ANALYSIS OF URINE CYTOLOGY AT A COMMUNITY HOSPITAL
Ibrahim Mansoor
Department of Pathology, St. John Hospital and Medical Center, Detroit.
Background: To review the pattern of urine cytology in our setting of a community hospital with age and gender distribution. Also to discuss the importance of this safe and inexpensive tool for diagnosing and screening urothelial cancers. We desire to encourage more wider and confident use of urine cytology in the routine practice. Method: We reviewed all the consecutive urine cytology specimens received at our institution during time frame of one year. The cytological diagnosis were grouped in four categories; 1: negative, benign or reactive cases; 2: cases showing acute inflammatory changes; 3: inconclusive cases and 4: malignant cases. Only the positive malignant cases were followed histologically to determine the accuracy and efficiency of urine cytological examination for positive cases. Results: A total of 1957 consecutive urine cytology specimens were reviewed. Majority of the cases were negative for tumour (67.19%). The most common diagnostic category was acute inflammatory case (17.3%) while inconclusive cases constituted 11.39% of total. There were 23 (1.18%) positive cases that were diagnosed malignant on urine cytology. These 23 malignant cases were followed histologically and 22 (95.6%) cases turned out to be malignant. Conclusion: Urine cytological examination is an efficient tool that has a good diagnostic yield in detecting malignant urothelial lesions. It should be used routinely for diagnosing, screening and for follow-up of all malignant urothelial lesions.
Keywords: Urine cytology, urothelial neoplasm.
INTRODUCTION
The urinary tract is lined by transitional epithelium and historically this epithelium was so named by Friedrich Henle, a 19th century German pathologist, because he thought that the urinary epithelium was ‘transitional’ between squamous and glandular1,2. It is now recognized as a specific type in its own right. Therefore, it is also called as ‘urothelium’. However, it is interesting that some tumours of the transitional epithelium do indeed express the ability to differentiate along squamous or glandular lines and that patches of squamous and glandular mucosa are commonly interspersed in benign transitional epithelium. Urine cytology is useful in diagnosing diseases that involve this mucosal surface and the urinary collecting system lined by transitional epithelium. There are three basic types of exfoliated urinary tract specimens: (1) voided urine, (2) catheterized urine, and (3) brushing/washing specimens. These specimens should be processed immediately or refrigerated and processed as soon as possible. If a delay is anticipated, immediate fixation with 50% ethanol may preserve the specimen for several days. In the cytology laboratory the ‘urinary fluid’ is treated as other body fluids and is centrifuged. The processed specimen is used to prepare smears.
Cytologic examination of a urine specimen is a simple, safe, and inexpensive method that may uncover a hidden urothelial cancer1,2. Tumours of the urinary tract are relatively inaccessible to direct biopsy, and the tumours are often multifocal. Since the entire mucosal surface, including the farthest reaches of the urinary tract, is bathed in this easily obtained fluid, in theory, urine is the perfect specimen to examine for evidence of tumour. The well known indications for urine cytology examination are 1: for tumour detection and diagnosis of aggressive neoplasms or their follow-up, carcinoma in situ, small or inaccessible lesion as in ureters, pelvis, diverticuli etc.; 2: for screening of high-risk asymptomatic patients, as with industrial chemical or metal exposure, those with schistosomiasis or smokers etc.; 3: monitor tumours and therapy, for example low-grade non-invasive tumours, carcinoma in-situ2. Cytology may become positive long before the cystoscopy or biopsy. But lesions cannot be anatomically localized with urine cytology alone.
This study is an attempt to review the practice of urine cytology examination in our setting of community hospital. The importance of urine cytology as a simple, safe, and inexpensive method for diagnosing and screening malignant lesions is also discussed.
MATERIAL AND METHODS
Our study sample consisted of 1957 consecutive urine cytology specimens examined at Department of Pathology at St. John Hospital and Medical Centre, Detroit. Cases during the time frame of one year from August 2001 to September 2002 were retrieved from laboratory archives. The cytological diagnosis were grouped in four categories according to WHO/ISUP (International Society of Uropathology 99)3; 1: negative, benign or reactive cases; 2: cases showing acute inflammatory changes; 3: inconclusive cases and 4: malignant cases. Only the positive malignant cases were followed with histological biopsy to determine the accuracy and efficiency of urine cytological examination for positive cases.
RESULTS
Majority of the cases were negative for tumour (67.19%). There were 35 cases (1.7%) that showed presence of RBCs, which could point to many lesions in the urinary tract. Twenty cases (1%) showed reactive urothelial cells only. The most common diagnostic category was acute inflammatory case (17.3%). Majority of the inflammatory cases showed acute inflammation with some reactive degenerated cells due to inflammation. Thirty-six cases showed candida hyphae with acute inflammation suggesting candida infection on cytology examination. Three cases showed trichomonas, 10 cases showed polyomavirus changes and 27 cases showed crystals with acute inflammation. Inconclusive cases constituted 11.39% of total. Majority of the cases were reported as atypical cells with significance unknown.
