High-grade Prostatic Intraepithelial Neoplasialike Ductal Adenocarcinoma of the Prostate: A Clinicopathologic Study of 28 Cases

Abstract

Most of the prostatic ductal adenocarcinomas of the prostate are characterized by cribriform and/or papillary architecture lined by columnar pseudostratified malignant epithelium. We report 28 cases of ductal adenocarcinomas on needle biopsy and transurethral resection of prostate closely resembling high-grade prostatic intraepithelial neoplasia (HGPIN) composed of simple glands with flat, tufting, or micropapillary architecture. The mean age of the patients was 68 years (range, 50 to 91 y). Prostate specific antigen serum level at diagnosis ranged from 1.2 to 12.1 ng/mL. Treatment included radical prostatectomy (n=9), hormone therapy (n=7), radiotherapy (n=5), and cryotherapy (n=1). Three patients had recent biopsies without information on treatment and 3 patients were lost to follow-up after diagnosis. The number of cores involved by tumor in each case ranged from 1 to 18, with more than 1 core involved in 13 cases. Flat was the most common pattern (42%), followed by tufted (41%), and micropapillary (17%) (some with more than 1 pattern). Fourteen cases revealed segments of dilated gland on the edge of the biopsies, suggesting a large gland component. In radical prostatectomies, tumor was primarily composed of small (25%), medium (17%), or cystically dilated (58%) cancer glands, with all cases demonstrating a mixture of different gland sizes. Cytologically, tumors were characterized by tall columnar atypical cells, basally located nuclei, and amphophilic cytoplasm. The tumors lacked marked pleomorphism, necrosis, solid areas, cribriform formation, or true papillary fronds. Immunohistochemically, alpha-methyl acyl coenzyme-A racemase staining was seen in 93% of cases, with the majority showing strong and diffuse staining. No basal cells were present on p63 and/or high molecular weight cytokeratin staining. In the radical prostatectomy specimens, tumor volumes ranged from a small focus (less than 0.01 cm3) to 1.2 cm3. Concurrent conventional acinar Gleason score 6 adenocarcinomas were seen in 6 of the 9 radical prostatectomy cases, in all cases as separate nodules from the PIN-like ductal adenocarcinomas. Only one of the PIN-like ductal adenocarcinomas at radical prostatectomy had extraprostatic extension, which was focal. PIN-like ductal adenocarcinoma differs from HGPIN by the presence of cystically dilated glands, a greater predominance of flat architecture, and less frequently prominent nucleoli. Verification often requires the immunohistochemical documentation of the absence of basal cells in numerous atypical glands. Although usual ductal adenocarcinoma is considered comparable to Gleason score 8, PIN-like ductal adenocarcinoma was accompanied by Gleason score 6 acinar carcinoma and behaved similar to Gleason score 6 acinar cancer. Recognition of this entity is critical to differentiate it from both HGPIN and conventional ductal adenocarcinoma.