Nguyen Jane K, Li Jianbo, Ding Chien-Kuang C, Weight Christopher J, McKenney Jesse K
Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH, United States of America.
Lerner Research Institute, Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, United States of America.
Ann Diagn Pathol. 2025 Apr;75:152427. doi: 10.1016/j.anndiagpath.2024.152427. Epub 2024 Dec 5.
Prostatic adenocarcinomas with large cribriform glands/intraductal carcinoma (LC/IDC), or the recently proposed unfavorable histology, are associated with adverse outcomes after radical prostatectomy. However, Gleason pattern 4 carcinomas without LC/IDC (or unfavorable histology) have minimal risk for aggressive clinical behavior after prostatectomy. As proof-of-principle study, we collected a cohort of 485 radical prostatectomy specimens to assess correlations between different subtypes of Gleason pattern 4 disease and the presence of adjacent high-risk prostatic adenocarcinoma, defined as LC/IDC or unfavorable histology. All prostatectomies were completely embedded, and all slides re-reviewed to record Gleason score/Grade Group, diameter of the largest cribriform gland (i.e. the longest cross-sectional distance), and all architectural patterns of carcinoma utilizing previously described Canary methodology. The presence and percent of LC/IDC (defined as >0.25 mm) was determined. We also evaluated correlation with the recently proposed "unfavorable histology" as a secondary endpoint. Complex Gleason pattern 4 subtypes, distinct from LC/IDC and unfavorable histology, were termed "borderline histology" and defined as the presence of any of the following patterns: small cribriform/glomeruloid architecture (≤0.25 mm), dominant population of poorly formed glands/small nests, simple glomerulations, and epithelial complexity associated with extravasated mucin (beyond typical mucinous fibroplasia pattern and not containing cribriform >0.25 mm). Comparisons between recorded variables and LC/IDC (or unfavorable histology) utilized the Wilcoxon test for continuous variables and chi-squared test or Fisher's test for categorical variables. Pearson or phi correlation coefficients were used to assess the association between two variables. "Borderline histology" was significantly correlated to LC/IDC (r = 0.55) and unfavorable histology (r = 0.607), both p < 0.001. Specifically, small cribriform/small glomeruloid architecture had the strongest correlation, compared to the other "borderline histology" subtypes (r = 0.646). We demonstrate that "borderline histology" has a strong association with the concomitant presence of high-risk prostate cancer by current histologic definitions (i.e. LC/IDC and unfavorable histology). This proof-of-principle study suggests that large cohort biopsy-RP correlation studies are needed, as the presence of these patterns on biopsy could potentially aid preoperative risk stratification for patients without other high-risk features at initial evaluation.
伴有大筛状腺体/导管内癌（LC/IDC）的前列腺腺癌，即最近提出的不良组织学类型，与根治性前列腺切除术后的不良预后相关。然而，不伴有LC/IDC（或不良组织学类型）的Gleason 4级癌在前列腺切除术后发生侵袭性临床行为的风险极小。作为一项原理验证研究，我们收集了485例根治性前列腺切除标本，以评估Gleason 4级疾病不同亚型与相邻高危前列腺腺癌（定义为LC/IDC或不良组织学类型）之间的相关性。所有前列腺切除术标本均完整包埋，所有切片重新评估以记录Gleason评分/分级组、最大筛状腺体的直径（即最长横截面距离），以及利用先前描述的金丝雀方法记录癌的所有结构模式。确定LC/IDC的存在情况及所占百分比（定义为>0.25 mm）。我们还将与最近提出的“不良组织学类型”的相关性作为次要终点进行评估。不同于LC/IDC和不良组织学类型的复杂Gleason 4级亚型被称为“临界组织学类型”，定义为存在以下任何一种模式：小筛状/肾小球样结构（≤0.25 mm）、主要为形态不良的腺体/小巢、单纯肾小球样结构，以及与外渗黏液相关的上皮复杂性（超出典型黏液性纤维增生模式且不包含>0.25 mm的筛状结构）。记录变量与LC/IDC（或不良组织学类型）之间的比较，对于连续变量采用Wilcoxon检验，对于分类变量采用卡方检验或Fisher检验。使用Pearson或phi相关系数评估两个变量之间的关联。“临界组织学类型”与LC/IDC（r = 0.55）和不良组织学类型（r = 0.607）均显著相关，两者p < 0.001。具体而言，与其他“临界组织学类型”亚型相比，小筛状/小肾小球样结构的相关性最强（r = 0.646）。我们证明，根据当前组织学定义（即LC/IDC和不良组织学类型），“临界组织学类型”与高危前列腺癌的并存密切相关。这项原理验证研究表明，需要进行大规模队列活检-根治性前列腺切除术相关性研究，因为活检中出现这些模式可能有助于对初始评估时无其他高危特征的患者进行术前风险分层。
