Pathology of Prostate

CPC4.3- 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’.

CPC4.3- 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

CPC4.3- 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)

SymptomSymptom PathologyPathology

Dysuria Inflammation urethra, UTI

Poor stream / dribbling.

Bladder neck obstruction.

Prostate BPH (rarely stricture/tumor)

Frequency Prostate, UTI, Polyuria

Retention Prostate, stone, stricture, tumor

Discharge UTI, urethritis, gonorrhoea

Ulceration STI, syphilis

Bone pain Prostate carcinoma

Raised acid Phos. Prostate carcinoma

Raised αFP/HCG Testicular tum teratoma.

Gynaecomastia Testicular tum

Causes of Obstructive UropathyCauses of Obstructive UropathyINTRINSIC:

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.

When you lose,When you lose, don’t lose the lesson.don’t lose the lesson.

Lao Tzu

Everyone makes Mistakes, only intelligent learn from it.

CPC 4.2: Core Learning Issues: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.

Pathology of ProstatePathology of Prostate

Dr. Shashidhar Venkatesh MurthyDr. Shashidhar Venkatesh MurthyAssociate Professor & Head of Pathology

IntroductionIntroduction

Anatomy – 5 lobes.Function – Semen, acid phosphatase.Hormone response – Estrogen likeMedian lobe – BPHLateral/Posterior lobes - Cancer)Enlargement – Inflammation / growthNeoplastic / Non neoplastic growth.BPH / Cancer.

Male Urogenital System - anatomyMale Urogenital System - anatomy

Male Urogenital System - anatomyMale Urogenital System - anatomy

Ca

BPH

Zonal Histology:Zonal Histology:

BPHBPH

Ca. Ca.

Normal Histology: Fibro-Musclular-GlandNormal Histology: Fibro-Musclular-Gland

Two Layer Ep.

Fibromuscular stroma

Secretions

Enlargement of Prostate:Enlargement of Prostate:

Inflammations – infectionsBPH – Benign Prostatic HyperplasiaNeoplasms – Carcinoma.

Disease Incidence location Morph -DRE SAP

BPH >80% at 80y Central / periurethra

Nodular Hyperplasia,

Firm, smooth Median grove

normal

Carcinoma

Latent is Common.

Clinical not.

Posterior

subcapsular

Adenocarcinoma

Hard stony, irregular, fixed No median grove.

Raised.

Prostatitis: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).

Prostatitis:Prostatitis:

BPH-IntroductionBPH-Introduction

Common non-neoplastic hormone induced hyperplasia.

75% among men aged 70-80years Over 90% in people aged over 90yInvolves peri urethral & central zones.Rare before the age of 40y.Hormone induced – Androgens.Castration no BPH

Patho-Physiology: Patho-Physiology: Testosterone Testosterone DHT DHT GFGF

Finasteride

BPH-MorphologyBPH-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.

Benign Prostatic Hyperplasia:Benign Prostatic Hyperplasia:

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

BPH-Bladder Gross – Identify Cues?BPH-Bladder Gross – Identify Cues?

Trabeculations Hypertrophy of wall Stone - urolithiasis Inflammation Median lobe- ball valve. Enlarged prostate.

BPH-Bladder morphology:BPH-Bladder morphology:

Hypertrophy of wall. Trabeculation Median lobe

protrusion (ball valve)

Prostatic enlargement.

Mucosal trabeculation: Muscular hypertrophyMucosal trabeculation: Muscular hypertrophy

Mucosal trabeculation: Muscular hypertrophyMucosal trabeculation: Muscular hypertrophy

Bulging BPH central Lobes

TURP-Bits (Diagnosis + Treat )TURP-Bits (Diagnosis + Treat )

Transurethral resection of Prostate - TURPPartial removal by resectoscope.

Complications: Hemorrhage,Infection, Granulomatous prostatitisRetrograde ejaculation.

BPH: BPH: Nodular, Gland+stromal hyperplasiaNodular, Gland+stromal hyperplasia

Cystic Gl

Nodule of BPH

Secret

ions

Secret

ions

BPH - MorphologyBPH - Morphology

Corpora Amylacea

BPH-Complications:BPH-Complications:

1. Obstructive Uropathy2. Bladder hypertrophy3. Trabeculation4. Diverticula formation5. Hydroureter – bilateral6. Hydronephrosis7. Lithiasis / stone.8. Secondary infection.

