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Leukoplakia of Renal Pelvis and Ureter
THE JOURNAL OF UROLOGY
VoL 72, No. 3, September 1954 Printed in U.S.A.
LEUKOPLAKIA OF RENAL PELVIS AND URETER CHARLES C. FALK
Leukoplakia of the urinary tract has long been recognized, but its occurrence in the renal pelvis or ureter has been so infrequent that we should accept every opportunity to obtain a better understanding of this curious tissue response. Since 1882, when Epstein apparently described it for the first time, less than 100 cases involving the renal pelvis and ureter have been presented (McCrea; Keesal and Rosner). It seems worth while to add another case and to review briefly the present concepts of the disease. Leukoplakia is a metaplastic change in the urinary tract in which the normal transitional epithelium is changed into the squamous or skin-like type, characterized by keratinization and almost always by desquamation. Writers generally agree that the lesion is precancerous. CASE REPORT
A well developed man of 35, married, and the father of four, employed as a stationary engineer on a logging operation, for the past 15 years had suffered intermittent attacks of colicky pain in the left flank, radiating downward along the course of the ureter. Several urological studies during the past 10 years had failed to reveal the cause of this pain. Meanwhile the attacks were occurring more frequently, and were becoming increasingly severe and incapacitating. He had just had an episode of this pain for about a week. There was no dysuria, frequency, nor hematuria, but he stated that the urine was always cloudy, even in teh interval between the attacks of colic. The physical examination revealed nothing outside the urinary tract. The urine was grossly hazy, had a pH of 6, a specific gravity of 1.020, and contained neither albumin nor sugar. The sediment showed 15 pus cells per high dry field and many strips and flakes of squamous epithelium. The Wassermann was negative and the blood count entirely normal. Non protein nitrogen was 32, and the bleeding and clotting times normal. The 24F cystoscope was introduced easily and immediately a pearl gray membrane was seen covering almost the entire trigone. The ureteral orifices were not involved, but were somewhat reddened and edematous. On attempting to catheterize the left ureter, an impermeable obstruction was met at 10 cm. above the orifice (figs. 1 and 2). Indigo carmine injected appeared in four minutes, but with poor concentration. Pyelo-ureterograms revealed several filling defects in the left ureter and an irregular and motheaten appearance. The capacity of the renal pelvis was increased and the terminal calyces were somewhat blunt. The urine from· the left kidney showed no acid fast bacilli and the guinea pig inoculation was negative for tuberculosis. Culture of this urine revealed a mixed growth of Escherichia Read at annual meeting, Western Section of American Urological Association, San Francisco, April 27-30, 1953. 310
LEUKOPLAKIA OF RENAL PELVIS AND URETER
311
FIG. 1. A, pyelo-ureterogram printed in positive showing moderate calycectasis and pyelectasis; tortuosity of ureter with filling defects. B, same as A, but printed in negative.
FIG. 2. A, same as figure 1, A except that ureteral catheter is in position to indicate level of impermeable obstruction. B, same as 11, but printed in negative. (These x-rays are used mainly to point out that urographic findings by means of technique used are not characteristic in leukoplakia.)
coli and Staphylococcus aureus. The presumptive diagnosis was made of leukoplakia of the urinary bladder and neoplastic involvement of the left ureter ·with obstruction to the left kidney. A ureteronephrectomy ,vas performed. The lower ureter, together with a cuff of the bladder, was first excised. The kidney was then removed through the usual lumbar incision. The gross specimens are shown in fig. 3. The pathologist, made the following diagnoses: 1) leukoplakia of the renal pelvis and ureter; 2) acute pyelonephritis; 3) cortical cysts of the kidney (fig. 4).
312
CHARLES C. FALK
Fm. 3. A, gross surgical specimen consisting of kidney, ureter and portion of bladder. Ureter has been sectioned longitudinally showing pathologic skin-like structure of upper two thirds of ureter and pelvis. B, same as A except that kidney and pelvis have been sectioned as well showing extensive involvement which affects entire pelvis.
