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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 20  |  Issue : 1  |  Page : 27-30

Role of urine cytology in bladder neoplasm – Cytopathological correlation and review of literature


1 Professor, Pathology and Oncopathology, INHS Asvini, Mumbai, Maharashtra, India
2 Associate Professor, Pathology and Oncopathology, INHS Asvini, Mumbai, Maharashtra, India
3 Associate Professor Anaesthesia, INHS Asvini, Mumbai, Maharashtra, India

Date of Web Publication9-Jul-2018

Correspondence Address:
Surg Cdr Kunal Tewari
INHS Asvini, Colaba, Mumbai - 400 005, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jmms.jmms_31_17

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  Abstract 

Background: Urinary bladder tumors are the second most common tumors affecting males. The aim of the study was to evaluate the various histopathological findings in various bladder tumors and their correlation with exfoliative urine cytology. Design: This is an observational study carried out over a period of 7 years at a tertiary care hospital between January 2010 and January 2017. Materials and Methods: Tumors were divided into invasive and noninvasive urothelial carcinoma and were further classified into high-grade or low-grade urothelial cancer. Urine cytology smears from all these patients were also were studied. Cytological findings were correlated with histopathological findings. Result showed that bladder tumors were commonly seen in males with average age of presentation being the sixth decade. The most common type of carcinoma seen was low-grade urothelial carcinoma-noninvasive type. Urine cytology was positive in 47.46% patients. Sample Size: In our study, 113 cystoscopic biopsies were included over a period of 7 years (85 males and 28 females). Conclusion: Accuracy of diagnosing malignancy in urine cytology varies, and it depends on the presence of diagnostic yield in the urine cytology, processing of the sample, and experience of the cytopathologist. Urine cytology should be reported in a background of detailed clinical information and should always be followed by histopathological examination.

Keywords: Invasive urothelial carcinoma, low-grade noninvasive urothelial carcinoma, urine cytology


How to cite this article:
Chawla N, Mehta R, Tewari K. Role of urine cytology in bladder neoplasm – Cytopathological correlation and review of literature. J Mar Med Soc 2018;20:27-30

How to cite this URL:
Chawla N, Mehta R, Tewari K. Role of urine cytology in bladder neoplasm – Cytopathological correlation and review of literature. J Mar Med Soc [serial online] 2018 [cited 2018 Dec 14];20:27-30. Available from: http://www.marinemedicalsociety.in/text.asp?2018/20/1/27/236250


  Introduction Top


Urothelial carcinoma of the bladder is the second most common carcinoma of the urinary tract after prostate carcinoma.[1] It is the sixth most common cancer. Urinary bladder tumor is commonly seen in males. It is thrice as common in males as in females and is usually seen in patients over 50 years of age.[2] Cigarette smoking is the most common etiological factor associated with urinary bladder tumors.[3] Other etiological factors associated with urothelial carcinomas are exposures to aryl amines, Schistosoma haematobium, and long-term use of analgesics.[4] The most common presenting complaint is the hematuria seen in 90% of the patients.[5] Most urothelial carcinomas are indolent in nature and hence carry good prognosis if detected and diagnosed early.

Approximately 70% of bladder tumors are superficially invasive or minimally invasive with approximately 50% of the patients showing recurrence on bladder biopsies.[6] Distant metastasis is commonly seen in the lung, bone, and lymph nodes.

Early diagnosis is the key for increasing the 5-year survival of these patients. Exfoliative urinary cytology is the simple, noninvasive, and cost-effective procedure for screening the patients with suspected urothelial malignancies as well as for monitoring known cases of urothelial carcinoma. Transurethral bladder biopsy is routinely done for histopathological diagnosis and for assessing the extent of the diseases. The aim of the present study is to review the cytological findings in exfoliative urine cytology and comparing it with histopathological findings in different urinary bladder lesions along with grade and type of bladder growth.


  Materials and Methods Top


The recent study was conducted at a tertiary care hospital in the department of pathology over a period of 7 years (January 2010 – January 2017) during which cystoscopic TURBT biopsies of 113 suspected patients (males/females) were studied. The clinical details, age, sex, and imaging details were obtained. Three consecutive urine samples were included in the study. Samples were centrifuged at 1000 rpm for 3 min and stained with MGG stain. Biopsies were fixed in 10% formal saline and hematoxylin and eosin staining was done. Lesions were classified according to the WHO classification of tumors of the urinary tract. All tumors were classified according to the histopathological examination, grade of the tumor, and depth of invasion. Cytology smears were divided into three categories based on the cellular morphology. The cytological findings were compared and correlated with histopathological findings.


