Neoplasms of Prostate.pdf

Neoplasms of Prostate Prostate Cancer Most common non-cutaneous cancer in men Slow growing cancer Occurs through metastatic disease is common Prostate Specific Antigen (PSA) Glycoprotein produced by prostate epithelial cells Increases due to Hypertrophy, cancer or infection Elevated serum levels see...

Neoplasms of Prostate Prostate Cancer Most common non-cutaneous cancer in men Slow growing cancer Occurs through metastatic disease is common Prostate Specific Antigen (PSA) Glycoprotein produced by prostate epithelial cells Increases due to Hypertrophy, cancer or infection Elevated serum levels seen in prostatic adenocarcinoma Normal PSA is < 4ng/mL o Normal seen in ductal carcinoma of prostate Nodular Hyperplasia Benign Prostatic Hyperplasia AKA benign prostatic hypertrophy (BPH) Hormonally dependent on testosterone and dihydrotestosterone production May occur with normal testosterone levels Periurethral (transitional zone) nodules compress urethra and cause obstructive symptoms Symptoms subsequent to chronic bladder obstruction Pathogenesis of Prostatic Nodular Hyperplasia o Prostatic enlargement depends on activation of androgen by DHT o Estrogen increases number of androgen receptors o Type II 5-a-reductase in stromal cells convert testosterone to DHT o DHT stimulates stromal and epithelial cell proliferation by autocrine and paracrine manners Pathologic Findings of Prostatic Nodular Hyperplasia o Enlarged lateral and medial lobe o Trabeculation of bladder due to chronic obstruction § Bladder calculus is present § Nodules within glands Benign hyperplasia can involve both glands and stroma Prominent glandular components Adenocarcinoma of Prostate Originated from luminal cells Most common noncutaneous cancer in men in the US Environmental factors Hormonal factors: androgens, insulin, insulin-like growth factor Genetic factors o Ashkenazi Jewish ancestry o BRCA1, BRCA2 o Lynch syndrome Higher risk o Increased consumption of animal fats o Cigarette smoking o Obesity Adenocarcinoma Pathogenesis o Androgen and androgen receptor signaling critical o CRPC: Castrate-Resistant Prostate Cancer o Autocrine signaling results in tumor independence to stromal cells o PSA increases o Androgen receptor normal o HK2: human kallikrein-2 (HK2) o Gritty and firm, gray-yellow, poorly delimited, but usually invisible o Only luminal cells, no basal cells o Large nuclei with prominent nucleoli o Immunohistochemistry profiles § Tumor cells: Overexpress alpha methylacyl-CoA racemace (AMACR) § Basal cells: Express high molecular keratin and p63; absent in cancer Clinical Features of Adenocarcinoma o Nonspecific symptoms including urinary complaints or retention, back pain, hematuria o Most cases asymptomatic o Abnormal digital rectal examination o PSA serum levels § 8% of 50% >10 ng/ml Gleason Scores Based on histologic pattern When one pattern present: primary and secondary patterns are given the same grade Score from 1-5 each Sum of 2-10 1: Very rare, single, separate, closely packed, uniform round glands in a circumscribed nodule with pushing borders 2: Like grade 1 but more variability in gland shape and more stroma separating glands, NO infiltration 3: Most common, single, separate, more variable glands, irregularly separated, poorly defined edge, infiltrative 4: Coalescent or fused glands 5: 2 patterns: comedocarcionoma (papillary / cribriform carcinomas with central necrosis) or solid cords without glandular differentiation solid sheets of tumors with minimal glandular differentiation Metastatic and Advanced Prostate Cancer Most prostatic cancers detected at early stage, due to PSA screening (helps monitor) Advanced disease less common, but more common in African American men Metastasis likely if Gleason score > 6 (common in bones) May become castration-resistant eventually Treatment: Androgen deprivation therapy, chemotherapy, secondary hormonal therapy, etc Quiz Which statement is CORRECT regarding the Prostate Specific Antigens (PSA)? A. B. C. D. C Decreased serum levels seen in prostatic adenocarcinoma Decreases with hypertrophy Elevated serum levels seen in prostatic adenocarcinoma Normal PSA range is > 12 ng/mL What is the range for Gleason scores? A. B. C. D. A 1 to 5 1 to 9 1 to 3 1 to 4 From which cells, Adenocarcinoma of prostate is originated? A. B. C. D. B Red blood cells Luminal cells Epithelia Stromal cells Which virus is associated with Penile intraepithelial neoplasia (PeIN)? A. B. C. D. A Human papillomavirus (HPV) Herpes simplex virus (HSV) SARS-CoV-2 None of the above Which gene is involved in penile squamous cell carcinoma? A. B. C. D. B p62 Tumor suppressor gene retinoblastoma (pRb) p63 None of the above