BLADDER LESIONS IN CYSTOSCOPIC BLADDER BIOPSIES-A CLINICOPATHOLOGICAL STUDY

Bladder Lesions In Cystoscopic Bladder Biopsies-a Clinicopathological Study


INTRODUCTION
The urothelium of the urinary bladder is considered to be lined by transi onal cells, which can transform into a variety of benign and malignant tumors. Diseases of the urinary bladder both non-neoplas c and neoplas c are quite common. Non-neoplas c diseases of the bladder cons tute 1 an important source of clinical signs and symptoms. They include hematuria, dysuria, frequency, urgency, nocturia and suprapubic pain. Usually, these disorders are more disabling leading to impairment in the quality of life and work performance. Some mes, they can mimic neoplas c lesions clinically leading to mismanagement. Neoplasms of bladder pose biologic and clinical challenges and are responsible for significant morbidity and mortality throughout the world. Since urothelial cancer is a cancer of the environment and age, the incidence and prevalence rates increase with age, peaking in the eighth decade of life, and there is a strong associa on between environmental 2 toxins and urothelial cancer evolu on. There is a geographic difference in bladder cancer incidence rates across the world, with the highest occurring in Southern and Eastern Europe, parts of Africa, the Middle East, and North America and the lowest occurring in Asia and underdeveloped areas 2,3 in Africa. An es mated 429,800 new cases of bladder 4 cancer and 165,100 deaths occurred in 2012 worldwide . There were 15,210 deaths recorded in 2013, including 10,820 men and 4390 women, and accounts for 3% of all 2,3,5 cancer deaths in United States Urothelial carcinoma is the most common tumor of the bladder, represen ng 90% of malignancies with this origin, 5% are squamous cell carcinomas, and less than 2% are adenocarcinoma or other variants. Urinary bladder cancer is the sixth most common cancer worldwide and the second most common malignancy of the genitourinary tract a er prostate cancer. Bladder neoplasms account for 6% and 2% of the cancer incidence in 1 men and women respec vely. Men are affected 3 to 4 mes more o en than women and about 80% of pa ents are between the age of 50 and 80 years. Hematuria is the most common presenta on, but they can also present clinically as lower urinary tract symptoms similar to non-neoplas c lesions delaying diagnosis and treatment. So, accurate diagnosis of urinary bladder lesion is important to deliver proper treatment mely. Significant progress has been evolved in the non-invasive imaging and the scien sts are con nuing effort to iden fy and characterize poten al markers or surrogate end points for bladder tumor. S ll clinical examina on, cystoscopic evalua on and histopathologic analysis of biopsy material are the mainstays 6 of bladder cancer diagnosis and treatment. Cystoscopy is the primary diagnos c tool for pa ents of bladder lesions. It provides informa on on appearance, number and loca on of bladder lesions and provides biopsy materials for histological evalua on for suspicious lesions. But, specimens obtained from cystoscopic biopsy is not sufficient for further characterizing neoplas c lesions in terms of depth of invasion and margin status. Transurethral resec on (TUR) of the bladder tumor is a therapeu c procedure that ensures the material necessary for histopathological diagnosis because it allows assessment of histological type and the degree of differen a on, depth of tumor invasion and other parameters which are useful in elabora on of diagnosis and subsequent treatment and 7 prognosis. In urinary bladder lesions, the clinical presenta on is quite variable, the nonneoplas c lesions can mimic neoplas c and vice-versa bothering both clinicians and pa ents. We are also facing the conflic ng scenario frequently in our ins tute, but no scien fic study has been done on it, ll date here. The present study focus on the clinico-pathological and histological features of various lesions of the urinary bladder in the specimens received through cystoscopic biopsy or transurethral resec on over a period of one year in a ter ary care hospital -BP Koirala Ins tute of Health Sciences, Dharan, Nepal.

OBJECTIVES
To study the clinico-pathological features of various bladder lesions and their frequencies with sub-typing i. e. neoplas c vs non-neoplas c. To correlate clinical diagnosis with histological diagnosis.

METHEDOLOGY
The study is descrip ve cross-sec onal involving pa ents with urinary bladder lesions requiring cystoscopic biopsy or transurethral resec on conducted in the Department

