Bilateral Renal-Cell
Diagnostic Radiology
Carcinomas 1
Fred W. Wright, M.A., D.M., M.R.C.P., F.F.R. The incidence of 5 cases of bilateral renal-cell carcinomas and one case of possible bilateral angiomyoliposarcomas over a period of 16 years suggests that these entities may be more frequent than previously thought. One patient successfully underwent surgery via the "workbench" technique, in which the tumor was dissected from one kidney which was then reinserted as an autograft. It is suggested that renal angiography should always be performed bilaterally when attempting to diagnose or exclude renal masses. INDEX TERMS: Kidney Neoplasms, diagnosis. Kidneys, transplantation • Renal Angiography, indications • Renal Angiography, technique
Radiology 115: 543-550, June 1975
ILATERAL renal tubular-cell carcinomas or hypernephromas are considered rare. Riches (22) stated, "If there is a hormonal background for the development of human renal adenocarcinoma one might expect the disease, at times, to be multifocal and bilateral. Adenocarcinoma involving both kidneys, is in fact, extremely rare." Vermillion et al. (28) found bilateral renal tumors in 6 (1.8 %) of 329 patients treated over a period of 30 years, with 6 more occurring in the subsequent 6-year period. The tumors developed simultaneously in approximately half of these patients and at different times in the other half. I have encountered 6 cases of synchronous bilateral renal tumors in the past 16 years and feel that they may be more frequent than previously recognized. Five cases involved renal carcinoma: one of these was in a 40-year-old man with Lindau-von Hippel syndrome, another in a 55-year-old man, a third in a
72-year-old woman, a fourth in a patient with polycystic renal disease, and a fifth in a 43-year-old man without other known disease. The sixth patient was a young woman with polycystic disease and renal hamartomas (angiomyolipomas), or possibly leiomyosarcomas. Details are given in the case reports and in TABLE I.
B
Table I: Case No.
Age (at Time of Diagnosis) and Sex
Year of Diagnosis
I.
40M
1963
7 yr.
II.
55M
1961
2 yr.+
III.
72F
1960
IV.
44M
1972
3 mo.
V.
43M
1972
6 mo.
VI.
20F
1970
18 mo.
Duration of Symptoms
CASE REPORTS CASE I: Bilateral renal tumors in Lindau-von Hippel disease. A 26-year-old man underwent removal of a cerebellar hemangioblastoma in 1949. Seven years later, hematuria developed. An excretory urogram (Fig. 1, A) was interpreted. as showing bilateral polycystic disease; however, on retrospect it revealed large masses involving primarily the lower poles of both kidneys. Six years later the hemangioblastoma recurred and was removed. Both kidneys were now huge to palpation, with the right kidney larger than the left, and polycythemia (18.5 g/100 ml) had developed as well. One year later the
Bilateral Renal Tumors
Underlying disease
Lindau-von Hippel syndrome
Polycystic disease and hypertension
Angiogra phy
Positive
Biopsy shortly before death
Not done; renal pu nctu re was positive for tumor Excretory urography and angiography not done Positive
Died from effects of second tumor
Positive
Polycystic disease
Comments
Positive
Died following lumbar disk operation Died of metastases soon after diagnosis Left nephrectomy and "work bench" surgery on right kidney; still alive after 3 yr. Bilateral nephrectomy and renal transplantation
1 From the X-Ray Department (F. W. W., Consultant Radiologist), Churchill Hospital, United Oxford Hospitals, Headington, Oxford, England. Accepted for publication in October 1974. sjh
543
544
FRED W. WRIGHT
June 1975
Fig. 1. CASE I. A. Excretory urogram taken in 1956 demonstrates large space-occupying lesions In both kidneys, with some calcification on the right. B. Excretory urogram with tomography taken in 1959 shows that the Intrarenal masses have increased in size. C. Repeat study in 1963 shows increased calcification in the intrarenal masses, particularly on the right. The masses have become much larger. D. Aortogram reveals enormously enlarged renal vessels with "pathological circulation." [Fig. 1, A, C, and D are reproduced from Butt and Wright (4) with the permission of the publisher] patient exhibited gross hematuria and clot retention and his kidneys were "hard and knobbly. Repeat excretory urograms (Fig. 1, Band C) demonstrated a marked increase in the size of the kidneys and bilateral faint, amorphous calcification. Aortography (Fig~ 1, D) revealed a gross increase. in the size and number of blood vessels in both kidneys. Biopsy showed bilateral renal carcinoma. The patient died a month later at the age of 33. II
CASE II: Bilateral renal tumors. A 53-year-old man presented with renal colic in 1960. An excretory urogram (Fig. 2, A) was Interpreted as showing a small right renal calculus and bilateral deformed calyces, suggesting polycystic disease; however, a single spaceoccupying lesion was later identified in the right kidney, accompanied by a large mass involving the lower two-thirds of the left kidney. Five months later, the colic and hematuria recurred. The left kidney was not palpable. A second excretory urogram was interpreted as unchanged, but the lesion in the left kidney had become larger and submucosal infiltration was present in the renal pelvis . .During the next 8 months, the patient had repeated attacks of hematuria, ac-
companied by anemia (8.9 g/100 ml), a blood urea level of 60 mg/ 100 ml, and an erythrocyte sedimentation rate of 107 mm in an hour. A third excretory urogram showed marked enlargement of the left kidney with amputation of the lower calyces and a "giant" upper-pole calyx. Renal angiography was unsuccessful because of marked tortuosity of the pelvic vessels, and the catheter could not be manipulated into the aorta. No cyst was found on renal puncture (Fig. 2, B), and contrast material injected into the tumor spread out within part of it. Upon removal, the left kidney was found to weigh 1,220 g and was completely replaced by tumor extending into the renal vein. The patient remained well for about six months, but during the next nine months he became progressively weaker, lost weight, and suffered anorexia. A barium-meal study was normal; however, a repeat excretory urogram showed that the mass in the right kidney had become much larger. The patient died soon afterward, following the development of inferior vena caval obstruction. CASE III: Bilateral renal tumors, not suspected during life. A 72year-old woman was admitted for excision of a lumbar disk but died
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Diagnost Radiolog
Fig. 2. CASE II. A. Excretory urogram with tomography taken in 1960 shows a large space-occupying lesion in the lower pole of the left kidney and another in the middle third of the right kidney. B Injection of contrast material into the left lesion by renal puncture demonstrates the typical appearance of a renal tumor. [Both parts of Fig. 2 are reproduced from Butt and Wright (4) with the permission of the publisher]
Fig. 3. CASE IV. A. Excretory urogram obtained in 1969 demonstrates multiple masses in both kidneys, consistent with polycystic disease. B. On a second excretory urogram made three years later, the middle portion of the right kidney is now very different from the earlier pattern. The upper and lower pole calyces are stretched out by a large mass. Note the calcification in the upper pole cysts (arrows). [Figure 3, B is reproduced from Wright et al. (31) with the permission of the publisher]
