PATHOLOGY

Update on the Gleason Grading System for Prostate Cancer: Results of an International Consensus Conference of Urologic Pathologists
Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL
Department of Pathology, Urology and Oncology, The Johns Hopkins Hospital, Baltimore, MD, USA
Adv Anat Pathol. 2006; 13: 57-9

• The Gleason system for prostate cancer was based on a study of 270 patients from the Minneapolis Veterans Administration Hospital in 1966-1967. In 1974, Gleason and the Veterans Administrative Cooperative Urological Research Group expanded this study to 1032 men. These studies formed the basis of the Gleason grading system, which is now endorsed as the primary grading system for prostate cancer by the World Health Organization, the Armed Forces Institute of Pathology Fascicle on prostate cancer, the Association of Directors of Anatomic and Surgical Pathology, and the College of American Pathologists. In the nearly 40 years since its inception, several aspects about prostate cancer and its management have changed, most notably serum prostate-specific antigen, transrectal ultrasonography, 18-gauge needle biopsy sampling, immunohistochemistry for the diagnosis of cancer, and radical prostatectomy and radiation therapy as primary treatment modalities. Several aspects of the disease, and consequently the reporting needs, have changed such as reporting cancer on multiple cases in needle biopsies, multiple nodules in prostatectomy, tertiary patterns, variants and variations in prostate cancer. The application of the Gleason system, therefore, has varied considerably in contemporary surgical pathology practice. An International Consensus Conference attended by 80 urologic pathologists from 20 countries was convened to discuss clarifications and modifications to the Gleason system. This article serves as a brief overview and summary of the proceedings that have been published in detail in recent literature.
  
  
• Editorial Comment
  In 2005 during the USCAP (United States and Canadian Academy of Pathology) meeting in San Antonio, Texas, there was a Consensus Conference on Gleason grading system sponsored by the International Society of Urological Pathology (ISUP). The results were published in the November issue of the American Journal of Surgical Pathology (1). There are several arguments favoring a need for a consensus on Gleason grading: 1) In the 1960s, there was no screening for prostate cancer other than by digital rectal examination; 2) The use of 18-gauge thin biopsy needles and the concept of sextant needle biopsies to more extensively sample the prostate were not developed until the 1980s; 3) Tertiary patterns were not addressed within the original Gleason system; 4) The Gleason system predated the use of immunohistochemistry (it is likely that many of Gleason’s original 1 + 1 = 2 adenocarcinomas would today be regarded as adenosis; 5) The original Gleason grading system was not applied to newly described variants of adenocarcinoma of the prostate; and, 6) The Gleason system varies considerably in contemporary surgical pathology practice and has led to several recent attempts to achieve consensus on Gleason grading.
  Some of the recommendations of the consensus conference are the following: 1) Cribriform pattern 3 should only be diagnosed for well circumscribed glands of the same size of normal glands; 2) Ill-defined glands with poorly formed glandular lumina also warrant the diagnosis of Gleason pattern 4; 3) In high-grade cancer, lower grade patterns should be ignored if they occupy less than 5% of the area of the tumor; and 4) For tertiary Gleason patterns, both the primary and the highest grade are recorded.
  A recent study described the impact of the consensus recommendations on a series of 172 consecutive needle prostatic biopsies of patients subsequently submitted to radical prostatectomy previously graded according to the standard Gleason system (2). There was a grading concordance in 83.14%, 63.37%, and 68.02% biopsies for Gleason primary pattern, Gleason secondary pattern, and Gleason score, respectively. There was a change of prognostic Gleason grading groups in 2.33% and 26.74% biopsies toward a lower group and toward a higher group, respectively. There was a change in 15.7%, 9.88%, 0.58% and 0.58% biopsies from group 5-6 toward group 7, 7 toward 8-10, 5-6 toward 8-10, and 2-4 toward 5-6, respectively. The conclusion was that the highest impact of the consensus recommendations was seen on the secondary pattern that had the lowest percentage of concordance. It reflected in a change toward a higher Gleason grading group in 46/172 (26.74%) of the cases. A further study is warranted to show how different are these 46 cases according to several clinicopathologic variables: preoperative PSA, positive surgical margins, tumor extent, pathologic staging and biochemical progression following radical prostatectomy.

References
1. Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL; ISUP Grading Committee: The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol. 2005; 29: 1228-42.
2. Guimaraes MS, Billis A, Quintal MM, Magna LA, Ferreira U. The impact of the 2005 International Society of Urological Pathology (ISUP) Consensus Conference on standard Gleason grading of prostatic carcinoma. Mod Pathol Suppl. 2006; 1: 139A.

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