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Renal Cell Carcinoma Metastatic to a Pheochromocytoma
0022-5347 /79/1224-0544$02.00/0 THE JOURNAL OF UROLOGY
Vol. 122, October
Copyright© 1979 by The Williams & Wilkins Co.
Printed in U.S.A.
RENAL CELL CARCINOMA METASTATIC TO A PHEOCHROMOCYTOMA PATRICK G. BEATTY, JOHN A. OATES AND ROBERT K. OLDHAM* From the Departments of Medicine and Pharmacology, Vanderbilt University Hospital, Nashville, Tennessee
ABSTRACT
A case of renal cell carcinoma coincident with and metastatic to a pheochromocytoma is reported. The coincidence is rare and the metastasis is unique. Although pheochromocytoma is a relatively rare neoplasm it has been found in association with a number of other tumors. The association of pheochromocytoma with medullary carcinoma of the thyroid in Sipple's syndrome is well known. 1 Von Rippel-Lindau syndrome, an autosomal dominant condition, is characterized by multiple tumors, including hemangioblastomas, pancreatic cysts, pheochromocytoma and renal cell carcinoma. However, of 84 well documented cases of this syndrome2-4 only 1 had a pheochromocytoma and a renal cell carcinoma. Pheochromocytoma and renal cell carcinoma have been reported in the same patient only 7 times in the literature.5-11 Herein we report on a patient who had had clinical manifestations of a pheochromocytoma for 10 years before this tumor was diagnosed, at which time the coexistence of a renal cell carcinoma was discovered. In addition to multiple metastases of the renal cell carcinoma in the lung, numerous focal metastases of the renal cell carcinoma were detected within the pheochromocytoma. CASE REPORT
C. T., VUH 680904, a 55-year-old white male farmer, had been in good health except for a chronic nervous stomach. During the last 10 years he had experienced numerous 10minute episodes characterized by tachycardia, headache, chest pain, abdominal pain and flushing. These attacks worsened 2 years previously and the patient discovered that they could be precipitated by lying on the right side. As a result he slept on the left side with his wife propped against his back. In June 1977 the patient was admitted to a local hospital for evaluation of these episodes. At that time he was found to have elevated urinary vanillyl mandelic acid and was transferred to our hospital. The patient was a slender, tanned, anxious man in no distress. Physical examination was unremarkable. His father had died oflung cancer but his mother, 7 siblings and 3 children are well. Significant history included daily exposure at work in the late 1940s to a 250 Rv. 10 max-ray machine used for examining tank car welds. A chest x-ray showed several 1 to 2 cm. nodules scattered throughout both lung fields. Urinary vanillyl mandelic acid and catecholamines were elevated consistently. While in the hospital a symptomatic episode was induced by rolling the patient onto the right side. Within 4 minutes the blood pressure increased from 135/75 to 220/160 and 3 injections of 5 mg. phentolamine intravenously quickly brought the blood pressure under control. After 3 days of a- and ,8-adrenergic blockade an arteriogram showed a well vascularized 7 X 8 cm. left suprarenal mass and a hypervascular mass in the lower pole of the same kidney (fig. 1). Left nephrectomy and lung biopsy were done. Pathologic examination revealed a 5.5 cm. renal cell carcinoma in the lower pole of the left kidney extending into the renal Accepted for publication January 19, 1979. * Requests for reprints: Division of Oncology, Vanderbilt University Hospital, 21st and Garland, Nashville, Tennessee 37232. 544
veins, a 7 cm. pheochromocytoma in the left adrenal, containing multifocal nests of renal cell carcinoma (fig. 2) and a lung nodule of clear cell carcinoma consistent with a renal primary. Postoperatively, the patient was asymptomatic and able to lie on the right side. After responding initially to a course of vinblastine and bleomycin, he refused further chemotherapy and is being managed conservatively for the slowly progressive metastatic renal cell carcinoma. DISCUSSION
This is the eighth case of coexistence of a pheochromocytoma and renal cell carcinoma, and the first in which one is metastatic to the other. Unlike the Sipple syndrome there is no known familial association of combined pheochromocytoma and renal cell carcinoma. Although with the von Rippel-Lindau syndrome pheochromocytomas and renal cell carcinomas have been reported, there is only 1 reported case in which they coexisted. 11 Neither have both tumors been found in the same family of individuals with the von Rippel-Lindau syndrome. Thus, the interesting association between these 2 tumors cannot at present be ascribed to a genetic syndrome. Metastases to other tumors are rare, with only 37 cases being reported according to a recent review. 12 Most of these cases involved various other tumors metastatic to a renal cell carcinoma but in none had the renal cell carcinoma metastasized to another tumor nor had a pheochromocytoma been found to harbor any metastases. 13· 14 Thus, the nests of metastatic renal cell carcinoma within the pheochromocytoma of this patient are unique. The abundance of renal cell carcinoma foci within this pheochromocytoma raises the question of whether the
Fm. 1. Arteriogram shows A, renal cell carcinoma and B, pheochromocytoma.