Recovery was without incident and the patient left the hospital on the twelfth postoperative day. He was examined every 2 weeks for the succeeding 4 months. The pyuria was greatly improved, though the urine continued to be grossly hazy and flakes of epithelium were still present. He regained his original weight in 2 months and had resumed his occupation. DISCUSSION
The cause of leukoplakia is unknown. Undoubtedly the most widely accepted explanation is that leukoplakia of the urinary tract is a true metaplasia arising as the result of chronic inflammation and irritation, and is the biological process of adaptation to environment in the form of protective cornification (Hinman, Kutzmann and Gibson). In the study of a larger series of cases two uniform observations have been made: 1) pyuria is present in all cases, and 2) leukoplakia usually occurs concomitantly with other diseases. It is suggested, there-
LEUKOPLAKIA OF RENAL PELVIS AND URETER
313
; fFw. 4. A, cornified stratified squamous epithelium has completely replaced transitional epithelium which normally lines ureter. Note thick layer of desquamated epithelial cells on epithelial surface.Hand Estain. B, same as A, but higher magnification to show cellular details.
fore, that the leukoplakia may be secondary to severe chronic infection, calculous or neoplastic disease, or urinary tract obstruction. It is no longer believed that it is a manifestation of syphilis. While there once appeared to be laboratory evidence that a lack of vitamin A was causative, this view seems to have been abandoned (Senger, Bottone, and Kelleher). The disease occurs most commonly in the age group between 30 and 50. There are few patients under 20, although occasional cases have been reported in childhood and also in extreme old age. This ·would lead to the conclusion that any hypothesis that the etiology of the disease is based on embryonal cell rests is untenable. The condition is found about twice as often in the male as in the female (Laughlin and Bilotta). There are no symptoms typical or characteristic of this condition except as a rule those of the coexisting disease. Frequency, urgency, dysuria, hematuria,
314
CHARLES C. FALK
any or all may be present. In my patient ureteral colic was the predominant complaint. The outstanding finding noted by several authors is the discovery of cornified epithelium in the urinary sediment. It is described by Senger, Bottone, and Kelleher as the passage of "gritty flakes in the urine." It is also mentioned by Laughlin and Bilotta, and Arnholdt considers it pathognomonic, though he points out that the disease may exist without this finding. It was certainly prominent in the present case. The difficulty in preoperative diagnosis is evidenced in the cases reported. Subjective symptoms are of little value, and one must re-emphasize the one important objective clue, the finding of large amounts of squamous epithelium in the urinary sediment. This observation should suggest leukoplakia at once. I certainly believe also that if leukoplakia is seen cystoscopically in the bladder, it should be considered possible, or even likely, that the disease may also affect the upper urinary tract. Kretschmer suggested this fact some years ago. Pyelo-ureterographic findings are certainly not diagnostic in this disease and are only of general value. All writers agree on this point except Arnholdt, who was able to demonstrate, by the use of a dilute medium for pyelography, an x-ray silhouette which he considered consistent with the leukoplakic folds and wrinkles in the mucosa of the kidney pelvis. His description did not apparently impress the later writers. One author described passing a cystoscopic rongeur into the lower ureter and obtaining a biopsy specimen from which a positive diagnosis was made. While the use of the technique must certainly be limited, its possibility might well be remembered. Leukoplakia in the upper urinary tract must be differentiated from tuberculosis, neoplastic disease, either squamous or transitional in type, calculosis, severe pyogenic pyelonephritis, and pyelitis and ureteritis cystica and glandularis (Stirling and Ash). The treatment of leukoplakia involving the kidney and ureter is preferably ureteronephrectomy, both to remove the potential malignancy and to relieve the symptoms. Fortunately in less than 5 per cent of the patients the condition has been bilateral and only conservative palliative measures could be instituted. In the light of our present knowledge such therapy must be directed toward control of infection and promotion of free drainage. SUMMARY
Leukoplakia of the renal pelvis, ureter, or both, is rare, less than 100 caseH having been reported in the last 80 years. Leukoplakia in the urinary tract is a precancerous lesion. The etiology is obscure, but the evidence strongly supports the concept that the causative factor is prolonged irritation in the form of chronic infection. Leukoplakia is usually concomitant with other diseases. Preoperative diagnosis of leukoplakia of the kidney or ureter is seldom made, but the disease should be suspected when the cystoscopic findings are inconclusive and there are masses of squ>1mous epithelial cells in the urinary sediment.
