Prostate Glands

Prostate Glands (Pathology) Prostate Size Changes Changes Birth Puberty Small Enlarged

13 y/o M aximum aximum

Benign Nodular Hyperplasia (BPH)

> 40 y/o Progressive Enlargement Enlargement

Sometimes – Undergo Atr ophy Prostate Gland

Definition Other Terms Glandular, Stromal Hyperplasia Benign Prostatic Hypertrophy, Hyperplasia – BPH Epidemiology Men > 40 y/o (20%) Men > 70 y/o (90%)

Pathogenesis Proliferation of Epithelial, Stromal Stromal Element (occurs (occurs extensively extensively in transition zone, zone, periuret hral regions) Androgens Androgens (Testosterone), Estrogen play a role •

Nodular Prostatic Hyperplasia Almost 90% Mal e develop develop by 90 y /o (Histologic BPH) BPH) Normal Prostate

Carcinoma Carcinoma of Prostate Significant Pathologies Pathologies Benign Nodular Enlargement (BPH) Prostatic Intr aepithelial aepithelial Neoplasia Neoplasia (PIN) (PIN) Carcinoma of Prostate Prostatitis Prostatic Intraepithelial Neoplasia ( PIN) Definition Precursor of Carcinoma

•

Not seen in Mal es castrated before puberty Dihydrotestosterone (DHT) (metabolite of testosterone) Mediator of Prostatic of Prostatic Growth o Synthesized in Prostate from circulating testosterone o (enzyme 5α-reductase 5α-reductase Type II – localized principally in st romal cells; hence those cells (stromal cells) are main site for synthesis of DHT)

Clinical Course Symptoms occur occur only in 10% of Men wit h Nodular Nodular Hyperplasia (Clinical (Clinical BPH) Lower Lower Urinary Tract Sym ptoms (LUTS) Bladder Outlet Obstruction Obstruction Incomp Incomplete lete Bladder Emptying (Nocturia, (Nocturia, Urg ency, ency, Hesitancy) Acute, Chronic Urinary Retention Urinary Tract Infection (UTI) Dysuria Bladder Stones Hematuria ↑ Prostate S pec pecific ific Antigen (PSA) (common (common ca use) Morphology

Focal Dy splasia/ Carcinoma-In-Situ Carcinoma-In-Situ (CIS) of Glandu Glandular lar Epithelium Can occur Beside Carcinoma On its own Anti-Androgenic Therapy - Can make i t Regress Regress ↓ Grade PIN ↑ Grade PIN Common Common Surveil lance for for Carcinoma Carcinoma (Manditory) • •

Benign Nodular Hyperplasia Hyperplasia of Glands of Glands Hypertrophy of smooth of smooth muscle stroma

Morphology

Benign Nodular Hyperplasia Hyperplastic Glands Secretory Cells – Normal Appearance, Markedly ↑ Absence Absence of any Nuclear Aty pia

Carcinoma Carcinoma of Prostate Epidemiology Most common visceral cancer

Etiology Genetics 5-10% Familial Gene Alteration in Chromosome 1, 17, X Hereditary Prostate Cancer 1 (HPC1) gene Prostate (PCAP) gene Race Blacks ↑ (Blacks – Testosterone Level ↑ 15% compared to Whites) Diet +ve Stim ulant (↑ Risk) -ve Stim ulant (Protective) (Protective)

70/100,000 men in US 200,000 new cases/yr cases/yr in US 20% are lethal lethal • nd 2 most common cause of Cancer Death in Men Peak Incidence of Clinical Cancer – 65-75 y/o Latent Cancer (↑ Prevalent) • •

•

> 50% in M en > 80 y/o

Omega-6 Omega-6 Fatt y Acid ↓ Vit amin A ↑ Fat

Omega-3 Omega-3 Fatt y Acid ↑ Vit amin E (Antioxidant) (Antioxidant) Selenium ↑ Soy (eg. Tofu) • •

↓ Incidence Incidence among A sians ↑ in J apanese American Men compared compared to Native Japanese Men

Hormones (↓ Prevalence) Androgen Ablat ion (Regression (Regression of Prostate Cancer) Cancer) Eunuchs Eunuchs (Do not develop Prostat e Cancer) 5α-Reductase 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% (95% ) TCC (Urothelial)(4%) Neuroendoc Neuroendocrine rine (1%)

Pathogenesis Pathogenesis ( Factors) Hormonal Does not occur in Eunuchs Inhibits Growth • •

Orchiectomy Estrogen Treat men mentt

Genetic ↑ Risk st (1 Order Relative) Blacks ↑ (Symptomati c Ca)

Environment Geographic differences in incidence of clinical cancer(not of Latent Ca) Change in incidence with migr ation ation

Clinical Course Clinically Silent (often) Prostatism (like BPH) Digita l Rectal Exam Exam Prostate Specific Antigen (PSA) > 4ng/ml in Peripheral Blood Free PS A < 25% • Transrectal Ultrasound Needle Biopsy •

Risk Factors > 60 y/o Blacks ↑ (↓ Caucasians, Asians) Family History History – 5-10% 5-10% ↑ Satura ted Fat Diet (Tofu is Protective)

Prostate Adenocarcinom Adenocarcinom a Irregular Yellowish Nodu Nodules les Coexist with Hyperplasia

Natural History ↓ Grade Indolent Indolent course course

↑ Grade Progress to Metastatic Disease with relative rapidity

↑ Gleason Score – Poor Survival Grade 3 – 30% Survive

Bone Scans Metastasis to th

12 Rib Thoracic Spine • Represented by ↑ Uptake of Isotope •

Gleason Score Based upon upon mi mi croscopi c appearance appear ance ↑ Gleason Score – ↑ A ggressive, Worse Prognosis Gleason Score = (a) + (b) (a) = Most common common tumour pat tern nd (b) = 2 grade to most common common

Screening Prostatic Specific Antigen (PSA) (Annually after 50 y/o) Normal Level < 4.5 ng/mL th th 5 Decade 6 Decade 2.5 ng/mL ng/mL 3.5 ng/mL

Bound, 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) (DRE) (Irregular Fir m Prostate, Nodule)(P Nodule)(Prostate rostate Consistency) Consistency) Patient lie on his Left Side Right Knee, Hip F lexed Both Knees drawn to Chest Inspect Skin, Perianal Region Wear Glove, Lubricate Finger Insert into Rectum Palpate Prostate through Anterior Rectal Rectal Wall (Normal (Normal – Gla nd should should feel Smooth, Rubbery, Size - Walnut) Transrectal Ultrasound ↑ False +ve Not commonly used Prostatitis Routes of Metastasis (Spread) Haematogenous Blood Lymphatic Common Sites Vertebrae, Pelvis Bone

Definition Inflammation of Gland Often accompanied by Cystiti Gland Enlarges, Tender Causes Gonorrhoea UTI STD Treatment Antibiotics Massage Symptoms Gonorrhoea UTI STD

th

7 Decade 4.5 ng/mL