Updates_of_Prostate_Cancer_from_the_2022_World_Health_Organization

Copyright: © 2023 The Author(s). Published under Creative Commons Attribution-Noncommercial 4.0 International License (CC BY-NC 4.0).
Citation: Guo CC, Czerniak B. Updates of Prostate Cancer from the 2022 World Health Organization Classification of the Urinary and Male Genital Tumors. J Clin Transl Pathol 2023;3(1):26–34.
Published Online: January 17, 2023.

Prostate cancer is a heterogeneous disease with diverse pathological, clinical, and molecular features.
The 5th edition of the World Health Organization (WHO) Classification of Urinary and Male Genital Tumors has been recently released, updating diagnostic criteria, grading, and genomics.
Key updates include developments related to high-grade prostatic intraepithelial neoplasia (HGPIN), acinar adenocarcinoma, intraductal carcinoma (IDC), ductal carcinoma, and neuroendocrine tumors.
Controversial issues around Gleason grading are addressed, particularly focusing on IDC and tertiary grades.
Genetic and epigenetic differences in prostate cancer are highlighted, enhancing understanding of its clinicopathological diversity.

Prostate cancer ranks as the 4th most common cancer globally, with 1,414,259 cases estimated in 2020.
In the USA, it is the most prevalent cancer among men, with 268,490 diagnosed cases in 2022 (27% of all male cancers).
Clinical studies report a prevalence of approximately 30-40% of prostate cancer found during autopsies in Western men.
Prostate cancer is the second leading cause of cancer-related deaths in men in the USA, with about 34,500 annual deaths.

The 5th edition (2022) was released six years after the previous edition, reflecting significant advancements in pathology and genomics.
This review emphasizes the new developments in diagnosing, nomenclature, cancer grading, and molecular features regarding common prostate malignancies, particularly prostatic adenocarcinoma and neuroendocrine tumors.

HGPIN is the most common in situ precursor lesion for prostate cancer, presenting certain morphological characteristics similar to adenocarcinoma, including enlarged nuclei and hyperchromatic secretory epithelial cells.
Presence of prominent nucleoli is a key diagnostic trait.
Forms of HGPIN and genetic alterations associated with it are discussed, including TMPRSS2-ERG gene fusion and loss of PTEN.

Growth Patterns: Updated classifications introduce tufting, micropapillary, and flat patterns for HGPIN, while recognizing less frequent forms like foamy and mucinous.
Cribriform Pattern: No longer recognized within HGPIN since it is associated with IDC and is reclassified as atypical intraductal proliferation (AIP).
AIP details: AIP represents a more complex form of intraductal proliferation without reaching IDC complexity, showing similarities in clinical and molecular features.

HGPIN does not require treatment on its own, but its discovery during biopsies indicates a higher risk (20-40%) for subsequent prostate cancer, warranting re-biopsy recommendations based on the number of cores involved.

IDC represents atypical epithelial cell proliferation within benign ducts or acini, often indicating advanced prostate cancer.
Clear morphological descriptions help differentiate IDC from HGPIN based on growth patterns, nuclear size, and presence of basal cells.

Detection in biopsy specimens requires independent reporting as a predictor for high-grade and advanced-stage prostate cancer.
While IDC's grading remains debated, it should not impact the Gleason score reporting unless linked with invasive cancer.

Ductal adenocarcinoma shows distinct growth features and is often found in combination with acinar adenocarcinoma.
Histological features include tall pseudostratified columnar cells and specific growth patterns, important for distinguishing it from other prostate cancer forms.

Acinar adenocarcinoma constitutes about 95% of prostate cancers. Diagnosis usually involves TRUS-guided core biopsies, with an increasing role for multiparametric MRI in recent practices.
Morphological evaluations include infiltrative patterns, nuclear atypia, and the loss of basal cells as key diagnostic indicators, along with specific architectural features noted for grading.

The Gleason system has evolved through various editions. Updates emphasize aspects such as the significance of the cribriform pattern and IDC in grading decisions. Different grading interpretations can significantly impact clinical outcomes.

The role of genetic and epigenetic modifications in the development and progression of prostate cancer is critical. Key alterations include gene fusions and mutations, particularly those affecting DNA repair mechanisms.

The 5th edition consolidates neuroendocrine tumors into a single chapter. Key histological characteristics are defined, alongside immunohistochemical profiles that may assist in diagnostics.

This new classification encompasses tumors that develop NE differentiation after androgen deprivation treatment, highlighting the complexity of treatment responses in aggressive variants of prostate cancer.

The 5th edition of the WHO classification offers a comprehensive update on prostate cancer features, clarifying diagnostic criteria and prognostic implications.
Emphasizes the integration of morphological, immunohistochemical, genomic, and clinical data to optimize disease management.