Clinical significance of subtypes of Gleason pattern 4 prostate cancer

Major updates in prostate cancer grading have been adopted in recent times. These include redefinitions of Gleason pattern (GP) 4 architectural variants and reporting of the grade group (GG) system, which divides prostate cancer into five groups that better stratify patients. Still, the GG system uses the GPs 3, 4 or 5 to define each GG. Patients belonging to GG 2, 3 and 4 have increasing amounts of GP 4 in the composition of their tumors. GP4 is a heterogeneous group of morphologic variants that include poorly formed glands, glomeruloid structures, cribriform glands, and fused glands. Recently published studies suggest that the morphologic subtypes of GP 4 have different clinical significance. While the diagnostic reproducibility of poorly formed glands and fused glands is low, glomeruloid structures and cribriform glands are easier to be distinguished from other morphologies. A growing body of evidence suggests that the presence of cribriform glands is associated with an aggressive clinical course compared with other architectural subtypes. The latest 2014 guidelines issued by the International Society of Urologic Pathology recommend that the percentage of GP 4 be reported on needle biopsies and radical prostatectomy (RP) specimens. The data reviewed here invites consideration for the need to report the subtype of GP 4, especially the presence or absence of cribriform glands.