Background: Pathological diagnosis of urothelial carcinoma (UC) is primarily based on cytological atypia. It has\npreviously been shown that high-grade (HG) UC, particularly UC in situ cells (CIS), can be over five times the size of\na lymphocyte. However, this has not been demonstrated in comparison to reactive urothelium. The objective of\nthis study was to empirically compare the difference in nuclear size of UC cells with reactive urothelial cells.\nMethods: Using CellSens imaging software, we measured urothelial nuclear length (l) and width (w) on digital\nimages of H&E sections. The area (a) of a nucleus was calculated based on the oval shape of most urothelial cells.\nLymphocytes were measured to calculate normalized urothelial linear and area ratios.\nResults: A total of 1085 urothelial cell nuclei from 60 cases were measured from reactive urothelium, low grade\n(LG) UC, HG UC and CIS. CIS nuclei were found to have an a 2.75 times larger than reactive nuclei (p < 0.001). A\nnuclear size cut-off of 11 um for l and 7 um for w was found to be sensitive [98.09 % (95 % CI: 95.60ââ?¬â??99.38 %) and\n89.31 % (95 % CI: 83.6ââ?¬â??91.82 %) for l and w, respectively] and specific [92.60 % (95 % CI: 87.13ââ?¬â??95.82 %) and 85.71 %\n(95 % CI: 79.49ââ?¬â??90.63 %) for l and w, respectively] for distinguishing CIS from reactive atypia.\nConclusions: Nuclear morphometry can be used to differentiate CIS from reactive atypia. A l over 11 um and a w\nover 7 um and is highly sensitive and specific for CIS compared to reactive urothelium. This difference in nuclear\nsize may be used as a tool for differentiating the flat urothelial lesions from reactive urothelium in daily practice.
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