Vol. 116, December
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1976 by The Williams & Wilkins Co.
SIGNIFICANCE OF URINARY CYTOLOGY IN THE EARLY DETECTION OF TRANSITIONAL CELL CANCER OF THE UPPER URINARY TRACT HORST ZINCKE,* JUAN J. AGUILO, GEORGE M. FARROW, DAVID C. UTZ
AND
ANSAR U. KHAN
From the Departments of Urology and Surgical Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
ABSTRACT
Cytologic study of urine from 100 patients with transitional cell cancer of the upper urinary tract revealed that findings on the voided and catheterized specimens correlated well with grade and stage of the tumor. However, there was a significantly greater positive yield with urine specimens obtained by ureteral catheterization than by voiding. Consequently, because concomitant bladder tumors, diagnosed or not, can give questionable positive results ureteral catheterization specimens should be used for cytologic study. Since Papanicolaou and Marshall first reported on the feasibility of applying cytologic study in cancer of the urinary tract 1 reports have been received with cautious enthusiasm. This is because of the variable results obtained in the diagnosis of cancer of the bladder, 2 • 13 which range from 26 to 100 per cent, 3 • 5 ' 7 • 9 with a median sensitivity of 76 per cent for positive cytologic diagnosis. 10 Nevertheless, urinary cytology has achieved particular importance and accuracy in the detection of high grade tumors 14 that have been difficult to recognize endoscopically. 10 • 15 · 17 Furthermore, such study is regarded by many as a valuable adjunct in the evaluation and followup of the patient with cancer of the bladder. 3 • 4 • 10• 14 - 16 • 18 However, its role in the detection and diagnosis of transitional cell cancer of the upper urinary tract has been considered poor 19 and difficult to determine because of the synchronous presence of bladder tumors. 14• 20 - 2 • This review was done to assess the significance and accuracy of urinary cytology in the detection of transitional cell cancer of the upper urinary tract. In particular, the value of voided urinary cytology in the presence or absence of concomitant bladder tumors was compared to that of ureteral urinary cytology. TECHNIQUE
The filtration technique was used for all urinary specimens. Fresh urine was obtained either by a clean-catch method or by retrograde ureteral catheterization. A urine sample (usually about 50 ml.) was filtered under slight negative pressure through a nucleopore membrane filter with pores 8 mµ,. in diameter. The retained cells of the urine were fixed in 95 per cent ethyl alcohol and stained according to Papanicolaou, Results were reported as negative, atypical or positive. MATERIAL AND METHODS
Cytologic investigation of the urine was performed for 100 patients (67 men and 33 women) with transitional cell cancer of the upper urinary tract who were seen between June 1970 and May 1975. Retrograde ureteral urinary cytology was performed under furosemide diuresis in 18 patients. All patients underwent surgical exploration, at which time the tumors were graded and staged. 20 Postoperative urinary cytology was done in 75 cases. The patients ranged in age from the fourth to the eighth decades of life, with most being between the fifth and the seventh decades. Accepted for publication May 21, 1976. Read at annual meeting of American Urological Association, Las Vegas, Nevada, May 16-20, 1976. * Requests for reprints: Mayo Clinic, 200 First St., S.W., Rochester, Minnesota 55901. 781
FINDINGS