RENAL CELL CARCINOMA METASTATIC TO PHEOCHROMOCYTOMA
545
FIG. 2. Photomicrograph shows renal cell carcinoma embedded in pheochromocytoma. Reduced from X25
peculiar biochemical milieu of the pheochromocytoma might have provided an environment that favored the growth of the renal carcinoma cells. Perhaps this experiment of nature offers a clue to a more significant clinical problem: the predilection of certain tumors to metastasize to certain organs. REFERENCES 1. Sipple, J. H.: The association of pheochromocytoma with carci-
noma of the thyroid gland. Amer. J. Med., 31: 163, 1961. 2. Horton, W. A., Wong, V. and Eldridge, R.: Von Hippel-Lindau disease: clinical and pathological manifestations in nine families with 50 affected members. Arch. Intern. Med., 136: 769, 1976. 3. Malek, R. S. and Greene, L. F.: Urologic aspects of Hippel-Lindau syndrome. J. Urol., 106: 800, 1971. 4. Melmon, K. L. and Rosen, S. W.: Lindau's disease. Review of the literature and study of a large kindred. Amer. J. Med., 36: 595, 1964. 5. Conley, J. E. and Junkerman, C. L.: Lack of specificity of piperoxan hydrochloride test for adrenal medullary tumors. J.A.M.A., 147: 921, 1951. 6. deKlerk, D. P., Catalona, W. J., Nime, F. A. and Freeman, C.: Malignant pheochromocytoma of the bladder: the late develop-
ment of renal cell carcinoma. J. Urol., 113: 864, 1975. 7. Harbitz, F.: Tumors of the sympathetic nervous system and the medulla of the adrenal glands, especially malignant neuroblastoma. Arch. Intern. Med., 16: 312, 1915. 8. McEllistrem, G. D.: Pheochromocytoma and ipsilateral renal cell carcinoma. Exarnination of important aspects. Minn. Med., 50: 653, 1967. 9. Minno, A. M., Bennett, W. A. and Kvale, W. F.: Pheochromocytoma; a study of 15 cases diagnosed at autopsy. New Engl. J. Med., 251: 959, 1954. 10. Siegelman, S. S., Zavod, R. and Hasson, J.: Hypemephroma, pheochromocytoma and thyroid carcinoma. J. Urol., 102: 402, 1969. 11. Wolf, A. and Wilens, S. L.: Multiple hemangioblastomas of the spinal cord with syringomyelia: a case of Lindau's disease. Amer. J. Path., HJ: 545, 1934. 12. Campbell, L. V., Jr., Gilbert, E., Chamberlain, C.R., Jr. and Watne, A. L.: Metastases of cancer to cancer. Cancer, 22: 635, 1968. 13. Rabson, S. M., Stier, P. L., Baumgartner, J.C. and Rosenbaum, D.: Metastasis of cancer to cancer. Amer. J. Clin. Path., 24: 572, 1954. 14. Richardson, J. F. and Katayama, I.: Neoplasm to neoplasm metastasis. An acidophil adenoma harbouring metastatic carcinoma: a case report. Arch. Path., 91: 135, 1971.
