Differentiate benign prostatic hyperplasia from carcinoma of the prostate.

Benign Prostatic Hyperplasia

• Extremely common with age — histological changes in about 70% of men by 60 and 90% by 80, though only a minority have symptoms
• Pathogenesis — dihydrotestosterone (DHT), produced from testosterone by 5-alpha-reductase type 2 in stromal cells, acts as the principal growth stimulus; oestrogen sensitises the tissue to it
• Morphology — enlarged prostate with well-demarcated nodules compressing the urethra into a slit; the peripheral zone is compressed into a "false capsule". Microscopy shows glandular hyperplasia with papillary infolding, two cell layers preserved, and corpora amylacea
• It is not premalignant — an essential point, since it arises in a different zone from carcinoma

Carcinoma of the Prostate

• The commonest cancer in men in many Western countries; incidence rising in India with longer life expectancy and increased detection
• Arises in the peripheral zone in about 70%, which is why it is palpable on rectal examination and why it causes urinary symptoms late
• Risk factors — increasing age, family history, African ancestry, high animal fat diet, BRCA2 mutation
• Morphology — firm, gritty, yellow-white ill-defined tissue. Microscopy shows small crowded glands with a single layer of cells and loss OF the basal cell layer (demonstrated by negative staining for high molecular weight cytokeratin and p63), prominent nucleoli, and perineural invasion
• Gleason grading — based on architecture, not nuclear features; the two most prevalent patterns (1 to 5) are added to give a score of 6 to 10; the strongest histological predictor of behaviour

Clinical Features and Spread

• Lower urinary tract symptoms — hesitancy, poor stream, terminal dribbling, frequency, nocturia, urgency, incomplete emptying
• Complications of obstruction — acute or chronic urinary retention, recurrent infection, bladder stones, bladder wall trabeculation and diverticula, hydroureter, hydronephrosis and renal failure
• Spread of carcinoma — local to seminal vesicles and bladder base; lymphatic to obturator and iliac nodes; and haematogenous to bone, characteristically the lumbar spine and pelvis, giving osteoblastic (sclerotic) metastases through the Batson vertebral venous plexus
• Osteoblastic bone metastases raise the alkaline phosphatase, and back pain in an older man with a hard prostate should always suggest the diagnosis

Applied Aspects

• PSA is prostate-specific but not cancer-specific — it rises with hyperplasia, prostatitis, catheterisation, rectal examination and cycling. Free-to-total ratio, velocity and density improve specificity
• Diagnosis requires biopsy, now usually MRI-targeted and transperineal
• Treatment of hyperplasia — alpha-blockers relax smooth muscle for rapid symptom relief; 5-alpha-reductase inhibitors shrink the gland over months; transurethral resection for failure or complications
• Treatment of carcinoma — active surveillance for low-risk disease, radical prostatectomy or radiotherapy for localised disease, and androgen deprivation for advanced disease, since the tumour is hormone-dependent
• PSA screening remains contentious — it detects many indolent cancers that would never have caused harm, so overdiagnosis and overtreatment are real harms weighed against the mortality benefit
• Many prostate cancers are indolent; more men die with prostate cancer than OF it, which is the central difficulty in managing the disease