Clinical manifestation. The most common symptom was gross hematuria, which occurred in 66 patients. Flank pain was noted in 26 patients. An investigation that led to the eventual diagnosis of cancer of the urinary tract was instituted for non-related symptoms in 12 patients and 11 patients had histories of transitional cell carcinoma. Eight patients had microhematuria only and 7 of the 100 patients had neither microhematuria nor gross hematuria. At evaluation 17 patients had active urinary tract infections and 2 had renal calculi. Location. The renal pelvis was involved unilaterally in 53 patients, the unilateral ureter was involved in 29, the pelvis and ureter on the ipsilateral side were involved in 10 and the upper tracts were involved bilaterally in 8. Twenty-eight patients had concomitant bladder tumors. Roentgenographic findings. All 100 patients underwent excretory urography. The findings were positive in 69 cases, indeterminate in 26 and negative in 5. Of the 62 patients who underwent retrograde ureteral pyelography 51 had a filling defect, 8 had indeterminate findings and 3 had negative findings. Of the 6 patients who underwent intravenous bolus nephrotomography 5 had a filling defect and 1 had an indeterminate finding. Arteriography was performed in 2 patients and was interpreted as negative in one and indeterminate in the other. Retrograde ileography demonstrated a filling defect in the ureter in 1 patient who had undergone bilateral ureteroileostomy and radical cystectomy for cancer of the bladder. Cytologic results. The results of urinary cytology correlated well with grade and stage of the tumor (tables 1 to 3), The yield of positive results was low in grade 1 papillary transitional cell carcinoma but better with grades 2, 3 and 4 transitional cell carcinoma, although 5 patients with grade 2 transitional cell carcinoma of the renal pelvis and concomitant bladder tumors had negative urinary cytology. Conversely, 10 of the 21 patients with positive results had synchronous bladder tumors. The frequencies of falsely negative results in grades 3 (17 per cent) and 4 (17 per cent) lesions were comparable. The correlation between positive cytologic findings and stage of lesion was lower than that seen with histologic grade. Forty-seven per cent of patients with stage III lesions had negative voided urinary cytology. Retrograde ureteral catheterization for urinary cytology yielded positive results in 11 of the 18 patients (61 per cent) who had upper urinary tract tumors, with the highest yield being in tumors of grades 2 and 3. This yield compares with a positive yield of only 33 per cent on voided urinary specimens in the same group of patients. The difference is even more obvious if one considers that of the 4 patients with grade 3
782
ZINCKE AND ASSOCIATES
TABLE
1. Relationship of voided urinary cytology to grade of upper urinary tract tumor Finding
Grade
Negative :fo.
Atypical
(%)
No.
(%)
1 2 3 4
23(2*) (79) 21(5*) (45) (17) 3 (17)
3 5(3*) 1 0
(10) (10) (5) (0)
Totals
48(7*) (48)
9(3*)
(9)
Positive No. 3 (2*) 21 (10*) 14 (6*) 5
Total Pts.
(%)
(10) (45) (78) (83)
29 47
43(18*) (43)
100
18 6
* Patients with concomitant bladder tumors.
TABLE
2. Relationship of voided urinary cytology to stage of upper
urinary tract tumor Finding Stage
Atypical
'.'-legative
I II III IV Totals
Positive
No.
(%)
No.
22(4*) 18(:3*) 8 0
(65) (41) (47) (0)
(9) 3 5(3*) (11) 1 (6) (0) 0
9 21 8 5
9(3*)
43(18*)
48(7*) (48)
(%)
(9)
No.
Total Pts.
(%)
(6*) (26) (9*) (48) (2*) (47) (1 *) (100)
34 44 17 5
(43)
100
* Patients with concomitant bladder tumors. TABLE
3. Relationship of retrograde and voided urinary cytology to grade of upper urinary tract tumor Finding
Grade
Negative
Positive
No. (%)
No. (%)
Total Pts.
Retrograde cytology 1
2
3 2
3
2
4 Totals
0 7
1
4
2
6 2 0 12
1 6 4
0 11 (61)
(39)
4 8 6 0 18
Voided cytology
3
4 Totals
0 (1 *)
2
(67)
4 (3*) 0 6 (33)
4 8 6 0 18
* Patients with concomitant bladder tumors.
