The term “grade” is used to describe the appearance of thin slices of cancer tissue sampled by ultrasound guided transrectal needle biopsy when observed under a microscope. In the case of prostate cancer tissue, the most common system used in the USA to grade the appearance of this tissue is called the Gleason grading system, after the physician who first described this The Gleason system is based exclusively on the architectural pattern of the glands of the prostate tumor. It evaluates how effectively the cells of any particular cancer are able to structure themselves into glands resembling those of the normal prostate. The ability of a tumor to mimic normal gland architecture is called its differentiation, and experience has shown that a tumor whose structure is nearly normal (well differentiated) will probably have a biological behavior relatively close to normal -that is not very aggressively malignant.
The principle is fairly simple, and Gleason grading from very well differentiated (grade 1) to very poorly differentiated (grade 5) is usually done for the most part by viewing the low magnification microscopic image of the cancer. There are important additional details which require higher magnification, and an ability to accurately grade any tumor is achieved only through much training and experience in pathology.
The Gleason Grades
Dr. Donald F. Gleason provided a diagram (oversimplified) in the figure below, to show the progressive deterioration of the cancer cell architecture, and the four dividing lines along this grading system which he discovered are able to identify patients with significantly different prognosis derived from a study which included 2,900 patients.
Gleason Grades 1 and 2: These two grades closely resemble normal prostate. They are the least important grades because they seldom occur in the general population and because they confer a prognostic benefit which is only slightly better than grade 3. Both of these grades are composed by very pale glands which grow closely together. In grade 1 they form a compact mass; in grade 2 they are more loosely aggregated, and some glands invade into the surrounding muscle of the gland.
Gleason Grade 3: This is the most common grade by far and is considered moderately well differentiated (slightly more dedifferentiated than grades 1 and 2). This is because all three grades have a normal “gland unit” like that of a normal prostate; that is, every cell is part of a circular row which forms the lining of a central space (the lumen). The lumen contains prostatic secretion like normal prostate, and each gland unit is surrounded by prostate muscle which keeps the gland units apart. In contrast to grade 2, wandering of glands (invading) into the stroma (muscle) is very prominent and is the main defining feature.
Gleason Grade 4: This 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.This is the main class of poorly differentiated prostate cancer, and its distinction from grade 3 is the most commonly important grading decision.
Gleason Grade 5:In the process of dedifferentiation this is a significant step towards poor prognosis. Its overall importance for the general population is reduced by the fact that it is less common than grade 4, and it is seldom seen in men whose prostate cancer is diagnosed early in its development. This grade too shows a variety of patterns, all of which demonstrate no evidence of any attempt to form gland units. This grade is often called undifferentiated, because its features are not significantly distinguishing to make it look any different from undifferentiated cancers which occur in other organs.
When a pathologist looks at prostate cancer specimens under the microscope and gives them a Gleason grade, he or she in fact will always try to identify the two most predominant architectural patterns of the specimen and assign a Gleason grade to each one. There may be a primary or most common pattern and then a secondary or second most common pattern which the pathologist will seek to describe for each specimen; alternatively, there may often be only a single pure grade.
In developing his system, Dr Gleason discovered that by giving a combination of the grades of the two most common patterns he could see in any particular patient’s specimens, he was better able to predict the likelihood that that particular patient would do well or badly. Therefore, the Gleason score is actually a combination or sum of two numbers. These combined Gleason sums or scores may be determined as follows:
1. The lowest possible Gleason score is 2 (1 + 1), where both the primary and secondary patterns have a Gleason grade of 1 and therefore when added together their combined sum is 2.
2. Very typical Gleason scores might be 5 (2 + 3), where the primary pattern has a Gleason grade of 2 and the secondary pattern has a grade of 3, or 6 (3 + 3), a pure pattern that is one of the most prevalent.
3. Another typical Gleason score might be 7 (3+ 4), where the primary pattern has a Gleason grade of 3 and the secondary pattern has a grade of 4.
4. Finally, the highest possible Gleason score is 10 (5 + 5), when the primary and secondary patterns both have the most disordered Gleason grades of 5.
In summary, with 5 Gleason grades there are 9 possible Gleason scores with 25 different combinations.
What is the significance of the Gleason Score?
The grade of a prostate cancer specimen is very valuable to doctors in helping them to understand how a particular case of prostate cancer can be treated. In general, the time for which a patient is likely to survive following a diagnosis of prostate cancer is related to the Gleason score. The lower the Gleason score, the better the patient is estimated to do. The Gleason Score is a measurement of how aggressive the cancer can potentially be and significantly impacts treatment decisions.