postoperatively of renal failure. No renal lesion had been suspected, and urography had not been performed. At postmortem examination, multiple bilateral renal tumors of varying sizes up to 4 cm in diameter were seen; these were thought to be multiple primary growths. CASE IV: Bilateral renal tumors complicating polycystic disease. A 24-year-old man presented with headaches. Four years later he complained of epigastric discomfort. Excretory urography revealed that both kidneys were enlarged (the left more so than the right) and contained multiple cysts. Blood pressure and blood urea were normal. His family history showed that a sister had died of polycystic disease shortly after pregnancy and that a cousin had the same con-
ditlon. At the age of 41, the patient noticed increased abdominal swelling. An excretory urogram (Fig. 3, A) showed very large kidneys with distorted calyces, accompanied by three cysts in the upper pole of the left kidney which contained ring-type calcification. His blood pressure had risen to 170/115, and the blood urea level was now 48 mgl 100 ml. He was given antihypertensive treatment using methyldopa. Three years later, he had four attacks of hematuria, accompanied by diminished appetite, night sweats, and mild pyrexia. A chest film showed three small, rounded shadows in the left lung, but it was uncertain whether they were infective or metastatic in nature. A second excretory urogram (Fig. 3, B) showed that the right kidney had become considerably enlarged, particularly the midportion. Renal angiography (Fig. 4) demonstrated a diffuse vascular abnor-
546
FRED W. WRIGHT
June 1975
Fig. 4. CASE IV. A. Right renal angiogram obtained in 1972 shows an extensive tumor circulation in the middle and lower portions of the kidney. The spindle-shaped vessels in the upper pole are consistent with polycystic disease. B. Left renal angiogram (subtraction print) demonstrates stretched vessels in the kidney with scattered areas of normal renal function, producing a patchy nephrogram, as well as two small areas of tumor circulation in the lower pole (arrows). [Both parts of Fig. 4 are reproduced from Wright et al. (31) with the permission of the publisher]
mality in the middle part of the right kidney, suggesting a tumor in addition to the polycystic disease. Two smaller areas of tumor circulation, each about 1.5 cm in diameter, were seen in the lower pole of the left kidney. The patient was given progestogens in an attempt to control tumor growth but died a few weeks later. At postmortem examination, both kidneys were very large and contained multiple cysts. In addition, there was an extensive, partly necrotic and hemorrhagic tumor involving the middle and lower portions of the right kidney, as well as two small tumors in the lower pole of the left kidney. Metastases were also present in the para-aortic lymph nodes. lungs. and brain, and the pancreas showed polycystic disease. The tumor in the right kidney contained typical clear cells and spindleshaped cells which were more pleomorphic and malignant in appearance; the metastases were all of the latter type, while the two small tumors in the left kidney were of the clear-cell type. These findings suggested that the tumors were multicentric in origin (23, 31).
Fig. 5. CASE V. Excretory urogram demonstrates a large mass in the lower two-thirds of the left kidney. The upper part of the left ureter is displaced medially and the tip of the middle right calyx is amputated.
CASE V: Bilateral renal tumors with successful surgical resection. A 43-year-old man was referred for renal angiography in 1972 after noticing bilateral loin discomfort for six months, accompanied
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BILATERAL RENAL-CELL CARCINOMAS
Diagnostic Radiology
Fig. 6. CASE V. Selective left renal angiogram shows a large, .primarily avascular tumor in the lower three-fourths of the left kidney. A. Arterial phase. B. Nephrogram phase. Fig. 7. CASE V. Selective right renal angiogram, oblique series (late arterial phase) shows a tumor extending from the midportion of the kidney. by two minor attacks of hematuria. An excretory urogram (Fig. 5) showed enlargement of the lower pole of the left kidney and poor filling of the calyces on that side. The right kidney was thought to be normal; however, re-evaluation showed that the tip of the middle calyx was amputated. A left selective renal angiogram showed that the lower three-fourths of the kidney was replaced by a largely avascular tumor (Fig. 6). Although there was no major vessel displacement, the tumor mass was seen as an extensive defect in the nephrogram phase. Anteroposterior radiographs of the contralateral kidney appeared to be almost normal; however, one or two tiny vessels seemed to pass beyond the confines of the kidney. In view of the abnormal calyx seen in the right kidney on the excretory urogram, oblique angiography was performed. This showed a tumor extending from the midportion of the kidney into the perirenal tissues (Fig. 7). Lymphangiography was normal. At surgery (R. Caine) (4), both kidneys were completely removed. The tumor was dissected from the right kidney, and the remainder was placed in the right lower abdomen as an autograft. The patient has remained well for three years now. CASE VI: Bilateral leiomyosarcomas or angiomyolipomas in polycystic disease: bilateral nephrectomy and renal transplantation. A 19-year-old girl presented in April 1969 with recurrent hematuria. An excretory urogram showed large, polycystic kidneys. There appeared to be a left pelviureteric obstruction, and a pyeloplasty was carried out the following year. Six months later severe hematuria occurred, necessitating transfusions. Renal angiography (Fig. 8) showed a very large left kidney extending from just below the left dome of the diaphragm to the pelvis. The intrarenal vessels were stretched and displaced as with polycystic disease, but in addition multiple small aneurysms or beaded vessels were present in many parts of the kidney, and similar though smaller areas of abnormal circulation were seen in the upper and lower poles of the right kidney. Renal failure increased, accompanied by persistent fever and leukocytosis. Blood transfusions could not keep pace with blood loss. At left nephrectomy, the kidney was found to contain numerous
cysts, some containing pus or blood. Macroscopically, no normal renal parenchyma could be seen. Soft yellowish tissue and areas of hemorrhage in various stages of organization were seen between the cysts. Microscopy showed few normal glomeruli, mostly associated with dilated tubules, as well as marked leiomyomatous proliferation involving both spindle-shaped and smooth muscle cells throughout the renal parenchyma. Some cellular pleomorphism and nuclear hypochromatism were evident, though mitoses were difficult to find. Although the patient improved following nephrectomy, renal failure occurred nine months later. The right kidney was removed; pathologically, it was similar to the left. Some pathologists thought it was an angiomyolipoma, but others considered it to be a leiomyosarcoma. Renal transplantation was carried out following hemodialysis treatment (8,31).