transitional cell carcinoma who had positive voided urinary cy cology 3 also had concomitant bladder tumors. Of the 75 patients who underwent voided urinary cytology after operation 57 (76 per cent), including the 8 patients with bladder tumors, had negative findings, 17 (23 per cent) had positive findings and 1 had an indeterminate finding. Of the 17 patients with positive urinary cytology 15 had histories of known bladder tumors, 1 had a conservatively treated tumor in a solitary kidney and 1 had positive cytologic findings that could not be explained, although a bladder tumor was suspected. DISCUSSION
Transitional cell cancer of the upper urinary tract is relatively rare. Its prognosis seems to be closely related to grade and stage of tumor. 20 • 25 • 26 Exfoliative urinary cytology is valuable in the early detection and followup of bladder tumors. 3 • 4 • 10 , 12 • 14 - 13 However, its role in the diagnosis of upper urinary tract tumors by use of voided urinary cytology has been controversial 19 • 20 • 22 • 23 and its accuracy does not seem to be influenced by whether the urine was collected from the bladder
or directly from the renal pelvis. 19 • 23 Only a few studies could demonstrate the definite value of urinary cytology from retrograde ureteral catheterization specimens. 14 • 21 In our series the ages of patients (most between the fifth and the seventh decades of life) and the male-to-female ratio (2 to 1) were comparable to those reported in most other series. 14 • 19 • 20 • 25 The frequency of gross hematuria and flank pain also was comparable, as were the roentgenographic findings. Retrograde ureteropyelography seemed to be the most reliable test in detecting a filling defect of the ureter or renal pelvis. In agreement with other investigators voided urinary cytology was of questionable value in detecting upper urinary tract transitional cell cancer in our series. 14 • 19 · 24 The yield of positive results was low in cases of low grade tumors (although increased positive yields correlated with increased grades of the tumor) and positive voided urinary cytology in the presence of a concomitant bladder tumor is of questionable significance in regard to the diagnosis of upper tract cancer. Similar results were obtained when staging and voided urinary cytology results were correlated (although a high percentage of positive voided urinary cytology was obtained with high stages). Still, an over-all positive voided urinary cytology was found in 43 of the 100 patients, including 18 patients with synchronous bladder tumors. The value of separate urinary cytology (bladder and pelvis) is well demonstrated in the results obtained in 18 patients who underwent both tests. Only 6 (33 per cent), including 3 patients who had synchronous bladder tumors, had positive voided urinary cytology, compared to 11 (61 per cent) who had positive urinary cytology on the retrograde study. Furthermore, the yield of positive urinary cytology was particularly high in grade 2 tumors as well as in higher grade tumors. Because transitional cell cancer of the urinary tract may be of multicentric origin 27 and because bladder involvement after upper tract involvement develops more rapidly than vice versa (21 versus 6 to 8 months), 20 separate sampling from the lower and upper urinary tracts is advisable when there is upper urinary tract involvement. This method not only will increase the chance of detecting upper urinary tract involvement more reliably but also will result in the earlier detection of lower tract tumors, which in their early stage as carcinoma in situ are difficult to diagnose. 15 ' 16 Also, followup postoperative urinary cytology is of value in monitoring recurrent cancer when used in conjunction with roentgenographic and cystoscopic evaluation of the patient. Furthermore, the addition of retrograde brushing, as popularized recently by Gill and associates and recently also employed by us, should improve the diagnostic accuracy of upper urinary tract transitional cell cancer. 28 The low positive yield in low grade transitional cell cancer may be improved by the use of these and other recently introduced techniques. 29 The cytologic diagnosis of upper urinary tract transitional cell cancer seems to be of greatest practical value when the situation is difficult to assess by roentgeriographic or cystoscopic studies. REFERENCES 1. Papanicolaou, G. N. and Marshall, V. F.: Urine sediment smears
2. 3.
4.
5.
as a diagnostic procedure in cancers of urinary tract. Science, 101: 519, 1945. Papanicolaou, G. N.: Cytology of the urine sediment in neoplasms of the urinary tract. J. Ural., 57: 375, 1947. Harrison, J. H., Botsford, T. W. and Tucker, M. R.: The use of the smear of the urinary sediment in the diagnosis and management of neoplasm of the kidney and bladder. Surg., Gynec. & Obst., 92: 129, 1951. Roland, S. I. and Marshall, V. F.: The reliability of the Papanicolaou technique when cancer cells are found in the urine. Surg., Gynec. & Obst., 104: 41, 1957. Hazard, J. B., McCormack, L. J. and Belovich, D.: Exfoliative cytology of the urine with special reference to neoplasms of the urinary tract: preliminary report. J. Urol., 78: 182, 1957.
