gleason classifaction histopathology and scoring

Grade group and score, prostatic carcinoma

1. Updated gleason grading & staging of Prostatic Carcinoma Moderator Speaker Dr. Alok Mohan Dr. Sumit Chahal Professor PG-JR 2 03-09-2021 1

2. Introduction Prostate gland is a fibromusculoglandular organ. It is a retro-peritoneal organ encircling the neck of bladder and urethra that lacks a distinct capsule. In a normal adult, the prostate weighs approximately 20 gm. 03-09-2021 2

3. 03-09-2021 3 Prostate can be divided into 4 biologically and anatomically distinct regions: Peripheral zone Central zone Transition zone Periurethral zone These zones are at risk for different types of proliferative lesions.

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5. 03-09-2021 5 Most hyperplasia arise in the transition zone and often produce urinary obstruction. Most carcinomas originate in the peripheral zone and may be palpable during digital examination of rectum.

6. Histological features The prostate consists of glands separated by abundant fibromuscular stroma. The glands are lined by two layers of cells: a basal layer of low cuboidal basal epithelium covered by a layer of columnar secretory cells which often contain small papillary infoldings. 03-09-2021 6

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8. Benign Prostatic Hyperplasia BPH (also referred to as nodular hyperplasia) is the most common benign prostatic disease in men older than age 50 years. BPH is characterised by proliferation of benign stromal and glandular elements. DHT , an androgen derived from testosterone is the major hormonal stimulus for proliferation. 03-09-2021 8

9. 03-09-2021 9 BPH most commonly affects the inner peri-urethral zone and transition zone of the prostate, producing nodules that compress the prostatic urethra.

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11. Carcinoma of Prostate Carcinoma of prostate is very common in older men. In the United States, it is the most common malignancy in men. Prostate carcinomas range from very indolent lesions, which are being increasing managed by active surveillance, to lethal disease that requires definitive therapy. 03-09-2021 11

12. 03-09-2021 12 Carcinoma of prostate arise most commonly in the outer, peripheral gland and may be palpable by rectal examination. The most common driver mutations in prostate cancer are gene rearrangements that result in androgen dependent overexpression of Ets family transcription factors, most commonly ERG or ETV1.

13. 03-09-2021 13 Characteristically, on cross section, the neoplastic tissue is gritty and firm to palpation but it is sometimes extremely difficult to visualise by eye. Histologically , most adenocarcinomas consists of glands arranged in well defined, easily recognised patterns, which are used to grade these tumours. The glands are typically smaller than benign glands and are lined by single uniform layer of cuboidal or low columnar epithelium.

14. 03-09-2021 14 In contrast to benign glands, malignant glands have tightly packed cells and characteristically lack branching and papillary infoldings. The outer basal layer typical of benign glands is absent. The cytoplasm of tumour cells ranges from pale clear to a distinctive amphophilic appearance.

15. 03-09-2021 15 Nuclei are enlarged and often contain one or more large nucleoli. There is some variation in nuclear size and but in general pleomorphism is not marked. Mitotic figures are uncommon.

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17. Prostatic Intraepithelial neoplasia(PIN) PIN consists of architecturally benign large, branching prostatic acini lined by atypical cells with prominent nucleoli that may be cytologically identical to carcinoma. Unlike malignant glands, glands involved by PIN retain, at least partially, a layer of basal cells and have an intact basement membrane. 03-09-2021 17

18. Gleason Grading System Grade and stage are the most important prognostic factors in prostate cancer. Grading is performed using the Gleason system, which stratifies prostate into 5 grades on the basis of glandular patterns of growth. 03-09-2021 18

19. Historical overview The Gleason Grading System for prostate adenocarcinoma originated in the 1960s- 1970s from a pioneering randomized, well controlled, prospective study initiated by the Veterans Administration of the USA, in which over 2900 patients were included. 03-09-2021 19

20. 03-09-2021 20 Dr. Donald Gleason detailed and summarized the histological growth patterns (grades) of prostate adenocarcinoma and the correlation with clinical data such as staging and prognosis were analysed.

21. Grades of Gleason Grading System There are 5 grades according to Gleason Grading System. Grade I corresponds to well differentiated tumours in which neoplastic glands are uniform and round in appearance and are packed into well-circumscribed nodules. 03-09-2021 21

22. 03-09-2021 22 In contrast, Grade V tumours do not form glands, with tumour cells infiltrating the stroma in cords, sheets and solid nests. Other grades fall between these extremes.

