Pathology of Prostate

1. Pathology of Prostate CPC4.3- MR 68y Carpenter <ul><li>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.” </li></ul><ul><li>Urine frequency (4-5xday; 2xnight); Terminal dribbling . </li></ul><ul><li>Worsening over months - ? couple of years ’. </li></ul>

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

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

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

6. When you lose, don’t lose the lesson. Lao Tzu Everyone makes Mistakes, only intelligent learn from it. 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: <ul><li>Pathology Major CLI : </li></ul><ul><ul><li>Nephrolithiasis – Types, Pathogenesis, clinical features. </li></ul></ul><ul><ul><li>Tumors of Kidney . – Renal cell carcinoma, Nephroblastoma, </li></ul></ul><ul><ul><li>Disorders of Prostate – Prostatitis, BPH and carcinoma. </li></ul></ul><ul><ul><li>Urinary tract infection – Microbiology common organisms and their lab diagnosis. </li></ul></ul><ul><li>Pathology Minor CLI : </li></ul><ul><ul><li>Differential diagnosis of hematuria. </li></ul></ul><ul><ul><li>Tumors of Urinary tract and bladder . </li></ul></ul><ul><ul><li>Cystic Diseases of Kidney </li></ul></ul><ul><ul><li>Hydronephrosis . </li></ul></ul><ul><ul><li>Recurrent UTIs </li></ul></ul><ul><ul><li>Congenital disorders of kidney. </li></ul></ul> CPC 4.2: Core Learning Issues: <ul><li>Pathology Major CLI : </li></ul><ul><ul><li>Nephrolithiasis – Types, Pathogenesis, clinical features. </li></ul></ul><ul><ul><li>Tumors of Kidney . – Renal cell carcinoma, Nephroblastoma, </li></ul></ul><ul><ul><li>Disorders of Prostate – Prostatitis, BPH and carcinoma. </li></ul></ul><ul><ul><li>Urinary tract infection – Microbiology common organisms and their lab diagnosis. </li></ul></ul><ul><li>Pathology Minor CLI : </li></ul><ul><ul><li>Differential diagnosis of hematuria. </li></ul></ul><ul><ul><li>Tumors of Urinary tract and bladder . </li></ul></ul><ul><ul><li>Cystic Diseases of Kidney </li></ul></ul><ul><ul><li>Hydronephrosis . </li></ul></ul><ul><ul><li>Recurrent UTIs </li></ul></ul><ul><ul><li>Congenital disorders of kidney. </li></ul></ul>

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

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

10. . Male Urogenital System - anatomy

11. . Male Urogenital System - anatomy Ca BPH

12. . Zonal Histology: <ul><li>BPH </li></ul><ul><li>Ca. </li></ul>

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

14. . Enlargement of Prostate: <ul><li>Inflammations – infections </li></ul><ul><li>BPH – Benign Prostatic Hyperplasia </li></ul><ul><li>Neoplasms – Carcinoma. </li></ul>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: <ul><li>Inflammation, edema, rectal pain, urinary obstruction. </li></ul><ul><li>Acute suppurative prostatitis </li></ul><ul><ul><li>E.coli, rarely Staph or N. gonorrhoeae </li></ul></ul><ul><li>Chronic non-specific prostatitis </li></ul><ul><ul><li>recurrent acute  fibrosis, lymph + plasma. </li></ul></ul><ul><li>Granulomatous prostatitis- </li></ul><ul><ul><li>BPH, infarction, post TURP, idiopathic, TB, or allergic(eosinophilic). </li></ul></ul>

16. . Prostatitis:

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

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

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

20. . Benign Prostatic Hyperplasia:

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

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

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

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: <ul><li>Obstructive Uropathy </li></ul><ul><li>Bladder hypertrophy </li></ul><ul><li>Trabeculation </li></ul><ul><li>Diverticula formation </li></ul><ul><li>Hydroureter – bilateral </li></ul><ul><li>Hydronephrosis </li></ul><ul><li>Lithiasis / stone. </li></ul><ul><li>Secondary infection. </li></ul><ul><li>Not a risk factor for Carcinoma prostate. </li></ul>

30. . Normal – Prostatitis - BPH

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

32. . Cancer Statistics – 2002 USA

33. . Cancer Statistics – 2002 USA

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

35. . Diagnosis: <ul><li>Clinical: Digital Rectal examination (DRE) </li></ul><ul><ul><li>hard, gritty, fixed tumor. </li></ul></ul><ul><ul><li>Loss of median groove. </li></ul></ul><ul><li>Imaging: </li></ul><ul><ul><li>Ultrasonography (transrectal), CT Scan, MRI. </li></ul></ul><ul><li>Laboratory: </li></ul><ul><ul><li>Tumor Marker – PSA </li></ul></ul><ul><ul><li>Biopsy - TURP </li></ul></ul><ul><li>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. </li></ul>

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 <ul><li>Posterior Lateral lobes: Carcinoma </li></ul><ul><li>Rectal examination. </li></ul><ul><li>Solid, hard, adenocarcinoma </li></ul>

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