Neoplastic Conditions

Benign tumours: inverted urothelial papilloma, villous adenoma, paraganglioma, leiomyoma, haemangioma and granular cell tumour of the bladder are occasionally encountered. Benign urothelial papilloma is a rarely-made diagnosis.

Urothelial dysplasia/carcinoma: many carcinogenic agents are known to predispose to urothe-lial malignancy. These include cigarette smoke, industrial aniline dyes (aromatic amines), petrochemicals, cyclophosphamide and the analgesic phenacetin. Most invasive tumours are associated with urothelial dysplasia or flat carcinoma in situ.

Urothelial carcinoma in situ: occurs rarely in the absence of invasive tumour, when it can closely mimic interstitial cystitis both clinically and cystoscopically, presenting with irritative bladder symptoms and appearing as multifocal red, velvety patches. More often seen in association with prior or synchronous invasive malignancy which can be multifocal. Diagnosis is made by urine cytology and bladder biopsy, which shows severe (often, but not necessarily, full-thickness) dysplasia of the surface urothelium. Papillary architecture is lacking. Lesser grades of atypia may merit the term urothelial dysplasia. Careful distinction should be made from "superficial carcinoma", which is used by urologists to describe tumours that have not invaded into the muscularis propria, regardless of histological type and grade. Carcinoma in situ is usually treated with intravesical chemotherapy (e.g., mitomycin) or immunotherapy (BCG vaccine), although localised disease may be controlled by transurethral resection (TURB). Radical surgery is indicated for widespread field change in the urothelium, which may involve the bladder, ureters, urethra, prostatic ducts and seminal vesicles. Careful follow-up with urine cytology and biopsy is advocated following conservative management to monitor recurrence or progression (up to 80% at five years). Particularly on cytological material, recurrent disease may be difficult to distinguish from reactive atypia due to treatment.

Urothelial carcinoma: urothelial (or transitional cell) carcinoma (TCC) accounts for over 90% of primary bladder tumours, most commonly presenting in elderly males as a cystoscopic mass showing an exophytic or endophytic growth pattern. Diagnosis is confirmed by biopsy which commonly shows a papillary or solid growth pattern. Urine cytology is of limited value in the initial evaluation of bladder tumours and is more useful in industrial screening and follow-up after treatment. Note that non-invasive papillary TCC (> 7 cell layers thick, stage pTa) is also classified as carcinoma to avoid confusion with flat carcinoma in situ (stage pTis). Pathological staging is extremely important for prognostic and treatment purposes and is determined by the extent of local tumour spread. Assessment of small bladder biopsies is crucial and they must be carefully examined. Specifically, the ill-defined muscularis mucosae must be distinguished from the muscularis propria, infiltration of which defines true deep or muscle-invasive urothelial carcinoma (stage pT2). In bladder biopsy material, distinction is not made between invasion of the inner (superficial, pT2a) and outer (deep, pT2b) muscularis propria due to problems of orientation (reported as "at least" stage pT2a). Biopsies should also be examined closely for coexistent carcinoma in situ. Separate biopsies may be submitted to assess prostatic involvement. There is a correlation between tumour stage and grade, based on the degree of nuclear atypia, in that more poorly differentiated tumours (WHO grade III) show a much higher rate of concurrent or subsequent muscle invasion. High-grade tumours commonly show focal squamous or glandular differentiation.

Non-muscle invasive papillary urothelial carcinoma (stages pTa and pT1) is treated primarily by transurethral resection, with adjuvant intravesical therapy for higher-risk or recurrent disease. Muscle-invasive tumours (and sometimes grade III, pT1 tumours) are treated surgically, usually by total cystectomy or cystoprostatectomy and pelvic lymphadenectomy, with or without adjuvant chemotherapy depending on pathological assessment of the resection specimen. Partial cystectomy is reserved for solitary tumours with no previous history of bladder tumours and no carcinoma in situ, bladder neck or trigone involvement. Radiotherapy as a treatment modality alone is not as effective as surgery and is more commonly administered in a palliative setting, with or without chemotherapy, in advanced, unresectable bladder cancer.

Prognosis: multifocality, tumour size, histological grade, depth of invasion, coexistent urothelial dysplasia/carcinoma in situ and cystoscopic appearance at three-month follow-up are the best predictors of recurrence or progression. Involvement of the prostatic stroma is an adverse prognostic sign. Prostatic urethra involvement is associated with a high rate of urethral recurrence. Overall prognosis depends largely on stage, with a 70% five-year survival rate for stages pTa and pT1 and 50% for pT2b. Within the pT1 group, grade III decreases the five-year survival to 60%.

Variants of urothelial carcinoma are: nested (mimics benign von Brunn's nests - look for deep invasion and cytological atypia); microcystic (cysts or tubules containing proteinaceous debris); inverted (architecturally like inverted papilloma but with marked atypia); also giant cell, clear cell, lymphoepithelioma-like and micropapillary variants.

Squamous cell carcinoma: accounts for less than 5% of bladder tumours in the UK. Chronic irritation from stones, long-term indwelling catheters, diverticula, chronic urinary infections and, in particular schistosomiasis predispose, hence a much higher incidence of bladder squamous cell carcinoma in countries where the latter is endemic e.g., Egypt. High-grade urothelial carcinoma showing squamous differentiation (look for urothelial carcinoma in situ) and secondary involvement by primary cervical carcinoma should be excluded. Disease is often of advanced stage at presentation and prognosis therefore poor (overall five-year survival 15%).

Adenocarcinoma: constitutes 2% of bladder malignancies; may arise from metaplastic epithelium (cystitis glandularis) following chronic inflammation (60%) or in bladders with exstrophy, diverticula or urachal remnants (occur at the dome and usually lack a bladder mucosal component). Mucinous, clear cell, enteric and signet ring cell types exist. Overall five-year survival is poor (30%).

Other cancers: spindle cell carcinoma, small cell carcinoma, malignant melanoma, leukaemia/ malignant lymphoma, leiomyosarcoma, rhabdomyosarcoma, choriocarcinoma, yolk sac tumour and metastases (direct spread - prostate, cervix, uterus, rectum; distant spread - breast, malignant melanoma, lung, stomach).

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