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Current practice of Gleason grading of prostate carcinoma

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Abstract

The Gleason grading system remains one of the most powerful prognostic factors in prostate cancer and is the dominant method around the world in daily practice. It is based solely on the glandular architecture performed at low magnification. The Gleason grading system should be performed in needle core biopsies and radical prostatectomy specimens where it shows a reasonable degree of correlation between both specimens, and most importantly, it remains vital in the treatment decision-making process. This review summarizes the current status of Gleason grading in prostate cancer, incorporating recent proposals for the best contemporary practice of prostate cancer grading.

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Acknowledgement

This work was supported by the Grant FIS 03/0952 (Madrid, Spain).

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Authors and Affiliations

  1. Department of Pathology, Faculty of Medicine, Reina Sofia University Hospital and Cordoba University Medical School, Avda. Menendez Pidal s/n, 14004, Cordoba, Spain

    Antonio Lopez-Beltran

  2. Department of Pathology, University of Innsbruck School of Medicine, Innsbruck, Austria

    Gregor Mikuz

  3. University Hospital of Jaen, Jaén, Spain

    Rafael J. Luque

  4. Institute of Pathological Anatomy and Histopathology, Polytechnic University of the Marche Region, Ancona, Italy

    Roberta Mazzucchelli & Rodolfo Montironi

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  1. Antonio Lopez-Beltran
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  2. Gregor Mikuz
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  4. Roberta Mazzucchelli
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  5. Rodolfo Montironi
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Corresponding author

Correspondence to Antonio Lopez-Beltran.

Appendix

Appendix

Gleason pattern 1

Nodule of separate, closely packed glands which do not infiltrate into adjacent benign prostatic tissue is very well circumscribed. The glands are of intermediate size and approximately equal in size and shape. The nucleus is typically small, and cytoplasm frequently is abundant and pale-staining. Nuclear and cytoplasm appearances are not taken into account in diagnosis. This pattern is exceedingly rare and usually seen in transition zone cancers (Fig. 1).

Fig. 1
figure 1

Examples of Gleason patterns 1 (a) and 2 (b), Gleason pattern 3 (c‒e), Gleason pattern 4 (f–h), and Gleason pattern 5 (i–k). a–k H & E staining

Full size image

Gleason pattern 2

This pattern is characterized with round to oval glands with smooth ends. The glands are more loosely arranged and not quite as uniform in size and shape as those of Gleason pattern 1. There may be minimal invasion by neoplastic glands into the surrounding non-neoplastic prostatic tissue. The glands are of intermediate size and larger than those in Gleason pattern 1. The variation in glandular size and separation between glands is less than that seen in pattern 3. Although not evaluated in Gleason grading, the cytoplasm of Gleason pattern 2 cancers is abundant and pale-staining (Fig. 1). Gleason pattern 2 is usually seen in transition zone cancers but may occasionally be found in the peripheral zone.

Gleason pattern 3

This pattern is the most common pattern but is morphologically heterogeneous. The glands are infiltrative, and the distance between them is more variable than that in patterns 1 and 2. Malignant glands often infiltrate between adjacent non-neoplastic glands. The glands of pattern 3 vary in size and shape and are often angular (Fig. 1). Small glands are typical for pattern 3, but there may also be large and irregular glands. Each gland has an open lumen and is circumscribed by stroma. Cribriform pattern 3 is rare and difficult to distinguish morphologically from cribriform high-grade prostatic intraepithelial neoplasia (PIN). The latter shows the presence of basal cells. These are lacking in cribriform pattern 3 prostate cancer. This heterogeneous expression of Gleason grade 3 raised an initial subdivision in patterns A, B, and C, respectively.

Gleason pattern 4

Glands appear fused, cribriform, or they may be poorly defined and small. Fused glands are composed of a group of glands that are no longer completely separated by stroma (Fig. 1). The edge of a group of fused glands is scalloped, and there are occasional thin strands of connective tissue within this group. The hypernephroid pattern described by Gleason is a rare variant of fused glands with clear or very pale-staining cytoplasm. Cribriform pattern 4 glands are large or they may be irregular with jagged edges. As opposed to fused glands, there are no strands of stroma within a cribriform gland. Most cribriform invasive cancers should be assigned a pattern 4 rather than pattern 3. Poorly defined glands do not have a lumen that is completely encircled by epithelium.

Gleason pattern 5

This pattern is characterized with an almost complete loss of glandular lumina which are only occasionally present. The epithelium forms solid sheets, solid strands, or single cells invading the stroma; comedonecrosis may be present (Fig. 1). Care must be applied when assigning a Gleason pattern 4 or 5 to limited cancer on needle biopsy to exclude an artifact of tangential sectioning of lower-grade cancer.

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Lopez-Beltran, A., Mikuz, G., Luque, R.J. et al. Current practice of Gleason grading of prostate carcinoma. Virchows Arch 448, 111–118 (2006). https://doi.org/10.1007/s00428-005-0102-4

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