This 68-year-old male carpenter presents with urinary symptoms including frequency, urgency, terminal dribbling, poor stream, and occasional incontinence. His differential diagnosis includes benign prostatic hyperplasia, prostatitis, prostate cancer, stones, and other causes. Further workup is needed to determine the underlying pathology and guide treatment.

1. CPC4.3- MR 68y Carpenter Lives in Kuranda. He attends the GP for a ‘check up’ and towards the end of the consultation mentions casually: “ I’ve also got a few things happening with the old waterworks , Doc.” Urine frequency (4-5xday; 2xnight); Terminal dribbling . Worsening over months - ? couple of years ’.

2. CPC4.3- Matthew Rice 68y Carpenter Urgency yes, but then doesn’t pass much urine on forcing. Cannot empty the bladder empty. Urinary stream - poor Urinary incontinence - occasional but embarrassing. Dysuria, Haematuria No Bowel habit no change, prone to slight constipation Sexual history - heterosexual; 2nd wife Dawn, monogamous for 23 years. Has early morning erections, but difficulty sustaining an erection . No hx STIs

3. CPC4.3- Differential Diagnosis Benign prostatic hyperplasia ( BPH ) Prostatitis, Cancer, stones , rectal tum. Strictures, UTI, Diuretics, Spinal injury, Autonomic neuropathy ??? What other causes of urinary obstruction? urine retention , lack of urine , urinary dribbling urinary urgency , urination pain , weak urination reduced urine (links to wrongdiagnosis.com)

4. Pathology Symptom Testicular tum Gynaecomastia Testicular tum teratoma. Raised α FP/HCG Prostate carcinoma Raised acid Phos. Prostate carcinoma Bone pain STI, syphilis Ulceration UTI, urethritis, gonorrhoea Discharge Prostate, stone, stricture, tumor Retention Prostate, UTI, Polyuria Frequency Bladder neck obstruction. Prostate BPH (rarely stricture/tumor) Poor stream / dribbling. Inflammation urethra, UTI Dysuria

5. Causes of Obstructive Uropathy INTRINSIC: Calculi - Lithiasis Strictures – congenital, inflammatory Tumors – Transitional cell Ca. Blood clots – UTI, Glomerulonephritis EXTRINSIC: Pregnancy Inflammation- PID, peritonitis, diverticulitis, salphingitis. Tumors: Prostate , rectum, bladder, ovaries etc.

6. When you lose, don’t lose the lesson. Lao Tzu Everyone makes Mistakes, only intelligent learn from it.

7. CPC 4.2: Core Learning Issues: Pathology Major CLI : Nephrolithiasis – Types, Pathogenesis, clinical features. Tumors of Kidney . – Renal cell carcinoma, Nephroblastoma, Disorders of Prostate – Prostatitis, BPH and carcinoma. Urinary tract infection – Microbiology common organisms and their lab diagnosis. Pathology Minor CLI : Differential diagnosis of hematuria. Tumors of Urinary tract and bladder . Cystic Diseases of Kidney Hydronephrosis . Recurrent UTIs Congenital disorders of kidney.

8. Pathology of Prostate Dr. Shashidhar Venkatesh Murthy Associate Professor & Head of Pathology

9. Introduction Anatomy – 5 lobes. Function – Semen, acid phosphatase. Hormone response – Estrogen like Median lobe – BPH Lateral/Posterior lobes - Cancer) Enlargement – Inflammation / growth Neoplastic / Non neoplastic growth. BPH / Cancer.