DISCUSSION
The ability to demonstrate bilateral renal lesions has been greatly increased by the use of (a) tomography with high-dose excretory urography and (b) angiography. Bilateral renal angiography should be almost mandatory, for it takes very little effort and may be of great importance; moreover, it is greatly comforting to the surgeon to know the appearance of the contralateral kidney and may also modify the planned surgical procedure considerably, especially if bilateral tumors are present. High-quality angiograms should be obtained; at present, I often use a simple technique employing three films and a Bucky tray (30) as well as or instead of a series taken with an automatic serial changer. In the differential diagnosis of bilateral renal masses, cysts are by far the most common finding. Indeed, finding a second "smooth" mass on the angiogram makes a cyst much more likely, since they are commonly multiple. My practice is to examine cysts by renal puncture
548
FRED W. WRIGHT
June 1975
Fig. 8. CASE VI. A. Right renal angiogram shows a small area of abnormal circulation in the upper pole of the kidney. A similar area was present in the "darker" part of the lower pole. B. On the left renal angiogram, the intrarenal vessels are markedly stretched, with multiple areas of abnormal circulation including small aneurysms and beading. [Figure 8, B is reproduced from Wright et et. (31) with the permission of the publisher]
immediately after removing the catheter and stopping any bleeding. Other abnormalities should also be considered. I have encountered a patient with renal failure who was found to have hydronephrosis on one side and a large renal tumor on the other. Renal hamartomas may also give rise to bilateral masses which demonstrate small "beaded" vessels on angiography; these are most common in patients with tuberous sclerosis but also occur in other conditions (31). They may also show varying degrees of malignant change, as in CASE VI. I have not had the opportunity to examine a case of renal adenomatosis such as that reported by Meisel (19). Renal metastases secondary to bronchogenic tumors are being recognized more frequently, not only at autopsy (29) but also during life; I found 5 such cases in 1973-74 which were revealed by high-dose urography and tomography; however, more were examined by an-
giography, since there seemed to be little doubt as to their nature. Such metastases are commonly bilateral (2).
In assessing bilateral renal tumors, the major consideration is whether both are primary lesions or one is a metastasis of the other. Bastable (1) reported one case of bilateral renal carcinoma and reviewed 20 previously reported cases which he considered to involve two primary tumors, each having a different histological pattern. Although Billroth has stated that each tumor should demonstrate individual metastases (3), Bastable noted that this is not always the case and that the incidence of renal metastasis to the contralateral kidney is low; he estimated it at about 1 % on the basis of clinical studies, though the incidence at postmortem examination may be much higher. Renal metastases may lie dormant and remain clinically unsuspected for many years; thus Bas-
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table rejected 7 additional cases of bilateral individual tumors as insufficiently proved on the basis that it was not reasonably certain they had arisen from a single source. Ljunggren (16), discussing partial nephrectomy in patients with renal tumors, reviewed 5 previously reported cases of bilateral renal tumors (6, 9, 21, 27). Additional single cases were reported by Krumbach and Ansell (15) and Marshall and Johnson (18). In 1968, Small et at. (25) reviewed the literature and found 17 cases, including 7 reviewed by Bastable. They also reported a case of their own involving a hypertensive 44-year-old woman who demonstrated bilateral renal tumors on excretory urography and angiography. Following removal of the right kidney, an encapsulated tumor was resected from the left kidney. Since then, Kobayashi et at. (13), Kolin et at. (14), and Hyman et at. (11) have each reported a single case of bilateral renal tumors. Parker et at. (20), Kaufman et at. (12), and Stackpole (26) found a total of 9 cases of bilateral renal tumors, none of which were synchronous. References to 9 additional cases are contained in the papers of Kaufman et at. (12) and Krumbach and Ansell (15). In addition, 6 cases of bilateral renal tumors associated with polycystic disease have been reported (10, 31). The total number of recorded cases is now more than 80, including my own and those recorded by Caine (5), one of which involved a patient treated at this hospital. He recommends accurate assessment and "workbench surgery" on the excised kidney prior to reinsertion of the salvaged portion as an autograft, a practice which he has followed successfully in 3 cases (including CASE V reported above). In another case (8) he removed both kidneys and inserted a donor transplant. Malament (17) removed one kidney and biopsied the lesion in the other kidney. Following radiotherapy, the patient lived for 10 years, finally dying of pulmonary metastases. I have also seen a single case of bilateral Wilms's tumor, but this is a separate problem which has been reviewed by Scott (24) and Close et at. (7). Scott found that 35 of the 908 Wilms's tumors he studied were bilateral but felt that most contralateral masses were probably metastatic. Hyman et at. (11) have stated that only 3 of the previously recorded cases they reviewed had been studied angiographically, and selective angiography was employed in only one case. Three of the cases described above were studied angiographically, and angiography was also attempted in a fourth case. Bilateral angiography is also referred to by Ben-Menachem et at. (2). Since only about one-fourth of a normal kidney is needed for life, and since surgeons can save part of one kidney either by partial resection or reimplantation following "workbench" renal surgery as described above, it is important for the radiologist to demonstrate bilateral tumors. The alternative is bilateral nephrectomy, which is not usually contemplated for malignant disease; and in any event, a patient's own renal tissue causes a far lesser problem than an artificial kidney or a donor kidney used as a homograft.