Vol. 122, October
Copyright© 1979 by The Williams & Wilkins Co.
Printed in U.S.A.
RENAL CELL CARCINOMA METASTATIC TO A PHEOCHROMOCYTOMA PATRICK G. BEATTY, JOHN A. OATES AND ROBERT K. OLDHAM* From the Departments of Medicine and Pharmacology, Vanderbilt University Hospital, Nashville, Tennessee
ABSTRACT
A case of renal cell carcinoma coincident with and metastatic to a pheochromocytoma is reported. The coincidence is rare and the metastasis is unique. Although pheochromocytoma is a relatively rare neoplasm it has been found in association with a number of other tumors. The association of pheochromocytoma with medullary carcinoma of the thyroid in Sipple's syndrome is well known. 1 Von Rippel-Lindau syndrome, an autosomal dominant condition, is characterized by multiple tumors, including hemangioblastomas, pancreatic cysts, pheochromocytoma and renal cell carcinoma. However, of 84 well documented cases of this syndrome2-4 only 1 had a pheochromocytoma and a renal cell carcinoma. Pheochromocytoma and renal cell carcinoma have been reported in the same patient only 7 times in the literature.5-11 Herein we report on a patient who had had clinical manifestations of a pheochromocytoma for 10 years before this tumor was diagnosed, at which time the coexistence of a renal cell carcinoma was discovered. In addition to multiple metastases of the renal cell carcinoma in the lung, numerous focal metastases of the renal cell carcinoma were detected within the pheochromocytoma. CASE REPORT
C. T., VUH 680904, a 55-year-old white male farmer, had been in good health except for a chronic nervous stomach. During the last 10 years he had experienced numerous 10minute episodes characterized by tachycardia, headache, chest pain, abdominal pain and flushing. These attacks worsened 2 years previously and the patient discovered that they could be precipitated by lying on the right side. As a result he slept on the left side with his wife propped against his back. In June 1977 the patient was admitted to a local hospital for evaluation of these episodes. At that time he was found to have elevated urinary vanillyl mandelic acid and was transferred to our hospital. The patient was a slender, tanned, anxious man in no distress. Physical examination was unremarkable. His father had died oflung cancer but his mother, 7 siblings and 3 children are well. Significant history included daily exposure at work in the late 1940s to a 250 Rv. 10 max-ray machine used for examining tank car welds. A chest x-ray showed several 1 to 2 cm. nodules scattered throughout both lung fields. Urinary vanillyl mandelic acid and catecholamines were elevated consistently. While in the hospital a symptomatic episode was induced by rolling the patient onto the right side. Within 4 minutes the blood pressure increased from 135/75 to 220/160 and 3 injections of 5 mg. phentolamine intravenously quickly brought the blood pressure under control. After 3 days of a- and ,8-adrenergic blockade an arteriogram showed a well vascularized 7 X 8 cm. left suprarenal mass and a hypervascular mass in the lower pole of the same kidney (fig. 1). Left nephrectomy and lung biopsy were done. Pathologic examination revealed a 5.5 cm. renal cell carcinoma in the lower pole of the left kidney extending into the renal Accepted for publication January 19, 1979. * Requests for reprints: Division of Oncology, Vanderbilt University Hospital, 21st and Garland, Nashville, Tennessee 37232. 544
veins, a 7 cm. pheochromocytoma in the left adrenal, containing multifocal nests of renal cell carcinoma (fig. 2) and a lung nodule of clear cell carcinoma consistent with a renal primary. Postoperatively, the patient was asymptomatic and able to lie on the right side. After responding initially to a course of vinblastine and bleomycin, he refused further chemotherapy and is being managed conservatively for the slowly progressive metastatic renal cell carcinoma. DISCUSSION
This is the eighth case of coexistence of a pheochromocytoma and renal cell carcinoma, and the first in which one is metastatic to the other. Unlike the Sipple syndrome there is no known familial association of combined pheochromocytoma and renal cell carcinoma. Although with the von Rippel-Lindau syndrome pheochromocytomas and renal cell carcinomas have been reported, there is only 1 reported case in which they coexisted. 11 Neither have both tumors been found in the same family of individuals with the von Rippel-Lindau syndrome. Thus, the interesting association between these 2 tumors cannot at present be ascribed to a genetic syndrome. Metastases to other tumors are rare, with only 37 cases being reported according to a recent review. 12 Most of these cases involved various other tumors metastatic to a renal cell carcinoma but in none had the renal cell carcinoma metastasized to another tumor nor had a pheochromocytoma been found to harbor any metastases. 13· 14 Thus, the nests of metastatic renal cell carcinoma within the pheochromocytoma of this patient are unique. The abundance of renal cell carcinoma foci within this pheochromocytoma raises the question of whether the
Fm. 1. Arteriogram shows A, renal cell carcinoma and B, pheochromocytoma.
