What are Gleason grades?

Understanding Gleason Grades in Prostate Cancer

Gleason grades are a standardized histopathological grading system that assigns scores from 1 (least aggressive) to 5 (most aggressive) based on the architectural pattern and degree of differentiation of prostate cancer cells, with these individual grades combined to create a Gleason score that directly predicts tumor aggressiveness and patient outcomes. 1

The Grading System Structure

Individual Gleason grades are assigned by pathologists examining prostate tissue under microscopy, evaluating how much the cancer cells differ from normal prostate architecture 1:

• Grade 1: Well-differentiated cells closely resembling normal prostate glands
• Grade 2: Moderately differentiated with some architectural distortion
• Grade 3: Moderately differentiated with recognizable but irregular glands
• Grade 4: Poorly differentiated with fused, cribriform, or poorly formed glands 2
• Grade 5: Undifferentiated cancer with solid sheets, cords, or comedonecrosis 2

How Gleason Scores Are Calculated

The Gleason score combines the two most predominant grade patterns observed in the biopsy specimen 1:

• The primary grade represents the most common pattern present
• The secondary grade represents the second most common pattern
• Exception: When the highest grade present is neither the primary nor secondary pattern, the score combines the most predominant pattern with the highest grade 1

Example: A tumor with 60% grade 3,35% grade 4, and 5% grade 5 would be reported as 3+4 with tertiary grade 5 1

Important Scoring Rules

When three grades are present, the highest grade and the dominant grade should be used for the final score 1. This is critical because the worst histological grade identified is most important in determining prognosis, and simple identification of only the two predominating grades may underestimate tumor aggressiveness 3.

Cribriform and glomeruloid patterns should always be assigned Gleason pattern 4, regardless of other morphological features 2.

Clinical Significance and Prognostic Value

Each increase in Gleason score directly correlates with increased tumor aggressiveness 1, 4:

• Gleason 6 (3+3): Well-differentiated, slow-growing tumors 4
• Gleason 7: Moderately differentiated with intermediate aggressiveness, where 3+4 has significantly better prognosis than 4+3 5
• Gleason 8-10: Poorly differentiated, rapidly growing tumors with markedly worse outcomes 4

The hazard ratios for biochemical recurrence after radical prostatectomy, relative to Gleason 6, demonstrate this progression: 1.9 for Gleason 3+4,5.1 for 4+3,8.0 for Gleason 8, and 11.7 for Gleason 9-10 5.

Integration into Risk Stratification

Gleason grades form the foundation of prostate cancer risk stratification when combined with PSA level and clinical stage 1, 6:

• Low risk: Gleason ≤6, PSA ≤10 ng/mL, clinical stage T1c-T2a 1
• Intermediate risk: Gleason 7 OR PSA 10-20 ng/mL OR clinical stage T2b 1
• High risk: Gleason 8-10 OR PSA >20 ng/mL OR clinical stage T2c 1

Pathology Reporting Requirements

Standard pathology reports must specify 1:

• The Gleason score (sum of two dominant grades)
• Length of tumor involvement in each biopsy core
• Proportion of Gleason grades 4 and 5 present (modified Gleason score) 1
• Presence of extraprostatic extension
• Number and location of positive cores

Critical Caveats

Tumor grade should not be assessed in patients who have received radiotherapy or hormonal therapy, as treatment-induced changes alter cellular morphology and obscure the original differentiation pattern 1.

The modified Gleason score, indicating the proportion of grade 4 and 5 disease present, provides additional prognostic information and is recommended for comprehensive reporting 1.

Contemporary Grade Group System

A newer Grade Group system (1-5) has been adopted alongside traditional Gleason scoring to address deficiencies in the original system 2, 5:

• Grade Group 1: Gleason ≤6 (3+3)
• Grade Group 2: Gleason 3+4=7
• Grade Group 3: Gleason 4+3=7
• Grade Group 4: Gleason 8 (4+4,3+5+3)
• Grade Group 5: Gleason 9-10

This system provides more accurate prognostic stratification and addresses the psychological impact of telling patients they have "Gleason 6 out of 10," which falsely implies intermediate-grade disease 2, 5.