WHO_Prostate

Page 1: WHO Classification of Tumours - Prostate Cancer Overview

James G Kench - Royal Prince Alfred Hospital, The University of Sydney, NSW Health Pathology
Mahul B Amin - University of Tennessee Health Science Center, etc.
Additional authors from various international institutions.

The fifth edition of the WHO Classification of Tumours of the Urinary and Male Genital Systems updates the classification, diagnosis, and prognosis of prostate cancer.
Key updates include recent grading modifications and significant advancements in assessing prognosis.

Prostatic Intraepithelial Neoplasia (PIN)-like Carcinoma
- Reclassified from being synonymous with ductal carcinoma to a subtype of acinar adenocarcinoma.
Treatment-related Neuroendocrine Prostatic Carcinoma
- Specific section acknowledging the correlation between androgen deprivation therapy and neuroendocrine morphology, focusing on lineage plasticity.
Renaming of Basal Cell Carcinoma
- Changed to Adenoid Cystic (Basal Cell) Carcinoma due to MYB::NFIB gene fusion presence in many cases.
Grading Issues
- Current discussions about the prognostic significance of cribriform growth patterns.
Intraductal Carcinoma of Prostate (IDC-P)
- Expanded understanding with a recommendation to refer to atypical intraductal proliferation (AIP) for less distinctive lesions.

Prostate cancer is the fourth most common cancer globally and the eighth leading cause of cancer-associated death.
Significant contributors to morbidity and mortality.

The prostate chapter reflects prevailing changes from earlier editions, particularly in:
- Third Edition: Adoption of Gleason grading.
- Fourth Edition: Introduction of the concept of grade groupings and IDC-P as a distinct entity.

Increasing recognition of various tumor growth patterns, especially in the context of grading and prognosis, particularly high-grade prostatic intraepithelial neoplasia (HGPIN) and IDC-P.
The new terminology incorporates terms that better reflect clinicopathological relationships.

Terminology now focuses on subtypes for distinct entities instead of variants, promoting clarity in clinical and pathological contexts.

Ductal adenocarcinoma remains a distinct type of prostate adenocarcinoma, although its classification as a subtype of acinar adenocarcinoma is under consideration due to overlap and interobserver variability.
Defined as radical prostatectomy cases with more than 50% ductal morphology.

Studies suggest ductal adenocarcinomas show clonal relatedness to coincident acinar adenocarcinomas, with shared ERG rearrangements and molecular alterations.
Differences in frequency of molecular aberrations indicate distinct clinical behaviors, leading to higher biochemical recurrence and lower overall survival rates compared to acinar adenocarcinoma.

Classified as tumors showing complete or partial neuroendocrine differentiation post-androgen deprivation therapy.
Defined to capture both primary and metastatic cases.

Found in 10.5% to 17% of patients with metastatic castration-resistant prostate cancer.
Distinguishes itself through unique clinical patterns and typically worse prognoses with a median overall survival between 7-53.5 months post-diagnosis.

Revised nomenclature to reflect similarities with salivary gland counterparts and the pathology of basaloid features.
Characterized histologically by patterns like adenoid cystic and basal comprising small nests of cells.

Identified presence of MYB::NFIB gene fusions in a notable subset (29%-47%) of cases, primarily those with adenoid cystic patterns.

Recognition of the importance of tumor growth pattern, particularly cribriform structures, significantly impacts tumor behavior and patient management outcomes.
Studies emphasize the relationship between cribriform patterns and biochemical recurrence, metastasis-free survival, and disease-specific survival.

The 2019 ISUP and GUPS recommend specifically reporting cribriform carcinoma presence due to its prognostic value. Current consensus definitions outline that cribriform pathology should involve visible glandular lumina without stroma interference.

Retained and expanded in the fifth edition due to clinical significance.
Characterized by architectural and cytological atypia beyond HGPIN and carries substantial prognostic implications for invasive carcinoma likelihood.

Current debates around whether IDC-P should influence Gleason scoring due to its associations with higher-grade carcinomas or possibly serve as a precursor to malignancies.

New category for lesions exhibiting more atypia than HGPIN but failing to meet IDC-P criteria—offers a diagnostic utility considering potential for higher-grade associations.

Ongoing developments in the WHO Classification around prostate cancer reflect advances in pathology, diagnostic practices, and emerging molecular insights which continue to pose dynamic challenges and opportunities in clinical management.