Can you explain the Gleason scoring system and what the notation 3‑4‑5 indicates?

Understanding the Gleason Score Notation 3-4-5

The notation "3-4-5" in Gleason scoring represents a three-part grading system where 3 is the most predominant cancer pattern, 4 is the second most predominant pattern, and 5 is a tertiary (minor) high-grade pattern present in the tumor. 1

How the Gleason Score is Constructed

The Gleason grading system assigns grades from 1 (least aggressive) to 5 (most aggressive) based on the architectural differentiation of prostate cancer cells under microscopic examination. 1

Standard two-pattern scoring:

• The pathologist identifies the primary grade (most predominant pattern) and secondary grade (second most predominant pattern) 1
• These two grades are added together to create the Gleason score (e.g., 3+4=7) 1
• An important exception: if the highest grade pattern is neither the most nor second most predominant, it replaces the secondary grade in the score 1

Three-pattern notation (tertiary grade):

• When a small component of tumor shows a pattern higher than the two most predominant patterns, it is reported as a tertiary grade 1
• Example: If a tumor contains 60% pattern 3,35% pattern 4, and 5% pattern 5, it should be reported as "3+4 with tertiary grade 5" 1
• This can also be displayed as "3-4-5" where the tertiary pattern is explicitly noted 1

Clinical Significance of Tertiary Patterns

Tumors with a tertiary Gleason grade 4 or 5 behave more aggressively than the sum of the two dominant patterns alone would suggest. 2 This is critical because:

• A Gleason score 3+4=7 with tertiary grade 5 carries worse prognosis than 3+4=7 without tertiary pattern 2
• The presence of any pattern 5, even if focal, indicates more aggressive disease 3
• This information directly impacts risk stratification and treatment planning 2, 4

Modern Grade Group Classification

The International Society of Urological Pathology introduced a simplified system that correlates with Gleason scores: 2, 3

• Grade Group 1: Gleason ≤6 (only well-formed glands) 2
• Grade Group 2: Gleason 3+4=7 (predominantly well-formed glands) 2
• Grade Group 3: Gleason 4+3=7 (predominantly poorly formed glands) 2
• Grade Group 4: Gleason 8 (only poorly formed glands) 2
• Grade Group 5: Gleason 9-10 (lack of gland formation) 2

Risk Stratification Impact

With each increase in Gleason score, there is a measurable increase in tumor aggressiveness and worse clinical outcomes. 1

The presence of pattern 5 as a tertiary grade elevates the tumor to high-risk category: 2, 4

• High Risk definition: Gleason score 8-10 OR PSA >20 ng/mL OR clinical stage T3-T4 2
• 5-year biochemical recurrence-free survival for Grade Group 5: 26% 2
• Treatment requirement: Aggressive definitive treatment is mandatory if life expectancy ≥5 years 4

Common Pitfalls

Critical distinction: Gleason 4+3=7 carries significantly worse prognosis than 3+4=7, despite both summing to 7. 1, 5 The order matters because it reflects which pattern is dominant.

Biopsy limitations: Needle biopsies underestimate tumor grade in 33-45% of cases due to sampling error and tumor heterogeneity. 6 The tertiary pattern may be missed on biopsy but found at prostatectomy.