Presentation on theme: "Prostate Pathophysiology Charles L. Hitchcock, MD PhD Associate Professor - Clinical Department of Pathology."— Presentation transcript:
Prostate Pathophysiology Charles L. Hitchcock, MD PhD Associate Professor - Clinical Department of Pathology
Learning Objectives Primary Objective: Discuss benign and cancerous growth of the prostate gland. Secondary Objectives: Discuss screening and diagnosis of prostatic tumors. Describe clinical and histological features of benign prostatic hyperplasia (BPH) and prostate cancers, their identification and treatments. Identify issues related to prostate cancer screening and modifiable behaviors that impact its development
Objective 1 Discuss screening and diagnosis of prostatic tumors.
Prostatic Zones B: bladder U: prostatic urethra SV: seminal vesicle 1: Peripheral zone 65% glands 2: Central zone 30% glands 3: Transitional zone 5% of glands 4: Anterior fibromuscular zone
Prostate Specific Antigen PSA PSA is a 33 kDa serine protease Normally produced by prostatic glandular epithelium. Functions in liquefaction of the seminal coagulum
What does a PSA Value Mean A PSA value between 4 ng/ml and 10 ng/ml do not distinguish between a benign and a neoplastic process, but does indicate a 20- 25% risk for prostate cancer. The most common benign processes include: glandular hyperplasia, prostatitis, trauma, and DRE. The risk of prostate cancer >50% for PSA values > 10 ng/mL, and then increases as the PSA level rises.
Key Points Transition zone around the urethra – most common site of BPH. Peripheral zone = most common site of cancers DRE - poor screen for cancer Cystoscopy good for BPH diagnosis
Key Points Elevated PSA is not diagnostic of cancer. PSA and DRE should be used together for screening. Cannot distinguish between a clinically indolent and aggressive carcinoma. Leads to increased biopsies and risk of infection and bleeding. PSA should not be performed without a patient’s informed consent.
Objective 2 Describe clinical and histological features of benign prostatic hyperplasia (BPH) and prostate cancers, their identification and treatments.
Clinical Presentations of Prostate Tumors – Early Onset Frequency Urgency Hesitancy Incomplete emptying Straining Decrease force Dribbling Nocturia Hematuria Benign Prostatic HyperplasiaProstate Cancer Yes NoYes
Clinical Features of Prostatic Tumors Late onset BPH Bladder diverticula Hydronephrosis Pyelonephritis Late onset prostatic cancer Metastatic disease Bone pain – low back Weight loss
Key Points Clinical presentation of BPH and prostatic cancer may be identical when early. Normal glandular tissue has two cell layers Fibromuscular stroma propel secretions out of the gland.
Glandular Tissue Ducts and acini have a similar caliber and appearance. Columnar secretory epithelial cells Underlying basal cells Basement membrane Neuroendocrine Cell
Normal Prostate Fibromuscular Stroma Gland Fibromuscular Stroma
Normal Prostate Fibromuscular Stroma Secretory Cells Basal Cells
Benign Prostatic Hyperplasia Normal Prostate Hyperplasia Nodules Urethra
Key Points Clinical presentation of BPH and prostatic cancer may be identical with early onset. Normal glandular tissue has two cell layers. Fibromuscular stroma propels secretions out of the gland. The incidence of BPH increases with age. Glandular and stromal hyperplasia commonly occurs in the transitional zone. TX: Watchful waiting, hormonal blockade, surgery
Key Points – 2 Prostate Cancer Often multifocal – separate tumors Adenocarcinomas Gleason grading system TNM Staging – incidental (I) to metastatic (IV) Six methods of treatment
Objective 3 Identify issues related to prostate cancer screening and modifiable behaviors that impact its development.
Risk Factors – Nodular Prostatic Hyperplasia Age – incidence increases with age, with 70% of men over 60 having it. Family history – does increase the risk Obesity High BP Low HDL Diabetes Peripheral vascular disease Poor diet and lack of exercise Heart Disease Risk Factors
Risk Factors – Prostate Cancer Gender Most common malignancy in U.S. men >217,000 new cases in 2013 (25% of new cancers in men) 2 nd leading cause of death among men >32,000 deaths in 2013. ~1/6 lifetime death risk mortality African-American men is 2x > Caucasian men Incidence increased in 1988-92 but has declined in 1992-95, and has leveled off since 1995
Risk Factors – Prostate Cancer Age Incidence of latent carcinoma is: 20% in men 50-59 ~70% in 70-80 64% of all prostate cancers are diagnosed in men > 65 years Ethnicity and Race incidence in AA 1.5 - 2x > Caucasian men U.S. >> Asia and South America High fat diet - ?
Risk Factors – Prostate Cancer Hereditary form in ~ 10% of all cases and up to 40 percent of early onset disease. Family history of prostate carcinoma Hereditary prostate cancer gene 1, or HPC1, linked in prostate cancer families to the RNASEL gene.
PSA – Key Points “The PSA test measures the blood level of PSA, a protein that is produced by the prostate gland. The higher a man’s PSA level, the more likely it is that he has prostate cancer. However, there are additional reasons for having an elevated PSA level, and some men who have prostate cancer do not have elevated PSA. The PSA test has been widely used to screen men for prostate cancer. It is also used to monitor men who have been diagnosed with prostate cancer to see if their cancer has recurred (come back) after initial treatment or is responding to therapy. Some advisory groups now recommend against the use of the PSA test to screen for prostate cancer because the benefits, if any, are small and the harms can be substantial. None recommend its use without a detailed discussion of the pros and cons of using the test.” http://www.cancer.gov/cancertopics/factsheet/detection/PSA
Key Points – Prostate Cancer Prostate cancer is primarily a disease of older men. African-American men have up to twice the incidence and mortality of Caucasian men. The RNASEL gene is associated with hereditary forms of prostate cancer. Early onset may be asymptomatic, or associated with hematuria or dysuria; whereas bone pain is a common symptom of late onset. DRE detection of prostatic cancer is derived from the fact that 70% arise in the peripheral zone.
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