  Results Top


In our study, there were 85 (75.2%) male and 28 (24.7%) were female [Table 1].
Table 1: Gender Distribution

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Age of the patients varied from 50 to 85 years with a maximum number of patients falling between 61 and 90 years. Out of 113 cases, 109 cases (96.4%) were above 60 years.

The most common presenting complaints were difficulty and burning in micturition seen in 62 patients (54.8%) and gross or microscopic hematuria seen in 51 patients (45.1%). A total of 110 patients were diagnosed as urothelial neoplasm (96.5%). Two cases were diagnosed as of primary adenocarcinoma of the urinary bladder and one patient as primary squamous cell carcinoma of the bladder. The most common histopathological diagnosis was noninvasive papillary urothelial carcinoma low grade, seen in cases 63 patients, followed by noninvasive urothelial carcinoma-high grade seen in 25 patients. Invasive urothelial carcinoma was seen in 21 patients. Papillary urothelial lesion of undetermined malignant potential was diagnosed in 1 patient [Table 2].
Table 2: Distribution of Histopathological Diagnosis

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Urine cytology was given as positive for malignant cells in 42 cases. In our study, malignancy was not recognized in 71 histologically confirmed cases. In three cases, atypical cells were given on cytology smears and further investigations were advised. In three patients whose urine cytology showed atypical cells, one turned out to be PUNLUMP and two patients were of low-grade urothelial carcinoma. Of the total of detected malignant urothelial lesions, 16 cases were of invasive urothelial neoplasm and 14 cases were of high-grade noninvasive urothelial neoplasm and 10 cases of low-grade noninvasive urothelial carcinoma [Table 3].
Table 3: Correlation of Cytological diagnosis with Histopathological Diagnosis

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  Discussion Top


Urinary bladder tumor is the sixth most common tumor diagnosed worldwide. It is the second most common tumor seen in males after prostate carcinoma. It is commonly seen in males in 6th and 7th decade. Cigarette smoking is the most important risk factor for urinary bladder tumors, accounting for approximately 50% of cases. Aromatic amines and aromatic hydrocarbons present in tobacco are excreted through the kidneys. Occupational exposure to chlorinated hydrocarbons is also associated with urinary bladder tumors. Occupational exposure occurs in industrial plants processing paint, dye, metal, and petroleum products. Genetic predisposition has been a known risk factor for bladder cancers. Other risk factors include exposure to ionizing radiation and schistosomiasis. Diagnosis of urothelial neoplasm is based on the clinical imaging findings, histopathological examination, and study of urine cytology. Urine cytology is a well-established and useful diagnostic as well as screening tool for urinary bladder tumors. However, sensitivity is more in high-grade urothelial tumors. The sensitivity and specificity of urine cytology in high-grade urothelial tumor is 90%.

In the present study, exfoliative urine cytology and cystoscopic biopsies of 113 patients with bladder growth were reviewed. Of these 75.2% were male and 24.7% were female. Male-to-female ratio was 3:1. This is in accordance with the earlier studies published.[7] Bladder cancer is more common in males due to various lifestyle-related risk factors such as smoking and occupational exposure. Despite being more in males, muscle-invasive bladder cancers are more common in females.[8] Urinary bladder tumors are commonly seen in 5th–7th decade of life .[2] In the present study, 109 cases (96.46%) cases were above 60 years. This is in correlation with other studies reported in the literature.[9] The most common presenting complaint in our study was dysuria and burning micturition seen in 62 patients (54.8%) and gross or microscopic hematuria was seen in 51 patients (45.1%). Urgency and frequency can be the other presenting symptoms in some patients.[9]

Histopathological examination was done in all 113 patients. A total of 110 patients were diagnosed as urothelial tumor in our study. This is in concordance with the other studies published in the literature. The most common histopathological diagnosis was noninvasive papillary urothelial carcinoma low grade, seen in cases in 63 patients followed by noninvasive high-grade urothelial carcinoma seen in 18 patients. Invasive urothelial carcinoma was seen in 21 patients. According to a study conducted by Swarnlata et al., the most common histological diagnosis was noninvasive papillary urothelial carcinoma, high grade seen in 29.1% patients followed by infiltrating urothelial carcinoma (22.6%) [Figure 1]. Noninvasive papillary urothelial carcinoma low grade was seen in 20.3%.[7] In our study, the most common histopathological diagnosis was noninvasive urothelial carcinoma low grade [Figure 2]. Two cases of adenocarcinoma urinary bladder and one case of squamous cell carcinoma were also identified which is in concordance with the other studies published in the literature. The most common site of involvement is lateral walls followed by posterior wall and trigone. In the present study, cystoscopic findings revealed posterolateral wall of the urinary bladder as the most common site in 67% of the cases.
Figure 1: Invasive urothelial carcinoma, (H and E, ×400)