• Not a risk factor for Carcinoma prostate.

Normal Normal – – ProstatitisProstatitis - BPH- BPH

Adenocarcinoma Prostate: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)

Cancer Statistics – 2002 USACancer Statistics – 2002 USA

Cancer Statistics – 2002 USACancer Statistics – 2002 USA

Pathogenesis: Pathogenesis: PIN & carcinomaPIN & carcinoma

• Prostatic intraepithelial neoplasia (PIN) Multilayered, pleomorphic (low & High grade).

• Malignancy is single layered, & well differentiated to start with …!

Diagnosis: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.

BPH with Adenocarcinoma:BPH with Adenocarcinoma:

BPH with Adenocarcinoma:BPH with Adenocarcinoma:

Ca

Ca

BPH

BPH

““The only gracious way to The only gracious way to accept an insult is to ignore it. If accept an insult is to ignore it. If

you can’t ignore it, top it. you can’t ignore it, top it. If you can’t top it, laugh at it. If If you can’t top it, laugh at it. If

you can’t laugh at it,you can’t laugh at it,it’s probably it’s probably deserveddeserved...!...!” ”

–Joseph Russell Lynes

Adeno-Ca ProstateAdeno-Ca Prostate

• Posterior Lateral lobes: Carcinoma• Rectal examination.• Solid, hard, adenocarcinoma

Adeno-Ca ProstateAdeno-Ca Prostate

Adeno-Carcinoma + BPHAdeno-Carcinoma + BPH

Adeno Carcinoma + BPHAdeno Carcinoma + BPH

Stone Solid-Ca Cystic, soft BPH

Low grade PIN

High grade PIN

PIN: PIN: Crowding, stratification

Pleomorphism

Nuclear enlargement.

Grade II - III

Prostatic Carcinoma: grade 4Prostatic Carcinoma: grade 4

Adenocarcinoma Prostate: (High grade)Adenocarcinoma Prostate: (High grade)

Gleason Grading & Scoring of Prostatic Ca.Gleason Grading & Scoring of Prostatic Ca.

Prostate CancerGleason Grading & Scoring.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

Gleason score – 1+1=2Gleason score – 1+1=2

Gleason score – 2+2=4Gleason score – 2+2=4

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.

Prostate Cancer – Gleason grade 3Prostate Cancer – Gleason grade 3

? Gleason Grade? Gleason Grade 4 – Gland Fusion, no stroma4 – Gland Fusion, no stroma

Small irregular nests & ribbons - Gleason grade 4+4. 

Prostate Cancer

Grade 5 – sheets, no attempts at gland or clustering.

Prostate Cancer-High grade.

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

Prostate Ad.Ca: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.

Prostate Cancer Poorly differentiated:

Normal Gl.

Malignant cells

Adenocarcinoma – PSA IPx +ve :Adenocarcinoma – PSA IPx +ve :

Prognosis of Adenocarcinoma:Prognosis of Adenocarcinoma:

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

Ca Prostate – Stage & Prognosis:Ca Prostate – Stage & Prognosis:

Stage Definition 10y Survival

A1 Incidental, <5% of volume 93-98%

A2 Incidental, >5% of volume, or high

grade 50%

B1 Palpable nodule in one lobe but <1.5 cm

in diameter 70-75%

B2 Larger palpable nodule 62%

C1 Invades capsule of prostate 40-50%

C2 Invades seminal vesicle 33-39%

D1 Metastases to regional lymph nodes, or

extensive regional spread 17-20%

D2 Evident distant metastases <10%

Transitional cell Neoplasms:Transitional cell Neoplasms:

90% of bladder ca. Precursor – papilloma Dysplasia, in-situ ca, Papillary carcinoma.

“The weak can never forgive. Forgiveness is the attribute of the strong.”

–Mohandas Gandhi

Urinary Calculi:Urinary Calculi:

Dr. Shashidhar Venkatesh MurthyDr. Shashidhar Venkatesh MurthyAssociate Professor & Head of Pathology

NephrolithiasisNephrolithiasis 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 "colic“)

“writhing in pain, pacing about, and unable to lie still”

Hematuria macro/micro Larger stones that cannot pass

produce hydronephrosis or hydroureter.

