Prostate cancer stands as the fourth most prevalent cancer worldwide, with an estimated 1.4 million cases in 2020. In the United States, it is the most common cancer among men, representing 27% of all male cancers with an estimated 268,490 new cases in 2022. One in nine American men will receive a prostate cancer diagnosis during their lifetime. Despite the high prevalence, many prostate cancers are indolent and undiagnosed, while a significant proportion are aggressive, making prostate cancer the second leading cause of cancer-related deaths among men in the U.S., with 34,500 deaths annually.
The 2022 edition of the World Health Organization (WHO) Classification of Urinary and Male Genital Tumors marks a substantial advancement in the pathology and genomics of prostate cancer. This review highlights new developments in diagnostic criteria, nomenclature, grading, and molecular features of common prostate malignancies, particularly prostatic adenocarcinoma and neuroendocrine tumors.
High-Grade Prostatic Intraepithelial Neoplasia (HGPIN)
HGPIN is considered a precursor to prostate cancer, characterized by cellular abnormalities confined to pre-existing glandular structures without stromal invasion. It is marked by architectural and cytological atypia, including nuclear enlargement, prominent nucleoli, and increased cellular density. HGPIN is often multifocal and associated with a higher risk of subsequent invasive cancer. The identification of genetic alterations, such as the TMPRSS2-ERG fusion and PTEN loss, has further clarified its role in prostate carcinogenesis.
Intraductal Carcinoma of the Prostate (IDC-P)
IDC-P is a distinct entity characterized by malignant cells filling and expanding prostatic ducts and acini, with preservation of basal cells. IDC-P is commonly associated with high-grade, high-volume invasive prostate cancer and indicates a poor prognosis. The Gleason grading system includes IDC-P, emphasizing its clinical significance. IDC-P often exhibits cribriform, solid, or dense cribriform patterns and shares molecular features with aggressive acinar adenocarcinomas.
Ductal Adenocarcinoma
Ductal adenocarcinoma is an aggressive subtype of prostate cancer, accounting for approximately 0.2-0.4% of prostate cancers in its pure form but often found mixed with acinar adenocarcinoma. It is characterized by large glands lined by tall pseudostratified columnar cells, displaying papillary and cribriform growth patterns. Ductal adenocarcinoma frequently arises in the peripheral zone and may cause urinary obstruction and hematuria when located near the urethra. It has a propensity for visceral metastasis and is associated with a poorer prognosis compared to acinar adenocarcinoma. Differentiation from IDC-P and HGPIN is essential for accurate diagnosis and treatment.
Acinar Adenocarcinoma
Acinar adenocarcinoma represents the majority of prostate cancers, about 95%. It is typically diagnosed through transrectal ultrasound (TRUS)-guided biopsies, often complemented by multiparametric MRI for enhanced accuracy. Morphologically, acinar adenocarcinoma displays a variety of patterns, including infiltrative growth, nuclear atypia, and loss of the basal cell layer. Specific subtypes such as atrophic, foamy gland, microcystic, and pseudohyperplastic variants can mimic benign conditions, complicating diagnosis. High-grade variants like signet-ring-cell, sarcomatoid, and pleomorphic subtypes exhibit aggressive behavior and poor prognosis.
Neuroendocrine Tumors
Neuroendocrine tumors of the prostate are rare and exhibit a spectrum from well-differentiated carcinoid tumors to poorly differentiated small cell carcinoma. These tumors are characterized by neuroendocrine differentiation confirmed by immunohistochemistry markers such as synaptophysin and chromogranin. Neuroendocrine tumors often present with advanced disease and poor prognosis. The updated WHO classification emphasizes the need for recognizing these tumors due to their distinct clinical and therapeutic implications.
Conclusions
The 2022 WHO classification provides a comprehensive framework for the diagnosis and management of prostate cancer, incorporating morphological, immunohistochemical, and genomic data. Understanding the distinct features of various prostate cancer subtypes is crucial for accurate diagnosis, prognosis, and treatment planning. This updated classification underscores the dynamic nature of prostate cancer pathology and the continuous integration of new scientific insights into clinical practice.
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The study was recently published in the Journal of Clinical and Translational Pathology.
Journal of Clinical and Translational Pathology (JCTP) is the official scientific journal of the Chinese American Pathologists Association (CAPA). It publishes high quality peer-reviewed original research, reviews, perspectives, commentaries, and letters that are pertinent to clinical and translational pathology, including but not limited to anatomic pathology and clinical pathology. Basic scientific research on pathogenesis of diseases as well as application of pathology-related diagnostic techniques or methodologies also fit the scope of the JCTP.
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