10. Male Urogenital System - anatomy

11. Male Urogenital System - anatomy Ca BPH

12. Zonal Histology: BPH Ca.

13. Normal Histology: Fibro-Musclular-Gland Two Layer Ep. Fibromuscular stroma Secretions

14. Enlargement of Prostate: Inflammations – infections BPH – Benign Prostatic Hyperplasia Neoplasms – Carcinoma. SAP Morph -DRE location Incidence Disease Raised. Adenocarcinoma Hard stony, irregular, fixed No median grove. Posterior subcapsular Latent is Common. Clinical not. Carcinoma normal Nodular Hyperplasia, Firm, smooth Median grove Central / periurethra >80% at 80y BPH

15. Prostatitis: Inflammation, edema, rectal pain, urinary obstruction. Acute suppurative prostatitis E.coli, rarely Staph or N. gonorrhoeae Chronic non-specific prostatitis recurrent acute  fibrosis, lymph + plasma. Granulomatous prostatitis- BPH, infarction, post TURP, idiopathic, TB, or allergic(eosinophilic).

16. Prostatitis:

17. BPH-Introduction Common non-neoplastic hormone induced hyperplasia. 75% among men aged 70-80years Over 90% in people aged over 90y Involves peri urethral & central zones. Rare before the age of 40y. Hormone induced – Androgens. Castration  no BPH

18. Patho-Physiology: Testosterone  DHT  GF Finasteride

19. BPH-Morphology Microscopically, nodular prostatic hyperplasia consists of nodules of glands and intervening stroma . (both) The glands variably sized, with larger glands have more prominent papillary infoldings, double layered epithelium (like normal) some may be cystic with secretions. Nodular hyperplasia is NOT a precursor to carcinoma.

20. Benign Prostatic Hyperplasia:

21. BPH-mechanism of obstruction: Median lobe (3 rd lobe) Ball valve mechanism Obstruction. Urgency/hesitation..

22. BPH-Bladder Gross – Identify Cues? Trabeculations Hypertrophy of wall Stone - urolithiasis Inflammation Median lobe- ball valve. Enlarged prostate.

23. BPH-Bladder morphology: Hypertrophy of wall. Trabeculation Median lobe protrusion (ball valve) Prostatic enlargement.

24. Mucosal trabeculation: Muscular hypertrophy

25. Mucosal trabeculation: Muscular hypertrophy Bulging BPH central Lobes

26. TURP-Bits (Diagnosis + Treat ) Transurethral resection of Prostate - TURP Partial removal by resectoscope. Complications: Hemorrhage, Infection, Granulomatous prostatitis Retrograde ejaculation.

27. BPH: Nodular, Gland+stromal hyperplasia Cystic Gl Nodule of BPH Secretions

28. BPH - Morphology Corpora Amylacea

29. BPH-Complications: Obstructive Uropathy Bladder hypertrophy Trabeculation Diverticula formation Hydroureter – bilateral Hydronephrosis Lithiasis / stone. Secondary infection. Not a risk factor for Carcinoma prostate.

30. Normal – Prostatitis - BPH

31. Adenocarcinoma Prostate: Most common cancer in elderly males. Adenocarcinoma. It is rare before the age of 50, but seen in over 70% of men over 70y old. Many of these carcinomas are small and clinically insignificant. (Incidental ca) Second common cause of death due to cancer in males. (First is lung carcinoma) Aetiology unknown - Hormones, genes & environment most likely. ( Not BPH )

32. Cancer Statistics – 2002 USA

33. Cancer Statistics – 2002 USA

34. Pathogenesis: PIN & carcinoma Prostatic intraepithelial neoplasia (PIN) Multilayered , pleomorphic (low & High grade). Malignancy is single layered , & well differentiated to start with …!

35. Diagnosis: Clinical: Digital Rectal examination (DRE) hard, gritty, fixed tumor. Loss of median groove. Imaging: Ultrasonography (transrectal), CT Scan, MRI. Laboratory: Tumor Marker – PSA Biopsy - TURP Note: None of these methods can reliably detect small cancers & microscopic occult cancers may remain in-situ for several years. (PSA misleading*). Occult cancer is more common than clinical ca.