Figure 5: Frequency of non-neoplas c lesions
In pa ents with neoplas c lesions, more than half of them (    In pa ents with cys s, 3 had squamous metaplasia, 2 had eosinophilic cys s and 1 had tubercular cys s. The characteris c histology of non-neoplas c lesions is illustrated in the annexures. The correla on of clinical diagnosis with histological diagnosis was 73.3% and 100% for neoplas c and nonneoplas c lesions respec vely which differed significantly rejec ng our research hypothesis (p-value<0.001) [ Table 3]. Eight cases which were clinically diagnosed as neoplas c turned out non-neoplas c on histological diagnosis. They were cys s cys ca-2, inverted papilloma-2, tubercular cys s-1, chronic cys s-1 and eosinophilic cys s-1. The pa ents were persistently symptoma c with symptom dura on ranging from 3-6 months and cystoscopic evalua on revealed mass lesions suspicious for carcinoma.   9 invasive in their study ( Fig.10). In our study, 55% of cases were neoplas c with urothelial carcinoma cons tu ng 86.26%and 45% were nonneoplas c which is comparable with above studies. But, Shruthi and colleagues reported 68% neoplas c and 32% non-neoplas c lesions in their specimens. Majority of malignant lesions were of urothelial 6 origin. Similar was the result in the study of Shah et al who detected 65% neoplas c and 35% non-neoplas c lesions in the bladder biopsy specimens. Urothelial tumor was most common malignancy ( 82.6%) and Forae et al reported 68% of neoplas c and 32% non-neoplas c lesions in their 75 bladder lesions received with urothelial carcinoma 16,17 accoun ng 65%. This slight higher incidence of neoplas c lesions in these studies compare to our findings can be due to difference in geography and pa ent habits.  respec vely. Papillary urothelial carcinoma was the most common lesion in NMIBC (80%) of which 60% were low grade and 20% were high grade respec vely followed by PUNLMP (20%) in our study. Our results are compared with other available studies. PUNLMP in our study is slightly higher than other studies possibly due to low threshold for cystoscopic evalua on and biopsy in our ins tui on for suspected bladder lesions resul ng in early-stage diagnosis. In current study, among the non-neoplas c lesions, cys s was the most common (72.22%), followed by cys s cys ca (11.11%), inverted papilloma (11.11%) and simple cyst (5.55%). Out of which, 23.07% had squamous metaplasia, 15.38% were eosinophilic and 7.69% was tubercular. Srikousthubha et al reported cys s in 84% of their non-neoplas c lesions of which 71.40% were non specific, 14.28% tubercular and 4.76% eosinophilic. Here, squamous metaplasia was seen in 4% of 1 cases . Cases of cys s were characterized by thickened bladder wall on ultrasonography and congested mucosa on cystoscopy but specimens under microscopic examina on revealed normal urothelium and congested lamina propria with inflammatory infiltrates. Tuberculous cys s showed ulcera ons with the characteris c granuloma of epithelioid cells, his ocytes, Langhan's giant cells, casea on necrosis and lymphocytes. Eosinophilic cys s revealed intact mucosa with predominant eosinophilic infiltra on in lamina propria. It can occur in associa on with allergic diseases or bladder trauma in the se ng of catheteriza on. Squamous metaplasia was characterized histologically by non-kera nizing stra fied squamous epithelium and glycogen rich cells with clear cytoplasm. Cys s cys ca revealed solid invasion of surface epithelium into lamina propria with Von Brunn's nests some of which had cys c spaces lined by cuboidal epithelium. It is uncommon lesion occurring in the se ng of trauma, calculus or inflamma on. Two of our cases were inverted papilloma mimicking bladder cancer clinically. They show endophy c growth into lamina propria forming different sized epithelial nests and normal lining surface urothelium. They are uncommon lesions of urothelium accoun ng for 1.4%-2.2% and mimic 22 bladder cancer clinically. One of our cases in a 74-year-old lady presented with cys c lesion in anterior bladder wall which was confirmed to be simple cyst on histopathological examina on (Fig.11). Simple cyst of bladder is a rare finding and such cyst in anterior wall should be differen ated from urachal cyst which typically appears as midline echogenic swelling extending from umbilicus to dome of the urinary bladder in ultrasound and lined by pseudostra fied columnar epithelium compared to cuboidal epithelium of 23 simple cyst.
Original Research Ar cle

CONCLUSION
Urinary bladder is a common site of diverse lesions; both neoplas c and nonneoplas c with neoplas c lesions being more common. Urothelial carcinoma is the most common type of neoplas c lesion and cys s is the most common type of nonneoplas c lesion. Non-neoplas c lesions can mimic neoplas c lesions clinically. High index of suspicion and mely and correct diagnosis is required to guide proper treatment which can reduce both morbidity and mortality. Histological diagnosis differs significantly from the clinical diagnosis indica ng the importance of histological diagnosis in planning treatment. So, it is recommended and advised to have the histological diagnosis whenever applicable before star ng treatment of bladder lesions.

RECOMMENDATION
We further suggest to conduct similar studies with larger number of pa ents and for longer dura on to see the outcomes of pa ents with histological markers for poor outcome. We also suggest studies involving Re-TUR specimens in high grade and T1 tumors to look for stage migra on.

LIMITATIONS OF THE STUDY
Limited dura on of the study resulted in fewer number of pa ents in which we could not get CIS, variants of urothelial differen a on and radical cystectomy specimens. Availability of radical cystectomy specimen could provide further informa on on staging. We could not follow up of our pa ents with neoplas c lesions even one year post treatment to look for recurrence and progression. So we have limita ons to comment on the outcome of pa ents with poor prognos c markers due to short follow up dura on.