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      Cribriform Patterned Lesions in the Prostate Gland with Emphasis on Differential Diagnosis and Clinical Significance

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      Cancers
      MDPI AG

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          Abstract

          Cribriform glandular formations are characterized by a continuous proliferation of cells with intermingled lumina and can constitute a major or minor part of physiologic (normal central zone glands), benign (clear cell cribriform hyperplasia and basal cell hyperplasia), premalignant (high-grade prostatic intraepithelial neoplasia), borderline (atypical intraductal cribriform proliferation) or clearly malignant (intraductal, acinar, ductal and basal cell carcinoma) lesions. Each displays a different clinical course and variability in clinical management and prognosis. The aim of this review is to summarize the current knowledge regarding the morphological features, differential diagnosis, molecular profile and clinical significance of the cribriform-patterned entities of the prostate gland. Areas of controversy regarding their management, i.e., the grading of Intaductal Carcinoma, will also be discussed. Understanding the distinct nature of each cribriform lesion leads to the correct diagnosis and ensures accuracy in clinical decision-making, prognosis prediction and personalized risk stratification of patients.

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          Most cited references105

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          The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading Patterns and Proposal for a New Grading System.

          In November, 2014, 65 prostate cancer pathology experts, along with 17 clinicians including urologists, radiation oncologists, and medical oncologists from 19 different countries gathered in a consensus conference to update the grading of prostate cancer, last revised in 2005. The major conclusions were: (1) Cribriform glands should be assigned a Gleason pattern 4, regardless of morphology; (2) Glomeruloid glands should be assigned a Gleason pattern 4, regardless of morphology; (3) Grading of mucinous carcinoma of the prostate should be based on its underlying growth pattern rather than grading them all as pattern 4; and (4) Intraductal carcinoma of the prostate without invasive carcinoma should not be assigned a Gleason grade and a comment as to its invariable association with aggressive prostate cancer should be made. Regarding morphologies of Gleason patterns, there was clear consensus on: (1) Gleason pattern 4 includes cribriform, fused, and poorly formed glands; (2) The term hypernephromatoid cancer should not be used; (3) For a diagnosis of Gleason pattern 4, it needs to be seen at 10x lens magnification; (4) Occasional/seemingly poorly formed or fused glands between well-formed glands is insufficient for a diagnosis of pattern 4; (5) In cases with borderline morphology between Gleason pattern 3 and pattern 4 and crush artifacts, the lower grade should be favored; (6) Branched glands are allowed in Gleason pattern 3; (7) Small solid cylinders represent Gleason pattern 5; (8) Solid medium to large nests with rosette-like spaces should be considered to represent Gleason pattern 5; and (9) Presence of unequivocal comedonecrosis, even if focal is indicative of Gleason pattern 5. It was recognized by both pathologists and clinicians that despite the above changes, there were deficiencies with the Gleason system. The Gleason grading system ranges from 2 to 10, yet 6 is the lowest score currently assigned. When patients are told that they have a Gleason score 6 out of 10, it implies that their prognosis is intermediate and contributes to their fear of having a more aggressive cancer. Also, in the literature and for therapeutic purposes, various scores have been incorrectly grouped together with the assumption that they have a similar prognosis. For example, many classification systems consider Gleason score 7 as a single score without distinguishing 3+4 versus 4+3, despite studies showing significantly worse prognosis for the latter. The basis for a new grading system was proposed in 2013 by one of the authors (J.I.E.) based on data from Johns Hopkins Hospital resulting in 5 prognostically distinct Grade Groups. This new system was validated in a multi-institutional study of over 20,000 radical prostatectomy specimens, over 16,000 needle biopsy specimens, and over 5,000 biopsies followed by radiation therapy. There was broad (90%) consensus for the adoption of this new prostate cancer Grading system in the 2014 consensus conference based on: (1) the new classification provided more accurate stratification of tumors than the current system; (2) the classification simplified the number of grading categories from Gleason scores 2 to 10, with even more permutations based on different pattern combinations, to Grade Groups 1 to 5; (3) the lowest grade is 1 not 6 as in Gleason, with the potential to reduce overtreatment of indolent cancer; and (4) the current modified Gleason grading, which forms the basis for the new grade groups, bears little resemblance to the original Gleason system. The new grades would, for the foreseeable future, be used in conjunction with the Gleason system [ie. Gleason score 3+3=6 (Grade Group 1)]. The new grading system and the terminology Grade Groups 1-5 have also been accepted by the World Health Organization for the 2016 edition of Pathology and Genetics: Tumours of the Urinary System and Male Genital Organs.
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            The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma.

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              The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part B: Prostate and Bladder Tumours.

              It has been 12 yr since the publication of the last World Health Organization (WHO) classification of tumours of the prostate and bladder. During this time, significant new knowledge has been generated about the pathology and genetics of these tumours. Intraductal carcinoma of the prostate is a newly recognized entity in the 2016 WHO classification. In most cases, it represents intraductal spread of aggressive prostatic carcinoma and should be separated from high-grade prostatic intraepithelial neoplasia. New acinar adenocarcinoma variants are microcystic adenocarcinoma and pleomorphic giant cell adenocarcinoma. Modifications to the Gleason grading system are incorporated into the 2016 WHO section on grading of prostate cancer, and it is recommended that the percentage of pattern 4 should be reported for Gleason score 7. The new WHO classification further recommends the recently developed prostate cancer grade grouping with five grade groups. For bladder cancer, the 2016 WHO classification continues to recommend the 1997 International Society of Urological Pathology grading classification. Newly described or better defined noninvasive urothelial lesions include urothelial dysplasia and urothelial proliferation of uncertain malignant potential, which is frequently identified in patients with a prior history of urothelial carcinoma. Invasive urothelial carcinoma with divergent differentiation refers to tumours with some percentage of "usual type" urothelial carcinoma combined with other morphologies. Pathologists should mention the percentage of divergent histologies in the pathology report.
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                Author and article information

                Contributors
                (View ORCID Profile)
                (View ORCID Profile)
                Journal
                CANCCT
                Cancers
                Cancers
                MDPI AG
                2072-6694
                July 2022
                June 21 2022
                : 14
                : 13
                : 3041
                Article
                10.3390/cancers14133041
                ae0274c1-9027-4d07-9e62-b1a4494bc814
                © 2022

                https://creativecommons.org/licenses/by/4.0/

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