36. BPH with Adenocarcinoma:

37. BPH with Adenocarcinoma: Ca Ca BPH BPH

38. “ The only gracious way to accept an insult is to ignore it. If you can’t ignore it, top it. If you can’t top it, laugh at it. If you can’t laugh at it, it’s probably deserved ...! ” –Joseph Russell Lynes

39. Adeno-Ca Prostate Posterior Lateral lobes: Carcinoma Rectal examination. Solid, hard, adenocarcinoma

40. Adeno-Ca Prostate

41. Adeno-Carcinoma + BPH

42. Adeno Carcinoma + BPH Stone Solid-Ca Cystic, soft BPH

43. PIN: Crowding, stratification Pleomorphism Nuclear enlargement. Low grade PIN  High grade PIN  Grade II - III 

44. Prostatic Carcinoma: grade 4

45. Adenocarcinoma Prostate: (High grade)

46. Gleason Grading & Scoring of Prostatic Ca.

47. Gleason Grading & Scoring. Grade/Pattern 1 – well defined glands with limited infiltration of the surrounding tissue. Grade/Pattern 2 – not well demarcated, pleopmorphic cells. Grade/Pattern 3 – Crowding of glands, irregular glands. Grade/Pattern 4 – Fusion of glands. Grade/Pattern 5 – cell clusters, No clear gland structure. Gleason Score: Add to most prominent grades in the slide. E.g. 3+4=7 Prostate Cancer

48. Gleason score – 1+1=2

49. Gleason score – 2+2=4

50. Prostate Cancer – Gleason grade 3 Gleason grade 3: Pleomorphic glands. There is considerable variation in size, shape, and spacing of the glands. The glands are haphazardly infiltrating the stroma; however, they are still discrete (i.e. there is no fusion of glands - a hallmark of Gleason grade 4). Some of the glands have occluded or abortive lumens.

51. ? Gleason Grade 4 – Gland Fusion, no stroma

52. Small irregular nests & ribbons - Gleason grade 4+4. Prostate Cancer

53. Prostate Cancer-High grade. Grade 5 – sheets, no attempts at gland or clustering.

54. Most prostatic tumours include components of two or more patterns and therefore current practice gives the grade of the two most common components and their sum. This is known as the combined Gleason grade or score. For example, in this image many glands in this example are fused (Gleason grade 4); others maintain individual outlines but are closely packed with their neighbours (Gleason grade 3). Therefore, the score is 7 (4+3). Prostate Cancer High grade

55. Prostate Ad.Ca: Benign: Double layer, Secretion (clear cytopl) Uniform cells Papillary folds Malignant Single / crowded. Less/no secretion. Uniform/Pleomorphic No papillary folds. But crowding & clustering. Normal Ca. Normal Ca.

56. Prostate Cancer Poorly differentiated: Normal Gl. Malignant cells

57. Adenocarcinoma – PSA IPx +ve :

58. Prognosis of Adenocarcinoma: Grade & Stage  Prognosis. Gleason score 2-4 – well differentiated. Gleason score 8-10 – poorly differentiated. Urinary obstruction Metastasize to lymph nodes and bones. Bladder, kidney damage - Hematuria. Spread to rectum – bleeding. Spread to Lungs or liver – rare.

59. Ca Prostate – Stage & Prognosis: <10% Evident distant metastases D2 17-20% Metastases to regional lymph nodes, or extensive regional spread D1 33-39% Invades seminal vesicle C2 40-50% Invades capsule of prostate C1 62% Larger palpable nodule B2 70-75% Palpable nodule in one lobe but <1.5 cm in diameter B1 50% Incidental, >5% of volume, or high grade A2 93-98% Incidental, <5% of volume A1 10y Survival Definition Stage

60. Transitional cell Neoplasms: 90% of bladder ca. Precursor – papilloma Dysplasia, in-situ ca, Papillary carcinoma.

61. “ The weak can never forgive. Forgiveness is the attribute of the strong.” –Mohandas Gandhi

62. Urinary Calculi: Dr. Shashidhar Venkatesh Murthy Associate Professor & Head of Pathology

63. Nephrolithiasis Usually unilateral, small 1-3 mm , Flank pain & tenderness – renal capsule. Passage marked by Paroxysmal, intense colicky pain in the back (loin) with radiation to anterior (renal or ureteral &quot;colic“) “ writhing in pain, pacing about, and unable to lie still” Hematuria macro/micro Larger stones that cannot pass produce hydronephrosis or hydroureter.