RENAL CELL CARCINOMA METASTATIC TO PHEOCHROMOCYTOMA
545
FIG. 2. Photomicrograph shows renal cell carcinoma embedded in pheochromocytoma. Reduced from X25
peculiar biochemical milieu of the pheochromocytoma might have provided an environment that favored the growth of the renal carcinoma cells. Perhaps this experiment of nature offers a clue to a more significant clinical problem: the predilection of certain tumors to metastasize to certain organs. REFERENCES 1. Sipple, J. H.: The association of pheochromocytoma with carci-
noma of the thyroid gland. Amer. J. Med., 31: 163, 1961. 2. Horton, W. A., Wong, V. and Eldridge, R.: Von Hippel-Lindau disease: clinical and pathological manifestations in nine families with 50 affected members. Arch. Intern. Med., 136: 769, 1976. 3. Malek, R. S. and Greene, L. F.: Urologic aspects of Hippel-Lindau syndrome. J. Urol., 106: 800, 1971. 4. Melmon, K. L. and Rosen, S. W.: Lindau's disease. Review of the literature and study of a large kindred. Amer. J. Med., 36: 595, 1964. 5. Conley, J. E. and Junkerman, C. L.: Lack of specificity of piperoxan hydrochloride test for adrenal medullary tumors. J.A.M.A., 147: 921, 1951. 6. deKlerk, D. P., Catalona, W. J., Nime, F. A. and Freeman, C.: Malignant pheochromocytoma of the bladder: the late develop-
ment of renal cell carcinoma. J. Urol., 113: 864, 1975. 7. Harbitz, F.: Tumors of the sympathetic nervous system and the medulla of the adrenal glands, especially malignant neuroblastoma. Arch. Intern. Med., 16: 312, 1915. 8. McEllistrem, G. D.: Pheochromocytoma and ipsilateral renal cell carcinoma. Exarnination of important aspects. Minn. Med., 50: 653, 1967. 9. Minno, A. M., Bennett, W. A. and Kvale, W. F.: Pheochromocytoma; a study of 15 cases diagnosed at autopsy. New Engl. J. Med., 251: 959, 1954. 10. Siegelman, S. S., Zavod, R. and Hasson, J.: Hypemephroma, pheochromocytoma and thyroid carcinoma. J. Urol., 102: 402, 1969. 11. Wolf, A. and Wilens, S. L.: Multiple hemangioblastomas of the spinal cord with syringomyelia: a case of Lindau's disease. Amer. J. Path., HJ: 545, 1934. 12. Campbell, L. V., Jr., Gilbert, E., Chamberlain, C.R., Jr. and Watne, A. L.: Metastases of cancer to cancer. Cancer, 22: 635, 1968. 13. Rabson, S. M., Stier, P. L., Baumgartner, J.C. and Rosenbaum, D.: Metastasis of cancer to cancer. Amer. J. Clin. Path., 24: 572, 1954. 14. Richardson, J. F. and Katayama, I.: Neoplasm to neoplasm metastasis. An acidophil adenoma harbouring metastatic carcinoma: a case report. Arch. Path., 91: 135, 1971.