An objective morphologic parameter to aid in the diagnosis of flat urothelial carcinoma in situ.

The diagnosis of carcinoma in situ (CIS) lacks objective criteria and is subject to misdiagnosis. We identified 20 bladder biopsy cases each of CIS, urothelial dysplasia, and normal urothelium according to the 1998 World Health Organization/International Society of Urological Pathology consensus classification of urothelial neoplasms. Lymphocytes from 10 bladder biopsy specimens were chosen as reference cells. Using an image analysis system, we measured the following nuclear features: area, diameter, roundness, ellipticity, and optical density (maximum, minimum, mean, median, standard deviation, and quartiles). We measured a mean of 75 urothelial nuclei/case and a total of 500 lymphocytes. Roundness and ellipticity were not useful in distinguishing among the 3 groups. The best discriminators were mean nuclear area and mean nuclear area of the 25% largest nuclei (upper quartile) of urothelial cells compared with lymphocytes. The mean nuclear area relative to lymphocytes was 1.8 times (1.2 to 2.5 times) in normal urothelium, 2.4 times (1.6 to 3.0 times) in urothelial dysplasia, and 3.6 times (2.8 to 5.7 times) in CIS. The mean upper quartile nuclear area relative to lymphocytes was 2.2 times (1.4 to 2.8 times) in normal urothelium (P <.0001), 2.9 times (1.8 to 3.6 times) in urothelial dysplasia (P <.0001), and 4.9 times (4.0 to 7.6 times) in CIS (P <.0001). The difference in optical density was statistically significant between CIS and the other 2 histologic categories (P <.0001). Nuclear area is an easy and objective morphologic parameter for the evaluation of bladder biopsy specimens. Pathologists can assess the size of urothelial nuclei without using an image analysis system and compare them with the size of nuclei of lymphocytes, which are almost always present in a bladder biopsy specimen. Dysplasia, which is a somewhat ambiguous lesion, overlaps in its measurements with those of benign urothelium. The most useful morphologic parameter is the mean nuclear area of the 25% largest nuclei; CIS nuclei are approximately 5 times the size of lymphocytes, whereas normal urothelial nuclei are only 2 times the size of lymphocytes.

CD28-B7-mediated T cell costimulation in chronic cardiac allograft rejection: differential role of B7-1 in initiation versus progression of graft arteriosclerosis.

Provision of adequate T cell costimulation is critical for the development of acute and chronic allograft rejection. We have previously reported that early blockade of CD28-B7 T cell costimulation prevents the development of graft arteriosclerosis, in the LEW into F344 rat cardiac transplant model. In this study, we used the same model to examine the requirement for CD28-B7-mediated T cell costimulation in the progression of established chronic rejection and examined the individual roles of B7-1 (CD80) and B7-2 (CD86) costimulatory molecules. Late blockade of CD28-B7 T cell costimulation by the fusion protein CTLA4Ig, which binds both CD80 and CD86, attenuated the development of transplant arteriosclerosis, mononuclear cell infiltration, and parenchymal fibrosis in this model. Selective blockade of CD80 using the mutant fusion protein Y100F was as effective as CTLA4Ig in this regard. In contrast to CTLA4Ig, blockade of CD80 alone by Y100F was ineffective at preventing early graft loss and prolonging graft survival when given early after transplantation. This study is the first to demonstrate that late blockade of CD28-B7 T cell costimulation interrupts chronic cardiac allograft rejection, and it indicates the importance of continued T cell activation in this process. This study further defines functional differences between CD80 and CD86 costimulatory molecules in vivo.

Infarct of the prostate gland: experience on needle biopsy specimens.

Prostatic infarcts are uncommon and in the past have only been reported on transurethral resections of the prostate. We reviewed 13 consults and 2 nonconsult cases of needle biopsies showing prostatic infarcts from two institutions. The incidence of infarcts on biopsy were 2 in 2958 (0.07%) and 1 in 108,586 (0.0009%) in our nonconsult cases. Men averaged 71 years of age (range, 57-84 yrs). No relationship was seen with histories of hypertension, diabetes, atherosclerotic coronary vascular disease, recent surgery, and steroid use. Four of 12 men with available information had acute urinary retention, with markedly enlarged prostates in three (90 cc, 92 cc, 94 cc); two of these men had hematuria. An additional two men also had large glands (84 cc, 150 cc), one also with hematuria. Of eight men without acute urinary retention, three had sudden prostate-specific antigen (PSA) rises (increases of 199 ng/mL, 219 ng/mL, 287 ng/mL). Infarcts were usually an isolated focus on one core and varied from 1 mm to 11 mm (mean, 6.3 mm). Six cases showed earlier-aged infarcts with coagulative necrosis and recent hemorrhage and six showed intermediate-aged infarcts with reactive stroma and epithelium without necrosis. In the remaining three cases, there were remote infarcts characterized by replacement of the stroma by dense fibrosis with metaplastic glands. Adjacent tissue revealed reactive nests of immature squamous metaplasia in 14 of 15 cases with visible nucleoli (12 cases), squamous atypia (7 cases), and mitoses ranging from 1-10 (7 cases). Pathologists sent in 10 of 13 consult cases (77%) for problems with interpretation of the infarcts; remaining consults had other pathology of concern. One case was misdiagnosed as urothelial cancer. Features helpful in recognizing infarcts' benign nature were cyst formation containing cellular debris with or without neutrophils (73%), corpora amylacea (20%), and rings of collagen around squamous islands (40%). Infarcts are typically, although not exclusively, found in large prostates and may result in sudden rises in serum PSA. Infarcts' distinctive histology must be recognized and distinguished from necrosis resulting from infection and prior cryotherapy, as we have seen such misdiagnoses. Pathologists' awareness of prostatic infarcts on needle biopsy and their potential for atypical histology can prevent the misdiagnosis of cancer.