There were 23 (1.18%) positive cases that were diagnosed malignant on urine cytology. These 23 malignant cases were compared with histological biopsy and 22 (95.6% true-positive) cases turned out to be malignant and 1 case (false-positive) showed polyomavirus change on biopsy. Tables 1 to 4 summarize the four cytological categories with their age and gender distribution.
Table-1: Summary of benign urine cytological lesions with their gender and age distribution.
|
Cytological Diagnosis |
Sex |
Total |
Age Range |
Total |
% of Total |
||||
|
Male |
Female |
1-39 |
40-59 |
60-89 |
>90 |
||||
|
Benign |
|||||||||
|
No evidence of tumour |
870 |
445 |
1315 |
139 |
492 |
675 |
9 |
1315 |
67.19 |
|
Blood in specimen |
31 |
4 |
35 |
1 |
8 |
25 |
1 |
35 |
1.79 |
|
Reactive urothelial cells presents |
18 |
2 |
20 |
— |
5 |
15 |
— |
20 |
1.02 |
|
Spermatozoa present |
1 |
— |
1 |
— |
— |
1 |
— |
1 |
0.05 |
|
Subtotal Benign |
920 |
451 |
1371 |
140 |
505 |
716 |
10 |
1371 |
70.06 |
Table-2: Summary of inflammatory urine cytological lesions with their gender and age distribution.
|
Cytological Diagnosis |
Sex |
Total |
Age Range |
Total |
% of Total |
||||
|
Male |
Female |
1-39 |
40-59 |
60-89 |
>90 |
||||
|
Acute inflammation |
109 |
60 |
169 |
7 |
43 |
113 |
6 |
169 |
8.64 |
|
Acute inflammation with reactive degenerated cells with bacteria |
43 |
28 |
71 |
1 |
14 |
46 |
10 |
71 |
3.63 |
|
Acute inflammation with bacteria |
13 |
11 |
24 |
3 |
7 |
14 |
— |
24 |
1.23 |
|
Acute inflammation with bacteria and candida |
3 |
2 |
5 |
— |
2 |
3 |
— |
5 |
0.26 |
|
Acute inflammation with candida |
16 |
15 |
31 |
4 |
14 |
13 |
— |
31 |
1.58 |
|
Acute inflammation with trichomonas |
1 |
2 |
3 |
2 |
1 |
— |
— |
3 |
0.15 |
|
Atypical cells of Polyomavirus |
7 |
3 |
10 |
|
3 |
7 |
— |
10 |
0.51 |
|
Acute inflammation with Crystals |
19 |
8 |
27 |
2 |
11 |
13 |
1 |
27 |
1.38 |
|
Subtotal Inflammation |
211 |
129 |
340 |
19 |
95 |
209 |
17 |
340 |
17.37 |
Table-3: Summary of inconclusive urine cytological lesions with their gender and age distribution.
|
Cytological Diagnosis |
Sex |
Total |
Age Range |
Total |
% of Total |
||||
|
Male |
Female |
1-39 |
40-59 |
60-89 |
>90 |
||||
|
Atypical cells favour reactive Inflammation |
27 |
11 |
38 |
1 |
7 |
30 |
— |
38 |
1.94 |
|
Atypical suspicious papillary low grade Carcinoma |
7 |
5 |
12 |
1 |
4 |
7 |
— |
12 |
0.61 |
|
Instrument reactive vs. low grade |
20 |
3 |
23 |
3 |
4 |
16 |
— |
23 |
1.18 |
|
Atypical squamous cells |
3 |
3 |
6 |
1 |
3 |
2 |
— |
6 |
0.31 |
|
Atypical significance unknown |
97 |
12 |
109 |
4 |
20 |
83 |
2 |
109 |
5.57 |
|
Atypical cells suspicious for Carcinoma |
29 |
6 |
35 |
1 |
6 |
28 |
— |
35 |
1.79 |
|
Subtotal Inconclusive |
183 |
40 |
223 |
11 |
44 |
166 |
2 |
223 |
11.39 |
Table-4: Summary of malignant urine cytological lesions with their gender and age distribution.
