Atypical Cribriform Lesions of the Prostate

Division of Urologic Pathology, Miraca Research Institute, Miraca Life Sciences, Irving, TX, USA.
Advances in anatomic pathology (Impact Factor: 3.23). 07/2012; 19(4):270-8. DOI: 10.1097/PAP.0b013e31825c6c0e
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Atypical cribriform lesions of the prostate gland consist of cribriform and rarely solid proliferation of prostate glands populated with cytologically atypical cells with partial or complete basal cell lining. It may represent cribriform "high-grade prostatic intraepithelial neoplasia" (HGPIN) or "intraductal carcinoma of the prostate" (IDC-P). IDC-P is almost always associated with clinically aggressive and high-volume prostate carcinoma. In contrast, cribriform HGPIN is a putative neoplastic precursor lesion, and recent data have questioned whether HGPIN on needle biopsy is associated with a significantly increased cancer risk in subsequent biopsies, and whether the diagnosis mandates rebiopsy within the first year after its diagnosis. As the result, the distinction between these 2 lesions has profound clinical implications, especially on needle biopsies. Since its original description, several studies have attempted to further refine histologic definition of IDC-P in the past decade. Even though presence of certain morphologic features (eg, pleomorphic nuclei or nuclei 6× the size of adjacent nuclei, intraluminal necrosis, and dense cribriform and solid architecture) are seen only in IDC-P, IDC-P may also exhibit "low-grade" morphologic features that overlap with cribriform HGPIN. Emerging molecular data on TMPRSS:ERG gene fusions further support the fact that these 2 lesions are biologically distinct. IDC-P is an uncommon finding in prostate biopsies; however, patients with IDC-P as sole findings without concomitant prostate carcinoma in biopsy are recommended for either definitive treatment or immediate repeat biopsy. This article summarizes the morphologic and molecular characteristics of IDC-P and cribriform HGPIN and an approach to work-up of atypical cribriform lesions in prostate needle biopsies.

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Available from: Rajal B Shah, May 06, 2015
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    • "The literature to date has focused on the histologic similarities and possible misinterpretation of IDC as other histological entities and the attendant management issues surrounding this [12] [13]. Among other entities , IDC can be mistaken for the large cribriform pattern of Gleason grade 4 prostate cancer (LC) or as high grade prostatic intra-epithelial neoplasia. "
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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 · 5.42 Impact Factor
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    • "IDC-P, intraductal carcinoma of the prostate; HGPIN, high-grade prostatic intraepithelial neoplasia; PCa, prostatic carcinoma. Reproduced from Shah and Zhou,22 Adv Anat Pathol 2012; 19: 270-8, with permission from Wolters Kluwer/Lippincott Williams & Wilkins. "
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    ABSTRACT: Intraductal carcinoma of the prostate (IDC-P) is defined as a proliferation of prostate adenocarcinoma cells distending and spanning the lumen of pre-existing benign prostatic ducts and acini, with at least focal preservation of basal cells. Studies demonstrate that IDC-P is strongly associated with high-grade (Gleason grades 4/5), large-volume invasive prostate cancers. In addition, recent genetic studies indicate that IDC-P represents intraductal spread of invasive carcinoma, rather than a precursor lesion. Some of the architectural patterns in IDC-P exhibit architectural overlap with one of the main differential diagnoses, high-grade prostatic intraepithelial neoplasia (HGPIN). In these instances, additional diagnostic criteria for IDC-P, including marked nuclear pleomorphism, non-focal comedonecrosis (>1 duct showing comedonecrosis), markedly distended normal ducts/acini, positive nuclear staining for ERG, and cytoplasmic loss of PTEN by immunohistochemistry, can help make the distinction. This distinction between IDC-P and HGPIN is of critical importance because IDC-P has an almost constant association with invasive carcinoma and has negative clinical implications, including shorter relapse-free survival, early biochemical relapse, and metastatic failure rate after radiotherapy. Therefore, IDC-P should be reported in prostate biopsies and radical prostatectomies, regardless of the presence of an invasive component. This article will review the history, diagnostic criteria, molecular genetics, and clinical significance of IDC-P.
    The Korean Journal of Pathology 08/2013; 47(4):307-315. DOI:10.4132/KoreanJPathol.2013.47.4.307 · 0.17 Impact Factor
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    ABSTRACT: TMPRSS2:ERG gene fusions, the most common molecular subtype of ETS family gene fusions occur in ∼50% of prostate carcinomas (PCas) and ∼20% of high-grade prostatic intraepithelial neoplasia (HGPIN) intermingled with adjacent PCa demonstrating identical gene fusions. ERG gene fusions have not yet been demonstrated in isolated benign prostate tissue, isolated high-grade prostatic intraepithelial neoplasia, or benign cancer mimics. Taken together, ERG gene fusions are the most prostate cancer-specific biomarker yet identified and define a specific molecular subtype of PCa with important clinical and biological implications. ERG gene fusions result in the overexpression of a chimeric fusion transcript that encodes a truncated ERG protein product. Recently, N-terminal epitope-targeted mouse (9FY) and C-terminal-targeted rabbit monoclonal (EPR 3864) ERG antibodies are commercially available and are increasingly utilized as a surrogate for TMPRSS2:ERG gene fusions. Until recently, because of lack of availability of reliable ERG antibody, the most commonly utilized methods for studying ERG aberrations in PCa specimens included fluorescence in situ hybridization or reverse transcriptase polymerase chain reaction. The knowledge gleaned from these studies has significantly improved our understanding of molecular biology of ERG gene fusions. With availability of highly specific anti-ERG monoclonal antibodies, there are now unprecedented opportunities to explore and validate clinical applications of ERG antibody in routine pathology practice, which has just started. This review provides a brief background of molecular biology of ERG gene fusions in PCa and focuses on characterizing the current state of ERG oncoprotein and determining the role of ERG immunohistochemistry in the diagnosis and biological stratification of prostate cancer.
    Advances in anatomic pathology 03/2013; 20(2):117-24. DOI:10.1097/PAP.0b013e3182862ac5 · 3.23 Impact Factor
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