LEUKOPLAKIA OF RENAL PELVIS AND URETER
315
When leukoplakia can be seen in the bladder through the cystoscope and there is any evidence of disease in the upper urinary tract, the same condition in the kidney and ureter should be considered a strong possibility. Treatment is ureteronephrectomy when leukoplakia involves the kidney and ureter and is unilateral, as it is in more than 90 per cent of the cases. Eureka, Calif. REFERENCES ARNHOLDT, FRIEDRICH: Ztschr. f. urol. Ohir. u. Gynak., 44: 292-298, 1938. HINMAN, FRANK: Principles and Practice of Urology. Philadelphia: W. B. Saunders Co., 1935, pp. 939, 940, 961. HINMAN, FRANK, KuTzMANN, A. A. AND GrnsoN, T. E.: Surg., Gynec. & Obst., 39: 472, 1924. KEESAL, S. AND RosNER, A.: Urol. & Cutan. Rev., 54: 717-720, 1950. KRETSCHMER, H. L.: Arch. Surg., 5: 348, 1922. LAUGHLIN, V. 0. AND BILOTTA, J. F. L.: J. Ural., 44: 358, 1940. McCREA, L. E.: Clinical Urology. Philadelphia: F. A. Davis Co., 1948, 2nd ed., pp. 289,290, 291. J.A.M.A., 142: 631, 1950. J. Ural., 64: 209, 1950. SENGER, F. L. ETAL.: J. Ural., 65: 528, 1951. STIRLING, W. 0. AND AsH, J.E.: J. Urol., 45: 342, 1941. South. Med. J., 34: 358, 1941. WESSON, M. B.: Urologic Roentgenology. Philadelphia: Lea and Febiger, 1950, pp. 132, 218, 219.
VoL 72, No. 3, September 1954 Printed in U.S.A.
LEUKOPLAKIA OF RENAL PELVIS AND URETER CHARLES C. FALK
Leukoplakia of the urinary tract has long been recognized, but its occurrence in the renal pelvis or ureter has been so infrequent that we should accept every opportunity to obtain a better understanding of this curious tissue response. Since 1882, when Epstein apparently described it for the first time, less than 100 cases involving the renal pelvis and ureter have been presented (McCrea; Keesal and Rosner). It seems worth while to add another case and to review briefly the present concepts of the disease. Leukoplakia is a metaplastic change in the urinary tract in which the normal transitional epithelium is changed into the squamous or skin-like type, characterized by keratinization and almost always by desquamation. Writers generally agree that the lesion is precancerous. CASE REPORT
A well developed man of 35, married, and the father of four, employed as a stationary engineer on a logging operation, for the past 15 years had suffered intermittent attacks of colicky pain in the left flank, radiating downward along the course of the ureter. Several urological studies during the past 10 years had failed to reveal the cause of this pain. Meanwhile the attacks were occurring more frequently, and were becoming increasingly severe and incapacitating. He had just had an episode of this pain for about a week. There was no dysuria, frequency, nor hematuria, but he stated that the urine was always cloudy, even in teh interval between the attacks of colic. The physical examination revealed nothing outside the urinary tract. The urine was grossly hazy, had a pH of 6, a specific gravity of 1.020, and contained neither albumin nor sugar. The sediment showed 15 pus cells per high dry field and many strips and flakes of squamous epithelium. The Wassermann was negative and the blood count entirely normal. Non protein nitrogen was 32, and the bleeding and clotting times normal. The 24F cystoscope was introduced easily and immediately a pearl gray membrane was seen covering almost the entire trigone. The ureteral orifices were not involved, but were somewhat reddened and edematous. On attempting to catheterize the left ureter, an impermeable obstruction was met at 10 cm. above the orifice (figs. 1 and 2). Indigo carmine injected appeared in four minutes, but with poor concentration. Pyelo-ureterograms revealed several filling defects in the left ureter and an irregular and motheaten appearance. The capacity of the renal pelvis was increased and the terminal calyces were somewhat blunt. The urine from· the left kidney showed no acid fast bacilli and the guinea pig inoculation was negative for tuberculosis. Culture of this urine revealed a mixed growth of Escherichia Read at annual meeting, Western Section of American Urological Association, San Francisco, April 27-30, 1953. 310
LEUKOPLAKIA OF RENAL PELVIS AND URETER
311
FIG. 1. A, pyelo-ureterogram printed in positive showing moderate calycectasis and pyelectasis; tortuosity of ureter with filling defects. B, same as A, but printed in negative.