64. Levels - Clinical symptoms Ureteropelvic junction - deep flank pain No radiation. Distension of the renal capsule. (Symp. T11-L2) Ureter – Acute, severe, colicky pain in the flank and ipsilateral lower abdomen with radiation to the testes/vulva (ilioinguinal n.). nausea / vomiting. Upper ureter – cholecystitis. Middle – appendicitis Distal ureter – Pelvic Infl. Dis. Ureterovesical junction - Cause irritative voiding, urinary frequency and dysuria. Calcium Oxalate

65. Nephrolithiasis: Organic matrix(3%) + salts (97%) ~ Calcium stones (80%): oxalate/phosphate/urate salts. Increased gut absorption or defective tubular reabsorphtion of calcium – Common, high pH. Hyperparathyroidism (10%) Hyperuricosuria – high pH Struvite Stones (15%) magnesium ammonium phosphate (triple phos). Staghorn stone. Chronic UTI with gram-negative rods (split urea) pH >7 Proteus, Pseudomonas, and Klebsiella (not E. coli) . Uric acid stones (6%): pH <5.5, high protein (meats), malignancy, 25% have gout. Cystine stones (2%) Genetic disorder - Failure of reabsorption Calcium Oxalate

66. Small renal calculus that would likely respond to extracorporeal shock-wave lithotripsy

67. Nephrolithiasis: Hypercalciuria, Hypocitraturia - commonest risk factor. A positive family history in 54%. UTI in 62%, recurrent UTI in 60% (T.Phosphate). Significant association with citrate & Phosphate excretion and UTI. Stone analysis, together with serum and 24-hour urine metabolic evaluation crucial for management.

68. Staghorn: (Triple Phos/Struvite) 10% of nephrolithiasis. Large stone moulds to pelvis and calyceal system. Secondary to obstruction / infection proteus sp. Proteus – break urea to form ammonia (alk. ph) Triple (struvite) Phos. magnesium ammonium phosphate. Chronic irritation, sq metaplasia & sq carcinoma rarely occur.

69. Staghorn Calculus:

70. Staghorn Calculus

71. Complications: Hydronephrosis Renal failure Ureteral stricture Infection, sepsis Urine extravasation Perinephric abscess Xanthogranulomatous pyelonephritis

72. Hydronephrosis:

73. CPC-4.3– REN–BPH Pathology - Core Learning Issues: Overview of gross & microscopic Pathology of Prostate BPH & Prostatic cancer. Laboratory diagnosis of prostatic tumors. (debate) Occult prostatic cancers (Recent media report on a Pathology report of cancer later denied). Pathology overview of chronic urinary retention.. Pathology of Nephrolithiasis, common types & their clinical presentation & Diagnosis. Basic science - Core Learning Issues: Anatomy & histology of Prostate gland. Prostate gland function, hormonal control.

74. “ Pleasure & Pain , Happiness & Suffering are our teachers”. Through their impact on the mind “ Character ” develops.

75. Prostate: M ost likely site of ? pathology Benign Hyperplasia. Prostatitis Stone formation Adenocarcinoma Transitional carcinoma

76. 62y male chronic urinary retention. ? Diagnosis Prostatic carcinoma Benign P. Hyperplasia Bladder carcinoma Trabeculations Bladder hypertrophy

77. BPH: what feature is shown ? Bladder Wall Thickening trabeculation Stone formation Ball valve obstruction Enlarged lateral lobes

78. Kidney: What type of stone ? Oxalate & calcium Calcium phosphate Pure Uric acid Triple phosphate Cystine

79. 74y M, dysuria, hematuria, prostate ? Diagnosis Prostatitis Benign Prostatic Hyperpl. Low grade carcinoma Transitional carcinoma High grade Carcinoma.

