PATHOLOGY

Multiple measures of carcinoma extent versus perineural invasion in prostate needle biopsy tissue in prediction of pathologic stage in a screening population
Bismar TA, Lewis JS Jr, Vollmer RT, Humphrey PA
Lauren V. Ackerman Laboratory of Surgical Pathology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
Am J Surg Pathol. 2003; 27: 432-40

• The capacity of perineural invasion by carcinoma in prostate needle biopsy tissue to independently predict pathologic stage in radical prostatectomy tissues remains uncertain. We sought to determine, in a prostate specific antigen-based screening population, the ability of needle biopsy histologic grade, tumor extent, and perineural invasion to independently predict pathologic stage and margin status in the whole prostate gland. Perineural invasion, Gleason grade, percentage Gleason pattern 4/5 carcinoma, and multiple measures of needle biopsy tumor extent, including number of positive cores, percentage of positive cores, total percentage of carcinoma, greatest percentage of carcinoma in a single core, and total carcinoma length in millimeters, were captured for 215 men from a prostate specific antigen-based screening program diagnosed with prostate cancer in a median of six procured needle biopsy cores. Pathologic stage and surgical margin status were evaluated in corresponding completely embedded radical prostatectomy specimens. A logistic regression model was used to relate the endpoints of extraprostatic extension by carcinoma and/or positive margins to needle biopsy tissue findings. In univariate analyses, total percentage of carcinoma (p = 0.003), greatest percentage of carcinoma in a single core (p = 0.004), total tumor length in millimeters (p = 0.009), and fraction of positive cores (p = 0.02) were all significantly associated with extraprostatic (pT3) carcinoma, whereas all five measures of carcinoma extent in needle biopsy tissue were related to positive margins. Correlation coefficient determinations showed that all five measures of needle biopsy carcinoma extent were highly interrelated. In multivariate analyses, total percentage of carcinoma was significantly related to pathologic T stage (p = 0.003) and positive margins (p = 0.0002). In a multivariate model with the radical prostatectomy whole gland endpoint of either pT3 disease or positive margins, fraction of positive cores (p = 0.00001) was the only variable with significant predictive value. Perineural invasion by carcinoma in needle biopsy tissue was detected in 11% of cases. Neither presence nor absence of perineural carcinoma nor number nor percentage of positive nerves related to pathologic stage in univariate or multivariate analyses. Amount of carcinoma in prostate needle biopsy tissue, using multiple measurements but not perineural invasion, is a significant histologic attribute predictive of pathologic stage and margin status for men with prostate specific antigen screening detected prostatic carcinoma. Reporting of several measures of carcinoma extent in needle biopsy tissue is recommended.
  
• Editorial Comment
  The significance of perineural invasion in needle biopsies is a controversial issue. Bastacky et al. (Am J Surg Pathol. 1993; 17: 336-41) from Johns Hopkins University found perineural invasion in 20% of needle biopsies with a specificity of 96% to predict extraprostatic extension. According to these authors, measuring perineural invasion on needle biopsy helps to identify extraprostatic extension and may help in planning nerve-sparing radical prostatectomy in the decision of whether to sacrifice part or all of the neurovascular bundle on the side of the biopsy. Based on this study, in 1994, the American College of Pathologists recommended to include this finding in the pathology report.
  Egan & Bostwick (Am J Surg Pathol. 1993; 17: 336-41) from Mayo Clinic found perineural invasion in 36% of needle biopsies with a specificity of 70% to predict extraprostatic extension. However, in a multivariate analysis, only pre-operative PSA, extent of tumor in the biopsy and Gleason grading were statistically significant. The authors conclude that the finding of perineural invasion in needle biopsy of prostatic carcinoma has no independent predictive value for the presence of extraprostatic extension. Accordingly, they recommend no longer routinely evaluate this finding in biopsy specimens.
  The paper of this editorial comment favors the findings of Egan & Bostwick. However, the controversy is far from being settled. More studies are needed for a clear significance of perineural invasion in needle biopsies.

Dr. Athanase Billis
Full-Professor of Pathology
State University of Campinas, Unicamp
Campinas, São Paulo, Brazil