Urothelial Tumours of the Urinary Bladder : A Histopathological Study of Cystoscopic Biopsies

Introduction: Bladder tumours constitute one of the most common urological conditions. Urothelial (transitional cell) carcinoma accounts for 90% of all primary tumours of the bladder. These tumours are an important cause of morbidity and mortality. The objective of this study was to present the histopathological patterns of urothelial tumours and to determine the grade and stage of these tumours. Methods: This is a 3 year descriptive study of urothelial tumours carried out in the Department of Pathology, Patan Academy of Health Sciences (PAHS), Lalitpur, Nepal. Data of all cystoscopic biopsies collected during this period were analyzed. Results: Of the 83 urinary bladder tumours, 81 (97.59%) cases were urothelial (transitional cell) tumours. Transitional cell carcinoma (TCC) was the most common bladder tumour which was seen in 67 (80.72%) cases. Thirty two (47.76%) cases of TCC were low grade while 35 (52.24%) were high grade. Forty three (64.18%) cases of TCC were superficial or in early stage (pTa and pT1) while 24 (35.82%) showed muscle invasion. Conclusions: Transitional cell carcinoma was the most common bladder cancer. Most of these tumours were high grade. A large percentage of high grade carcinomas presented with muscle invasion. Pathological grade and muscle invasion are the most valuable prognostic predictors of survival. The importance of including smooth muscle in the biopsy specimens needs to be emphasized. _______________________________________________________________________________________


INTRODUCTION
Bladder tumours constitute one of the most common urological conditions. 1 The prevalence of these tumours is higher in developed countries as compared to developing countries. 2In the United States alone, an estimated 70,980 new cases were diagnosed with an estimated 14,330 deaths in 2009. 1 They are an important cause of both morbidity and mortality. 3In more than 75% of the patients, the most common sign is gross and microscopic haematuria. 4rothelial (transitional cell) tumours represent about 90% of all bladder tumours and run the gamut from small, benign lesions that might never recur to aggressive cancers associated with high risk of death. 5t affects men more often than women (3 to 4:1). 3,6bout 80% of patients are between the ages of 50 and 80 years. 3About 90% of bladder carcinoma reported from the West is of transitional cell type. 7In a large series reported from Egypt, squamous cell carcinoma (SCC) accounted for 59-73% of bilharzial bladder cases. 8portant risk factors that have been implicated in the causation of bladder cancer include cigarette smoking, industrial exposure to arylamines, Schistosomahaematobium, long term use of analgesics, heavy long term exposure to cycophosphamides and prior exposure of the bladder to radiation. 3

METHODS
This is a descriptive study carried out in the Department of Pathology, Patan Academy of Health Sciences (PAHS), Lalitpur, Nepal, over a period of 3 years from April 2010 to March 2013.Data of all cystoscopic biopsies done during this period were collected and analyzed using SPSS version 17.0.
The World Health Organization (WHO)/International Society of Urological Pathology (ISUP) classification (2004) was used to grade the tumours into: urothelial papilloma, papillary urothelial neoplasm of low malignant potential (PUNLMP), low and high grade urothelial (transitional cell) carcinomas (TCC). 9Pathological staging of the urothelial cancers was done according to the TNM system and data recorded as pTa: tumour limited to mucosa, pT1: invasion of lamina propria and pT2 as invasion of muscle. 9
Transitional cell carcinoma (TCC) was the most common bladder tumour which was seen in 67 (80.72%) cases.Of these, 32 (47.76%) were low grade TCC while 35 (52.24%) were high grade TCC.A case each of an adenocarcinoma and a small cell carcinoma were also seen (Table 2).The median age at presentation of bladder tumours was 65 years (range: 16-88 years) and its peak incidence was between 61-70 years.Sixty eight (81.93%)cases of bladder tumours were seen in males while 15 (18.07%) were seen in females.Male to female ratio was 4.5:1 (Table 3).The WHO (2004)/ISUP classification of urothelial bladder tumours was used to grade the tumours (Table 4).Staging of TCC was done according to the TNM classification.Out of the 67 cases of TCC, 43 (64.18%) were superficial /or in the early stage (pTa and pT1) and 24 (35.82%) were muscle invasive (pT2).
The detrusor muscle was absent in 16 (23.88%)cases of TCC.Hence, muscle invasion could only be assessed in the remaining 51 (76.12%) cases.Four (16%) cases of low grade and 20 (76.92%) cases of high grade TCC showed muscle invasion (Table 5).

