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Atypical cribriform lesions of the prostate: Relationship to prostatic carcinoma and implication for diagnosis in prostate biopsies

Department of Pathology, University of Michigan, Ann Arbor, USA.
The American journal of surgical pathology (Impact Factor: 4.59). 02/2010; 34(4):470-7. DOI: 10.1097/PAS.0b013e3181cfc44b
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ABSTRACT Atypical cribriform lesions of the prostate (ACL) are cribriform glands lined by cytologically malignant cells with partial or complete basal cell lining. They represent cribriform high-grade PIN (cribriform HGPIN), which can be an isolated finding not associated with PCa (isolated ACL), or "intraductal carcinoma (IDC-P)" that is almost always associated with infiltrative high-grade prostate carcinoma (PCa) (cancer-associated ACL, ACL-PCa). We report the incidence, topographic relation to cancer, and morphologic differences of these 2 lesions in radical prostatectomy and discuss the potential biologic basis and implication for diagnosis in prostate biopsy. ACL was defined as cribriform glands comprising cytologically malignant cells that spanned the entire glandular lumens with partial or complete basal cell lining confirmed by basal cell immunostaining. ACL intermixed with, or within 3 mm from the border of infiltrative PCa was categorized as ACL-PCa and was considered to be equivalent to IDC-P. ACLs other than ACL-PCa were considered as isolated ACL and equivalent to cribriform HGPIN. These histologic features of ACL were reviewed: number of ACL/prostate gland, size, glandular contour (round, irregular, branching), architectural pattern (dense cribriform, irregular cribriform, solid), comedonecrosis, and nuclear features (round and uniform, round with varying sizes, pleomorphic, giant nuclei [6x adjacent nuclei]). In 117 consecutive radical prostatectomy specimens, ACL-PCa and isolated ACLs were found in 21 (17.9%) and 15 (12.8%), respectively. ACL-PCa was more common in PCa with Gleason score more than or equal to 7 and higher tumor volume. The isolated ACLs were more common in Gleason score 6 PCa and their incidence was not significantly different among PCa with different tumor volumes. The mean number of ACL per prostate was 23.8 for ACL-PCa and 2.4 for isolated ACL (P=0.008). The size ranged from 0.2 to 9.0 mm for ACL-PCa, and from 0.2 to 1 mm for isolated ACL. The branching contour was present in 36/43 ACL-PCa, but only in 1/23 isolated ACL (P<0.001). The dense cribriform and solid architecture were present in 6 (14.0%) and 4 (9.3%) of ACL-PCa, but none of the isolated ACLs. Comedonecrosis was present in 14/43 (32.6%) ACL-PCa, and in none of the isolated ACL (P=0.001). The pleomorphic nuclei or giant nuclei at least 6X of the adjacent nuclei, were present in 12 (27.9%) ACL-PCa, but in none of the isolated ACL (P=0.005). ACL can be found both in association with PCa or without associated infiltrative PCa. Isolated ACL is uncommon, and the overwhelming majority of ACLs is associated with high grade (GS> or =7) and high-volume PCa and represents IDC-P. Large gland size (>1 mm), large focus involving many glands (number>6), complex architecture, and high-grade nuclei are characteristic of IDC-P. However, cribriform HGPIN and IDC-P overlap at the "low grade" architectural and morphologic spectrum and are difficult to distinguish based on morphologic criteria alone. If a biopsy contains a small number of ACL glands with "low grade" morphology, it should be diagnosed as "atypical cribriform lesion, cannot distinguish between cribriform HGPIN and IDC-P" and a repeat biopsy should be strongly recommended to rule out unsampled PCa. In contrast, if a biopsy contains ACL with one or several features of large focus, architectural complexity with large branching glands, pleomorphic or giant nuclei, or comedonecrosis, the biopsy should be diagnosed as IDC-P and definitive therapy should be recommended.

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Available from: Rajal B Shah, May 27, 2015
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    • "Please cite this article as: Iczkowski KA, et al, Intraductal carcinoma of the prostate: interobserver reproducibility survey of 39 urologic pathologists, Ann Diagn Pathol (2014), http://dx.doi.org/10.1016/j.anndiagpath.2014.08.010 [9] [10] [11] [12] [13]. In a study of 53 patients with borderline lesions on biopsy, Han et al [9] recommended repeat biopsy for all. "
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    ABSTRACT: The diagnosis of intraductal carcinoma (IDC) of the prostate remains subjective because 3 sets of diagnostic criteria are in use. An internet survey was compiled from 38 photomicrographs showing duct proliferations: 14 signed out as high-grade prostatic intraepithelial neoplasia (HGPIN), 17 IDC, and 7 invasive cribriform/ductal carcinoma. Each image was assessed for the presence of 9 histologic criteria ascribed to IDC. Thirty-nine respondents were asked to rate images as (1) benign/reactive, (2) HGPIN, (3) borderline between HGPIN and IDC, (4) IDC, or (5) invasive cribriform/ductal carcinoma. Intraclass correlation coefficient was 0.68. There was 70% overall agreement with HGPIN, 43% with IDC, and 73% with invasive carcinoma (P < .001, χ(2)). Respondents considered 19 (50%) of 38 cases as IDC candidates, of which 5 (26%) had a two-thirds consensus for IDC; two-thirds consensus for either borderline or IDC was reached in 9 (47%). Two-thirds consensus other than IDC was reached in the remaining 19 of 38 cases, with 15 supporting HGPIN and 4 supporting invasive carcinoma. Findings that differed across diagnostic categories were lumen-spanning neoplastic cells (P < .001), 2× benign duct diameters (P < .001), duct space contours (round, irregular, and branched) (P < .001), papillary growth (P = .048), dense cribriform or solid growth (both P = .023), and comedonecrosis (P = .015). When the 19 of 38 images that attained consensus for HGPIN or invasive carcinoma were removed from consideration, lack of IDC consensus was most often attributable to only loose cribriform growth (5/19), central nuclear maturation (5/19), or comedonecrosis (3/19). Of the 9 histologic criteria, only 1 retained significant correlation with a consensus diagnosis of IDC: the presence of solid areas (P = .038). One case that attained IDC consensus had less than 2× duct enlargement yet still had severe nuclear atypia and nucleomegaly. Six fold nuclear enlargement was not significant (P = .083), although no image had both 6× nuclei and papillary or loose cribriform growth: a combination postulated as sufficient criteria for IDC. Finally, 20.5% of respondents agreed that an isolated diagnosis of IDC on needle biopsy warrants definitive therapy, 20.5% disagreed, and 59.0% considered the decision to depend upon clinicopathologic variables. Although IDC diagnosis remains challenging, we propose these criteria: a lumen-spanning proliferation of neoplastic cells in preexisting ducts with a dense cribriform or partial solid growth pattern. Solid growth, in any part of the duct space, emerges as the most reproducible finding to rule in a diagnosis of IDC. Comedonecrosis is a rarer finding, but in most cases, it should rule in IDC. Duct space enlargement to greater than 2× the diameter of the largest, adjacent benign spaces is usually present in IDC, although there may be rare exceptions.
