Background. Nested variant of urothelial carcinoma was added to the WHO’s classification in 2004. Aims. To review the literature on nested variant of urothelial carcinoma. Results. About 200 cases of the tumour have been reported so far and it has the ensuing morphological features: large numbers of small confluent irregular nests of bland-appearing, closely packed, haphazardly arranged, and poorly defined urothelial cells infiltrating the lamina propria and the muscularis propria. The tumour has a bland histomorphologic appearance, has an aggressive biological behaviour, and has at times been misdiagnosed as a benign lesion which had led to a significant delay in the establishment of the correct diagnosis and contributing to the advanced stage of the disease. Immunohistochemically, the tumour shares some characteristic features with high-risk conventional urothelial carcinomas such as high proliferation index and loss of p27 expression. However, p53, bcl-2, or EGF-r immunoreactivity is not frequently seen. The tumour must be differentiated from a number of proliferative lesions of the urothelium. Conclusions. Correct and early diagnosis of this tumour is essential to provide early curative treatment to avoid diagnosis at an advanced stage. A multicentre trial is required to identify treatment options that would improve the outcome of this tumour. 1. Introduction Carcinoma of the urinary bladder is the most common malignancy involving the urinary tract system. Urothelial carcinomas can also occur in the renal pelvis, ureter, or urethra but their occurrence is far less common than in the urinary bladder. The histology of urothelial carcinoma is variable. On the whole about 70% of urothelial carcinomas of the urinary bladder are noninvasive or superficially invasive and these tumours are usually papillary and exhibit different degrees of differentiation; on the other hand, most muscle-invasive urothelial carcinomas are nonpapillary and usually exhibit high-grade cytomorphology. These types of classic urothelial carcinomas can be easily diagnosed histologically and they do not pose a problem to the pathologist. A number of systems have been utilized to grade and classify urinary bladder tumours. In 1972, the World Health Organization (WHO) adopted a system which distinguished papillomas from grades I, II, and III papillary transitional cell carcinomas. Subsequently in 1998, The World Health Organization in a collaborative effort conjointly with the International Society of Urological Pathologists (ISUP) published a consensus opinion classification system
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