Accepted for publication November 3, 1978. * Requests for reprints: 4301 W. Markham, Little Rock, Arkansas 72201.
CASE REPORT
P. F., a 42-year-old white man, had had multifocal cerebellar hemangioblastomas requiring 3 craniotomies between 1958 and 1972. In 1976 he was hospitalized for excision of a recurrent cerebellar hemangioblastoma and an abdominal mass was palpated. Abdominal radiography and excretory urography (IVP) revealed a calcified right upper quadrant abdominal mass (fig. 1, A). Further examination showed bilateral epididymal cysts and bilateral hemangiomas of the retina. The patient had no paroxysmal symptoms. Numerous previous blood pressures ranged from 110 to 120 systolic and from 80 to 90 diastolic. He had no hypertensive crises with the previous operations. On physical examination there was no postural decrease in the blood pressure. An electrocardiogram was normal. Family history was significant in that his father had bilateral retinal hemangiomas with hemorrhage, his sister died of a brain tumor and his niece has had recurrent cerebellar hemangioblastomas. Abdominal aortography with bilateral selective renal angiography revealed a large tumor of the right adrenal gland (fig. 1, B). There was no evidence of metastatic disease and no evidence of renal carcinoma in either kidney. The 24-hour urinary catecholamines, metanephrines and van-
FIG. 1. A, IVP demonstrates calcified mass above right kidney. B, selective right renal arteriogram shows inferior adrenal artery supplying
tumor.
230
CALCIFIED PHEOCHROMOCYTOMA IN VON RIPPEL-LINDAU SYNDROME
Measurement of 24-hour urine excretion of catecholamines and metabolites
Date
4/27 /77 5/11/77 5/12/77
Total Catecholamines * (µg./24 hrs.) (norma! 0-140)
Norepinephrinet (µg./24 hrs.) (norma! 0-75)
Epinephrinet (µg. /24 hrs.) (normal 0-
407
0 0
25)
327
Vanillyl Mandelic Acid (mg./ 24 hrs.) (normal 18)
Total Metanephrines* (mg./24 hrs.) (norma! 0.2-1.0)
8.8 111
11.4
2.0
13.0
Pheochromocytoma removed 5/26/77 6/23/77 6/24/77
19 25
14
11
'" Southwest Iviedical Laboratories. t Dr. Nornian Kirshner, Duke University.
231
neuroectodermal origin it is not surprising that neurocutaneous syndromes are associated with a high incidence of pheochromocytoma. 12 • i:i It is interesting that our patient was completely asymptomatic from the pheochromocytoma. The natural history of these tumors is not well understood. However, since the consequences of an untreated pheochromocytoma can be catastrophic excision of the lesion should be done even in the rare instance in which it is found in an asymptomatic individual. Calcification in a pheochromocytoma is also rare, with only 23 cases been reported previously. 10• 11 Urologic investigations are :required in families with the von Hippel-Lindau syndrome, not at the time of the initial examination but at each examination for early detection of renal ,,,.~H"'"·w•~.r Chemical analysis for a pheochromoshould in all with the von
REFERENCES l. Collins, E.
2. 3.
4.
5.
FJG. 2. Microphotograph of excised adrenal pheochromocytoma 6.
7. 8.
Convalescence was uneventful. determinations were uc,uua,, as shown in the table. Arrangements have been made to evaluate the relatives of the patient regarding manifestations of the von Hippel-Lindau syndrome.
9. 10. 11.
DISCUSSION
12.
von Hippel-Lindau disease and other neurocutaneous syndromes are considered related dysplasias of tissues arising from neuroectodermal Since the adrenal medulla is also of
13.
X. Intra-ocular growths. Trans. Ophth. Soc. U.K., 14: 141, 1894. von Hippe!, E.: Ueber eine sehr seltene Erkrankung der Netzhaut: Klinische Beobachtungen. Arch. F. Ophth., 59: 83, 1904. Lindau, A.: Studien i.iber Kleinhimcysten: Bau, Pathogenese und Beziehungen zur Angiomatosis Retinae. Acta Path. Microbiol. 1: 1, 1926. Horton, Wong, V. and Eldridge, R.: von Rippel-Lindau disease: clinical and pathological manifestations in nine families with 50 affected members. Arch. Intern. Med., 136: 769, 1976. Malek, R. S. and Greene, L. F.: Urologic aspects of Hippel-Lindau syndrome. J. Urol., 106: 800, 1971. Fetner, C. D., Barilla, D. E., Scott, T., Ballard, J. and Peters, P.: Bilateral renal cell carcinoma in von Hippel-Lindau syndrome: treatment with staged bilateral nephrectomy and hemodialysis. J. Urol., 117: 534, 1977. DeTure, F. A.: Uro!ogic implications of von Rippel-Lindau syndrome. Urology, 11: 612, 1978. Chapman, R. C., Kemp, V. E. and Taliaferro, I.: Pheochromocytoma associated with multiple neurofibromatosis and intracranial hemangioma. Amer. J. Med., 26: 883, 1959. Lowden, B. A. and Harris, G. S.: Pheochromocytoma and von Hippe!-Lindau's disease. Canad. J. Ophth., 11: 282, 1976. fv'.!eyers, M. A. and King, M. C.: Unusual radiologic features of pheochromocytoma. Clin. Radio!., 20: 52, 1969. Mori, Y., Kiyohara, H., Miki, T. and Kotake, T.: Pheochromocytoma with prominent calcification and associated pancreatic islet cell tumor. J. Urol., 118: 843, 1977. G!ushien, A. S., Mansuy, M. M. and Littman, D. S.: Pheochromocytoma; its relationship to neurocutaneous syndromes. Amer. J. Med., 14: 318, 1953. Chapman, R. C. and Diaz-Perez, R.: Pheochromocytoma associated with cerebellar hemangioblastoma. J.A.M.A., 182: 1014, 1962.