CYTOLOGY AND UPPER URINARY TRACT CANCER
6. Foot, N. C., Papanicolaou, G. N., Holmquist, N. D. and Seybolt, J. F.: Exfoliative cytology of urinary sediments; a review of 2,829 cases. Cancer, 11: 127, 1958. 7. Feeney, M. J., Mullenix, R. B., Prentiss, R. J., Martin, P. L. and Slate, T. A.: Cytological studies of the urine: preliminary report. J. Urol., 79: 589, 1958. 8. Booth, E.: Cytological screening tests for chemical workers exposed to bladder carcinogens. J. Med. Lab. Techn., 16: 123, 1959. 9. Elwi, A. M., Fam, A. and Ramzy, I.: Exfoliative cytology of the bilharzia! ulcer and cancer of the urinary bladder'. J. Egypt. Med. Ass., 45: 235, 1962. 10. Umiker, W. 0.: Cytologic diagnosis of carcinoma of the urinary bladder by fluorescence microscopy. Acta Cytol., 5: 245, 1961. 11. Umiker, W.: Accuracy of cytologic diagnosis of cancer of the urinary tract. Acta Cytol., 8: 186, 1964. 12. Macfarlane, E.W., Ceelen, G. H. and Taylor, J. N.: Urine cytology after treatment of bladder tumors. Acta Cytol., 8: 288, 1964. 13. Connolly, J. G., Promislow, C. and Marriott, J.: Intermittent exfoliation of epithelial cells in carcinoma of the urinary bladder. Canad. J. Surg., 13: 144, 1970. 14. Sarnacki, C. T., McCormack, L. J., Kiser, W. S., Hazard, J. B., McLaughlin, T. C. and Belovich, D. M.: Urinary cytology and the clinical diagnosis of urinary tract malignancy: a clinicopathologic study of 1,400 patients. J. Urol., 106: 761, 1971. 15. Utz, D. C. and Zincke, H.: The masquerade of bladder cancer in situ as interstitial cystitis. J. Urol., 111: 160, 1974. 16. Zincke, H. and Utz, D. C.: Die Harnzytologie: ein wichtiges Hilfsmittel bei der Differentialdiagnose der interstitiellen Zystitis und des carcinoma in situ der Blase. Aktuel. Urol., 5: 229, 1974. 17. Farrow, G. M., Utz, D. C. and Rife, C. C.: Morphological and clinical observations of patients with early bladder cancer treated with total cystectomy. Cancer Res., 36: 2495, 1976.