    Annals of Diagnostic Pathology 09/2014; 18(6). DOI:10.1016/j.anndiagpath.2014.08.010 · 1.11 Impact Factor
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    • "Preoperative clinical and biopsy characteristics analyzed included age, serum prostate-specific antigen (PSA), the number of biopsy cores, the number of positive cores, % involvement of biopsy cores by PCa, the number of cores involved by Gleason pattern 5, % involvement of Gleason pattern 5 of the carcinoma cores, and the presence of perineural invasion, extraprostatic extension, and intraductal spread of invasive PCa. The diagnosis of intraductal spread of invasive PCa was based on previously published diagnostic criteria [12] [13] [14] "
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    ABSTRACT: Accurate recognition of Gleason pattern 5 (GP5) prostate adenocarcinoma (PCa) on core biopsy (NBX) is critical as it is associated with disease progression and the worst clinical outcome. We evaluated 1557 consecutive and prospectively collected NBXs to determine the frequency of diagnosis, morphological subpatterns and its relation to the amount and pattern distribution of GP5 PCa based on the 2005 modified Gleason grading system. Tertiary GP5 was upgraded to a secondary pattern to derive final Gleason score. GP5 accounted for 6% of all NBXs and 14% of PCa cases. GP5 PCas were associated with high-risk pre-operative clinical and biopsy characteristics, regardless of the amount of GP5. Majority (85%) of patients with % GP5> 5% of PCa had the final Gleason score 9–10, compared to % GP5 ≤ 5% of PCa (p < 0.0001). The morphologic subpatterns of GP5 PCas were as follows: infiltrating cords (96%), single cells (76%), solid sheets (29%) and comedocarcinoma (2%). Infiltrating cords and single cells patterns frequently co-existed (76%). The GP5 was distributed in a tertiary (66%), followed by secondary (32%), and primary (2%) component of PCa. Infiltrating cords and single cells were two most frequently encountered patterns, specifically when GP5 involved ≤5% of PCa and represented secondary or tertiary component of PCa. GP5 PCa is a relatively frequent presentation in the contemporary NBX practice. Due to its important prognostic and therapeutic implications, pathologists must be aware of its varied morphological presentations and to the fact that majority of GP5 represent a tertiary component of PCa.
    Human pathology 08/2014; 45(11). DOI:10.1016/j.humpath.2014.07.012 · 2.81 Impact Factor
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    • "While it has been recognised for many years, its clinical importance and prognostic significance are only now being fully acknowledged. Criteria for its diagnosis have been proposed and utilising such criteria, it is recognised that up to 20% of prostate cancers (PCa) will harbour IDC [1] [2] [3] [4]. IDC usually co-exists with high grade, conventional acinar type adenocarcinoma and in cohorts that included men treated mostly between 1980 and 1996 without neoadjuvant treatment. "
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    ABSTRACT: Intraductal carcinoma (IDC) of prostate is a distinct entity associated with higher Gleason score and poor prognosis. The prognostic significance of large cribriform Gleason pattern 4 (LC) in conjunction with IDC has not been previously investigated. The aim of our study was to determine the impact of IDC and LC on biochemical recurrence-free rate (bRFR) in a contemporary prostatectomy cohort. Prostate cancers of 246 prostatectomies, median follow-up 130.6months, were graded with the International Society of Urological Pathology (ISUP) 2005 modified Gleason score (GS) and assessed for the presence of LC and/or IDC. In 57 cases with LC and/or IDC, immunostaining was performed to distinguish LC and IDC. The Kaplan-Meier (KM) method was used to estimate 5-year bRFR probabilities. Cox proportional hazards models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs). Multivariable analysis showed that the presence of any amount of LC or IDC had a highly significant prognostic effect on bRFR (HR 2.98, 95% CI: 1.68-5.28, p=0.0002) after adjusting for GS, surgical margin status and pathological stage. Although IDC alone tended to be associated with a worse prognosis, LC and IDC did not appear to be associated with a difference in bRFR when analysed separately. We demonstrate that the presence of any amount of LC/IDC is a significant prognostic factor after adjusting for Gleason score and T stage in determining patient outcome and we advocate including the presence of either in routine pathology reporting.
    European journal of cancer (Oxford, England: 1990) 04/2014; 50(9). DOI:10.1016/j.ejca.2014.03.009 · 4.82 Impact Factor
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