549
Diagnostic Radiology
ACKNOWLEDGMENTS: I am grateful to Brian Higgs, F.R.C.S., Consultant Surgeon, Amersham Hospital, Buckinghamshire, for referring the patient in CASE V for angiography and to Roy Caine, F.R.C.S., F.R.S., Professor of Surgery, University of Cambridge, for details of his operative procedures.
REFERENCES 1. Bastable JRG: Bilateral carcinoma of the kidneys. Br J Urol 32:60-68, Mar 1960 2. Ben-Menachem Y, Marcos J, Wallace S, et al: Angiography of renal metastases. Br J Radiol 47:869-874, Dec 1974 3. Billroth T, von Winiwarter A: Die allgemeine chirurgische Pathologie und Therapie in elnundfunfzlq Vorlesungen. Ein Handbuch fUr Studirende und Aerzte. Berlin, Reimer, 1889, Vol 14, P 908 4. Butt WP, Wright FW: Renal tumours masquerading as polycystic disease. Br J Radiol 37:952-954, Dec 1964 5. Caine RY: Treatment of bilateral hypernephromas by nephrectomy, excision of tumour, and autotransplantation. Report of three cases. Lancet 2:1164-1167,24 Nov 1973 6. Cibert J: Discussion of Aubert J: Un cas de sarcome Iipoet fibroblastique du rein chez I'adulte. J Urol Med Chir 64:78-82, Jan-Feb 1958 7. Close MB, Peterson CA, Johnson RP: Bilateral embryoma of the kidney: patient alive and well three years after treatment. Radiology 67:99-101, Jul 1956 8. Evans DB, Caine RY: Renal transplantation in patients with carcinoma. Br Med J 4:134-136,19 Oct 1974 9. Hanley HG: Discussion on partial nephrectomy. Proc R Soc Med 43:1027-1038, Dec 1950 10. Howard RM, Young JD Jr: Two malignant tumors in a polycystic kidney. J UroI102:162-164, Aug 1969 11. Hyman RA, Voges V, Finby N: Bilateral hypernephroma. Am J RoentgenoI117:104-107, Jan 1973 12. Kaufman JJ, Chaffey BT, Goodwin WE: Renal cell carcinoma in the solitary kidney: report of six cases. Br J Urol 40: 12-21, Feb 1968 13. Kobayashi A, Hoshino H, Ohbe Y, et al: Bilateral renal cell carcinoma. Arch Dis Child 45:141-143, Feb 1970 14. Kolin CP, Boldus RA, Brandon DNK, et al: Bilateral partial nephrectomy for bilateral renal cell carcinoma: a case report. J Urol 105:45-48, Jan 1971 15. Krumbach RW, Ansell JS: Partial resection of the right kidney and radical removal of the left kidney in a patient with bilateral hypernephroma. Surgery 45:585-592, Apr 1959 16. Ljunggren E: Partial nephrectomy in renal tumour. Acta Chir Scand (Suppl 253):37-44, 1960 17. Malament M: Bilateral renal cell carcinoma: a 14-year survival. J Urol 94:348-355, Oct 1965 18. Marshall F, Johnson AJ: Double primary urinary tumors: case report. J Urol 85:724-726, May 1961 19. Meisel HJ: Bilateral polyadenomatous kidneys: adenomatosis of the kidneys sirnulatlnq polycystic disease. J Urol 72:11401145, Dec 1954 20. Parker RM, Timothy RP, Harrison JH: Neoplasia of the solitary kidney. J UroI101:283-296, Mar 1969 21. Puigvert A: (quoted in) Mocellini J: Comentarios a 115 nefrectornias parciales. Arch Esp UroI12:85-95, Apr 1956 22. Riches EW: Tumours of the Kidney and Ureter. Edinburgh, Livingstone, 1964, p 320 23. Roberts PF: Bilateral renal carcinoma associated with polycystic kidneys. Br Med J 3:273-274,4 Aug 1973 24. Scott LS: Bilateral Wilms' tumour. Br J Surg 42:513-516, Mar 1955 25. Small MP, Anderson EE, Atwill WH: Simultaneous bilateral renal cell carcinoma: case report and review of the literature. J Urol 100:8-14, Jul 1968 26. Stackpole RH: Treatment of carcinoma in a solitary kidney: case report and review of the literature. J Urol 93:353-360, Mar 1965 27. Svab J: Zwei seltene Faile von NierengeschwUlsten. Kasuistischer Beitrag zur grawitzschen Geschwulst in solltarer Niere und zu den beiderseitigen Nierengeschwulsten. Z Urol 49:241-251, 1956 .
