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The Diagnostic Value of Urinary Cytology in Patients with Bladder Carcinoma
Vol. 106, November Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright © 1971 by The Williams & Wilkins Co.
THE DIAGNOSTIC VALUE OF URINARY CYTOLOGY IN PATIENTS WITH BLADDER CARCINOMA RIKUS SCHOONEES, MARIE G. GAMARRA, ROBERT H. MOORE AND GERALD P. MURPHY From the Roswell Park Memorial Institute, New York State Department of Health and the State University of New York, Buffalo, New York
Exfoliative cytology of urinary sediments has proved to be a useful aid in the diagnosis of bladder carcinoma. Cytologic study of the urine as a diagnostic procedure was introduced first by Papanicolaou and Marshall in 1945. 1 Since then many reports have been published on the value, techniques and interpretation of exfoliative cytology of the urine. The finding of malignant cells in the urine is highly suggestive of the presence of cancer arising from the transitional epithelium. Falsely positive cytological reports are less than 5 per cent in most series. 2- 4 The high percentage ( > 95 per cent) of correct positive cytologic interpretations of the urinary sediment necessitates a thorough search of the complete urinary tract for the neoplasm that almost certainly exists. The percentage of falsely negative reports depends on the method of urine collection, the experience of the cytologist in recognizing malignant cells and the number of urine specimens examined. Park and associates considered it advisable to have at least 3 specimens of morning urine examined to minimize the percentage of falsely negative reports. 5 Foot and associates reported that correct positive interpretations were made upon the examination of the first urine specimen submitted in 77.5 per cent of cases of proved bladder carcinoma. 4 Our findings of exfoliative cytology of urinary Accepted for publication December 1970. Papanicolaou, G. N. and Marshall, V. F.: Urine sediment smears as a diagnostic procedure in cancers of the urinary tract. Science, 101: 519 1
1945.
'
Roland, S. I. and Marshall, V. F.: The reliability of the Papanicolaou technique when cancer cells are found in the urine. Surg., Gynec. & Obst., 2
104: 41, 1957.
3 Deden, C.: Cancer cells in urinary sediment. Acta Radial., suppl. 115, p. 1, 1954. 4 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. 5 Park, C-H., Britsch, C., Uson, A. C. and Veenema, R. J.: Reliability of positive exfoliative cytologic study of the urine in urinary tract malignancy. J. Urol., 102: 91, 1969. ·
sediments were correlated with the cell type, grade and stage of bladder carcinoma. 6 MATERIALS AND METHODS
The records of 114 patients with known bladder carcinoma seen between January 1966 and June 1969 were selected at random for this review. Routine cytologic examination of urine specimens of all patients admitted to the urology service was commenced approximately 1 year earlier. One morning urine specimen was collected for exfoliative cytologic study on all patients prior to endoscopy. Diagnosis was histologically confirmed in all cases and all tumors were graded using Broders' 4 grades. 6 Histologically, the cell type of all bladder tumors was classified as transitional, squamous or anaplastic. The stage of the bladder carcinoma was determined by combined clinical assessment of the patient under general anesthesia and histological examination of biopsy and/or surgical and/or autopsy material. The system of staging advocated by Jewett and Strong was used.7 Most patients had solitary bladder tumors; in approximately 40 per cent of patients, the urine was infected as judged by culture and microscopic examination. The interpretations of exfoliative cytologic study of the urine specimens were classified as negative (normal), doubtful (atypical cells or suspicious of malignancy) or positive (malignant). The appearance of a typical malignant urinary sediment is shown in the figure. All pertinent data relating to the diagnosis of bladder carcinoma and the cytological findings were recorded on specially prepared coding schedules and then were transcribed onto IBM punch 6 Broders, A. C.: Carcinoma: grading and practical application. Arch. Path., 2: 376, 1926. 7 Jewett, H. J. and Strong, G. H.: Infiltrating carcinoma of the bladder: relation of depth of penetration of the bladder wall to incidence of local extension and metastases. J. Urol., 66: 366
19~.
