Diagnosis of “Poorly Formed Glands” Gleason Pattern 4 Prostatic Adenocarcinoma on Needle Biopsy

Abstract

Accurate recognition of Gleason pattern (GP) 4 prostate carcinoma (PCa) on needle biopsy is critical for patient management and prognostication. "Poorly formed glands" are the most common GP4 subpattern. We studied the diagnostic reproducibility and the quantitative threshold of grading GP4 "poorly formed glands" and the criteria to distinguish them from tangentially sectioned GP3 glands. Seventeen urologic pathologists were first queried for the definition of "poorly formed glands" using cases representing a spectrum of PCa glandular differentiation. Cancer glands with no or rare lumens, elongated compressed glands, and elongated nests were considered "poorly formed glands" by consensus. Participants then graded a second set of 23 PCa cases that potentially contained "poorly formed glands" with a fair interobserver agreement (κ = 0.34). The consensus diagnoses, defined as agreement by > 70% participants, were then correlated with the quantitative (≤ 5, 6 to 10, >10) and topographic features of poorly formed glands (clustered, immediately adjacent to, and intermixed with other well-formed PCa glands) in each case. Poorly formed glands immediately adjacent to other well-formed glands regardless of their number and small foci of ≤ 5 poorly formed glands regardless of their location were not graded as GP4. In contrast, large foci of >10 poorly formed glands that were not immediately adjacent to well-formed glands were graded as GP4. Grading "poorly formed glands" is challenging. Some morphologic features are, however, reproducible for and against a GP4 diagnosis. This study represents an important step in standardization of grading of "poorly formed glands" based on quantitative and topographic morphologic features.

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.…”

Light-sheet microscopy for slide-free non-destructive pathology of large clinical specimens

“…Unfortunately, many studies have shown that the evaluation afforded by current histopathology techniques is often neither accurate nor reproducible, with high levels of inter-observer variability between pathologists regarding critical elements such as carcinoma grade and molecular phenotype [ 6 , 51 , 52 ]. For example, a recent study examined the inter-observer agreement within a panel of genitourinary pathologists in distinguishing between the “poorly formed gland” variant of Gleason pattern 4 prostate carcinoma versus tangentially sectioned Gleason pattern 3 glands (i.e., “well-formed glands”), and reported relatively poor inter-observer concordance ( κ = 0.34) [ 53 ]. The distinction between Gleason pattern 3 and 4 carcinoma can result in dramatically different treatment recommendations: namely, active surveillance (Gleason pattern 3) versus radical prostatectomy (Gleason pattern 4), with its associated iatrogenic risks (incontinence, impotence, etc.).…”

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.…”