FIG. 2. A, same as figure 1, A except that ureteral catheter is in position to indicate level of impermeable obstruction. B, same as 11, but printed in negative. (These x-rays are used mainly to point out that urographic findings by means of technique used are not characteristic in leukoplakia.)
coli and Staphylococcus aureus. The presumptive diagnosis was made of leukoplakia of the urinary bladder and neoplastic involvement of the left ureter ·with obstruction to the left kidney. A ureteronephrectomy ,vas performed. The lower ureter, together with a cuff of the bladder, was first excised. The kidney was then removed through the usual lumbar incision. The gross specimens are shown in fig. 3. The pathologist, made the following diagnoses: 1) leukoplakia of the renal pelvis and ureter; 2) acute pyelonephritis; 3) cortical cysts of the kidney (fig. 4).
312
CHARLES C. FALK
Fm. 3. A, gross surgical specimen consisting of kidney, ureter and portion of bladder. Ureter has been sectioned longitudinally showing pathologic skin-like structure of upper two thirds of ureter and pelvis. B, same as A except that kidney and pelvis have been sectioned as well showing extensive involvement which affects entire pelvis.
Recovery was without incident and the patient left the hospital on the twelfth postoperative day. He was examined every 2 weeks for the succeeding 4 months. The pyuria was greatly improved, though the urine continued to be grossly hazy and flakes of epithelium were still present. He regained his original weight in 2 months and had resumed his occupation. DISCUSSION
The cause of leukoplakia is unknown. Undoubtedly the most widely accepted explanation is that leukoplakia of the urinary tract is a true metaplasia arising as the result of chronic inflammation and irritation, and is the biological process of adaptation to environment in the form of protective cornification (Hinman, Kutzmann and Gibson). In the study of a larger series of cases two uniform observations have been made: 1) pyuria is present in all cases, and 2) leukoplakia usually occurs concomitantly with other diseases. It is suggested, there-
LEUKOPLAKIA OF RENAL PELVIS AND URETER
313
; fFw. 4. A, cornified stratified squamous epithelium has completely replaced transitional epithelium which normally lines ureter. Note thick layer of desquamated epithelial cells on epithelial surface.Hand Estain. B, same as A, but higher magnification to show cellular details.