693
'
694
SCHOONEES AND ASSOCIATES
This group of cells in urinary sediment shows nuclear and cytoplasmic characteristics of neoplasia. Nuclei manifest irregularity in chromatin content and marked variation of nuclear pattern, size and shape. Cytoplasm is indistinct and cell borders are not apparent. Papanicolaou, reduced from Xl,100. TABLE
Grade
1. Grade of bladder carcinoma* No. Pts.
% 8.1
33
29. 7
33
29. 7
36
32.4
specimens submitted were adequate for a satisfactory cytologic analysis. The highest stage of the tumor as determined pathologically and/or clinically was correlated 2. Correlation of tumor stage with cytologic study of urine, cell type and grade of bladder carcinoma*
TABLE
Stage
Cell Type
Cytology
Gradef
• Graded according to Broders' method. 6 0
(11)
Transitional (11) Squamous (0) Ana plastic (0)
Positive Negative Doubtful
A
(25)
Transitional (24) Squamous (I) Anaplastic (0)
Positive (19) Negative (4) Doubtful (2)
(5) 2 (14) 3 (2)
B
(28)
Transitional (26) Squamous (0) Anaplastic (2)
Positive (19) Negative (4) Doubtful (5)
1 (O) 2 (3) 3 (13) (11)
C
(12)
Transitional (11) Squamous (0) Ana plastic (1)
Positive Negative Doubtful
cards. Data were analyzed using an IBM 1130 computer and standard statistical methodology. RESUUl'S
The predominant cell type of the primary bladder tumor was transitional in 96 cases (84.2 per cent). In 9 patients (7.9 per cent) the tumor was reported as squamous cell carcinoma and in another 9 patients (7.9 per cent) the extreme degree of anaplasia of the tumor prevented recognition of a specfic primary cell type. The primary bladder tumor was satisfactorily graded in 111 of 114 cases under review (table 1). Less than 10 per cent of the patients in this study had grade 1 bladder lesions. Exfoliative cytologic study of the urine was positive for malignant cells in 80 cases (70.2 per cent), negative in 23 patients (20.2 per cent) and doubtful in 11 cases (9.6 per cent). All urine
(4) (6) (1)
1 2
(2) (6) (3) (0)
(4)
(7) (2) (3)
(I) 2
4
D (38)
Transitional (24) Squamous (8) Ana plastic (6)
Positive (31) Negative (7) Doubtful (O)
(I) (5) (3)
1 2
(1) (9) (10) 4 (18)
* Numbers in parentheses indicate number of patients. t Three tumors from total of 114 were not satisfactorily graded.
695
URINARY CYTOLOGY IN PATIENTS WITH BLADDER CANCER
with the cell type and of the tumor and the cytologic interpretation of the sediment (table 2). The majority of the had stage B or more advanced stages of their disease. A highly significant (p < 0.01) correlation existed among the squamous cell and anaplastic tumors and stage D lesions. it highly significant (p < 0.001) direct relationship existed between the tumor grade and the stage of the disease, that is the higher the tumor the greater the likelihood of an advanced stage. No significant correlation could be demonstrated among the percentage of reports and the cell type, stage or grade of the tumor 2 to 4).
TABLJ<:
3. Correlation of grade of bladder carcinorna
with cytologic study of urine Grade of Tumor
Cytology*
Ko, Pts. Positive
33
24
33
21
36
29
Negative
Doubtful
* Numbers indicate number of pa.tients in each group.
4. Correlation of cell type of bladder carcinoma with cytologic study of wine
TABLE
Cytology''
Cell Type of Tumor
Positive l,,,Tegative Doubtful
LJSCUSSION
In 70.2 per cent of the ca:,es, correct positi\ e cytologic interpretations were made on the first and only urine specimen submitted. This percentage correlates well with the 77.5 per cent coron the first urine rectly positive rn,,,,rnr,""" specimen by Foot and associates. 4 The percentage of falsely reports was relahigh per cent) in our series. The finding of negative exfoliative with histologically but can be 0
the search for malignant sediment. If 2 urine specimens or more are submitted per and urinary infection adequately treated can be than 70 per cent. Park and associate.s considered it advisable to have at least 3 urine specimens from each patient submitted for evaluation in order to minimize the incidence of negative The highly significant tween of tumor and stage of the disease is of Whitmore and in agreement with the
Transitional, 96 pts.
