PATHOLOGY

Widespread High-Grade Prostatic Intraepithelial Neoplasia on Prostatic Needle Biopsy: A Significant Likelihood of Subsequently Diagnosed Adenocarcinoma
Netto GJ, Epstein JI
Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, USA
Am J Surg Pathol. 2006; 30: 1184-8

• In comparison with earlier studies, recent reports have demonstrated a lower incidence of prostate carcinoma after an initial diagnosis of high-grade prostatic intraepithelial neoplasia (HGPIN). The latter has led to a general tendency to reconsider the absolute need for a rebiopsy in this setting. The current retrospective study assesses the subsequent likelihood of identifying prostatic adenocarcinoma (PCa) in 41 patients with an initial diagnosis of “widespread” HGPIN defined as HGPIN present in 4 or more biopsy cores. All patients underwent at least 1 follow-up (F/U) sampling procedure in a period of 1 to 41 months. PCa was found in 16/41 patients (39%), all except 1 identified on the first F/U biopsy with the remaining patients diagnosed on a transurethral resection after a negative first F/U biopsy. All but 1 prostatic carcinoma diagnoses were obtained within 2 years from initial biopsy with 10 rendered within the first year. On average, prostate cancer was identified at 10.4 months (range: 1 to 36). One-fourth of all identified prostatic carcinomas were of Gleason score 7 or more. In 4 additional patients (9.7%), F/U biopsy revealed HGPIN with adjacent atypical small glands suspicious but not diagnostic of carcinoma (PINATYP). Of 41 patients, 10 (24.3%) continued to show HGPIN with the remaining 11/41 patients (26.8%) showing benign prostatic tissue. Patients >or=70 years of age at the time of initial biopsy had a statistically significant higher rate of PCa or HGPIN/PINATYP diagnosis on repeat biopsy compared with younger patients (P=0.02), with 55% of older men being diagnosed with cancer as compared with 33% in younger men. Patients with fewer cores sampled on initial biopsy were more likely to be diagnosed with carcinoma as opposed to HGPIN/PINATYP on F/U (P=0.015). Other factors such as the number of F/U procedures, serum prostate-specific antigen level before initial HGPIN biopsy, number of cores per F/U biopsy, and F/U interval length did not affect the likelihood of finding carcinoma. In summary, our study reveals a 39% risk of finding PCa on repeat biopsies obtained after an initial diagnosis of widespread HGPIN. Our findings support the need for a repeat biopsy in this subset of patients.
  
  
• Editorial Comment
  There are many evidences for the association of high-grade prostatic intraepithelial neoplasia (HGPIN) and prostatic carcinoma (1): the cytologic features are similar, both are located most frequently in the peripheral zone, both have more than 3 times the proliferative activity of benign glands, highest grade of PIN has loss of basal cell layer that is similar to carcinoma, increased frequency, extent and severity of PIN in the presence of carcinoma, age incidence peak precedes carcinoma, and similar immunophetype.
  Atypical glandular proliferation, dysplastic lesion, atypical lesion, intraductal dysplasia among others were designations used to refer to this lesion. In 1989 (2), in a workshop sponsored by the American Cancer Society in Bethesda, a unified comenclature was adopted: prostatic intraepithelial neoplasia (PIN). Considering that grade 1 (low-grade) PIN has a very poor reproducibility among pathologists and a very low (if any) association to carcinoma, it is proposed to report only grade 2 or 3 PIN (high-grade PIN)
  Recent reports have shown that due to an increased needle biopsy core sampling, which detects many associated cancers on initial biopsy, there is a decreased incidence of cancer following a diagnosis of HGPIN. Due to this facts, it is now recommended that men do not need routine repeat needle biopsy within the first year following the diagnosis of HGPIN (3). The study surveyed showed that there is an exception to this recommendation in case HGPIN is extensive (present in 4 or more cores). In this case there is a 39% risk of finding prostate cancer on repeat biopsies.

References
1. Bostwick DG, Srigley JR: Premalignant Lesions. In: Bostwick DG (ed.), Pathology of the Prostate. New York, Churchill Livingstone,1990; pp.37-59.
2. Drago JR, Mostofi FK, Lee F: Introductory remarks and workshop summary. Urology. (suppl) 1989; 34: 2-3.
3. Epstein JI, Herawi M: Prostate needle biopsies containing prostatic intraepithelial neoplasia or atypical foci suspicious for carcinoma: Implications for patient care. J Urol 2006; 175: 820-34.

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