Gleason Grading of Prostatic Carcinoma

Overview of Gleason Grading

This schematic diagram developed by Gleason is familiar to all pathologists. Note that in this diagram there are no sharp demarcations between the various Gleason patterns. Rather, there is a gradual transition from one pattern into the other. Assigning a pattern to these "borderline areas", as in any grading system, is highly subjective and is one of the major obstacles (See "Problem Areas") to achieving good interobserver reproducibility.

The Gleason grading system has two unique features. First, it is based solely on architectural pattern; cytologic features are not evaluated. The standard schematic diagram created by Gleason and his group separated architectural features into 1 of 5 histologic patterns of decreasing differentiation, pattern 1 being most differentiated and pattern 5 being least differentiated. These patterns should be assessed at relatively power. The second unique feature of Gleason grading is that the grade is not based on the highest (least differentiated) pattern within the tumor. Gleason realized that most prostatic carcinomas have multiple histologic patterns and found that the prognosis of prostatic carcinoma was intermediate between that of the most predominant pattern of carcinoma and that of the second most predominant pattern. Consequently, in the Gleason system, the most prevalent and the second most prevalent pattern (if at least 5% of the tumor) are added together to obtain a Gleason score - e.g. Gleason grade 3+4=7.

It is important that the primary and secondary patterns always be recorded, followed by the Gleason score as shown. (See "Problem Areas") Synonyms for Gleason score include Gleason sum, and combined Gleason grade. In some settings, authors use the term "grade" for "pattern". We believe that this is potentially confusing and consequently, recommend that the term "pattern" be used when referring to individual pattern grade 1-5. If the tumor has only one pattern, the number of the pattern is simply doubled to obtain the Gleason score - e.g. for a tumor consisting of all pattern 3, the Gleason score, or sum or combined Gleason grade,would be 3+3=6. At times,in addition to the primary and secondary patterns, a third pattern might be present. When this third, or "tertiary" pattern is 4 of 5, it should be reported, in addition to the Gleason score, even when it is less than 5% of the tumor - e.g. Gleason score 3+3=6, with tertiary pattern 4. (See "Proposed Modifications")

Gleason Pattern 1

Gleason pattern 1 is composed of a very well circumscribed nodule of single, separate, closely packed, virtually back-to-back glands which do not infiltrate into adjacent benign prostatic tissue. The glands are round or oval. They are fairly large, relative to most pattern 3 tumors, and are approximately equal in size and shape. Although not evaluated for Gleason grading, the cytoplasm of pattern 1 and 2 carcinomas is usually more abundant and pale-staining than that of the remaining patterns.

Gleason pattern 1 is usually seen in transition zone carcinomas and is very rare. When present, it is typically associated with pattern 2 tumor. Furthermore, its distinction from pattern 2 is not so critical since both patterns have a similar prognosis.

Gleason Pattern 2

Gleason pattern 2 is composed of a fairly well circumscribed nodule of single, separate glands. However, the glands are more loosely arranged and not quite as uniform as those in pattern 1. There may be minimal invasion by neoplastic glands into the surrounding non-neoplastic prostatic tissue. As in pattern 1, the glands are generally larger than those of most pattern 3 tumors. They are round or oval and have open lumens. The glands are smoothly rounded; they are not angular as seen in pattern 3. As in pattern 1, the cytoplasm of pattern 2 is generally more abundant and pale staining than intermediate grade tumors. Pattern 2 is also usually, but not always, seen in transition zone carcinomas.

Gleason Pattern 3

Gleason pattern 3, unlike patterns 1 and 2 (see "Problem Areas"), is clearly infiltrative with extension into adjacent non-neoplastic prostatic tissue. The glands of pattern 3 vary in size and shape and are often elongated or angular. They are usually small ("microglands") and are usually smaller than Gleason pattern 1 or 2 glands. However, some of the glands of pattern 3 may be moderate-sized to large. The small glands of pattern 3, in contrast to small poorly defined glands of pattern 4, are distinct glandular units and one should be able mentally to draw a circle around each of them (see "Undergrading"). Often, the cytoplasm of pattern 3 glands, although not a component of Gleason grading, is amphophilic and may be helpful in distinguishing pattern 3 from patterns 1 and 2 (see "Undergrading").

Cribriform glands may also be Gleason pattern 3. These glands are slightly larger than benign prostatic glands and have regular outer contours. They are reminiscent of intraductal cribriform carcinoma of the breast. Cribriform pattern 3 must be separated from cribriform pattern 4, intraductal cribriform proliferations, and prostatic duct adenocarcinoma (see "Cribriform Patterns"). Small infiltrating glands of Gleason pattern 3 almost always accompany cribriform pattern 3.

Gleason Pattern 4

Gleason pattern 4 glands are not longer single and separate as seen in pattern 1-3. They appear fused, poorly defined with only occasional lumen formation, or cribriform.

Fused glands are chains, nests, or masses of glands that are no longer completely separated by intervening stroma. Fused glands contain occasional strands of residual stroma which may give the appearance of partial separation of the glands. Consequently, fused glands may have a scalloped appearance peripherally. The "hypernephromatoid" pattern described by Gleason is an uncommon variant of fused glands resembling renal cell carcinoma.

Poorly defined glands were not in Gleason's original description of pattern 4. However, most authorities believe that poorly defined glands should now be included. The separation of small-acinar pattern 3 and poorly defined glands of pattern 4 can, at times, be difficult. (see "Borderline Histology")

The cribriform glands of pattern 4 are either large cribriform glands, including cribriform sheets, or small cribriform glands with irregular infiltrating borders. The small cribriform glands with irregular infiltrating borders of pattern 4 must be distinguished from cribriform pattern 3, in which the small cribriform glands have regular borders. Fragments of cribriform carcinoma in needle biopsies of prostate imply a large cribriform gland or sheets with little supporting stroma and are designated pattern 4. (see "Cribriform Patterns")

It is important to be able to separate pattern 3 from pattern 4 because this separation usually distinguishes Gleason score 6 from Gleason score 7 tumors, the latter having a significantly worse prognosis (see "Borderline histology", "Prognosis" and "Tertiary Gleason Patterns").

Gleason Pattern 5

Gleason pattern 5 tumor has virtually no glandular differentiation. It is composed of solid sheets, solid cords, or single cells. Nests of tumor with central comedonecrosis are also classified as pattern 5. It is controversial whether cribriform glands of cancer, that otherwise would be considered Gleason pattern 4, should be considered Gleason pattern 5 if comedonecrosis is present. Separating poorly defined pattern 4 glands from cords and nests of tumor with virtually no glandular differentiation or with only vacuoles is a problem (see "Borderline Histology"). However, this separation is usually not critical because in this instance any combination of the two patterns will lead to a Gleason score 8, 9, or 10, all of which are considered to be poorly differentiated.