Gleason grade 4 is probably the most important grade because it is fairly common and because of the fact that if a lot of it is present, patient prognosis is usually (but not always) worsened by a considerable degree.
Here also there is a big jump in loss of architecture. For the first time, we see disruption and loss of the normal gland unit. In fact, grade 4 is identified almost entirely by loss of the ability to form individual, separate gland units, each with its separate lumen (secretory space).
This important distinction is simple in concept but complex in practice. The reason is that there are a variety of different-appearing ways in which the cancer’s effort to form gland units can be distorted. Each cancer has its own partial set of tools with which it builds part of the normal structure. Grade 4 is like the branches of a large tree, reaching in a number of directions from the (well differentiated) trunk of grades 1, 2, and 3.
Much experience is required for this diagnosis, and not all patterns are easily distinguished from grade 3. Figure 5 and Figure 6 show two such patterns. This is the main class of poorly differentiated prostate cancer, and its distinction from grade 3 is the most commonly important grading decision.
Figure 5 (above) and Figure 6 (below): Grade 4 carcinomas with two different architectural patterns, each of which has lost the expression of complete “gland units,” seen at higher magnification. There are sheets of cells with randomly scattered lumens.
Illustration courtesy of the late John E. McNeal, MD, Department of Urology, Stanford University School of Medicine.