Updates of Prostate Cancer from the 2022 World Health Organization Classification of the Urinary and Male Genital Tumors

Abstract

Prostate cancer is a heterogeneous disease with a wide spectrum of pathological, clinical, and molecular features. The diagnosis and classification of prostate cancer have been constantly modified with the incorporation of new data. The 5^th edition of the World Health Organization (WHO) Classification of Urinary and Genital Tumors was recently published six years after the 4^th edition. In this new edition, the classification of prostate cancer has been refined in the diagnostic criteria, grading, nomenclature, and genomics. This paper reviews significant updates to the new WHO classification of prostate cancer, including high-grade prostatic intraepithelial neoplasia, acinar adenocarcinoma, intraductal carcinoma, ductal carcinoma, and neuroendocrine tumors. Controversial issues in the Gleason grading are discussed, such as intraductal carcinoma and tertiary grade. We also highlight distinct genetic and epigenetic alterations in prostate cancer that may contribute to its diverse clinicopathologic features. Overall, the 5^th edition of the WHO classification provides a comprehensive assessment of prostate cancer with morphologic, immunohistochemical, genomic, and clinical data, which may represent an optimal paradigm for diagnosing and treating prostate cancer.

Keywords: Acinar carcinoma; Ductal carcinoma; High-grade prostatic intraepithelial neoplasia; Intraductal carcinoma; Neuroendocrine differentiation; Prostate cancer.

Fig. 1.. High-grade prostatic intraepithelial neoplasia (HGPIN) shows flat and papillary growth patterns, with the overlying epithelial cells having enlarged nuclei with prominent nucleoli.

Note benign prostatic glands for comparison on the left (a) (×200). Cribriform pattern is not recognized as HGPIN in the 5^th edition. On immunostain, HGPIN is positive for racemase and basal cell markers (CK903 and p63) (b) (×200).

Fig. 2.

Atypical intraductal proliferation (AIP) shows atypical loose cribriform glands (a) (×200). On immunostain, AIP is positive for racemase and basal cell markers (CK903 and p63) (b) (×200).

Fig. 3.

Intraductal carcinoma (IDC) shows atypical dense cribriform glands (a) (×100), which are positive for racemase and basal cell markers (CK903 and p63) (b) (×100). IDC exhibits a solid growth pattern (c) (×200) and is positive for racemase and p63 (d) (×200).

Fig. 4.

IDC coexists with acinar adenocarcinoma (a) (×100). On immunostain, IDC is positive for racemase and CK903 and p63, while acinar carcinoma is positive for racemase and negative for CK903 and p63 (b) (×100). Per the GUPS guidelines, the Gleason score is graded as 6 (3 + 3) with IDC, as IDC is not included in the Gleason score. Per the ISUP guidelines, the Gleason score is graded as 7 (4 + 3) with IDC, as IDC is included in the Gleason score.

Fig. 5.. Ductal carcinoma exhibits cribriform and papillary growth patterns.

The cribriform pattern shows small, narrow, slit-like spaces (a) (×200), while the papillary pattern is characterized by the fibrovascular cores lined by columnar cells (b) (×200).

Fig. 6.. Treatment-related neuroendocrine prostatic carcinoma.

It shows mixed features of small-cell carcinoma and poorly differentiated acinar adenocarcinoma (a) (×200). It is positive for synaptophysin (b) (×200) and chromogranin (c) (×200). It shows high mitotic activity with the K-67 labeling index >50% (d) (×200).