65
20
11
Squamous, 9 pts. Anaplastic: fl pts.
* Numbers indicate number of patients in eacb group.
:-farnhall. 8 cancern are usually more cancers are more incidence of squarncus cell and nomas among patients with stage D lesions indicate that these carcinomas tend to grow more rapidly and to metastasize earlier to lymph nodes than transitional cell. lesions. The high percentage of with advanced stages of bladder carcinoma reflect,, in part the of selection of cases referred our institute. In our no significant correla, exfoliatirn tion was detected among of the urine and the stage, and type of cancer. The percentage of correct cytologic not affected by the extent of carcinoma. Although no correlation between the cell type of the tumor and the percentage of
patients with squamous or 8 Whitmore, W. F, Jr. and Marshall, V. F. for carcinoma of the urinnry Radical bladder. In: Tumours: Edited by V. F. Marshall.
Lippincott Co., p. 54, 1956.
696
SCHOONEES AND ASSOCIATES
(83.3 per cent) than in patients with transitional cell carcinomas (67 .7 per cent). SUMMARY
The interpretation of exfoliative cytology of urinary sediment of 114 patients with bladder carcinoma was correlated with the stage, grade and cell type of the tumor. One morning urine
specimen per patient was submitted for cytologic investigation. A first-time correctly positive interpretation was made in 70.2 per cent of cases. No correlation existed among the percentage of positive reports, the grade of the tumor and the stage of disease. The percentage of positive cytologic interpretations was markedly higher in patients with squamous and anaplastic carcinomas than in patients with transitional cell carcinoma.
THE JOURNAL OF UROLOGY
Copyright © 1971 by The Williams & Wilkins Co.
THE DIAGNOSTIC VALUE OF URINARY CYTOLOGY IN PATIENTS WITH BLADDER CARCINOMA RIKUS SCHOONEES, MARIE G. GAMARRA, ROBERT H. MOORE AND GERALD P. MURPHY From the Roswell Park Memorial Institute, New York State Department of Health and the State University of New York, Buffalo, New York
Exfoliative cytology of urinary sediments has proved to be a useful aid in the diagnosis of bladder carcinoma. Cytologic study of the urine as a diagnostic procedure was introduced first by Papanicolaou and Marshall in 1945. 1 Since then many reports have been published on the value, techniques and interpretation of exfoliative cytology of the urine. The finding of malignant cells in the urine is highly suggestive of the presence of cancer arising from the transitional epithelium. Falsely positive cytological reports are less than 5 per cent in most series. 2- 4 The high percentage ( > 95 per cent) of correct positive cytologic interpretations of the urinary sediment necessitates a thorough search of the complete urinary tract for the neoplasm that almost certainly exists. The percentage of falsely negative reports depends on the method of urine collection, the experience of the cytologist in recognizing malignant cells and the number of urine specimens examined. Park and associates considered it advisable to have at least 3 specimens of morning urine examined to minimize the percentage of falsely negative reports. 5 Foot and associates reported that correct positive interpretations were made upon the examination of the first urine specimen submitted in 77.5 per cent of cases of proved bladder carcinoma. 4 Our findings of exfoliative cytology of urinary Accepted for publication December 1970. Papanicolaou, G. N. and Marshall, V. F.: Urine sediment smears as a diagnostic procedure in cancers of the urinary tract. Science, 101: 519 1
1945.
'
Roland, S. I. and Marshall, V. F.: The reliability of the Papanicolaou technique when cancer cells are found in the urine. Surg., Gynec. & Obst., 2
104: 41, 1957.
