PATHOLOGY

Risk of prostate cancer on re-biopsy following a diagnosis of high-grade prostatic intraepithelial neoplasia (HGPIN) is related to the number of cores sampled
Herawi M, Cavallo C, Kahane H, Epstein JI
The Johns Hopkins Hospital, Baltimore, MD, Dianon Corp., Stratford, CT, USA
Mod Pathol. 2005; 18 (suppl.1): abst #668, 145A

• Background: We aimed to determine whether the extent of needle biopsy sampling both on the initial biopsy that showed HGPIN and on re-biopsy would influence the detection rate of cancer.
• Design: 4,237 patients with an initial diagnosis of only HGPIN on needle biopsy were identified; patients who in addition to HGPIN had a focus of atypical glands, suspicious for cancer were excluded. Of these, 937 patients had at least one follow up biopsy and were the subject of this study. The mean age was 67.5 (range from 39 to 87 years). The mean interval from diagnosis of HGPIN to rebiopsy was 4.8 months. In the initial biopsy resulting in a diagnosis of HGPIN, 371 men had > 8 cores (median 10; range 8-26) and 399 men had 6 core sampling.
• Results: Not taking into account the number of cores on rebiopsy, in the 6 core initial sampling group, the risk of cancer on rebiopsy was 22.1% versus 15.1% in the > 8 core group (p value = 0.013). The table shows the combined influence of numbers of cores in the initial and rebiopsy sampling.

The differences between groups 1 and 3 as compared to group 2 were statistically significant (p = 0.001 and p < 0.0001, respectively).

• Conclusions: Many cases of HGPIN on biopsy are associated with adjacent unsampled cancer. With relatively poor sampling (6 cores) on the initial biopsy, associated cancers are missed resulting in only HGPIN on biopsy, and with relatively poor sampling on rebiopsy there is also a relatively low risk of finding cancer on rebiopsy. With poor sampling on the initial biopsy and better sampling on rebiopsy, some of these missed cancers are detected on rebiopsy yielding a higher detection of cancer. Sampling more extensively on the initial biopsy detects many associated cancers, such that when only HGPIN is found they often represent isolated HGPIN; rebiopsy even with good sampling does not detect many additional cancers. Our study demonstrates that the risk of cancer following a diagnosis of HGPIN (15.1%) is not that predictive of cancer on rebiopsy if good sampling (> 8 cores) is initially performed. Routine rebiopsy of men with HGPIN may not be necessary in the modern era of more extensive needle biopsy sampling.
  
  
• Editorial Comment
  The detection of adenocarcinoma on a re-biopsy varies from 23% to 79% (1). The study from the Johns Hopkins University shows a declining trend for this frequency. The authors clearly give the most important cause: sampling more extensively on the initial biopsy (extended biopsy) detects many associated cancers, such that when only high-grade intraprostatic neoplasia (HGPIN) is found they often represent isolated HGPIN; re-biopsy even with good sampling does not detect many additional cancers.
  It is worth mentioning that HGPIN is different that ASAP; with the latter a re-biopsy is always indicated. ASAP was coined by Iczkowski, MacLennon & Bostwick (2) to refer to a condition when the pathologist is not sure with the diagnosis of adenocarcinoma. Unfortunately, many urologists equate the term ASAP with HGPIN and since the diagnosis of HGPIN has diminished relevance as a marker lesion to detect adenocarcinoma (as recent data seem to indicate), if the term ASAP is used by pathologists and misunderstood by urologists, a clinically significant suspicion for cancer may trigger a less than adequate clinical follow-up.
  Considering these facts, a 2004 WHO-sponsored International Consultation Consensus held in Stockholm on prognostic and predictive factors and reporting of prostate carcinoma in prostate needle biopsy specimens, recommended to use the terms “suspicious or highly suspicious for adenocarcinoma” instead of ASAP.

References
1. Epstein JI, Potter SR: The pathological interpretation and significance of prostate needle biopsy findings: Implications and current controversies. J Urol. 2001; 166: 402-10.
2. Iczkowski KA, MacLennan GT, Bostwick DG: Atypical small acinar proliferation suspicious for malignancy in prostate needle biopsies: clinical significance in 33 cases. Am J Surg Pathol. 1997; 21: 1489-95.

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