PATHOLOGY

A Working Group Classification of Focal Prostate Atrophy Lesions
De Marzo AM, Platz EA, Epstein JI, Ali T, Billis A, Chan TY, Cheng L, Datta M, Egevad L, Ertoy-Baydar D, Farree X, Fine SW, Iczkowski KA, Ittmann M, Knudsen BS, Loda M, Lopez-Beltran A, Magi-Galluzzi C, Mikuz G, Montironi R, Pikarsky E, Pizov G, Rubin MA, Samaratunga H, Sebo T, Sesterhenn IA, Shah RB, Signoretti S, Simko J, Thomas G, Troncoso P, Tsuzuki TT, van Leenders GJ, Yang XJ, Zhou M, Figg WD, Hoque A, Lucia MS
Johns Hopkins University School of Medicine, USA
Am J Surg Pathol. 2006; 30: 1281-91

• Focal atrophy is extremely common in prostate specimens. Although there are distinct histologic variants, the terminology is currently nonstandardized and no formal classification has been tested for interobserver reliability. This lack of standardization hampers the ability to study the biologic and clinical significance of these lesions. After informal and formal meetings by a number of the authors, focal atrophy lesions were categorized into 4 distinct subtypes as follows: (i) simple atrophy, (ii) simple atrophy with cyst formation, (iii) postatrophic hyperplasia, and (iv) partial atrophy. In phase 1 of the study, pathologists with varying levels of experience in prostate pathology were invited to view via the Internet a set of “training” images with associated descriptions of lesions considered typical of each subtype. In phase 2 of the study, each participant provided diagnoses on a series of 140 distinct “test” images that were viewed over the Internet. These test images consisted of the 4 subtypes of atrophy and images of normal epithelium, high grade prostatic intraepithelial neoplasia, and carcinoma. The diagnoses for each image from each pathologist were compared with a set of “standard” diagnoses and the kappa statistic was computed. Thirty-four pathologists completed both phases of the study. The interobserver reliability (median kappa) for classification of lesions as normal, cancer, prostatic intraepithelial neoplasia, or focal atrophy was 0.97. The median kappa for the classification of atrophy lesions into the 4 subtypes was 0.80. The median percent agreement with the standard diagnosis for the atrophy subtypes were: simple 60.6%, simple with cyst formation 100%; postatrophic hyperplasia 87.5%; partial atrophy 93.9%. The lower percentage for simple atrophy reflected a propensity to diagnose some of these as simple atrophy with cyst formation. Seven pathologists completed the phase 2 analysis a second time, and their intraobserver reproducibility was excellent. Three of 4 pathologists with low agreement with the standard diagnosis for simple atrophy improved their scores after repeating the analysis after re-examination of the “training set” of images. In conclusion, these criteria for variants of focal prostate atrophy may facilitate studies to examine the relation between various patterns of prostate atrophy and prostate cancer.
  
  
• Editorial Comment
  Seven pathologists with interest and expertise in genitourinary pathology took part in a sponsored meeting to present a morphological classification for prostatic atrophy: simple atrophy, postatrophic hyperplasia, simple atrophy with cyst formation and partial atrophy. Other morphological classifications for prostatic atrophy also exist (1,2). The histologic subtypes of prostatic atrophy do not represent distinct entities but a morphologic continuum of acinar atrophy (3). Subtyping atrophy is useful only to allow recognition of the lesion and to distinguish it from mimics. The study surveyed checked the inter-reproducibility among 34 pathologists from 25 different institutions from 10 different countries of the morphological classification proposed by 7 pathologists.
  Prostatic atrophy is one of the most frequent benign mimickers of prostatic adenocarcinoma (4). Atrophy is commonly associated with chronic prostatitis which may have an active component characterized by presence of neutrophils. The lesion can also be the result of treatment with radiation and antiandrogens. Although many examples of atrophy are still considered idiopathic in nature, in cases of age related atrophy there is strong evidence that it may be a manifestation of chronic ischemia due to local arteriosclerosis (1).
  Some reports suggest that focal atrophy may be causally linked to prostate cancer and to other pre-neoplastic lesions (5). However, other studies do not support this hypothesis (1,2). Another exciting link of atrophy is related to serum PSA levels. We have just finished in our Institution a study showing that, regardless of cause, there is a significant positive association between extent of atrophy and serum total or free PSA elevation in patients with biopsies showing no cancer, high-grade prostatic intraepithelial neoplasia (HGPIN) or areas suspicious for cancer (ASAP). The findings suggest that damaged epithelial cells in atrophic acini may be source of serum PSA elevation.

References
1. Billis A: Prostatic atrophy: An autopsy study of a histologic mimic of adenocarcinoma. Mod Pathol. 1998;11: 47-54.
2. Postma R, Schröder FH, van der Kwast TH: Atrophy in prostate needle biopsy cores and its relationship to prostate cancer incidence in screened men. Urology. 2005; 65: 745-9.
3. Cheville JC, Bostwick DG: Postatrophic hyperplasia of the prostate. A histologic mimic of prostatic adenocarcinoma. Am J Surg Pathol. 1995; 19: 1068-76.
4. Srigley JR: Benign mimickers of prostate cancer. Mod Pathol. 2004; 17: 328-48.
5. De Marzo AM, Marchi VL, Epstein JI, Nelson WG: Proliferative inflammatory atrophy of the prostate. Implications for prostatic carcinogenesis. Am J Pathol 1999; 155: 1985-92.

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