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28. Vermillion CD, Skinner DG, Pfister RC: Bilateral renal cell carcinoma. J UroI108:219-222, Aug 1972 29. Wright FW: The Radiological Diagnosis of Lung and Mediastinal Tumours. London, Butterworths, 1973, p 187 30. Wright FW: Simplified selective renal angiography. Letter to the editor. Br J RadioI46:145, Feb 1973 31. Wright FW, Ledingham JGG, Dunnill MS, et al: Polycystic
June 1975
kidneys, renal hamartomas, their variants and complications. Clin RadioI25:27-43, Jan 1974 X-Ray Department Churchill Hospital Oxford OX3 7LJ England
Diagnostic Radiology
Carcinomas 1
Fred W. Wright, M.A., D.M., M.R.C.P., F.F.R. The incidence of 5 cases of bilateral renal-cell carcinomas and one case of possible bilateral angiomyoliposarcomas over a period of 16 years suggests that these entities may be more frequent than previously thought. One patient successfully underwent surgery via the "workbench" technique, in which the tumor was dissected from one kidney which was then reinserted as an autograft. It is suggested that renal angiography should always be performed bilaterally when attempting to diagnose or exclude renal masses. INDEX TERMS: Kidney Neoplasms, diagnosis. Kidneys, transplantation • Renal Angiography, indications • Renal Angiography, technique
Radiology 115: 543-550, June 1975
ILATERAL renal tubular-cell carcinomas or hypernephromas are considered rare. Riches (22) stated, "If there is a hormonal background for the development of human renal adenocarcinoma one might expect the disease, at times, to be multifocal and bilateral. Adenocarcinoma involving both kidneys, is in fact, extremely rare." Vermillion et al. (28) found bilateral renal tumors in 6 (1.8 %) of 329 patients treated over a period of 30 years, with 6 more occurring in the subsequent 6-year period. The tumors developed simultaneously in approximately half of these patients and at different times in the other half. I have encountered 6 cases of synchronous bilateral renal tumors in the past 16 years and feel that they may be more frequent than previously recognized. Five cases involved renal carcinoma: one of these was in a 40-year-old man with Lindau-von Hippel syndrome, another in a 55-year-old man, a third in a
72-year-old woman, a fourth in a patient with polycystic renal disease, and a fifth in a 43-year-old man without other known disease. The sixth patient was a young woman with polycystic disease and renal hamartomas (angiomyolipomas), or possibly leiomyosarcomas. Details are given in the case reports and in TABLE I.
B
Table I: Case No.
Age (at Time of Diagnosis) and Sex
Year of Diagnosis
I.
40M
1963
7 yr.
II.
55M
1961
2 yr.+
III.
72F
1960
IV.
44M
1972
3 mo.
V.
43M
1972
6 mo.
VI.
20F
1970
18 mo.
Duration of Symptoms
CASE REPORTS CASE I: Bilateral renal tumors in Lindau-von Hippel disease. A 26-year-old man underwent removal of a cerebellar hemangioblastoma in 1949. Seven years later, hematuria developed. An excretory urogram (Fig. 1, A) was interpreted. as showing bilateral polycystic disease; however, on retrospect it revealed large masses involving primarily the lower poles of both kidneys. Six years later the hemangioblastoma recurred and was removed. Both kidneys were now huge to palpation, with the right kidney larger than the left, and polycythemia (18.5 g/100 ml) had developed as well. One year later the
Bilateral Renal Tumors
Underlying disease
Lindau-von Hippel syndrome
Polycystic disease and hypertension
Angiogra phy
Positive
Biopsy shortly before death
Not done; renal pu nctu re was positive for tumor Excretory urography and angiography not done Positive
Died from effects of second tumor
Positive
Polycystic disease
Comments
Positive
Died following lumbar disk operation Died of metastases soon after diagnosis Left nephrectomy and "work bench" surgery on right kidney; still alive after 3 yr. Bilateral nephrectomy and renal transplantation
1 From the X-Ray Department (F. W. W., Consultant Radiologist), Churchill Hospital, United Oxford Hospitals, Headington, Oxford, England. Accepted for publication in October 1974. sjh
543
544
FRED W. WRIGHT
June 1975
Fig. 1. CASE I. A. Excretory urogram taken in 1956 demonstrates large space-occupying lesions In both kidneys, with some calcification on the right. B. Excretory urogram with tomography taken in 1959 shows that the Intrarenal masses have increased in size. C. Repeat study in 1963 shows increased calcification in the intrarenal masses, particularly on the right. The masses have become much larger. D. Aortogram reveals enormously enlarged renal vessels with "pathological circulation." [Fig. 1, A, C, and D are reproduced from Butt and Wright (4) with the permission of the publisher] patient exhibited gross hematuria and clot retention and his kidneys were "hard and knobbly. Repeat excretory urograms (Fig. 1, Band C) demonstrated a marked increase in the size of the kidneys and bilateral faint, amorphous calcification. Aortography (Fig~ 1, D) revealed a gross increase. in the size and number of blood vessels in both kidneys. Biopsy showed bilateral renal carcinoma. The patient died a month later at the age of 33. II
CASE II: Bilateral renal tumors. A 53-year-old man presented with renal colic in 1960. An excretory urogram (Fig. 2, A) was Interpreted as showing a small right renal calculus and bilateral deformed calyces, suggesting polycystic disease; however, a single spaceoccupying lesion was later identified in the right kidney, accompanied by a large mass involving the lower two-thirds of the left kidney. Five months later, the colic and hematuria recurred. The left kidney was not palpable. A second excretory urogram was interpreted as unchanged, but the lesion in the left kidney had become larger and submucosal infiltration was present in the renal pelvis . .During the next 8 months, the patient had repeated attacks of hematuria, ac-
companied by anemia (8.9 g/100 ml), a blood urea level of 60 mg/ 100 ml, and an erythrocyte sedimentation rate of 107 mm in an hour. A third excretory urogram showed marked enlargement of the left kidney with amputation of the lower calyces and a "giant" upper-pole calyx. Renal angiography was unsuccessful because of marked tortuosity of the pelvic vessels, and the catheter could not be manipulated into the aorta. No cyst was found on renal puncture (Fig. 2, B), and contrast material injected into the tumor spread out within part of it. Upon removal, the left kidney was found to weigh 1,220 g and was completely replaced by tumor extending into the renal vein. The patient remained well for about six months, but during the next nine months he became progressively weaker, lost weight, and suffered anorexia. A barium-meal study was normal; however, a repeat excretory urogram showed that the mass in the right kidney had become much larger. The patient died soon afterward, following the development of inferior vena caval obstruction. CASE III: Bilateral renal tumors, not suspected during life. A 72year-old woman was admitted for excision of a lumbar disk but died
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Fig. 2. CASE II. A. Excretory urogram with tomography taken in 1960 shows a large space-occupying lesion in the lower pole of the left kidney and another in the middle third of the right kidney. B Injection of contrast material into the left lesion by renal puncture demonstrates the typical appearance of a renal tumor. [Both parts of Fig. 2 are reproduced from Butt and Wright (4) with the permission of the publisher]
