Atypical Cribriform Lesions of the Prostate: Clinical Significance, Differential Diagnosis and Current Concept of Intraductal Carcinoma of the Prostate

Division of Urologic Pathology, Miraca Research Institute, Miraca Life Sciences, Irving, TX, USA.
Advances in anatomic pathology (Impact Factor: 3.1). 07/2012; 19(4):270-8. DOI: 10.1097/PAP.0b013e31825c6c0e
Source: PubMed

ABSTRACT 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.


Available from: Rajal B Shah, May 06, 2015
1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Intraductal carcinoma of the prostate and high-grade prostatic intraepithelial neoplasia (PIN) have markedly different implications for patient care but can be difficult to distinguish in needle biopsies. In radical prostatectomies, we demonstrated that PTEN and ERG immunostaining may be helpful to resolve this differential diagnosis. Here, we tested whether these markers are diagnostically useful in the needle biopsy setting. Separate or combined immunostains were applied to biopsies containing morphologically identified intraductal carcinoma, PIN, or borderline intraductal proliferations more concerning than PIN but falling short of morphologic criteria for intraductal carcinoma. Intraductal carcinoma occurring with concurrent invasive tumor showed the highest rate of PTEN loss, with 76% (38/50) lacking PTEN and 58% (29/50) expressing ERG. Of biopsies containing isolated intraductal carcinoma, 61% (20/33) showed PTEN loss and 30% (10/33) expressed ERG. Of the borderline intraductal proliferations, 52% (11/21) showed PTEN loss and 27% (4/15) expressed ERG. Of the borderline cases with PTEN loss, 64% (7/11) had carcinoma in a subsequent needle biopsy specimen, compared with 50% (5/10) of PTEN-intact cases. In contrast, none of the PIN cases showed PTEN loss or ERG expression (0/19). On needle biopsy, PTEN loss is common in morphologically identified intraductal carcinoma yet is very rare in high-grade PIN. Borderline intraductal proliferations, especially those with PTEN loss, have a high rate of carcinoma on resampling. If confirmed in larger prospective studies, these results suggest that PTEN and ERG immunostaining may provide a useful ancillary assay to distinguish intraductal carcinoma from high-grade PIN in this setting.
    American Journal of Surgical Pathology 12/2014; 39(2). DOI:10.1097/PAS.0000000000000348 · 4.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    ABSTRACT: Intraductal carcinoma of the prostate (IDC-P) and high-grade prostatic intraepithelial neoplasia (HGPIN) are two distinct intraductal lesions; the former is usually associated to invasive carcinoma and has an aggressive course while the latter is considered a precancerous lesion. In addition, there are morphologically not well characterized lesions that fall between IDC-P and HGPIN, consequently termed “atypical cribriform lesions (ACLs).” Using whole mounted radical prostatectomy specimens, we evaluated the relationship between these intraductal proliferative lesions and clinicopathological parameters. In this study, ACLs were characterized as a loose cribriform intraductal proliferation with greater architectural complexity when compared to HGPIN, but lacking significant nuclear pleomorphism and/or comedonecrosis. Of 901 radical prostatectomies (2006-2012), IDC-P, ACL, and HGPIN were recorded in 155, 22, 436 cases, respectively. Patients with IDC-P showed more aggressive pathologic features when compared to HGPIN. Invasive cancers in patients with ACL had higher Gleason score (P = 0.00016), larger tumor volume (P = 0.025), and more advanced pT stage (P = 0.023) than those with HGPIN. Cases with ACL showed a higher risk of biochemical recurrence than those with HGPIN and a lower risk than those with IDC-P based on log-rank tests. (P = 0.0045 and P = 0.0069, respectively). In multivariate analysis, the presence of HGPIN was identified as an independent predictor for infrequent biochemical recurrence (P = 0.0058). We confirmed IDC-P as a marker of adverse pathologic features and clinical aggressiveness. Our results suggest that ACL should be distinguished from HGPIN and these lesions mandate active clinical surveillance.
    Human pathology 08/2014; 45(8). DOI:10.1016/j.humpath.2014.03.011 · 2.81 Impact Factor