Gleason grading system

Most often, a urologist or radiologist will remove a cylindrical sample (biopsy) of prostate tissue through the rectum (or, sometimes the perineum), 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.

Gleason Pattern 3. H&E stain.

Gleason pattern 4. H&E stain.

Gleason pattern 4 (left of image) and Gleason pattern 5 (right of image). H&E stain.

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.

In the present form of the Gleason system, prostate cancer of Gleason patterns 1 and 2 are rarely seen. Gleason pattern 3 is by far the most common.

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 (has to be greater than 50% of the total pattern seen).
• Secondary grade - assigned to the next-most frequent pattern (has to be less than 50%, but at least 5%, of the pattern of the total cancer observed).
• Tertiary grade - increasingly, pathologists provide details of the "tertiary" component. This is where there is a small component of a third (generally more aggressive) pattern.

The pathologist then sums the pattern-number of the primary and secondary grades to obtain the final Gleason score. If only two patterns are seen, the first number of the score is that of the tumor's primary grade while the second number is that of the secondary grade, as described in the previous section. If three patterns are seen, the first number of the score would be the primary grade and the second number the pattern with the highest grade. 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 (i.e., the grade of the second-most common cell line pattern).[4]

• 
  Gleason pattern 6 (3+3).
• 
  Gleason pattern 7 (3+4).
• 
  Gleason pattern 8 (4+4).
• 
  Gleason pattern 9 (4+5).
• 
  Gleason pattern 10 (5+5).

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 (well-differentiated), intermediate-grade, moderate to poorly differentiated or high-grade.[5]

More recently, an investigation of the Johns Hopkins Radical Prostatectomy Database (1982-2011) led to the proposed reporting of Gleason grades and prognostic grade groups as: Gleason score ≤ 6 (prognostic grade group I); Gleason score 3+4=7 (prognostic grade group II) indicating the majority is pattern 3; Gleason score 4+3=7 (prognostic grade group III) where pattern 4 is dominant;[6] Gleason score 4+4=8 (prognostic grade group IV); Gleason scores 9-10 (prognostic grade group V).[7] Prostate cancers with a Gleason score ≤ 6 usually have rather good prognoses.

Gleason architectural pattern and Gleason grade are interchangeable terms.

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.[4][7] Differentiation is the degree to which the tissue, in this case the tumor, resembles native tissue. Greater resemblance (lower grade) is typically associated with a better prognosis.)

However, the Gleason score is not simply the highest grade (least differentiated) 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 (if at least 5% of the total), are added together to yield the overall Gleason score.[4][7]

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 (1+1), while the most undifferentiated neoplasm (not resembling native prostate tissue) would have the highest score, Gleason 10 (5+5). Gleason scores range from 2 to 10; by definition there is no score of 0 or 1.[4][7]

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 (bottom, usually cuboidal type) cell layer is lost, with only the top layer (usually columnar to pseudostratified) remaining.

• 
  Gleason score 6 (3+3)
• 
  Cribriform pattern: Gleason grade 4
• 
  Gleason score 7 (3+4) with minor component of cribriform glands
• 
  Gleason score 8 (4+4) with glomeruloid glands
• 
  Gleason score 8 (4+4) with irregular cribriform glands
• 
  Gleason score 8 (4+4) with fused glands with cytoplasmic vacuoles
• 
  Gleason score 8 (4+4) with poorly-formed glands
• 
  Gleason score 9 (4+5) with cribriform glands, some with necrosis
• 
  Gleason score 10 (5+5) with cords of cells
• 
  Gleason score 10 (5+5) with individual cells
• 
  Gleason score 10 (5+5) with solid sheets of cells

The Gleason scoring system takes its name from Donald Gleason, a pathologist at the Minneapolis Veterans Affairs Hospital, who developed it with colleagues at that facility in the 1960s.[8][9]

In 2005 the International Society of Urological Pathology altered the Gleason system, refining the criteria and changing the attribution of certain patterns.[4] It has been shown that this "modified Gleason score" has higher performance than the original one, and is currently assumed standard in urological pathology. In this form, it remains an important tool.[10]

However, problematic aspects of the original Gleason grading system still characterize the 2005 revision. The predominant lowest score assigned is Gleason 3+3 = 6. Patients who are told their Gleason score is 6 out of 10 may interpret that they have a more aggressive intermediate cancer and experience greater anxiety.[11] More importantly, some classification systems fail to clearly distinguish between Gleason 3+4 = 7 and Gleason 4+3 = 7, with the latter having a worse prognosis.

Therefore, in 2014 an international multidisciplinary conference was convened to revise the 2005 system. A 5-point Gleason Grade grouping similar to those such as PI-RADS used with prostate MRI evaluations was proposed to denote prognostically distinct stratification. Grade 1 would indicate the lowest-risk cancer while Grade 5 would indicate the most aggressive disease. The system was tested and validated against 20,000 prostatectomy specimens and at least 16,000 biopsy samples. The majority of conference participants concurred on the superiority of the scale over the 2005 Gleason grading system, pointing to the likelihood that overtreatment could be avoided for those patients whose cancer was assigned Grade 1. The World Health Organization's 2016 edition of Pathology and Genetics: Tumours of the Urinary System and Male Genital Organs has accepted the 2014 system, which can be used in conjunction with the 2005 Gleason system.[12]

• Histopathologic diagnosis of prostate cancer

• Thorson P, Humphrey PA (December 2000). "Minimal adenocarcinoma in prostate needle biopsy tissue". American Journal of Clinical Pathology. 114 (6): 896–909. doi:10.1309/KVPX-C1EM-142L-1M6W. PMID 11338479. Pathology slides and explanation. [Free]
• WHO, Geneva Foundation for Medical Education and Research, Prostate cancer, Gleason score. 51 images.