Atypical cribriform lesions of the prostate: relationship to prostatic carcinoma and implication for diagnosis in prostate biopsies.
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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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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ABSTRACT: Intraductal carcinoma of the prostate is characterized by prostatic carcinoma cells growing within ducts and/or acini. These tumors are usually associated with a high-grade Gleason score, large tumor volume and advanced stage. Intraductal carcinoma of the prostate is also a well-known adverse independent prognostic factor regardless of treatment. Recent studies have shown that intraductal carcinoma of the prostate is a distinctive disease entity that is different from invasive prostate carcinoma, which is generally invasive. Although the Gleason score does not consider intraductal carcinoma of the prostate, some cribriform prostate carcinomas graded as pattern 4 could be considered as intraductal carcinomas. The definition of intraductal carcinoma of the prostate is not unified, because it can occur with or without invasive prostate carcinoma. Furthermore, diagnosis of intraductal carcinoma of the prostate without invasive prostate carcinoma by needle biopsy is crucial, but is a rare event. Differential diagnosis of intraductal carcinoma of the prostate includes several pathologies. This is especially true for high-grade prostatic intraepithelial neoplasia, although its distinction is not always straightforward. The present review discusses the concept of intraductal carcinoma of the prostate, and also describes its morphological characteristics, molecular features and clinical outcome. Given the current state of knowledge, the presence of intraductal carcinoma of the prostate should be evaluated and documented correctly in both radical prostatectomy and needle biopsy, and the clinical implications should be taken into consideration during treatment and follow up.International Journal of Urology 11/2014; DOI:10.1111/iju.12657 · 1.80 Impact Factor
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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; DOI:10.1016/j.anndiagpath.2014.08.010 · 1.11 Impact Factor