Fig. 3. CASE IV. A. Excretory urogram obtained in 1969 demonstrates multiple masses in both kidneys, consistent with polycystic disease. B. On a second excretory urogram made three years later, the middle portion of the right kidney is now very different from the earlier pattern. The upper and lower pole calyces are stretched out by a large mass. Note the calcification in the upper pole cysts (arrows). [Figure 3, B is reproduced from Wright et al. (31) with the permission of the publisher]
postoperatively of renal failure. No renal lesion had been suspected, and urography had not been performed. At postmortem examination, multiple bilateral renal tumors of varying sizes up to 4 cm in diameter were seen; these were thought to be multiple primary growths. CASE IV: Bilateral renal tumors complicating polycystic disease. A 24-year-old man presented with headaches. Four years later he complained of epigastric discomfort. Excretory urography revealed that both kidneys were enlarged (the left more so than the right) and contained multiple cysts. Blood pressure and blood urea were normal. His family history showed that a sister had died of polycystic disease shortly after pregnancy and that a cousin had the same con-
ditlon. At the age of 41, the patient noticed increased abdominal swelling. An excretory urogram (Fig. 3, A) showed very large kidneys with distorted calyces, accompanied by three cysts in the upper pole of the left kidney which contained ring-type calcification. His blood pressure had risen to 170/115, and the blood urea level was now 48 mgl 100 ml. He was given antihypertensive treatment using methyldopa. Three years later, he had four attacks of hematuria, accompanied by diminished appetite, night sweats, and mild pyrexia. A chest film showed three small, rounded shadows in the left lung, but it was uncertain whether they were infective or metastatic in nature. A second excretory urogram (Fig. 3, B) showed that the right kidney had become considerably enlarged, particularly the midportion. Renal angiography (Fig. 4) demonstrated a diffuse vascular abnor-
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Fig. 4. CASE IV. A. Right renal angiogram obtained in 1972 shows an extensive tumor circulation in the middle and lower portions of the kidney. The spindle-shaped vessels in the upper pole are consistent with polycystic disease. B. Left renal angiogram (subtraction print) demonstrates stretched vessels in the kidney with scattered areas of normal renal function, producing a patchy nephrogram, as well as two small areas of tumor circulation in the lower pole (arrows). [Both parts of Fig. 4 are reproduced from Wright et al. (31) with the permission of the publisher]
mality in the middle part of the right kidney, suggesting a tumor in addition to the polycystic disease. Two smaller areas of tumor circulation, each about 1.5 cm in diameter, were seen in the lower pole of the left kidney. The patient was given progestogens in an attempt to control tumor growth but died a few weeks later. At postmortem examination, both kidneys were very large and contained multiple cysts. In addition, there was an extensive, partly necrotic and hemorrhagic tumor involving the middle and lower portions of the right kidney, as well as two small tumors in the lower pole of the left kidney. Metastases were also present in the para-aortic lymph nodes. lungs. and brain, and the pancreas showed polycystic disease. The tumor in the right kidney contained typical clear cells and spindleshaped cells which were more pleomorphic and malignant in appearance; the metastases were all of the latter type, while the two small tumors in the left kidney were of the clear-cell type. These findings suggested that the tumors were multicentric in origin (23, 31).
Fig. 5. CASE V. Excretory urogram demonstrates a large mass in the lower two-thirds of the left kidney. The upper part of the left ureter is displaced medially and the tip of the middle right calyx is amputated.
CASE V: Bilateral renal tumors with successful surgical resection. A 43-year-old man was referred for renal angiography in 1972 after noticing bilateral loin discomfort for six months, accompanied
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Fig. 6. CASE V. Selective left renal angiogram shows a large, .primarily avascular tumor in the lower three-fourths of the left kidney. A. Arterial phase. B. Nephrogram phase. Fig. 7. CASE V. Selective right renal angiogram, oblique series (late arterial phase) shows a tumor extending from the midportion of the kidney. by two minor attacks of hematuria. An excretory urogram (Fig. 5) showed enlargement of the lower pole of the left kidney and poor filling of the calyces on that side. The right kidney was thought to be normal; however, re-evaluation showed that the tip of the middle calyx was amputated. A left selective renal angiogram showed that the lower three-fourths of the kidney was replaced by a largely avascular tumor (Fig. 6). Although there was no major vessel displacement, the tumor mass was seen as an extensive defect in the nephrogram phase. Anteroposterior radiographs of the contralateral kidney appeared to be almost normal; however, one or two tiny vessels seemed to pass beyond the confines of the kidney. In view of the abnormal calyx seen in the right kidney on the excretory urogram, oblique angiography was performed. This showed a tumor extending from the midportion of the kidney into the perirenal tissues (Fig. 7). Lymphangiography was normal. At surgery (R. Caine) (4), both kidneys were completely removed. The tumor was dissected from the right kidney, and the remainder was placed in the right lower abdomen as an autograft. The patient has remained well for three years now. CASE VI: Bilateral leiomyosarcomas or angiomyolipomas in polycystic disease: bilateral nephrectomy and renal transplantation. A 19-year-old girl presented in April 1969 with recurrent hematuria. An excretory urogram showed large, polycystic kidneys. There appeared to be a left pelviureteric obstruction, and a pyeloplasty was carried out the following year. Six months later severe hematuria occurred, necessitating transfusions. Renal angiography (Fig. 8) showed a very large left kidney extending from just below the left dome of the diaphragm to the pelvis. The intrarenal vessels were stretched and displaced as with polycystic disease, but in addition multiple small aneurysms or beaded vessels were present in many parts of the kidney, and similar though smaller areas of abnormal circulation were seen in the upper and lower poles of the right kidney. Renal failure increased, accompanied by persistent fever and leukocytosis. Blood transfusions could not keep pace with blood loss. At left nephrectomy, the kidney was found to contain numerous
cysts, some containing pus or blood. Macroscopically, no normal renal parenchyma could be seen. Soft yellowish tissue and areas of hemorrhage in various stages of organization were seen between the cysts. Microscopy showed few normal glomeruli, mostly associated with dilated tubules, as well as marked leiomyomatous proliferation involving both spindle-shaped and smooth muscle cells throughout the renal parenchyma. Some cellular pleomorphism and nuclear hypochromatism were evident, though mitoses were difficult to find. Although the patient improved following nephrectomy, renal failure occurred nine months later. The right kidney was removed; pathologically, it was similar to the left. Some pathologists thought it was an angiomyolipoma, but others considered it to be a leiomyosarcoma. Renal transplantation was carried out following hemodialysis treatment (8,31).