DISCUSSION
Neoplasms of the bladder are one of the commonest urological conditions.They are a heterogenous group of tumours with different subtypes and behavioural patterns. 10In the world literature, about 95% of bladder tumours are of epithelial origin, the remainder being mesenchymaltumours.Most epithelial tumours are composed of urothelial (transitional) type cells (90%) and are thus interchangeably called urothelial (transitional cell) tumours, but squamous and glandular carcinomas also occur. 3adder cancer is the 7 th most common cancer worldwide, with an estimated 260,000 new cases occurring each year in men and 76,000. 11It is considerably more common in males than in females (ratio worldwide is 3 to 4:1). 3,6stoscopic biopsies of 107 patients included in this study revealed a spectrum of different pathological lesions.Bladder tumours were the most common type of lesion and was seen in 83 (77.57%) cases, followed by 21 (19.63%)cases of inflammation.All 83 cases of bladder tumours were of epithelial origin, of which 81 (97.59%) were urothelial (transitional cell) tumours.
Transitional cell carcinoma (TCC) was the most common bladder neoplasm in our study and was diagnosed in 67 (80.72%) cases.Similar data (81.81%) was published by Mahesh et al. from India. 2 In the western literature, these tumours account for 90% of bladder cancers. 7Small cell carcinoma and adenocarcinoma are uncommon tumours of the bladder and account for about 0.5 and 2% of all bladder cancers, respectively. 12,13In our study, 1 (1.45%) case each of small cell carcinoma and an adenocarcinoma were seen.
The demographic characteristics of the patients in the current study were relatively similar to a number of previous studies which describe a peak incidence of bladder cancer in the seventh decade and predominance in men with male to female ratio of 4.5:1. 10,14,157][18][19] A higher incidence of bladder cancers in males than in females is probably related to difference in smoking habits and occupational exposure. 3,17 our study, WHO (2004)/ISUP grading of urothelial tumours reveal a higher incidence of high grade TCC compared to low grade TCC.High grade TCC was seen in 35 (43.21%) cases while 32 (39.51%) cases were low grade TCC.This may be due to late presentation of the patient.Mahesh et al. 2 also observed higher incidence of high grade TCC (53.57%) compared to low grade TCC (42.85%).However, a higher incidence of low grade TCC was revealed in studies by Laishramet al. 16 and Ahmed et al. 20 (53.85% and 44%, respectively) compared to high grade TCC (26.41% and 29.5%, respectively).
Transitional cell carcinoma (TCC) was diagnosed in 67 cases in this study.Of these, 43 (64.18%) were superficial /or in the early stage (pTa and pT1) while 24 (35.82%) were muscle invasive (pT2).In studies by Gupta et al 17 and Laishram et al 16 muscle invasion was seen in 26% and 30.77%, respectively.
Tumour grading and staging are currently the two major factors for recurrence, progression and for determination of treatment options for patients with bladder carcinoma. 18In our study, the detrusor muscle was absent in the 16 (23.88%)cases of TCC.Hence, muscle invasion could only be assessed in the remaining 51 (76.12%) cases.Of the 51 cases of TCC, muscle invasion was seen in 4 (16%) cases of low grade and 20 (6.92%) cases of high grade TCC.Similar observation was also made by Laishram et al. (18% and 75%, respectively). 16Not including muscle layer in the cystoscopic biopsy specimens may lead to understaging of tumours in many patients.The importance of including smooth muscle in the biopsy specimens needs to be emphasized. 16

CONCLUSIONS
In our study, bladder tumours were the commonest lesions seen in cystoscopic biopsies, most of which were of urothelial origin.Transitional cell carcinoma was the most common bladder tumour in our study.Most of these tumours were high grade.A large percentage of high grade transitional cell carcinomas presented with muscle invasion.Pathological grade and muscle invasion are the most valuable prognostic predictors of survival.The importance of including smooth muscle in the biopsy specimens needs to be emphasized.