783
18. Crabbe, J. G. S., Cresdee, W. C., Scott, T. S. and Williams, M. H. C.: The cytological diagnosis of bladder tumours amongst dyestuff workers. Brit. J. lndust. Med., 13: 270, 1956. 19. Grace, D. A., Taylor, W. N., Taylor, J. N. and Winter, C. C.: Carcinoma of the renal pelvis: a 15-year review. J. Urol., 98: 566, 1967. 20. Grabstald, H., Whitmore, W. F. and Melamed, M. R.: Renal pelvic tumors. J.A.M.A., 218: 845, 1971. 21. Cullen, T. H., Popham, R.R. and Voss, H.J.: Urine cytology and primary carcinoma of the renal pelvis and ureter. Aust. New Zeal. J. Surg., 41: 230, 1972. 22. De Voogt, H. J.: Rapid urinary cytology by phase contrast microscopy: a preliminary report. Urol. Res., 1: 113, 1973. 23. Say, C. C. and Hori, J.M.: Transitional cell carcinoma of the renal pelvis: experience from 1940 to 1972 and literature review. J. Urol., 112: 438, 1974. 24. Cummings, K. B., Correa, R. J., Jr., Gibbons, R. P., Stoll, H. M., Wheelis, R. F. and Mason, J. T.: Renal pelvic tumors. J. Urol., 113: 158, 1975. 25. McDonald, J. R. and Priestley, J. T.: Carcinoma of renal pelvis: histopathologic study of seventy-five cases with special reference to prognosis. J. Urol., 51: 245, 1944. 26. Hawtrey, C. E.: Fifty-two cases of primary ureteral carcinoma: a clinical-pathologic study. J. Urol., 105: 188, 1971. 27. Kaplan, J. H., McDonald, J. R. and Thompson, G. J.: Multicentric origin of papillary tumors of the urinary tract. J. Urol., 66: 792, 1951. 28. Gill, W. B., Lu, C. T. and Thomsen, S.: Retrograde brushing: a new technique for obtaining histologic and cytologic material from ureteral, renal pelvic and renal caliceal lesions. J. Urol., 109: 573, 1973. 29. Constantian, H. M. and De Girolami, E.: Urothelial tumors detected by cytology: new cell block technique. J. Urol., 109: 304, 1973.
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1976 by The Williams & Wilkins Co.
SIGNIFICANCE OF URINARY CYTOLOGY IN THE EARLY DETECTION OF TRANSITIONAL CELL CANCER OF THE UPPER URINARY TRACT HORST ZINCKE,* JUAN J. AGUILO, GEORGE M. FARROW, DAVID C. UTZ
AND
ANSAR U. KHAN
From the Departments of Urology and Surgical Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
ABSTRACT
Cytologic study of urine from 100 patients with transitional cell cancer of the upper urinary tract revealed that findings on the voided and catheterized specimens correlated well with grade and stage of the tumor. However, there was a significantly greater positive yield with urine specimens obtained by ureteral catheterization than by voiding. Consequently, because concomitant bladder tumors, diagnosed or not, can give questionable positive results ureteral catheterization specimens should be used for cytologic study. Since Papanicolaou and Marshall first reported on the feasibility of applying cytologic study in cancer of the urinary tract 1 reports have been received with cautious enthusiasm. This is because of the variable results obtained in the diagnosis of cancer of the bladder, 2 • 13 which range from 26 to 100 per cent, 3 • 5 ' 7 • 9 with a median sensitivity of 76 per cent for positive cytologic diagnosis. 10 Nevertheless, urinary cytology has achieved particular importance and accuracy in the detection of high grade tumors 14 that have been difficult to recognize endoscopically. 10 • 15 · 17 Furthermore, such study is regarded by many as a valuable adjunct in the evaluation and followup of the patient with cancer of the bladder. 3 • 4 • 10• 14 - 16 • 18 However, its role in the detection and diagnosis of transitional cell cancer of the upper urinary tract has been considered poor 19 and difficult to determine because of the synchronous presence of bladder tumors. 14• 20 - 2 • This review was done to assess the significance and accuracy of urinary cytology in the detection of transitional cell cancer of the upper urinary tract. In particular, the value of voided urinary cytology in the presence or absence of concomitant bladder tumors was compared to that of ureteral urinary cytology. TECHNIQUE
The filtration technique was used for all urinary specimens. Fresh urine was obtained either by a clean-catch method or by retrograde ureteral catheterization. A urine sample (usually about 50 ml.) was filtered under slight negative pressure through a nucleopore membrane filter with pores 8 mµ,. in diameter. The retained cells of the urine were fixed in 95 per cent ethyl alcohol and stained according to Papanicolaou, Results were reported as negative, atypical or positive. MATERIAL AND METHODS