DISCUSSION
The ability to demonstrate bilateral renal lesions has been greatly increased by the use of (a) tomography with high-dose excretory urography and (b) angiography. Bilateral renal angiography should be almost mandatory, for it takes very little effort and may be of great importance; moreover, it is greatly comforting to the surgeon to know the appearance of the contralateral kidney and may also modify the planned surgical procedure considerably, especially if bilateral tumors are present. High-quality angiograms should be obtained; at present, I often use a simple technique employing three films and a Bucky tray (30) as well as or instead of a series taken with an automatic serial changer. In the differential diagnosis of bilateral renal masses, cysts are by far the most common finding. Indeed, finding a second "smooth" mass on the angiogram makes a cyst much more likely, since they are commonly multiple. My practice is to examine cysts by renal puncture
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Fig. 8. CASE VI. A. Right renal angiogram shows a small area of abnormal circulation in the upper pole of the kidney. A similar area was present in the "darker" part of the lower pole. B. On the left renal angiogram, the intrarenal vessels are markedly stretched, with multiple areas of abnormal circulation including small aneurysms and beading. [Figure 8, B is reproduced from Wright et et. (31) with the permission of the publisher]
immediately after removing the catheter and stopping any bleeding. Other abnormalities should also be considered. I have encountered a patient with renal failure who was found to have hydronephrosis on one side and a large renal tumor on the other. Renal hamartomas may also give rise to bilateral masses which demonstrate small "beaded" vessels on angiography; these are most common in patients with tuberous sclerosis but also occur in other conditions (31). They may also show varying degrees of malignant change, as in CASE VI. I have not had the opportunity to examine a case of renal adenomatosis such as that reported by Meisel (19). Renal metastases secondary to bronchogenic tumors are being recognized more frequently, not only at autopsy (29) but also during life; I found 5 such cases in 1973-74 which were revealed by high-dose urography and tomography; however, more were examined by an-
giography, since there seemed to be little doubt as to their nature. Such metastases are commonly bilateral (2).
In assessing bilateral renal tumors, the major consideration is whether both are primary lesions or one is a metastasis of the other. Bastable (1) reported one case of bilateral renal carcinoma and reviewed 20 previously reported cases which he considered to involve two primary tumors, each having a different histological pattern. Although Billroth has stated that each tumor should demonstrate individual metastases (3), Bastable noted that this is not always the case and that the incidence of renal metastasis to the contralateral kidney is low; he estimated it at about 1 % on the basis of clinical studies, though the incidence at postmortem examination may be much higher. Renal metastases may lie dormant and remain clinically unsuspected for many years; thus Bas-
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table rejected 7 additional cases of bilateral individual tumors as insufficiently proved on the basis that it was not reasonably certain they had arisen from a single source. Ljunggren (16), discussing partial nephrectomy in patients with renal tumors, reviewed 5 previously reported cases of bilateral renal tumors (6, 9, 21, 27). Additional single cases were reported by Krumbach and Ansell (15) and Marshall and Johnson (18). In 1968, Small et at. (25) reviewed the literature and found 17 cases, including 7 reviewed by Bastable. They also reported a case of their own involving a hypertensive 44-year-old woman who demonstrated bilateral renal tumors on excretory urography and angiography. Following removal of the right kidney, an encapsulated tumor was resected from the left kidney. Since then, Kobayashi et at. (13), Kolin et at. (14), and Hyman et at. (11) have each reported a single case of bilateral renal tumors. Parker et at. (20), Kaufman et at. (12), and Stackpole (26) found a total of 9 cases of bilateral renal tumors, none of which were synchronous. References to 9 additional cases are contained in the papers of Kaufman et at. (12) and Krumbach and Ansell (15). In addition, 6 cases of bilateral renal tumors associated with polycystic disease have been reported (10, 31). The total number of recorded cases is now more than 80, including my own and those recorded by Caine (5), one of which involved a patient treated at this hospital. He recommends accurate assessment and "workbench surgery" on the excised kidney prior to reinsertion of the salvaged portion as an autograft, a practice which he has followed successfully in 3 cases (including CASE V reported above). In another case (8) he removed both kidneys and inserted a donor transplant. Malament (17) removed one kidney and biopsied the lesion in the other kidney. Following radiotherapy, the patient lived for 10 years, finally dying of pulmonary metastases. I have also seen a single case of bilateral Wilms's tumor, but this is a separate problem which has been reviewed by Scott (24) and Close et at. (7). Scott found that 35 of the 908 Wilms's tumors he studied were bilateral but felt that most contralateral masses were probably metastatic. Hyman et at. (11) have stated that only 3 of the previously recorded cases they reviewed had been studied angiographically, and selective angiography was employed in only one case. Three of the cases described above were studied angiographically, and angiography was also attempted in a fourth case. Bilateral angiography is also referred to by Ben-Menachem et at. (2). Since only about one-fourth of a normal kidney is needed for life, and since surgeons can save part of one kidney either by partial resection or reimplantation following "workbench" renal surgery as described above, it is important for the radiologist to demonstrate bilateral tumors. The alternative is bilateral nephrectomy, which is not usually contemplated for malignant disease; and in any event, a patient's own renal tissue causes a far lesser problem than an artificial kidney or a donor kidney used as a homograft.
