Spread of Adenocarcinoma Within Prostatic Ducts and Acini

Abstract

Malignant epithelial masses within prostatic duct lumens have been equated with several conflicting entities, including Gleason cribriform grade 3 carcinoma and cribriforming dysplasia. We identified 51 radical prostatectomy cancers containing intraductal lesions among 130 cases, with total cancer volumes between 4 and 10 cc. Such lesions with duct lumen-spanning septa or masses were rare in areas away from invasive cancer (22 foci), while dysplasia (prostatic intraepithelial neoplasia) was common (1,490 foci). Consequently, these lesions were interpreted as being part of the evolution of invasive carcinoma rather than precursors; they were designated "intraductal carcinoma" as distinct from dysplasia. Intraductal cancer areas within invasive carcinoma usually represented cancer extension within the branches of a single segment of the duct-acinar system from near the urethra to the gland capsule. In 51% of cases with intraductal spread, the invasive component produced large ( > 0.5 mm) tumor masses in perineural spaces, which in turn correlated strongly with extensive capsule penetration and frequent positive surgical margins selectively at the superior nerve pedicle. The amount of grade 4/5 cancer, the amount of intraductal carcinoma, and the large perineural tumor mass appeared to be related to postprostatectomy progression of cancer, as measured by elevation of ultrasensitive serum prostate-specific antigen. It was concluded that intraductal prostatic adenocarcinoma is a common morphologic entity with precisely defined histologic criteria and a unique biologic significance, as reflected by an enhanced capacity for extensive spread within ducts and perineural spaces. It was proposed that the diversity of diagnoses attached to most cribriform malignant lesions can be unified by the concept of this single entity.

Cribriform growth is highly predictive for postoperative metastasis and disease-specific death in Gleason score 7 prostate cancer

“…20 First, established Gleason grade 4 or 5 prostate cancer could infiltrate and expand preexisting glands; this theory is supported by the fact that intraductal carcinoma is rarely found in absence of high-grade prostate cancer. 21 Alternatively, high-grade prostatic intraepithelial neoplasia, which is generally accepted as prostate cancer precursor, might evolve into intraductal carcinoma and consecutively invasive high-grade prostate cancer. The molecular and biological connections of separate intraductal and invasive growth patterns are intriguing and clinically important, but still poorly understood.…”

The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs—Part B: Prostate and Bladder Tumours

“…This term has been used for several decades, dating back to at least 1985 [2], and it has been variably used to describe intraductal spread or in situ E U R O P E A N U R O L O G Y X X X ( 2 0 1 6 ) X X X -X X X growth of acinar or ductal adenocarcinoma of the prostate and intraductal proliferation of urothelial carcinoma [3][4][5][6][7][8][9][10][11]. The 2016 WHO definition is as follows: ''Intraductal carcinoma of the prostate is intra-acinar and/or intraductal neoplastic epithelial proliferation that has some features of high-grade prostatic intraepithelial neoplasia (HGPIN) but exhibits much greater architectural and/or cytological atypia, typically associated with high-grade, high-stage prostate carcinoma.''…”

“…In whole prostate glands, the incidence is dependent on the grade and stage of the prostatic adenocarcinoma in the series and ranges from 20% to 40% of RP cases [5,10].…”

ERG expression in intraductal carcinoma of the prostate: comparison with adjacent invasive prostatic adenocarcinoma

“…1 However, its recognition is important as intraductal carcinoma of the prostate has been shown in previous studies to be associated with high Gleason scores and tumor stage in radical prostatectomy specimens, and has an aggressive clinical course. 2 Whether intraductal carcinoma of the prostate represents conversion of high-grade prostatic intraepithelial neoplasia to carcinoma or invasion of benign glands by invasive prostatic carcinoma is still debatable. The transcriptional regulator ERG is a member of the ETS gene family that can fuse with the TMPRSS2 protein.…”