Gleason grading system
The Gleason grading system is used to help evaluate the prognosis of patients with prostate cancer using samples from a prostate biopsy. Together with other parameters, it is incorporated into a strategy of prostate cancer staging which predicts prognosis and helps guide therapy. A Gleason score is given to prostate cancer based upon its microscopic appearance.
Cancers with a higher Gleason score are more aggressive and have a worse prognosis. Pathological scores range from 2 to 10, with higher numbers indicating greater risks and higher mortality. The system is widely accepted and used for clinical decision making even as it is recognised that certain biomarkers, like ACP1 expression, might yield higher predictive value for future disease course.
The histopathologic diagnosis of prostate cancer has implications for the possibility and methodology of Gleason scoring. For example, it is not recommended in signet-ring adenocarcinoma or urothelial carcinoma of the prostate, and the scoring should discount the foamy cytoplasms seen in foamy gland carcinoma.
A total score is calculated based on how cells look under a microscope, with the first half of the score based on the dominant, or most common cell morphology, and the second half based on the non-dominant cell pattern with the highest grade. These two numbers are then combined to produce a total score for the cancer.
Specimens and processing
Most often, a urologist or radiologist will remove a cylindrical sample of prostate tissue through the rectum, using hollow needles, and biomedical scientists in a histology laboratory prepare microscope slides for H&E staining and immunohistochemistry for diagnosis by a pathologist. If the prostate is surgically removed, a pathologist will slice the prostate for a final examination.Histologic patterns
A pathologist microscopically examines the biopsy specimen for certain "Gleason" patterns. These Gleason patterns are associated with the following features:- Pattern 1 – The cancerous prostate closely resembles normal prostate tissue. The glands are small, well-formed, and closely packed. This corresponds to a well differentiated carcinoma.
- Pattern 2 – The tissue still has well-formed glands, but they are larger and have more tissue between them, implying that the stroma has increased. This also corresponds to a moderately differentiated carcinoma.
- Pattern 3 – The tissue still has recognizable glands, but the cells are darker. At high magnification, some of these cells have left the glands and are beginning to invade the surrounding tissue or having an infiltrative pattern. This corresponds to a moderately differentiated carcinoma.
- Pattern 4 – The tissue has few recognizable glands. Many cells are invading the surrounding tissue in neoplastic clumps. This corresponds to a poorly differentiated carcinoma.
- Pattern 5 – The tissue does not have any or only a few recognizable glands. There are often just sheets of cells throughout the surrounding tissue. This corresponds to an anaplastic carcinoma.
Primary, secondary and tertiary grades
After analyzing the tissue samples, the pathologist then assigns a grade to the observed patterns of the tumor specimen.- Primary grade – assigned to the dominant pattern of the tumor.
- Secondary grade – assigned to the next-most frequent pattern.
- Tertiary grade – increasingly, pathologists provide details of the "tertiary" component. This is where there is a small component of a third pattern.
Scores and prognoses
For example, if the primary tumor grade was 2 and the secondary tumor grade was 3 but some cells were found to be grade 4, the Gleason score would be 2+4=6. This is a slight change from the pre-2005 Gleason system where the second number was the secondary grade.
Key- blue: Gleason pattern 3 region, yellow: Gleason pattern 4 region, red: Gleason pattern 5 region
Gleason scores range from 2 to 10, with 2 representing the most well-differentiated tumors and 10 the least-differentiated tumors. Gleason scores have often been categorized into groups that show similar biologic behavior: low-grade, intermediate-grade, moderate to poorly differentiated or high-grade.
More recently, an investigation of the Johns Hopkins Radical Prostatectomy Database led to the proposed reporting of Gleason grades and prognostic grade groups as:
- Gleason score ≤ 6 ;
- Gleason score 3+4=7 indicating the majority is pattern 3;
- Gleason score 4+3=7 where pattern 4 is dominant;
- Gleason score 4+4=8 ;
- Gleason scores 9–10.
Grading mechanism
The Gleason grade of architectural pattern is sometimes referred to as the Gleason architectural pattern.The Gleason grade is based on tissue architectural patterns rather than purely cytological changes. These tissue patterns are classified into 5 grades, numbered 1 though 5. Lower numbers indicate more differentiation, with pattern 5 being the least differentiated. Differentiation is the degree to which the tissue, in this case the tumor, resembles native tissue. Greater resemblance is typically associated with a better prognosis.
However, the Gleason score is not simply the highest grade pattern within the tumor. Rather, it is a combination of the most two most frequent patterns seen. This recognizes that prostatic carcinomas have multiple patterns and that prognosis is more accurately determined by adding the scores of the two most prevalent patterns. Using this system, the grades of the most prevalent and second most prevalent patterns, are added together to yield the overall Gleason score.
For example, if the most prevalent pattern/grade is 2, and the second most prevalent grade is 1, then the Gleason score is 2+1=3. If the neoplasm has only one pattern, the grade of that pattern is doubled to obtain the score. For example, if a tumor is entirely grade 1, the Gleason score would be 1+1=2. The most differentiated tumor would have the lowest score, Gleason 2, while the most undifferentiated neoplasm would have the highest score, Gleason 10. Gleason scores range from 2 to 10; by definition there is no score of 0 or 1.
Cytological differences between normal prostate and neoplastic glands are evident in changes to the typical two cell layers of the gland. In prostatic adenocarcinoma, the basal cell layer is lost, with only the top layer remaining.