Grading & Staging

The Gleason grading system is the most commonly employed grading system in the United States. It is truly a system that relies upon the low-power appearance of the glandular architecture under the microscope. In assigning a grade to a given tumor, pathologists assign a primary grade to the pattern of cancer that is most commonly observed and a secondary grade to the second most commonly observed pattern in the specimen. Grades range from 1 to 5. If the entire specimen has only one pattern present, then both the primary and secondary grade are reported as the same grade. The Gleason score or Gleason sum is obtained by adding the primary and secondary grades together. As Gleason grades range from 1 to 5, Gleason scores or sums thus range from 2 to 10. Well-differentiated tumors have a Gleason sum of 2-4; moderately differentiated tumors have a Gleason sum of 5-6; and poorly differentiated tumors have a Gleason sum of 8-10. Historically, tumors having a Gleason sum of 7 have sometimes been grouped with the moderately differentiated tumors and at other times with the poorly differentiated tumors. One point that needs to be clarified is that the primary Gleason grade is perhaps the most important with respect to placing patients in prognostic groups. This is most important in assessing patients with a Gleason sum of 7. Patients with a Gleason sum of 7 who have a primary Gleason grade of 4 (4 + 3) tend to have a worse prognosis than those who have a primary Gleason grade of 3 (3 + 4). Many clinical series have failed to distinguish between these two populations and, therefore, caution must be exercised in reviewing these series.

Gleason grades 1 and 2 are characterized by small, uniformly shaped glands, closely packed, with little intervening stroma. Gleason grade 3 is characterized by variable-sized glands that percolate between normal stroma. A variant of Gleason grade 3 is referred to as a cribriform pattern. Here a small mass of cells is perforated by several gland lumens with no intervening stroma.

This results in a cookie-cutter-like appearance of cell nests. The border of these cribriform glands is smooth. Gleason grade 4 has several histologic appearances. The characteristic observation common to all Gleason grade 4 patterns is incomplete gland formation. Sometimes glands appear fused, sharing a common cell border. At other times sheets of cell nests are seen or long cords of cells are observed. Cribriform glands can also occur in Gleason grade 4, but the cell masses are large and borders tend to appear ragged, with infiltrating fingerlike projections. Gleason grade 5 usually has single infiltrating cells, with no gland formation or lumen appearance. Comedocarcinoma is an unusual variant of Gleason grade 5 carcinoma that has the appearance of cribriform glands with central areas of necrosis.

The TNM staging system for CaP is presented in

Table 22-3 (American Joint Committee on Cancer, 1997). Note that with respect to the primary tumor categorization (T stage), the clinical staging system uses results of the DRE and transrectal ultrasound (TRUS), but not the results of the biopsy. Some examples to illustrate this staging system follow. If a patient has a palpable abnormality on one side of the prostate, even though biopsies demonstrate bilateral disease, his clinical stage remains T2a. If a patient has a normal DRE, with TRUS demonstrating a lesion on one side and a biopsy confirming cancer, his clinical stage is also T2a (using results of DRE and TRUS). A T1c cancer must have both a normal DRE and a normal TRUS.

Another popular staging system from a historical perspective is the Whitmore-Jewett staging system. One modification of this system is presented in

Table 22-4 to assist the reader in the review of older published series. This system predates the use of TRUS and thus does not incorporate its findings.