Stereological estimates of nuclear volume in the prognostic evaluation of primary flat carcinoma in situ of the urinary bladder

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Abstract
Primary, flat carcinoma in situ of the urinary bladder is rare and its behaviour is unpredictable. The aim of this retrospective study was to obtain base-line data and investigate the prognostic value of unbiased, stereological estimates of the volume-weighted mean nuclear volume, nuclear Vv, in 78 bladder biopsies from 22 patients with primary flat carcinoma in situ (Bergkvist grades III-IV). On average, nuclear Vv was 77 μm3 in nine biopsies with morphologically normal urothelium, 292 μm3 in 56 isolated primary lesions and 266 μm3 in lesions of luminal urothelium in 13 biopsies with co-existing invasive carcinoma. No recognizable developmental pattern of nuclear Vv in relation to the time course of disease was found. Nuclear volume in the first biopsy was of the same magnitude in lesions with and without co-existing invasive carcinoma (2P=0.55), and in lesions with short and long duration of invasion-free period (2P < 0.20). Nuclear Vv in the first biopsy did not differ between patients who survived and those who died from their primary flat carcinoma in situ (2P=0.07). Dividing the patients on the basis of the group median of the first biopsy showing flat carcinoma in situ (nuclear Vv= 261 μm3), the survival was the same in patients with nuclear Vv above and below the cut-off point (2P=0.16). However, the survival curves showed a tendency to differ in the first 2-8 years of observation. Stereological estimates of nuclear Vv provide objective, quantitative information, but their prognostic value in patients with primary flat carcinoma in situ of the bladder needs further clarification in larger data bases.