The Gleason grading system is the most widely accepted method for assessing the aggressiveness of prostate cancer. This system assigns a grade to the tumor based on the microscopic patterns of cell growth, which directly informs treatment decisions and predicts patient outcomes. A pathologist examines a tissue sample, often obtained from a biopsy, to determine how closely the cancer cells resemble normal, healthy prostate tissue. The classification focuses on the architectural organization of the tumor, and Gleason Pattern 4 is a specific finding that indicates a significant increase in the cancer’s potential for progression.
Understanding the Gleason Grading System
The Gleason system was developed by pathologist Donald Gleason in the 1960s to classify prostate tumors based solely on their architectural features. This methodology assigns a number from 1 to 5 to describe the degree of glandular organization compared to normal tissue. Pattern 1 represents the most differentiated, least aggressive cancer, featuring well-formed, uniform, and closely packed glands. Pattern 5, conversely, signifies the least differentiated, most aggressive form, where cancer cells are so disorganized that they form sheets or cords with no recognizable glandular structure.
In current practice, Pattern 1 and 2 are almost never used in a biopsy report, meaning the lowest score assigned to prostate cancer is generally 6. Cancers are almost always heterogeneous, containing a mix of different patterns, which is why two numbers are ultimately added together to form the final score.
The Specific Characteristics of Pattern 4
Gleason Pattern 4 describes cancer cells that have begun to lose their distinct glandular formation. Microscopically, this pattern is characterized by the cells starting to merge, creating fused glands where the spaces between them are diminished or completely absent. This fusion signifies that the tumor is no longer neatly contained.
The presence of Pattern 4 often includes specific, complex growth formations recognized as aggressive features. These features include cribriform structures, which are gland-like formations with multiple holes, and glomeruloid structures, which resemble the filtering units of the kidney. Poorly formed or ill-defined glands are also included in this pattern, distinguishing it from Pattern 3 where glands remain individually formed and separate. The recognition of these architectural features places the tumor in a higher risk category than those composed solely of Pattern 3.
Calculating Scores That Include Pattern 4
The final Gleason Score is determined by adding the two most prevalent patterns found in the tissue sample. A pathologist identifies the primary pattern, the most dominant type of cancer growth, and the secondary pattern, the next most common type. For example, if a tumor is mostly Pattern 3 with a secondary component of Pattern 4, the score is reported as 3+4=7. The presence of Pattern 4 means the final score is 7 or higher, immediately placing the cancer into an intermediate or high-risk category.
The order in which the patterns are listed is highly significant and reflects the volume of the more aggressive disease. A score of 3+4=7 means the majority of the cancer is the less aggressive Pattern 3, with a secondary amount of Pattern 4. Conversely, 4+3=7 indicates that the more aggressive Pattern 4 is the primary, dominant component. This distinction is important because the two scores, while mathematically the same, carry a different prognosis. Scores of 4+4=8, 4+5=9, and 5+4=9 all demonstrate that Pattern 4 is a major component, indicating a highly aggressive tumor.
Prognosis and Treatment Pathways
The presence of Gleason Pattern 4 signifies that the cancer is more likely to grow and potentially spread outside the prostate gland, directly influencing the treatment plan. All scores of 7 or higher, which include Pattern 4, are classified into intermediate or high-risk groups. The International Society of Urological Pathology introduced a simplified Grade Group system to better communicate this risk, which is now widely used alongside the traditional Gleason Score.
A Gleason Score of 3+4=7 corresponds to Grade Group 2, representing a favorable intermediate-risk status. However, a score of 4+3=7 is assigned to Grade Group 3, indicating an unfavorable intermediate-risk classification due to the dominance of Pattern 4. Tumors with a score of 8, such as 4+4=8, fall into Grade Group 4, a high-risk category.
For patients diagnosed with Pattern 4, active surveillance is typically not an option, as it is reserved for the lowest-risk cancers. Instead, this more aggressive pattern necessitates definitive treatments like surgery (radical prostatectomy) or radiation therapy. In cases of very high-risk disease, such as 4+5=9 (Grade Group 5), systemic therapies like hormone therapy may be added to the treatment plan.