PATHOLOGY

Predictive value of pathologic parameters of high-grade prostatic intraepithelial neoplasia (HGPIN) in the initial biopsy for the subsequent detection of prostatic carcinoma (PCa)
Mendrinos SE, Amin MB, Lim SD, Herrera CM, Srigley JR
Emory University, School of Medicine, Atlanta, GA, USA, and Credit Valley Hospital, Mississauga, ON, Canada
Mod Pathol. 2004; 171(suppl 1): 168A

• Background: Recent experience suggests that PCa will be detected on rebiopsy in approximately 27% of patients with initial diagnosis of HGPIN. Knowledge of pathologic parameters of HGPIN that have a higher predictive power would help further stratify management of patients who are at a greater likelihood of having undetected carcinoma in the prostate gland.
• Design: 153 initial biopsy cores from 80 patients with HGPIN (41 diagnosed subsequently with PCa and 39 without PCa on rebiopsy) with a minimum follow up of 2 years were evaluated. In each case the following parameters of HGPIN were assessed without knowledge of which cases had subsequently developed PCa : number of cores involved, number of glands with HGPIN per core, architectural pattern (micropapillary, tufted, flat, cribriform), cytoplasmic features, nuclear pleomorphism, presence of mitoses, nucleolar features [prominent nucleoli (<50% or =50% in PIN glands), ease of nucleolar recognition (at 10X, 20X or 40X objective), presence of multiple nucleoli], presence of necrosis, apoptosis, intraluminal crystalloids, blue mucin and presence of associated features including atrophy, inflammation and stromal reaction. Pathologic parameters of HGPIN were correlated with detection of PCa in subsequent biopsy (ies).
• Results: 66.7% of patients with two or more cores involved by HGPIN had PCa on subsequent biopsy. In contrast, 38.6% of patients with only one core with HGPIN were detected to have PCa (p=0.015, Fishers exact test). Tufted and flat were the most common architectural patterns. The presence of micropapillary HGPIN was associated with greater likelihood of subsequent PCa detection (p=0,041, Pearson x2 test). By multivariate analysis, pattern of HGPIN (micropapillary and cribriform) was the only independent predictor of cancer on rebiopsy (p=0.013, RR 4.586). Other pathologic variables failed to have predictive value for subsequent detection of PCa.
• Conclusions: Patients with initial diagnosis of HGPIN, which demonstrates micropapillary or cribriform architecture or is present in multiple cores, should be candidates for more aggressive investigation to detect PCa, potentially by early rebiopsy and more aggressive sampling.
  
  
• Editorial Comment
  High-grade prostatic intraepithelial neoplasia (HGPIN) is considered a precursor lesion of invasive prostate carcinoma. This is evidenced by several findings: HGPIN is more frequent in patients with than without prostate carcinoma; in some rare cases, it is possible to document a transition between HGPIN and invasive carcinoma; the mean age of patients with HGPIN is lower than patients with invasive carcinoma; and, there are similarities between phenotypic and genotypic findings between these 2 conditions.
  Many terms were used to refer to this condition. In 1989, during a consensus workshop held in Bethesda, MD, USA (Urology. 1989; 34: (suppl.) 2-3) it was suggested to use the term prostatic intraepithelial neoplasia (PIN). In this consensus meeting was also agreed to refer in the pathology report only high-grade PIN (grades 2 or 3) and not low-grade PIN (grade 1). Bostwick et al. (Hum Pathol. 1993; 24: 298-10) described 4 architectural patterns of HGPIN: micropapillary, tufted, flat, and cribriform. These are considered morphologic variants without any predictive value.
  This paper showed that the architectural patterns of HGPIN might have importance to predict prostate cancer on subsequent biopsies. By multivariate analysis, the micropapillary and cribriform patterns of HGPIN were independent predictors of cancer on rebiopsy. Based on this paper, for the urologist is worth asking the pathologist to include in the pathology report the architectural pattern of HGPIN.

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