80. 74y male, dysuria, hematuria, prostate ? Diagnosis Prostatitis BPH Adenocarcinoma Transitional carcinoma BPH with carcinoma

81. 74y male, dysuria, hematuria, prostate ? Diagnosis Prostatitis BPH Adenocarcinoma Transitional carcinoma BPH with carcinoma

82. 70y backpain, DRE-rock-hard, enlarged prostate. X-rays show multicentric, osteoblastic lesions of the lumbar vertebral bodies. An orchiectomy is performed. What is the rationale for this surgical procedure? Leydig cells release tumor chemotactic factors. Prostate carcinomas frequently metastasize to the gonads. Sertoli cells release tumor chemotactic factors. The tumor is well known to invade the testes. Tumor cells exhibit androgen-dependent growth.

83. 68y male, painless hematuria 4wk. Bladder image. What is the most likely risk factor? Bladder calculi Chronic HPV infection Diabetes mellitus Exposure to Azo dyes Previous catheterization.

84. 68y male, Image shows prostate biopsy. What is the most likely complication of this lesion ? Destructive vertebral lesions. Bladder hypertrophy. Calcium oxalate nephrolithiasis. Gram negative septicaemia. Lead to Prostatic carcinoma

85. 68y man elevated serum PSA (>6 ng/mL). Biopsy of the prostate reveals a poorly differentiated adenocarcinoma. Which of the following best describes the putative precursor of this neoplasm? Basal cell hyperplasia Chronic prostatitis Obstructive uropathy Nodular BPH PIN.

86. 55y man, urinary urgency and frequency. DRE enlarged prostate. PSA of 4.9 (normal = 0–4). Needle biopsy - two cancer-positive needle cores: Gleason grades 4 and 5. Which of the following is the appropriate diagnosis? Adenocarcinoma Nodular BPH PIN-3 Squamous Carcinoma Transitional Carcinoma

87. 68y male, Image shows prostate biopsy. What is the most likely complication? Destructive vertebral lesions. Bladder hypertrophy. Calcium oxalate nephrolithiasis. Gram negative septicemia. Infertility.

88. 68y male, Image shows Bladder & prostate. What complication is not shown? Invasive bladder cancer. BPH. Ball valve obstruction. Bladder diverticula. Tumor necrosis & hemorrhage.

89. Today is the First Day, of Rest of Your Life...!

90. CPC-4.3– KFP Questions: BPH – etiology, Pathogenesis, morphology & complications. Testosterone, DHT, Fenosteride. TURP – brief notes. Prostatic carcinoma – etiology, Pathogenesis, morphology & spread, metastases. Staging, Grading & Prognosis. Urolithiasis : Renal stones Other obstructive uropathy.

91. Referral - if >5 mm or has not passed after two weeks. US X-Ray no contrast Helical CT Management

92. 70y male Problems passing urine. Difficult to start even though he badly needs to go. After passing.. He feels the urge but cannot pass.. High frequency, 2-3 times in the night. For several months getting slowly worse Now urine dribbles, Added to this, the force with which he can urinate is very much reduced and it is difficult for him to avoid soiling his clothing.

93. 70y male What are differential diagnosis? What complication he has? Should PSA be tested for all? When is biopsy indicated? Does BPH lead to Carcinoma? What is the best screening test for Ca? What investigations are available?

94. Prostatic neoplasms: Overview Rare Normal Microscopic focus of adenocarcinoma Any site Commoner than clinical carcinoma; 80% of glands over 75 years Latent (incidental) carcinoma Bone Lymph node Lung Liver Raised in approximately 60% of cases Infiltrating adenocarcinoma Posterior subcapsular zone Common tumour; peak 60-85 years Clinical (symptomatic) carcinoma None Normal Nodular hyperplasia of glands and stroma Peri-urethral zone 75% of men >70 years Benign nodular hyperplasia Metastases Serum acid phosphatase Morphology Location in gland Incidence Condition