Cytologic investigation of the urine was performed for 100 patients (67 men and 33 women) with transitional cell cancer of the upper urinary tract who were seen between June 1970 and May 1975. Retrograde ureteral urinary cytology was performed under furosemide diuresis in 18 patients. All patients underwent surgical exploration, at which time the tumors were graded and staged. 20 Postoperative urinary cytology was done in 75 cases. The patients ranged in age from the fourth to the eighth decades of life, with most being between the fifth and the seventh decades. Accepted for publication May 21, 1976. Read at annual meeting of American Urological Association, Las Vegas, Nevada, May 16-20, 1976. * Requests for reprints: Mayo Clinic, 200 First St., S.W., Rochester, Minnesota 55901. 781
FINDINGS
Clinical manifestation. The most common symptom was gross hematuria, which occurred in 66 patients. Flank pain was noted in 26 patients. An investigation that led to the eventual diagnosis of cancer of the urinary tract was instituted for non-related symptoms in 12 patients and 11 patients had histories of transitional cell carcinoma. Eight patients had microhematuria only and 7 of the 100 patients had neither microhematuria nor gross hematuria. At evaluation 17 patients had active urinary tract infections and 2 had renal calculi. Location. The renal pelvis was involved unilaterally in 53 patients, the unilateral ureter was involved in 29, the pelvis and ureter on the ipsilateral side were involved in 10 and the upper tracts were involved bilaterally in 8. Twenty-eight patients had concomitant bladder tumors. Roentgenographic findings. All 100 patients underwent excretory urography. The findings were positive in 69 cases, indeterminate in 26 and negative in 5. Of the 62 patients who underwent retrograde ureteral pyelography 51 had a filling defect, 8 had indeterminate findings and 3 had negative findings. Of the 6 patients who underwent intravenous bolus nephrotomography 5 had a filling defect and 1 had an indeterminate finding. Arteriography was performed in 2 patients and was interpreted as negative in one and indeterminate in the other. Retrograde ileography demonstrated a filling defect in the ureter in 1 patient who had undergone bilateral ureteroileostomy and radical cystectomy for cancer of the bladder. Cytologic results. The results of urinary cytology correlated well with grade and stage of the tumor (tables 1 to 3), The yield of positive results was low in grade 1 papillary transitional cell carcinoma but better with grades 2, 3 and 4 transitional cell carcinoma, although 5 patients with grade 2 transitional cell carcinoma of the renal pelvis and concomitant bladder tumors had negative urinary cytology. Conversely, 10 of the 21 patients with positive results had synchronous bladder tumors. The frequencies of falsely negative results in grades 3 (17 per cent) and 4 (17 per cent) lesions were comparable. The correlation between positive cytologic findings and stage of lesion was lower than that seen with histologic grade. Forty-seven per cent of patients with stage III lesions had negative voided urinary cytology. Retrograde ureteral catheterization for urinary cytology yielded positive results in 11 of the 18 patients (61 per cent) who had upper urinary tract tumors, with the highest yield being in tumors of grades 2 and 3. This yield compares with a positive yield of only 33 per cent on voided urinary specimens in the same group of patients. The difference is even more obvious if one considers that of the 4 patients with grade 3
782
ZINCKE AND ASSOCIATES
TABLE
1. Relationship of voided urinary cytology to grade of upper urinary tract tumor Finding
Grade
Negative :fo.
Atypical
(%)
No.
(%)
1 2 3 4
23(2*) (79) 21(5*) (45) (17) 3 (17)
3 5(3*) 1 0
(10) (10) (5) (0)
Totals
48(7*) (48)
9(3*)
(9)
Positive No. 3 (2*) 21 (10*) 14 (6*) 5
Total Pts.
(%)
(10) (45) (78) (83)
29 47
43(18*) (43)
100
18 6
* Patients with concomitant bladder tumors.
TABLE
2. Relationship of voided urinary cytology to stage of upper
urinary tract tumor Finding Stage
Atypical
'.'-legative
I II III IV Totals
Positive
No.
(%)
No.
22(4*) 18(:3*) 8 0
(65) (41) (47) (0)
(9) 3 5(3*) (11) 1 (6) (0) 0
9 21 8 5
9(3*)
43(18*)
48(7*) (48)
(%)
(9)
No.
Total Pts.