|
Cytological Diagnosis |
Sex |
Total |
Age Range |
Total |
% of Total |
||||
|
Male |
Female |
1-39 |
40-59 |
60-89 |
>90 |
||||
|
Malignant cells Present |
1 |
— |
1 |
— |
1 |
— |
— |
1 |
0.05 |
|
High grade urothelial Carcinoma |
20 |
2 |
22 |
— |
2 |
19 |
1 |
22 |
1.12 |
|
Subtotal Malignant |
21 |
2 |
23 |
0 |
3 |
19 |
1 |
23 |
1.18 |
|
Total |
1335 |
622 |
1957 |
170 |
647 |
1110 |
30 |
1957 |
100.00 |
DISCUSSION
Urine cytology is primarily used for diagnosis of symptomatic patients, detection of cancer in high-risk patients (e.g., those exposed to industrial chemicals and metals, cigarette smokers, and those with schistosomiasis), and follow-up of patients with history of urinary tract neoplasia. It complements, but does not replace, cystoscopy and biopsy. However, lesions may be detected cytologically before they can be seen cystoscopically. Urinary cytologic examination is capable of detecting small or hidden lesions (e.g. in diverticuli, ureters, renal pelvis, prostatic ducts, residual urethras). Unfortunately, however, the lesions cannot be localized by cytologic study of urine.
Urinary cytology can detect most aggressive neoplasms and carcinoma in situ4. Patients with low-grade noninvasive tumours can be followed up cytologically5. Patients with negative cytologic findings have a very low risk of recurrence, while high-grade cytologic abnormalities predict an aggressive tumour course6. Urine cytology is also a better indicator of the presence of concomitant urothelial atypia than pre-selected mucosal biopsies7.
Clinical history is important in proper evaluation of the specimen and should include previous diagnoses, therapy, and surgery; previous instrumentation (including catheterization); history of stones; method of specimen collection; cystoscopic findings; and any other pertinent clinical data. The most common symptoms of patients with bladder cancer are haematuria (gross or microscopic) or cystitis-like symptoms (frequency, urgency, pain).
Unfortunately, the diagnosis of urinary tract specimens is less perfect even among experts8-14. A review of 17 published series showed that at their worst, the false-negative rates were more than 50% for primary bladder cancer and averaged nearly 75% for papillomas15. An important diagnostic principle is that the higher the grade of the tumour, the more accurate the diagnosis16-19. In our case series, accuracy was almost 95% for high-grade malignant lesions. Urine cytology is however, not reliable in detection of renal cell or prostatic carcinoma.
As the incidence of urothelial carcinoma increases, so too does the demand for urine cytology. Accuracy of diagnosis is always important, but conservative management of bladder cancer depends on accurate cytodiagnosis. Clinical history is imperative for the reduction of misdiagnoses16,20.
There are several reasons for diagnostic inaccuracy. Urine is an inhospitable environment for cells; consequently degenerative changes that make diagnosis difficult are common10. Reactive changes caused by stones, inflammation, infection, therapy among many others, as well as ‘papillary clusters’, are responsible for most false diagnoses1,8,21-24. In addition, transitional cells can normally show marked variation in size and shape, can be multinucleated and polyploid, and can frequently exhibit nuclear and cytoplasmic degenerative changes that can mimic malignancy. The paradox of urine cytology is that pleomorphic cells with enlarged hyperchromatic nuclei containing prominent nucleoli can be benign while cancer can be composed of nearly normal-appearing monomorphic cells with bland nuclei. The most difficult types of urinary specimens to interpret are those from the upper urinary tract (ureters and renal pelvis)10.
False-positive diagnoses are higher in urinary cytologic specimens than in most other cytodiagnostic specimens. However, they are of less consequence because a positive cytologic diagnosis of bladder cancer should not lead directly to radical therapy10. A positive urine cytologic diagnosis should always be confirmed histologically before definitive therapy is instituted. False-positive diagnoses are commonly seen in cases involving stones, chemotherapy, radiation, viruses, reactive or degenerative changes, benign prostatic hyperplasia, prostatitis, and pseudopapillary clusters. In our series we found only one false-positive case (4.4%) that showed cellular atypia on urine cytology and was proved to be polyomavirus change on biopsy.
False-negative diagnosis may be of more clinical consequence. Unfortunately, false-negative findings are also common in urine cytologic specimens. Cytologic diagnosis of papillomas and well-differentiated papillary transitional cell carcinoma (TCC) can be difficult or impossible because the cells are nearly normal appearing10. Also, cytologic examination of urine specimens is not very good for evaluation of primary tumours of the kidney or prostate, which exfoliate cells late or not at all.
A variety of newer diagnostic techniques, including flow cytometry1,12,13, image analysis/ quantitative cytology1, cytogenetics, immunology (e.g. blood group isoantigens and monoclonal antibodies to a variety of tumour-associated antigens)1, and molecular biology have been studied in an effort to increase diagnostic accuracy. However, at least for the moment, urinary cytopathologic examination remains one of the most clinically useful means of diagnosing urothelial cancer and predicting its biologic behaviour.
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Address of Correspondence:
Ibrahim Mansoor, 21441 Sloan Drive # 104B, Harper Woods, MI 48225, USA. Fax: 1-847-664-7257
Email: Ibrahim.Mansoor@stjohn.org