Diagnosis of Gleason Pattern 5 Prostate Adenocarcinoma on Core Needle Biopsy

Abstract

Accurate recognition of Gleason pattern 5 (GP5) prostate adenocarcinoma on needle biopsy is critical as it is associated with disease progression and adverse clinical outcome. Despite important implications of this diagnosis, interobserver variation in the diagnosis of GP5 has not been adequately studied. Digital images of 66 prostate adenocarcinoma cases that potentially contained a GP5 component were distributed to 16 urologic pathologists who were asked to classify whether GP5 was present. Each image was initially classified into 1 of 4 morphologic subpatterns by 2 coauthors (R.B.S. and M.Z.): solid nests (15), comedocarcinoma (8), single cells and/or cords (35), and variant morphology (8). Additional features captured included: size (large: >20 cells, medium: 10 to 20 cells, and small: <10 cells) and distribution of nuclei (uniform vs. nonuniform) for nests pattern; intraluminal coagulative tumor necrosis, karyorrhectic debris, and amorphous material for comedocarcinoma pattern; and quantity (≤5, 6 to 10, and >10) and distribution (clustered vs. intermixed with adjacent well-formed glands) for single cells/cords pattern. Interobserver reproducibility of a diagnosis of GP5 was assessed and the morphologic subpatterns and features were correlated with the consensus diagnosis (defined as 75% agreement). Interobserver reproducibility for overall diagnostic agreement was fair (κ=0.376). Among subpatterns, comedocarcinoma had highest reproducibility (κ=0.499), followed by variant morphology (κ=0.443), single cells/cords (κ=0.369), and nests (κ=0.347). All cases with the following features achieved consensus for GP5: large nests regardless of nuclear distribution; coagulative necrosis with or without karyorrhectic debris; single cells/cords >10 or 6 to 10 in a cluster; and signet ring-like cells in single cells or within nests pattern. A majority of cases with the following features achieved consensus against GP5: medium-size nests; exclusive intraluminal amorphous material; single cells/cords ≤5; and Paneth cell change. Remaining morphologic features did not reach consensus for or against GP5. A majority (86%) of participants would diagnose a small focus of GP5 only when it is present in >1 level. The diagnostic reproducibility of GP5 within certain morphologies was only fair among urologic pathologists. However, the diagnosis of GP5 was more reproducible when certain restrictive morphologic and quantitative criteria were applied. These findings suggest that additional studies are needed to find highly reproducible features of GP5 associated with documented aggressive clinical outcome.

Development and validation of a deep learning algorithm for improving Gleason scoring of prostate cancer

“…Substantial additional variability arises from applying discrete categorizations to glandular differentiation that lies on a continuous spectrum, such as the Gleason pattern 3/4 transition between small glands and poorly defined acinar structures or the Gleason pattern 4/5 transition between fused glands and nests or cords. 12,44,45 Our data show that for regions where pathologists are discordant in Gleason pattern categorization, where the underlying histology is likely closer to the cusp between patterns, the DLS reflects this ambiguity in its prediction scores (Fig. 4b) and demonstrates the potential to assign finer-grained Gleason patterns (Fig.…”

Comedonecrosis Gleason pattern 5 is associated with worse clinical outcome in operated prostate cancer patients

“…Based on the above-mentioned mutual relation of growth patterns, we hypothesize that small solid nests might be precursor lesions of fused glands prior to lumen-formation. Interestingly, Shah et al found overall consensus among 16 urologic pathologists for calling large (>20 cells) solid fields Gleason pattern 5, but not for medium (10-20 cells) or small (<10 cells) solid nests, further questioning the precise clinicopathologic relevance of smaller sized solid fields [46].…”

Three-dimensional analysis reveals two major architectural subgroups of prostate cancer growth patterns

“…The three-dimensional continuity of these patterns is reflected by the substantial inter-observer variability in daily pathology practice. Distinguishing, on one hand, tangentially sectioned Gleason pattern 3 glands from poorly formed and fused Gleason pattern 4 glands, and, on the other hand, poorly formed Gleason pattern 4 glands from Gleason pattern 5 cords on hematoxylin and eosin slides is the principal area of difficulty [12, 14, 27, 28]. Secondly, there are serpentine compact irregular epithelial proliferations, consisting of cribriform Gleason pattern 4 and solid Gleason pattern 5, with decreasing inter-epithelial lumen sizes and frequencies.…”