(1)
Department of Pathology, Sinai Hospital of Baltimore Pathology, Baltimore, MD, USA
Keywords
Gleason gradeGleason scoreProstatectomyPINProstate intraepithelial neoplasiaMost biopsies are performed for an elevated prostate-specific antigen (PSA) level, a palpable nodule, or a history of an abnormal biopsy. In the prostate, you are generally looking only for carcinoma and other rare malignancies, as opposed to non-neoplastic processes.
A typical sextant biopsy are cores from left apex, mid, and base and right apex, mid, and base. Increasingly, urologists sample from the lateral aspect of the gland as well, generating 10–12 different cores or containers. Each container is processed and reported separately.
Approach to the Core Biopsy
On 4× to 10×, scan the length of the core looking for glands that stand out and look different.
Low-power features of prostate cancer (Figure 11.1):
Small individual glands infiltrating among groups of larger benign glands (low-grade cancer).
Crowded glands.
Cribriform glands.
Sheets of cells, or an unusually cellular infiltrate (individual cells of high-grade cancer).
A different color or texture to the glands (cancer cytoplasm may appear a denser pink or more blue; the exact alteration varies by histology lab).
Blue mucin, crystalloids, or dense pink secretions in the lumen.
Absence of desmoplastic response.
Figure 11.1.
Low-power features of carcinoma. Adenocarcinoma (arrows) is seen infiltrating throughout benign glands (arrowheads) in this core biopsy specimen. The malignant glands are often back to back and have relatively denser cytoplasm, no basal layer, and straight luminal borders.
Low-power features of benign glands (Figure 11.2):
Irregularly shaped glands with papillary infoldings (a “frilly” look)
Glands with a modest amount of intervening stroma
Corpora amylacea
Figure 11.2.
Benign prostate glands. These glands have a distinct basal cell layer underlying the epithelial cells (arrowhead) and papillary fronds in the lumen (arrow). Corpora amylacea (CA) are concentrically laminated concretions associated with benign glands.
At high power (20× − 40×), examine any suspicious areas. Look for features of carcinoma:
Large, often cherry-red nucleoli (Figure 11.3).
Figure 11.3.
High-power features of carcinoma. Malignant glands show distinct nucleoli (arrowhead), sharp luminal borders, and an absence of basal cells. Benign glands are seen adjacent to the cancer (arrow).
Straight, crisp luminal borders to the glands.
Enlarged and/or hyperchromatic nuclei (however, pleomorphism is minimal).
Lack of basal cell layer (can be confirmed by immunostains).
Although none of these findings is completely sensitive and specific for cancer, having more malignant than benign features is a pretty good indication. There are three features that, although uncommon, are only seen in cancer:
- 1.
Perineural invasion: the nerve appears as a discrete oval profile with wavy parallel stripes, and the malignant gland must be within the nerve sheath to count as perineural invasion (Figure 11.4). Often the gland will fill up the nerve sheath circumferentially, so the nerve appears to be floating in a gland.
Figure 11.4.
Perineural invasion. A nerve (N) is identified by the undulating axons and nerve sheath nuclei. Malignant glands are seen nearly surrounding the nerve (arrow).
- 2.
Mucinous fibroplasia : hyalinized whorls of organized mucin in the lumen; sometimes the surrounding gland epithelium may be compressed and indistinct. This is analogous to collagenous spherulosis in the breast.
- 3.
Glomeruloid forms: proliferative tangles of cells project into the larger gland lumen, resembling a glomerulus.
Gleason Grading
Once you have identified adenocarcinoma, you must give it a histologic score. Prostatic adenocarcinoma is graded by the Gleason system, which is based on architectural pattern. Cytology (nuclear morphology) is pretty monotonous in prostate cancer and therefore does not affect grade. Historically there were five patterns of adenocarcinoma, from 1 to 5, with 5 being the least differentiated. However, in practice, patterns 1 and 2 have fallen out of use, such that pattern 3 is synonymous with well-differentiated carcinoma and pattern 5 is poorly differentiated. The first and second most prevalent patterns are combined to create the Gleason score, which runs from 6 to 10 (combinations of 3, 4, or 5). A pure pattern 3 tumor would be a 3 + 3 = 6; a mixture of 3 and 4 could be signed out as 4 + 3 = 7 or 3 + 4 = 7, depending on the prevalence of each pattern.
The patterns are as follows:
3: Well differentiated, with well-formed glands. Pattern 3 should have discrete and individual gland profiles such that you can draw a circle around each gland (Figure 11.5).
Figure 11.5.
Gleason pattern 3. Individual, well-formed malignant glands make up pattern 3 cancer. Blue mucin, often associated with carcinoma, is present (arrow).
4: Moderately differentiated, with at attempt at gland formation. Pattern 4 includes fused or ill-defined glands, sheets of cribriform glands, or poorly formed lumens (Figure 11.6).
Figure 11.6.
Gleason pattern 4. The area of cribriform growth (arrow) and adjacent fused glands is typical of pattern 4.
5: Poorly differentiated, with a complete absence of glandular differentiation. Pattern 5 tumors may have solid sheets of single cells or cords of cells (Figure 11.7).
Figure 11.7.
Gleason pattern 5. Individual malignant cells, without evidence of gland formation, are typical of pattern 5. The individual cells still cytologically resemble well-differentiated carcinoma, with round nuclei and prominent nucleoli (circle).
What if all three patterns are present? The guiding principle is that the highest pattern present MUST be worked into the score, as those tumors will be more aggressive. On a biopsy, your Gleason score is comprised of the most common pattern + the highest pattern. For example, a tumor with mostly pattern 3, a bit of 4, and a tiny bit of 5 would be graded 3 + 5 = 8. On a radical prostatectomy, the Gleason score is the first and second most prevalent patterns, and if there is a minor or third component of higher grade, that is assigned a tertiary pattern. In this case, that same tumor would be classified as 3 + 4 = 7 with tertiary pattern 5.
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