3 Deden, C.: Cancer cells in urinary sediment. Acta Radial., suppl. 115, p. 1, 1954. 4 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. 5 Park, C-H., Britsch, C., Uson, A. C. and Veenema, R. J.: Reliability of positive exfoliative cytologic study of the urine in urinary tract malignancy. J. Urol., 102: 91, 1969. ·
sediments were correlated with the cell type, grade and stage of bladder carcinoma. 6 MATERIALS AND METHODS
The records of 114 patients with known bladder carcinoma seen between January 1966 and June 1969 were selected at random for this review. Routine cytologic examination of urine specimens of all patients admitted to the urology service was commenced approximately 1 year earlier. One morning urine specimen was collected for exfoliative cytologic study on all patients prior to endoscopy. Diagnosis was histologically confirmed in all cases and all tumors were graded using Broders' 4 grades. 6 Histologically, the cell type of all bladder tumors was classified as transitional, squamous or anaplastic. The stage of the bladder carcinoma was determined by combined clinical assessment of the patient under general anesthesia and histological examination of biopsy and/or surgical and/or autopsy material. The system of staging advocated by Jewett and Strong was used.7 Most patients had solitary bladder tumors; in approximately 40 per cent of patients, the urine was infected as judged by culture and microscopic examination. The interpretations of exfoliative cytologic study of the urine specimens were classified as negative (normal), doubtful (atypical cells or suspicious of malignancy) or positive (malignant). The appearance of a typical malignant urinary sediment is shown in the figure. All pertinent data relating to the diagnosis of bladder carcinoma and the cytological findings were recorded on specially prepared coding schedules and then were transcribed onto IBM punch 6 Broders, A. C.: Carcinoma: grading and practical application. Arch. Path., 2: 376, 1926. 7 Jewett, H. J. and Strong, G. H.: Infiltrating carcinoma of the bladder: relation of depth of penetration of the bladder wall to incidence of local extension and metastases. J. Urol., 66: 366
19~.
693
'
694
SCHOONEES AND ASSOCIATES
This group of cells in urinary sediment shows nuclear and cytoplasmic characteristics of neoplasia. Nuclei manifest irregularity in chromatin content and marked variation of nuclear pattern, size and shape. Cytoplasm is indistinct and cell borders are not apparent. Papanicolaou, reduced from Xl,100. TABLE
Grade
1. Grade of bladder carcinoma* No. Pts.
% 8.1
33
29. 7
33
29. 7
36
32.4
specimens submitted were adequate for a satisfactory cytologic analysis. The highest stage of the tumor as determined pathologically and/or clinically was correlated 2. Correlation of tumor stage with cytologic study of urine, cell type and grade of bladder carcinoma*
TABLE
Stage
Cell Type
Cytology
Gradef
• Graded according to Broders' method. 6 0
(11)
Transitional (11) Squamous (0) Ana plastic (0)
Positive Negative Doubtful
A
(25)
Transitional (24) Squamous (I) Anaplastic (0)
Positive (19) Negative (4) Doubtful (2)
(5) 2 (14) 3 (2)
B
(28)
Transitional (26) Squamous (0) Anaplastic (2)
Positive (19) Negative (4) Doubtful (5)
1 (O) 2 (3) 3 (13) (11)
C
(12)
Transitional (11) Squamous (0) Ana plastic (1)
Positive Negative Doubtful
cards. Data were analyzed using an IBM 1130 computer and standard statistical methodology. RESUUl'S
The predominant cell type of the primary bladder tumor was transitional in 96 cases (84.2 per cent). In 9 patients (7.9 per cent) the tumor was reported as squamous cell carcinoma and in another 9 patients (7.9 per cent) the extreme degree of anaplasia of the tumor prevented recognition of a specfic primary cell type. The primary bladder tumor was satisfactorily graded in 111 of 114 cases under review (table 1). Less than 10 per cent of the patients in this study had grade 1 bladder lesions. Exfoliative cytologic study of the urine was positive for malignant cells in 80 cases (70.2 per cent), negative in 23 patients (20.2 per cent) and doubtful in 11 cases (9.6 per cent). All urine
(4) (6) (1)
1 2
(2) (6) (3) (0)
(4)
(7) (2) (3)
(I) 2
4
D (38)
Transitional (24) Squamous (8) Ana plastic (6)
Positive (31) Negative (7) Doubtful (O)
(I) (5) (3)
1 2
(1) (9) (10) 4 (18)
* Numbers in parentheses indicate number of patients. t Three tumors from total of 114 were not satisfactorily graded.