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ACKNOWLEDGMENTS: I am grateful to Brian Higgs, F.R.C.S., Consultant Surgeon, Amersham Hospital, Buckinghamshire, for referring the patient in CASE V for angiography and to Roy Caine, F.R.C.S., F.R.S., Professor of Surgery, University of Cambridge, for details of his operative procedures.
REFERENCES 1. Bastable JRG: Bilateral carcinoma of the kidneys. Br J Urol 32:60-68, Mar 1960 2. Ben-Menachem Y, Marcos J, Wallace S, et al: Angiography of renal metastases. Br J Radiol 47:869-874, Dec 1974 3. Billroth T, von Winiwarter A: Die allgemeine chirurgische Pathologie und Therapie in elnundfunfzlq Vorlesungen. Ein Handbuch fUr Studirende und Aerzte. Berlin, Reimer, 1889, Vol 14, P 908 4. Butt WP, Wright FW: Renal tumours masquerading as polycystic disease. Br J Radiol 37:952-954, Dec 1964 5. Caine RY: Treatment of bilateral hypernephromas by nephrectomy, excision of tumour, and autotransplantation. Report of three cases. Lancet 2:1164-1167,24 Nov 1973 6. Cibert J: Discussion of Aubert J: Un cas de sarcome Iipoet fibroblastique du rein chez I'adulte. J Urol Med Chir 64:78-82, Jan-Feb 1958 7. Close MB, Peterson CA, Johnson RP: Bilateral embryoma of the kidney: patient alive and well three years after treatment. Radiology 67:99-101, Jul 1956 8. Evans DB, Caine RY: Renal transplantation in patients with carcinoma. Br Med J 4:134-136,19 Oct 1974 9. Hanley HG: Discussion on partial nephrectomy. Proc R Soc Med 43:1027-1038, Dec 1950 10. Howard RM, Young JD Jr: Two malignant tumors in a polycystic kidney. J UroI102:162-164, Aug 1969 11. Hyman RA, Voges V, Finby N: Bilateral hypernephroma. Am J RoentgenoI117:104-107, Jan 1973 12. Kaufman JJ, Chaffey BT, Goodwin WE: Renal cell carcinoma in the solitary kidney: report of six cases. Br J Urol 40: 12-21, Feb 1968 13. Kobayashi A, Hoshino H, Ohbe Y, et al: Bilateral renal cell carcinoma. Arch Dis Child 45:141-143, Feb 1970 14. Kolin CP, Boldus RA, Brandon DNK, et al: Bilateral partial nephrectomy for bilateral renal cell carcinoma: a case report. J Urol 105:45-48, Jan 1971 15. Krumbach RW, Ansell JS: Partial resection of the right kidney and radical removal of the left kidney in a patient with bilateral hypernephroma. Surgery 45:585-592, Apr 1959 16. Ljunggren E: Partial nephrectomy in renal tumour. Acta Chir Scand (Suppl 253):37-44, 1960 17. Malament M: Bilateral renal cell carcinoma: a 14-year survival. J Urol 94:348-355, Oct 1965 18. Marshall F, Johnson AJ: Double primary urinary tumors: case report. J Urol 85:724-726, May 1961 19. Meisel HJ: Bilateral polyadenomatous kidneys: adenomatosis of the kidneys sirnulatlnq polycystic disease. J Urol 72:11401145, Dec 1954 20. Parker RM, Timothy RP, Harrison JH: Neoplasia of the solitary kidney. J UroI101:283-296, Mar 1969 21. Puigvert A: (quoted in) Mocellini J: Comentarios a 115 nefrectornias parciales. Arch Esp UroI12:85-95, Apr 1956 22. Riches EW: Tumours of the Kidney and Ureter. Edinburgh, Livingstone, 1964, p 320 23. Roberts PF: Bilateral renal carcinoma associated with polycystic kidneys. Br Med J 3:273-274,4 Aug 1973 24. Scott LS: Bilateral Wilms' tumour. Br J Surg 42:513-516, Mar 1955 25. Small MP, Anderson EE, Atwill WH: Simultaneous bilateral renal cell carcinoma: case report and review of the literature. J Urol 100:8-14, Jul 1968 26. Stackpole RH: Treatment of carcinoma in a solitary kidney: case report and review of the literature. J Urol 93:353-360, Mar 1965 27. Svab J: Zwei seltene Faile von NierengeschwUlsten. Kasuistischer Beitrag zur grawitzschen Geschwulst in solltarer Niere und zu den beiderseitigen Nierengeschwulsten. Z Urol 49:241-251, 1956 .
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28. Vermillion CD, Skinner DG, Pfister RC: Bilateral renal cell carcinoma. J UroI108:219-222, Aug 1972 29. Wright FW: The Radiological Diagnosis of Lung and Mediastinal Tumours. London, Butterworths, 1973, p 187 30. Wright FW: Simplified selective renal angiography. Letter to the editor. Br J RadioI46:145, Feb 1973 31. Wright FW, Ledingham JGG, Dunnill MS, et al: Polycystic
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kidneys, renal hamartomas, their variants and complications. Clin RadioI25:27-43, Jan 1974 X-Ray Department Churchill Hospital Oxford OX3 7LJ England