fore, that the leukoplakia may be secondary to severe chronic infection, calculous or neoplastic disease, or urinary tract obstruction. It is no longer believed that it is a manifestation of syphilis. While there once appeared to be laboratory evidence that a lack of vitamin A was causative, this view seems to have been abandoned (Senger, Bottone, and Kelleher). The disease occurs most commonly in the age group between 30 and 50. There are few patients under 20, although occasional cases have been reported in childhood and also in extreme old age. This ·would lead to the conclusion that any hypothesis that the etiology of the disease is based on embryonal cell rests is untenable. The condition is found about twice as often in the male as in the female (Laughlin and Bilotta). There are no symptoms typical or characteristic of this condition except as a rule those of the coexisting disease. Frequency, urgency, dysuria, hematuria,
314
CHARLES C. FALK
any or all may be present. In my patient ureteral colic was the predominant complaint. The outstanding finding noted by several authors is the discovery of cornified epithelium in the urinary sediment. It is described by Senger, Bottone, and Kelleher as the passage of "gritty flakes in the urine." It is also mentioned by Laughlin and Bilotta, and Arnholdt considers it pathognomonic, though he points out that the disease may exist without this finding. It was certainly prominent in the present case. The difficulty in preoperative diagnosis is evidenced in the cases reported. Subjective symptoms are of little value, and one must re-emphasize the one important objective clue, the finding of large amounts of squamous epithelium in the urinary sediment. This observation should suggest leukoplakia at once. I certainly believe also that if leukoplakia is seen cystoscopically in the bladder, it should be considered possible, or even likely, that the disease may also affect the upper urinary tract. Kretschmer suggested this fact some years ago. Pyelo-ureterographic findings are certainly not diagnostic in this disease and are only of general value. All writers agree on this point except Arnholdt, who was able to demonstrate, by the use of a dilute medium for pyelography, an x-ray silhouette which he considered consistent with the leukoplakic folds and wrinkles in the mucosa of the kidney pelvis. His description did not apparently impress the later writers. One author described passing a cystoscopic rongeur into the lower ureter and obtaining a biopsy specimen from which a positive diagnosis was made. While the use of the technique must certainly be limited, its possibility might well be remembered. Leukoplakia in the upper urinary tract must be differentiated from tuberculosis, neoplastic disease, either squamous or transitional in type, calculosis, severe pyogenic pyelonephritis, and pyelitis and ureteritis cystica and glandularis (Stirling and Ash). The treatment of leukoplakia involving the kidney and ureter is preferably ureteronephrectomy, both to remove the potential malignancy and to relieve the symptoms. Fortunately in less than 5 per cent of the patients the condition has been bilateral and only conservative palliative measures could be instituted. In the light of our present knowledge such therapy must be directed toward control of infection and promotion of free drainage. SUMMARY
Leukoplakia of the renal pelvis, ureter, or both, is rare, less than 100 caseH having been reported in the last 80 years. Leukoplakia in the urinary tract is a precancerous lesion. The etiology is obscure, but the evidence strongly supports the concept that the causative factor is prolonged irritation in the form of chronic infection. Leukoplakia is usually concomitant with other diseases. Preoperative diagnosis of leukoplakia of the kidney or ureter is seldom made, but the disease should be suspected when the cystoscopic findings are inconclusive and there are masses of squ>1mous epithelial cells in the urinary sediment.
LEUKOPLAKIA OF RENAL PELVIS AND URETER
315
When leukoplakia can be seen in the bladder through the cystoscope and there is any evidence of disease in the upper urinary tract, the same condition in the kidney and ureter should be considered a strong possibility. Treatment is ureteronephrectomy when leukoplakia involves the kidney and ureter and is unilateral, as it is in more than 90 per cent of the cases. Eureka, Calif. REFERENCES ARNHOLDT, FRIEDRICH: Ztschr. f. urol. Ohir. u. Gynak., 44: 292-298, 1938. HINMAN, FRANK: Principles and Practice of Urology. Philadelphia: W. B. Saunders Co., 1935, pp. 939, 940, 961. HINMAN, FRANK, KuTzMANN, A. A. AND GrnsoN, T. E.: Surg., Gynec. & Obst., 39: 472, 1924. KEESAL, S. AND RosNER, A.: Urol. & Cutan. Rev., 54: 717-720, 1950. KRETSCHMER, H. L.: Arch. Surg., 5: 348, 1922. LAUGHLIN, V. 0. AND BILOTTA, J. F. L.: J. Ural., 44: 358, 1940. McCREA, L. E.: Clinical Urology. Philadelphia: F. A. Davis Co., 1948, 2nd ed., pp. 289,290, 291. J.A.M.A., 142: 631, 1950. J. Ural., 64: 209, 1950. SENGER, F. L. ETAL.: J. Ural., 65: 528, 1951. STIRLING, W. 0. AND AsH, J.E.: J. Urol., 45: 342, 1941. South. Med. J., 34: 358, 1941. WESSON, M. B.: Urologic Roentgenology. Philadelphia: Lea and Febiger, 1950, pp. 132, 218, 219.