Prostate Tumors Overview

The prostate gland can be separated into four sections: anterior, posterior, apical, and basal. The base is located near the bladder, the apex points downwards towards the urogenital diaphragm.

Within the prostate gland, there are four zones: anterior, transitional, central, and peripheral. The peripheral zone is most commonly affected by adenocarcinoma.

The Denonvillier fascia separates the prostate from the rectum, acting as a surgical landmark. This fascia is used to resect the prostate during surgical procedures.

Unlike benign prostatic hyperplasia, prostate cancer commonly originates from epithelial cells, specifically secretory and basal cells. These cells line the glands and produce secretions.

Acinar adenocarcinoma, accounting for 95% of cases, constitutes the most common type of prostate cancer. Acinar structures are the basic functional units of the prostate gland.

Ductal adenocarcinoma, less common than acinar, originates from the ducts that carry secretions. This type is located near the urethra, in the area between the central and transitional zones.

Prostate cancer is the most frequent cancer amongst males in numerous countries. Genetic factors play a significant role; for example, individuals of African descent are at an increased risk, although somatic cases still occur.

Prostate cancer accounts for approximately 14% of all cancers in the United States but has a relatively low mortality rate, around 5%. The rate of death from prostate cancer has remained stable over the past decade.

Prostate-specific antigen (PSA) is a hormone produced by epithelial cells. Elevated PSA levels in blood are associated with prostate cancer, but can also increase in cases of inflammation, infection, or physical trauma.

PSA testing, introduced in the 1990s, led to an apparent increase in new prostate cancer cases. However, this was primarily due to earlier detection of smaller, less aggressive tumors.

Prostate cancer discovered at autopsy is more prevalent across all age groups than clinically diagnosed cases. This suggests that numerous small, non-threatening tumors may go undetected.

The incidence of prostate cancer increases with age, although a small risk exists even in younger men (ages 30-39). Mesodermal/mesenchymal tumors are more common in younger men.

Individuals who have not undergone puberty, have been castrated, or have 5-alpha-reductase deficiency, cannot develop prostate cancer. These conditions are related to testosterone levels.

Surgical castration, estrogen therapies, and anti-androgen drugs can all reduce the incidence of prostate cancer and its spread (metastasis).

Prostate adenocarcinomas are often multifocal, meaning they occur in multiple areas. Most (75-80%) originate in the peripheral zone. Tumors arising in the transitional zone are typically less aggressive.

The anterior zone shows less prostate cancer, possibly due to limited sampling by urologists during biopsies.

Fine needle biopsy is the gold standard for diagnosing prostate cancer. Tissue samples are preserved with formalin, numbered, and ordered.

Transurethral resection for benign prostatic hyperplasia (BPH) can reveal occult (hidden) prostate cancer in 10-16% of cases, mostly affecting the transitional zone.

Imaging techniques like ultrasound, MRI, and PET scans help identify regions of interest (ROI) for biopsy. 3D reconstructions of the prostate can be created for better visualization.

Diagnosis of prostate cancer considers clinical history (PSA levels, US, rectal exam), prior treatments, and histological features. It’s important to distinguish between prostate cancer and changes caused by previous therapies.

Fine needle aspiration is not recommended for prostate cancer diagnosis. It provides cell information but not tissue organization, which is crucial for prostate cancer identification.

Surgical specimens are marked (inked) and sliced for detailed analysis of all zones. Prostate adenocarcinomas often appear as white areas in the peripheral zone and exhibit infiltrative growth.

Gleason score, based on tumor architecture, is used to classify prostate adenocarcinomas into grades reflecting their differentiation and aggressiveness.

Gleason score ranges from 6 to 10, representing different tumor patterns. The two most prevalent patterns within a tumor are identified and their numbers are added together.

The ISUP (International Society of Urological Pathology) classification system was introduced to simplify Gleason score interpretation and provide a clearer indication of prognosis.

ISUP grades 1-5 provide information about tumor aggressiveness and risk of relapse. ISUP 1 (Gleason 3+3) suggests a low risk of metastasis, while ISUP 5 has a high relapse rate even after surgery.

Gleason score is a powerful predictive and prognostic factor for prostate cancer. It can be used to predict tumor volume, margin status, lymph node involvement, probability of relapse, and overall survival.

Gleason 3+3 tumors are characterized by isolated acinar structures. These appear well-defined compared to normal prostate tissue, but basal cells might not be visible.

Gleason 4+3 indicates fusion of acinar structures, forming complex structures with “glomerular proliferation.” This pattern is referred to as pattern 4.

Gleason 4+4 is characterized by “cribriform structures” resembling a sieve. These structures are due to extensive fusion of acinar glands.

Gleason 5+5 is the most aggressive grade, characterized by the complete loss of glandular structure. Other features include solid nets, single cells, and often crystalloids.

Immunocytochemical markers, particularly basal cell markers (P63, cytokeratin 34betaE12) and secretory cell markers (P504, PSA, NKX3.1) are used to aid in the diagnosis of prostate adenocarcinoma.

Evaluation of resection margins after surgery is crucial for predicting biochemical relapse and guiding further treatment. Margins are evaluated both during surgery and afterward.

Intraoperative evaluation of resection margins using frozen section techniques allows for rapid assessment of tumor involvement and helps determine the need for nerve-sparing procedures.

Perineural invasion, where tumor cells grow along nerves, is a common feature of prostate adenocarcinoma. It can be observed during margin evaluation.

Margin positivity, defined as tumor directly touching the inked margin, is a strong predictor of a poor prognosis. The Gleason score of the tumor infiltrating the margin further influences prognosis.

Prostate adenocarcinoma can spread (metastasize) both locally and to distant sites. Local infiltration can involve the bladder, seminal vesicles, and fascia. Metastasis can occur via lymph nodes or blood.

PT4 indicates the tumor has spread to another organ. The specific organs involved vary, and are often associated with the primary tumor location.

ASAP (Atypical Small Acinar Proliferation) is not a cancer diagnosis, but an indication of abnormal tissue requiring further investigation, usually with a repeat biopsy in 6 months.

Prostatic cancer subtypes other than acinar adenocarcinoma are considered high-risk, including ductal adenocarcinoma, mucinous adenocarcinoma, urothelial carcinoma, neuroendocrine carcinoma, basal cell carcinoma, and carcinomas with squamous differentiation.

Prostate cancer can metastasize from other organs, primarily the colon, liver, lungs, and kidneys, but this is rare.