695
URINARY CYTOLOGY IN PATIENTS WITH BLADDER CANCER
with the cell type and of the tumor and the cytologic interpretation of the sediment (table 2). The majority of the had stage B or more advanced stages of their disease. A highly significant (p < 0.01) correlation existed among the squamous cell and anaplastic tumors and stage D lesions. it highly significant (p < 0.001) direct relationship existed between the tumor grade and the stage of the disease, that is the higher the tumor the greater the likelihood of an advanced stage. No significant correlation could be demonstrated among the percentage of reports and the cell type, stage or grade of the tumor 2 to 4).
TABLJ<:
3. Correlation of grade of bladder carcinorna
with cytologic study of urine Grade of Tumor
Cytology*
Ko, Pts. Positive
33
24
33
21
36
29
Negative
Doubtful
* Numbers indicate number of pa.tients in each group.
4. Correlation of cell type of bladder carcinoma with cytologic study of wine
TABLE
Cytology''
Cell Type of Tumor
Positive l,,,Tegative Doubtful
LJSCUSSION
In 70.2 per cent of the ca:,es, correct positi\ e cytologic interpretations were made on the first and only urine specimen submitted. This percentage correlates well with the 77.5 per cent coron the first urine rectly positive rn,,,,rnr,""" specimen by Foot and associates. 4 The percentage of falsely reports was relahigh per cent) in our series. The finding of negative exfoliative with histologically but can be 0
the search for malignant sediment. If 2 urine specimens or more are submitted per and urinary infection adequately treated can be than 70 per cent. Park and associate.s considered it advisable to have at least 3 urine specimens from each patient submitted for evaluation in order to minimize the incidence of negative The highly significant tween of tumor and stage of the disease is of Whitmore and in agreement with the
Transitional, 96 pts.
65
20
11
Squamous, 9 pts. Anaplastic: fl pts.
* Numbers indicate number of patients in eacb group.
:-farnhall. 8 cancern are usually more cancers are more incidence of squarncus cell and nomas among patients with stage D lesions indicate that these carcinomas tend to grow more rapidly and to metastasize earlier to lymph nodes than transitional cell. lesions. The high percentage of with advanced stages of bladder carcinoma reflect,, in part the of selection of cases referred our institute. In our no significant correla, exfoliatirn tion was detected among of the urine and the stage, and type of cancer. The percentage of correct cytologic not affected by the extent of carcinoma. Although no correlation between the cell type of the tumor and the percentage of
patients with squamous or 8 Whitmore, W. F, Jr. and Marshall, V. F. for carcinoma of the urinnry Radical bladder. In: Tumours: Edited by V. F. Marshall.
Lippincott Co., p. 54, 1956.
696
SCHOONEES AND ASSOCIATES
(83.3 per cent) than in patients with transitional cell carcinomas (67 .7 per cent). SUMMARY
The interpretation of exfoliative cytology of urinary sediment of 114 patients with bladder carcinoma was correlated with the stage, grade and cell type of the tumor. One morning urine
specimen per patient was submitted for cytologic investigation. A first-time correctly positive interpretation was made in 70.2 per cent of cases. No correlation existed among the percentage of positive reports, the grade of the tumor and the stage of disease. The percentage of positive cytologic interpretations was markedly higher in patients with squamous and anaplastic carcinomas than in patients with transitional cell carcinoma.