(%)
(6*) (26) (9*) (48) (2*) (47) (1 *) (100)
34 44 17 5
(43)
100
* Patients with concomitant bladder tumors. TABLE
3. Relationship of retrograde and voided urinary cytology to grade of upper urinary tract tumor Finding
Grade
Negative
Positive
No. (%)
No. (%)
Total Pts.
Retrograde cytology 1
2
3 2
3
2
4 Totals
0 7
1
4
2
6 2 0 12
1 6 4
0 11 (61)
(39)
4 8 6 0 18
Voided cytology
3
4 Totals
0 (1 *)
2
(67)
4 (3*) 0 6 (33)
4 8 6 0 18
* Patients with concomitant bladder tumors.
transitional cell carcinoma who had positive voided urinary cy cology 3 also had concomitant bladder tumors. Of the 75 patients who underwent voided urinary cytology after operation 57 (76 per cent), including the 8 patients with bladder tumors, had negative findings, 17 (23 per cent) had positive findings and 1 had an indeterminate finding. Of the 17 patients with positive urinary cytology 15 had histories of known bladder tumors, 1 had a conservatively treated tumor in a solitary kidney and 1 had positive cytologic findings that could not be explained, although a bladder tumor was suspected. DISCUSSION
Transitional cell cancer of the upper urinary tract is relatively rare. Its prognosis seems to be closely related to grade and stage of tumor. 20 • 25 • 26 Exfoliative urinary cytology is valuable in the early detection and followup of bladder tumors. 3 • 4 • 10 , 12 • 14 - 13 However, its role in the diagnosis of upper urinary tract tumors by use of voided urinary cytology has been controversial 19 • 20 • 22 • 23 and its accuracy does not seem to be influenced by whether the urine was collected from the bladder
or directly from the renal pelvis. 19 • 23 Only a few studies could demonstrate the definite value of urinary cytology from retrograde ureteral catheterization specimens. 14 • 21 In our series the ages of patients (most between the fifth and the seventh decades of life) and the male-to-female ratio (2 to 1) were comparable to those reported in most other series. 14 • 19 • 20 • 25 The frequency of gross hematuria and flank pain also was comparable, as were the roentgenographic findings. Retrograde ureteropyelography seemed to be the most reliable test in detecting a filling defect of the ureter or renal pelvis. In agreement with other investigators voided urinary cytology was of questionable value in detecting upper urinary tract transitional cell cancer in our series. 14 • 19 · 24 The yield of positive results was low in cases of low grade tumors (although increased positive yields correlated with increased grades of the tumor) and positive voided urinary cytology in the presence of a concomitant bladder tumor is of questionable significance in regard to the diagnosis of upper tract cancer. Similar results were obtained when staging and voided urinary cytology results were correlated (although a high percentage of positive voided urinary cytology was obtained with high stages). Still, an over-all positive voided urinary cytology was found in 43 of the 100 patients, including 18 patients with synchronous bladder tumors. The value of separate urinary cytology (bladder and pelvis) is well demonstrated in the results obtained in 18 patients who underwent both tests. Only 6 (33 per cent), including 3 patients who had synchronous bladder tumors, had positive voided urinary cytology, compared to 11 (61 per cent) who had positive urinary cytology on the retrograde study. Furthermore, the yield of positive urinary cytology was particularly high in grade 2 tumors as well as in higher grade tumors. Because transitional cell cancer of the urinary tract may be of multicentric origin 27 and because bladder involvement after upper tract involvement develops more rapidly than vice versa (21 versus 6 to 8 months), 20 separate sampling from the lower and upper urinary tracts is advisable when there is upper urinary tract involvement. This method not only will increase the chance of detecting upper urinary tract involvement more reliably but also will result in the earlier detection of lower tract tumors, which in their early stage as carcinoma in situ are difficult to diagnose. 15 ' 16 Also, followup postoperative urinary cytology is of value in monitoring recurrent cancer when used in conjunction with roentgenographic and cystoscopic evaluation of the patient. Furthermore, the addition of retrograde brushing, as popularized recently by Gill and associates and recently also employed by us, should improve the diagnostic accuracy of upper urinary tract transitional cell cancer. 28 The low positive yield in low grade transitional cell cancer may be improved by the use of these and other recently introduced techniques. 29 The cytologic diagnosis of upper urinary tract transitional cell cancer seems to be of greatest practical value when the situation is difficult to assess by roentgeriographic or cystoscopic studies. REFERENCES 1. Papanicolaou, G. N. and Marshall, V. F.: Urine sediment smears
2. 3.
