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Prostate Glands (Pathology) Benign Nodular Hyperplasia (BPH)

Prostate Size Changes Definition

Birth Puberty 13 y/o > 40 y/o Other Terms
Small Enlarged Maximum Progressive Enlargement Glandular, Stromal Hyperplasia
Sometimes – Undergo Atrophy Benign Prostatic Hypertrophy, Hyperplasia – BPH
Epidemiology
Prostate Gland Men > 40 y/o (20%)
Men > 70 y/o (90%)

Pathogenesis
Proliferation of Epithelial, Stromal Elements
(occurs extensively in transition zone, periurethral regions)
Androgens (Testosterone), Estrogen play a role
• Not seen in Males castrated before puberty
• Dihydrotestosterone (DHT) (metabolite of testosterone)
Nodular Prostatic Hyperplasia o Mediator of Prostatic Growth
Almost 90% Male develop by 90 y/o o Synthesized in Prostate from circulating testosterone
(Histologic BPH) (enzyme 5α-reductase Type II – localized principally in stromal cells;
Normal Prostate hence those cells (stromal cells) are main site for synthesis of DHT)

Clinical Course
Symptoms occur only in 10% of Men with Nodular Hyperplasia (Clinical BPH)
Lower Urinary Tract Symptoms (LUTS)
Bladder Outlet Obstruction
Carcinoma of Prostate Incomplete Bladder Emptying (Nocturia, Urgency, Hesitancy)
Significant Pathologies Acute, Chronic Urinary Retention
Benign Nodular Enlargement (BPH) Urinary Tract Infection (UTI)
Prostatic Intraepithelial Neoplasia (PIN) Dysuria
Carcinoma of Prostate Bladder Stones
Prostatitis Hematuria
↑ Prostate Specific Antigen (PSA) (common ca use)
Prostatic Intraepithelial Neoplasia (PIN)
Morphology
Definition
Precursor of Carcinoma
Focal Dysplasia/ Carcinoma-In-Situ (CIS) of Glandular Epithelium
Can occur
• Beside Carcinoma
• On its own
Anti-Androgenic Therapy - Can make it Regress Benign Nodular Hyperplasia
↓ Grade PIN ↑ Grade PIN Hyperplasia of Glands
Common Surveillance for Carcinoma (Manditory) Hypertrophy of smooth muscle stroma

Morphology

Benign Nodular Hyperplasia

Hyperplastic Glands
Secretory Cells – Normal Appearance, Markedly ↑
Absence of any Nuclear Atypia
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Carcinoma of Prostate

Epidemiology Etiology
Most common visceral cancer Genetics
• 70/100,000 men in US 5-10% Familial
• 200,000 new cases/yr in US Gene Alteration in Chromosome 1, 17, X
• 20% are lethal Hereditary Prostate Cancer 1 (HPC1) gene
2nd most common cau se of Cancer Death in Men Prostate (PCAP) gene
Peak Incidence of Clinical Cancer – 65-75 y/o Race
Latent Cancer (↑ Prevalent) Blacks ↑
• > 50% in Men > 80 y/o (Blacks – Testosterone Level ↑ 15% compared to Whites)
Diet
+ve Stimulant (↑ Risk) -ve Stimulant (Protective)
Omega-6 Fatty Acids Omega-3 Fatty Acids
↓ Vitamin A ↑ Vitamin E (Antioxidant)
↑ Fat Selenium
↑ Soy (eg. Tofu)
• ↓ Incidence among Asians
• ↑ in Japanese American Men compared to
Native Japanese Men
Hormones (↓ Prevalence)
Androgen Ablation (Regression of Prostate Cancer)
Eunuchs (D o not develop Prostate Cancer)
5α-Reductase Inhibitor (Finasteride)
• ↓ Prevalence of Prostate Cancer
• Carcinoma is ↑ Aggressive (if in Prostate Cancer)

Morphology
Site
Peripheral zone (70%)
Central zone (15-20%)
Transitional zone (10-15%)
Multifocal (mostly)(due to Clonal, Nonclonal Tumours)
Histology
Adenocarcinoma (95% )
TCC (Urothelial)(4%)
Neuroendocrine (1% )

Pathogenesis (Factors)
Hormonal Genetic Environment
Does not occur in ↑ Risk Geographic differences
Eunuchs (1st Order Relative) in incidence of clinical
Inhibits Growth Blacks ↑ cancer(not of Latent Ca)
• Orchiectomy (Symptomatic Ca) Change in incidence
• Estrogen Treatment with migration

Clinical Course
Clinically Silent (often)
Prostatism (like BPH)
Digital Rectal Exam
Prostate Specific Antigen (PSA)
• > 4ng/ml in Peripheral Blood
Prostate Adenocarcinoma
• Free PSA < 25%
Irregular
Transrectal Ultrasound
Yellowish Nodules
Needle Biopsy
Coexist with Hyperplasia
Risk Factors
> 60 y/o
Blacks ↑ (↓ Caucasians, Asians)
Family History – 5-10%
↑ Saturated Fat Diet
(Tofu is Protective)
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Natural History Bone Scans

↓ Grade ↑ Grade Metastasis to
Indolent course Progress to Metastatic Disease • 12th Rib
with relative rapidity • Thoracic Spine
↑ Gleason Score – Poor Survival Represented by ↑ Uptake of Isotope
Grade 3 – 30% Survive

Gleason Score
Based upon mi croscopi c appearance
↑ Gleason Score – ↑ Aggressive, Worse Prognosis
Gleason Score = (a) + (b)
(a) = Most common tumour pattern
(b) = 2nd grade to most common

Screening
Prostatic Specific Antigen (PSA)
(Annually after 50 y/o)
Normal Level < 4.5 ng/mL
5th Decade 6th Decade 7th Decade
2.5 ng/mL 3.5 ng/mL 4.5 ng/mL
Bound, Free PSA Level – Total PSA
(Free PSA is reported as %)
↑ Likelihood of Cancer
↓ Ratio of Free:Total PSA (↓ Free, ↑ Total)
Digital Rectal Examination (DRE)
(Irregular Firm Prostate, Nodule)(Prostate Consistency)
Patient lie on his Left Side
Right Knee, Hip Flexed
Both Knees drawn to Chest
Inspect Skin, Perianal Region
Wear Glove, Lubricate Finger
Insert into Rectum
Palpate Prostate through Anterior Rectal Wall
(Normal – Gland should feel Smooth, Rubbery, Size - Walnut)
Transrectal Ultrasound
↑ False +ve
Not commonly used

Prostatitis
Routes of Metastasis (Spread)
Haematogenous Definition
Blood Inflammation of Gland
Lymphatic Often accompanied by Cystitis
Common Sites Gland Enlarges, Tender
Vertebrae, Pelvis
Bone Causes
Gonorrhoea
UTI
STD

Treatment
Antibiotics
Massage

Symptoms
Gonorrhoea
UTI
STD