The plexiform lesions of severe pulmonary hypertension (PH) are complex vascular structures composed primarily of endothelial cells. In this study, we use immunohistochemical markers to identify the various cell layers of pulmonary vessels and to identify different endothelial cell phenotypes in pulmonary arteries affected by severe PH. Our computerized three-dimensional reconstructions of nine vessels in five patients with severe PH demonstrate that plexiform (n = 14) and concentric-obliterative (n = 6) lesions occur distal to branch points of small pulmonary arteries. And, whereas plexiform lesions occur as solitary lesions, concentric-obliterative lesions appear to be only associated with, and proximal to, plexiform structures. The endothelial cells of plexiform lesions express intensely and uniformly the vascular endothelial growth factor (VEGF) receptor KDR and segregate phenotypically into cyclin-kinase inhibitor p27/kip1-negative cells in the central core of the plexiform lesion and p27/kip1-positive cells in peripheral areas adjacent to incipient blood vessel formation. Using immunohistochemistry and three-dimensional reconstruction techniques, we show that plexiform lesions are dynamic vascular structures characterized by at least two endothelial cell phenotypes. Plexiform arteriopathy is not merely an end stage or postthrombotic change--it may represent one stage in an ongoing, angiogenic endothelial cell growth process.

Proper grading of the cribriform prostate cancer pattern has not previously been supported by outcome-based evidence. Among 153 men who underwent radical prostatectomy, 76 with prostate-specific antigen (PSA) failure (≥0.2 ng/mL [0.2 µg/L]) were matched to 77 without failure. Frequencies of high-grade patterns included fused small acini, 83.7%; papillary, 52.3%; large cribriform, 37.9%; small (≤12 lumens) cribriform, 17.0%; and individual cells, 22.9%. A cribriform pattern was present in 61% (46/76) of failures but 16% (12/77) of nonfailures (P < .0001). Multivariate analysis showed the cribriform pattern had the highest odds ratio for PSA failure, 5.89 (95% confidence interval, 2.53–13.70; P < .0001). The presence of both large and small cribriform patterns was significantly linked to failure. The cumulative odds ratio of failure per added square millimeter of cribriform pattern was 1.173 (P = .008), higher than for any other pattern. All 8 men with a cribriform area sum of 25 mm2 or more had failure (range, 33–930). Regrading cribriform cancer as Gleason 5 improved the grade association with failure, although half of all cases with individual cells also had a cribriform pattern, precluding a precise determination of the independent importance of the latter. The cribriform pattern has particularly adverse implications for outcome.

biopsies, depending on the size of the prostate. Clinically threatening cancers were defined as having volumes of ≥ 0.5 mL or Gleason sum ≥ 7. RESULTSMethod A detected significantly more carcinomas than method B in both the autopsy and prostatectomy specimens (autopsy, 72 vs 51; prostatectomy, 50 vs 32, both P < 0.001). Method A also detected more clinically threatening cancers found at autopsy (38/40 vs 31/40, P = 0.008). Among autopsy patients with negative sextant biopsies whose disease was localized to one side, method A detected 72% and method B detected 29-43% ( P < 0.001). CONCLUSIONSThe results of this computer simulation show that 5-and 10-mm grid biopsies detect threequarters and a third, respectively, at autopsy, of patients with the disease localized to one side of the prostate, which may be useful when planning highly selective ablative treatments in the future.

Background Extended transrectal ultrasound guided biopsies (TRUSB) of the prostate may not accurately convey true morphometric information and Gleason score (GS) of prostate cancer (PCa) and the clinical use of template-guided (5-mm grid) transperineal mapping biopsies (TPMBs) remains controversial. Methods We correlated the clinical-pathologic results of 1,403 TPMB cores obtained from 25 men diagnosed with PCa with 64 cancer lesions found in their corresponding radical prostatectomy (RP) specimens. Special computer models of three-dimensional, whole-mounted radical prostatectomy (3D-WMRP) specimens were generated and used as gold standard to determine tumor morphometric data. Between-sample rates of upgrade and downgrade (highest GS and a novel cumulative GS) and upstage and downstage (laterality) were determined. Lesions ≥ 0.5 cm3 or GS ≥ 7 were considered clinically significant. Results From 64 separate 3D-WMRP lesions, 25 had significant volume (mean 1.13 cm3) and 39 were insignificant (mean 0.09 cm3) (P < 0.0001); 18/64 lesions were missed by TPMB, but only one was clinically significant with GS-8 (0.02 cm3). When comparing the cumulative GS of TPMB versus RP, 72% (n = 18) had identical scores, 12% (n = 3) were upgraded, and only 16% (n = 4) were downgraded. Laterality of TPMB and RP was strongly correlated, 80% same laterality, 4% were up-staged, and 16% down-staged. Conclusions Our clinical-pathology correlation showed very high accuracy of TPMB with a 5-mm grid template to detect clinically significant PCa lesions as compared with 3D-WMRP, providing physicians and patients with a reliable assessment of grade and stage of disease and the opportunity to choose the most appropriate therapeutic options.