23. Gleason grade 1 Closely packed but separate, uniform, rounded to oval, medium-sized acini. Infiltration of malignant acini into surrounding stroma, including encirclement of benign glands, or penetration between benign glands, is indicative of a higher grade carcinoma. Also, the back-to-back glands should be separated by thin stromal rims. If tumor cells form back-to-back glands, without intervening stroma, then the Gleason pattern is high-grade 4, not pattern 1 or 2.  03-09-2021 23

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25. Gleason grade 2 Well-defined masses that are not as circumscribed as pattern 1 Tumor–stromal boundary that is not as rounded as pattern 1.  Glands of pattern 2 display a degree of separation by stroma with an average separation distance of less than one gland diameter.  Distinctive characteristic of pattern 2 adenocarcinoma is the increase in variability in gland size and shape. 03-09-2021 25

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27. Gleason grade 3 Moderately differentiated grade is the most common pattern of growth of prostatic adenocarcinoma. It comprises of individual, discrete and distinct neoplastic glands, typically small but often of variable sizes and infiltrating into the stroma in between the benign glands. 03-09-2021 27

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29. Gleason grade 4 Gleason pattern 4 features fused glands, which are no longer individual or distinct, resulting in broad, irregular fused glandular or cribriform patterns. A variant is the hypernephroid pattern with sheets of cells with abundant clear cytoplasm. 03-09-2021 29

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31. Gleason grade 5 Most poorly differentiated pattern of prostatic carcinoma, which presents in two forms—5A and 5B. Pattern 5A - resembles the comedo type of intraductal carcinoma of the breast, with smooth, rounded masses, cords or cylinders of carcinoma. The necrosis is typically central, being surrounded by papillary, cribriform, or solid masses of carcinoma 03-09-2021 31

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34. 03-09-2021 34 Most tumours contain more than one pattern; in such instances, a primary grade is assigned to the dominant pattern and a secondary grade is assigned to the second most frequent pattern. The two numeric grades are then added to obtain a combined Gleason Score.

35. 03-09-2021 35 The sum of the primary ( eg. Gleason 3) and secondary ( eg. Gleason 4) patterns (grades) yields the Gleason Score ( eg. Gleason score = 3+4 = 7).

36. 03-09-2021 36 Tumours with only one pattern are treated as if their primary and secondary grades are the same and hence, the number is doubled for the score. Eg. 3, the primary and secondary patterns are considered the same, yielding a Gleason score of 3+3 = 6.

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42. Reporting Gleason grade /score For needle biopsies , identifiable high grade component of any quantity should always be included in the Gleason score, as it indicates high probability of finding significant high grade tumor in the prostate. In contrast, lower grade patterns occupying less than 5% of tumor should be ignored (5% cut off rule). 03-09-2021 42

43. 03-09-2021 43 In addition to the basic operation of summing up the primary and secondary patterns to yield the Gleason score, one must remember that when tertiary component (i.e., occupying the smallest percentage when three patterns are present) is identified, but is of the highest grade among the three in needle biopsy, this component should be included as the second grade.

44. 03-09-2021 44 That is, Gleason score = primary pattern + the highest pattern, in this scenario. For eg. , in a biopsy with Gleason patterns 3(80%), 4(15%) and 5(5%), the Gleason scores should be 3+5=8, rather than 3+4=7.

45. 03-09-2021 45 For multiple biopsy cores with different grades , grading individual cores has been recommended, as long as the anatomical sites of the cores could be identified (by submission in separate containers and separate embedding/sectioning, or by inking in different colours), whereas an overall score may also be provided.

46. 03-09-2021 46 For radical prostatectomy specimens and TURP samples , the basic rules (Gleason score= primary + secondary patterns, and the 5% cut-off rule for lower-grade secondary pattern)apply. It differs from reporting needle biopsies in that tertiary, highest grade should be reported separately, preferably with an accompanying note, rather than incorporated into the Gleason score.

47. 03-09-2021 47 Also separate Gleason score should be assigned to each dominant tumor nodule in cases of multiple nodules with different grades. Rarely, a non-dominant nodule may show a higher score, and the grade for this nodule should be reported separately because it likely will drive the biologic behaviour of the cancer.

48. Staging of prostatic adenocarcinoma Pathologic staging of prostatic cancer is used in combination with the grade to stratify management of prostate cancer. pTNM staging is based on tumor extent (T) and presence of nodal or distant metastasis (N and M). 03-09-2021 48

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50. 03-09-2021 50 THANK YOU