Atypical cribriform lesions of the prostate: Clinical significance, differential diagnosis and current concept of intraductal carcinoma of the prostate

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.