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Figure 2: Low-grade noninvasive urothelial carcinoma, (H and E, ×200)

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Urine cytology was divided into three categories – benign, atypical, and positive for malignancy. Of 113 patients, urine cytology smears were reported as benign in 71 patients (53.9%) patients. In these patients, urine cytology smears showed benign urothelial cells, with maintained nuclear-cytoplasmic ratio. Three patients were reported as positive for atypical cells. The urine cytology smear from these atypical cytology showed cytological changes exceed those described as for benign cellular changes but does not qualify for malignancy. These changes can be seen in the presence of inflammation, bladder calculi, or following chemotherapy and bladder catheterization. However, in our study, one of the patients was a case of papillary urothelial carcinoma of undetermined significance and other two cases of low-grade noninvasive urothelial carcinoma Positive for malignancy was reported in 42 patients (37.1%). The cytological changes seen in malignancy were nuclear enlargement, high nucleocytoplasmic, hyperchromasia, and prominent nucleoli [Figure 3].
Figure 3: Leishman stain – urine cytology (×400) showing atypical urothelial cells with high nuclear–cytoplasmic ratio, hyperchromatic nuclei, and prominent nucleoli

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In our study, the urine cytology was not reported as malignant despite the tumor being reported as invasive high-grade urothelial carcinoma on histopathological examination. Accuracy of diagnosing malignancy by cytology is highly variable and depends on the presence of diagnostic yield, processing of the sample, and expertise of the cytopathologist. Diagnosis is all the more difficult in low-grade noninvasive carcinoma as the sensitivity of detection of malignant cells is very low.[10] Various problems encountered while reporting exfoliative urine cytology include scant cellularity and cellular degeneration before fixation. False positivity can be seen in patients with reactive changes secondary to infection, stone, previous instrumentation, and intravesical therapy. Urine cytology should always be reported in a background of detailed clinical information and followed by histopathological examination for urinary bladder tumor.


  Conclusion Top


To conclude urine cytology is a good tool for diagnosis as well as for follow up of patients of bladder cancers. Sensitivity of urine cytology is high in high grade neoplasm than in low grade bladder neoplasm. Cytological findings should always be correlated with imaging findings, histopathological findings and immunohistochemistry. Urine cytology is still valuble in bladder cancer diagnosis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Al-Samawi AS, Aulaqi SM. Urinary bladder cancer in Yemen. Oman Med J 2013;28:337-40.  Back to cited text no. 1
    
2.
Laishram RS, Kipgen P, Laishram S, Khuraijam S, Sharma DC. Urothelial tumors of the urinary bladder in Manipur: A histopathological perspective. Asian Pac J Cancer Prev 2012;13:2477-9.  Back to cited text no. 2
    
3.
Zeegers MP, Tan FE, Dorant E, van Den Brandt PA. The impact of characteristics of cigarette smoking on urinary tract cancer risk: A meta-analysis of epidemiologic studies. Cancer 2000;89:630-9.  Back to cited text no. 3
    
4.
Wynder EL, Goldsmith R. The epidemiology of bladder cancer: A second look. Cancer 1977;40:1246-68.  Back to cited text no. 4
    
5.
Ahmed Z, Muzaffer S, Khan M, Kayani N, Pervez S, Husseini AS, et al. Transitional cell carcinomas of the urinary bladder. A histopathological study. J Pak Med Assoc 2002;52:396-8.  Back to cited text no. 5
    
6.
Kumar UM, Yelikar BR. Spectrum of lesions in cystoscopic bladder biopsies – A histopathological study. Al Ameen J Med Sci 2012;5:132-6.  Back to cited text no. 6
    
7.
Ajmera S, Ajmera R. Histopathological study of urinary bladder tumors – A 10 year study. Int J Sci Res 2016;5:83-95.  Back to cited text no. 7
    
8.
Nicholson BD, McGrath JS, Hamilton W. Bladder cancer in women. BMJ 2014;348:g2171.  Back to cited text no. 8
    
9.
Jonathan I, Lotan TL. Pathological Basis of Disease – Robbins & Cotran: South Asia Edition. 9th ed., Vol. 2. Elsevier; 2014. p. 967-8.  Back to cited text no. 9
    
10.
Garbar C, Mascaux C, Wespes E. Is urinary tract cytology still useful for diagnosis of bladder carcinomas? A large series of 592 bladder washings using a five-category classification of different cytological diagnoses. Cytopathology 2007;18:79-83.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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