Prostate Pathology: What is New in the 2022 WHO Classification of Urinary and Male Genital Tumors?

Abstract

In 2022, after a six-year interval, the International Agency for Research on Cancer (IARC) has published the 5th edition of the WHO Classification of Urinary and Male Genital Tumors, which provides a comprehensive update on tumor classification of the genitourinary system. This review article focuses on prostate carcinoma and underscores changes in the prostate chapter as well as those made across the entire series of the 5th edition of WHO Blue Books. Although no major alterations were made to this chapter, some of the most notable updates include restructure of contents and introduction of a new format; standardization of mitotic counts, genomic nomenclatures, and units of length; refined definition for the terms "variant", "subtype", and "histologic pattern"; reclassification of prostatic intraepithelial neoplasia (PIN)-like adenocarcinoma as a subtype of prostatic acinar adenocarcinoma; and recognition of treatment-related neuroendocrine prostatic carcinoma as a distinct tumor type. Evolving and unsettled issues related to grading of intraductal carcinoma of the prostate and reporting of tertiary Gleason pattern, the definition and prognostic significance of cribriform growth pattern, and molecular pathology of prostate cancer will also be covered in this review.

Keywords: WHO classification; cribriform; intraductal carcinoma; pathology; prostate cancer.

Figure 1.

Prostatic ductal adenocarcinoma (ductal PCa). Ductal PCa showing papillary (A, 200x) and cribriform glands (B, 200x), both of which are lined by the characteristic tall pseudostratified columnar cells with elongated nuclei. Lumens of the cribriform glands in ductal PCa tend to have slit-like shape as opposed to the rounded shape of acinar PCa.

Figure 2.

PIN-like adenocarcinoma. PIN-like adenocarcinoma showing acinar (A, 200x) and ductal (C, 200x) morphology with flat or tufted architecture. Each individual gland is morphologically indistinguishable from HGPIN when taken out of context. IHC stain for p63 demonstrates loss of basal cells in the cancer glands (B, 200x) and preserved basal cell layer in benign glands elsewhere in the same core (not shown).

Figure 3.

Cribriform HGPIN. A cribriform gland (A, 100x) with many prominent nucleoli (B, 400x) among benign glands in an RP specimen. In the authors’ opinion, this cribriform gland can be diagnosed as cribriform HGPIN, a diagnosis that should, however, be avoided in biopsy specimens.

Figure 4.

Atypical intraductal proliferation (AIP). A cribriform lesion (A, 200x) with intact basal cell layer demonstrated by PIN4 stain (B, 200x). The proportion of lumens approaches 50%, which is borderline, and no other features of IDC-P are present. The authors tend to be conservative and would diagnose this lesion as AIP.

Figure 5.

Intraductal carcinoma of the prostate (IDC-P). An intraductal proliferative lesion showing the degree of nuclear atypia that the authors think is sufficient for the diagnosis of IDC-P (A, 400x). PIN4 stain also confirms the presence of basal cell layer (B, 400x).

Figure 6.

Treatment-related neuroendocrine prostatic carcinoma (t-NEPC). t-NEPC composed of prostatic adenocarcinoma (PCa), Gleason pattern 5, and small cell carcinoma (SmCC) with abrupt transition (A, 200x). The high-grade PCa component (upper half) shows relatively ample cytoplasm and distinct nucleoli, whereas the SmCC component (lower half) shows scant cytoplasm, nuclear molding, and inconspicuous nucleoli (B, 600x). PSA is positive in the former but negative in the latter (C, 200x).

Figure 7.

Paneth cell–like differentiation. Prostatic adenocarcinoma (PCa), Gleason score 4 + 3 = 7 (Grade Group 3), with focal Paneth cell–like differentiation (A, 100x), characterized by brightly eosinophilic granules in cytoplasm (B, 600x). Most cancer cells with Paneth cell–like differentiation in this area show cribriform pattern (Gleason pattern 4) and cords of tumor cells (Gleason pattern 5; C, 200x), which were excluded from grading.

Figure 8.

Well-differentiated neuroendocrine tumor (NET). Well-differentiated NET composed of cords and trabeculae of monotonous tumor cells (A, 100x) exhibiting the so-called salt-and-pepper chromatin (B, 600x). A focus of unrelated prostatic adenocarcinoma, Gleason score 3 + 3 = 6, is also incidentally discovered elsewhere in the prostate away from the NET (C, 200x).