4.
5.
as a diagnostic procedure in cancers of urinary tract. Science, 101: 519, 1945. Papanicolaou, G. N.: Cytology of the urine sediment in neoplasms of the urinary tract. J. Ural., 57: 375, 1947. Harrison, J. H., Botsford, T. W. and Tucker, M. R.: The use of the smear of the urinary sediment in the diagnosis and management of neoplasm of the kidney and bladder. Surg., Gynec. & Obst., 92: 129, 1951. Roland, S. I. and Marshall, V. F.: The reliability of the Papanicolaou technique when cancer cells are found in the urine. Surg., Gynec. & Obst., 104: 41, 1957. Hazard, J. B., McCormack, L. J. and Belovich, D.: Exfoliative cytology of the urine with special reference to neoplasms of the urinary tract: preliminary report. J. Urol., 78: 182, 1957.
CYTOLOGY AND UPPER URINARY TRACT CANCER
6. Foot, N. C., Papanicolaou, G. N., Holmquist, N. D. and Seybolt, J. F.: Exfoliative cytology of urinary sediments; a review of 2,829 cases. Cancer, 11: 127, 1958. 7. Feeney, M. J., Mullenix, R. B., Prentiss, R. J., Martin, P. L. and Slate, T. A.: Cytological studies of the urine: preliminary report. J. Urol., 79: 589, 1958. 8. Booth, E.: Cytological screening tests for chemical workers exposed to bladder carcinogens. J. Med. Lab. Techn., 16: 123, 1959. 9. Elwi, A. M., Fam, A. and Ramzy, I.: Exfoliative cytology of the bilharzia! ulcer and cancer of the urinary bladder'. J. Egypt. Med. Ass., 45: 235, 1962. 10. Umiker, W. 0.: Cytologic diagnosis of carcinoma of the urinary bladder by fluorescence microscopy. Acta Cytol., 5: 245, 1961. 11. Umiker, W.: Accuracy of cytologic diagnosis of cancer of the urinary tract. Acta Cytol., 8: 186, 1964. 12. Macfarlane, E.W., Ceelen, G. H. and Taylor, J. N.: Urine cytology after treatment of bladder tumors. Acta Cytol., 8: 288, 1964. 13. Connolly, J. G., Promislow, C. and Marriott, J.: Intermittent exfoliation of epithelial cells in carcinoma of the urinary bladder. Canad. J. Surg., 13: 144, 1970. 14. Sarnacki, C. T., McCormack, L. J., Kiser, W. S., Hazard, J. B., McLaughlin, T. C. and Belovich, D. M.: Urinary cytology and the clinical diagnosis of urinary tract malignancy: a clinicopathologic study of 1,400 patients. J. Urol., 106: 761, 1971. 15. Utz, D. C. and Zincke, H.: The masquerade of bladder cancer in situ as interstitial cystitis. J. Urol., 111: 160, 1974. 16. Zincke, H. and Utz, D. C.: Die Harnzytologie: ein wichtiges Hilfsmittel bei der Differentialdiagnose der interstitiellen Zystitis und des carcinoma in situ der Blase. Aktuel. Urol., 5: 229, 1974. 17. Farrow, G. M., Utz, D. C. and Rife, C. C.: Morphological and clinical observations of patients with early bladder cancer treated with total cystectomy. Cancer Res., 36: 2495, 1976.
783
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