Levels - Clinical symptomsLevels - 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

Calcium Oxalate

Nephrolithiasis: Nephrolithiasis: Organic matrix(3%) + salts (97%) ~Organic matrix(3%) + salts (97%) ~

Calcium stones (80%):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%)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%):Uric acid stones (6%): pH <5.5, high protein (meats), malignancy, 25% have gout.

Cystine stones (2%) Cystine stones (2%) Genetic disorder - Failure of reabsorption

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

Nephrolithiasis: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.

Staghorn: (Triple Phos/Struvite)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.

Staghorn Calculus:Staghorn Calculus:

Staghorn CalculusStaghorn Calculus

Complications:Complications:

HydronephrosisRenal failureUreteral strictureInfection, sepsisUrine extravasationPerinephric abscessXanthogranulomatous

pyelonephritis

Hydronephrosis:Hydronephrosis:

CPC-4.3– REN–BPHCPC-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.

““Pleasure & Pleasure & PainPain, , Happiness & Happiness & SufferingSuffering

are our teachers”. are our teachers”. Through their impact Through their impact

on the mind on the mind ““CharacterCharacter” develops.” develops.

Prostate: MProstate: Most likely site ofost likely site of ? pathology ? pathology

1 2 3 4 5

15%

0% 0%

85%

0%

A. Benign Hyperplasia.B. ProstatitisC. Stone formationD. AdenocarcinomaE. Transitional carcinoma

62y male chronic urinary retention. 62y male chronic urinary retention. ? Diagnosis? Diagnosis

1 2 3 4 5

6%

81%

4%9%

0%

1.Prostatic carcinoma

2.Benign P. Hyperplasia

3.Bladder carcinoma

4.Trabeculations

5.Bladder hypertrophy

BPH: BPH: what feature is shownwhat feature is shown??

1 2 3 4 5

0% 0% 0%

98%

2%

A. Bladder Wall Thickening

B. trabeculation

C. Stone formation

D. Ball valve obstruction

E. Enlarged lateral lobes

Kidney: What type of Kidney: What type of stonestone??

1 2 3 4 5

9% 7%0%

83%

0%

A. Oxalate & calciumB. Calcium phosphateC. Pure Uric acidD. Triple phosphateE. Cystine

74y M, dysuria, hematuria, prostate 74y M, dysuria, hematuria, prostate ? Diagnosis? Diagnosis

1 2 3 4 5

6%

71%

6%2%

15%

A. Prostatitis

B. Benign Prostatic Hyperpl.

C. Low grade carcinoma

D. Transitional carcinoma

E. High grade Carcinoma.

74y male, dysuria, hematuria, prostate 74y male, dysuria, hematuria, prostate ? Diagnosis? Diagnosis

1 2 3 4 5

4%

17%

37%

0%

43%

A. Prostatitis

B. BPH

C. Adenocarcinoma

D. Transitional carcinoma

E. BPH with carcinoma

74y male, dysuria, hematuria, prostate 74y male, dysuria, hematuria, prostate ? Diagnosis? Diagnosis

1 2 3 4 5

0%

37%

27%

0%

35%

A. Prostatitis

B. BPH

C. Adenocarcinoma

D. Transitional carcinoma

E. BPH with carcinoma

70y backpain, DRE-rock-hard, enlarged prostate. 70y backpain, DRE-rock-hard, enlarged prostate. X-rays show multicentric, osteoblastic lesions of X-rays show multicentric, osteoblastic lesions of the lumbar vertebral bodies. An the lumbar vertebral bodies. An orchiectomyorchiectomy is is performed. performed. What is the rationale for this surgical What is the rationale for this surgical procedure?procedure?

1 2 3 4 5

0% 2%

94%

0%4%

1. Leydig cells release tumor chemotactic factors.

2. Prostate carcinomas frequently metastasize to the gonads.

3. Sertoli cells release tumor chemotactic factors.

4. The tumor is well known to invade the testes.5. Tumor cells exhibit androgen-dependent

growth.

68y male, painless hematuria 4wk. Bladder 68y male, painless hematuria 4wk. Bladder image. What is the most likely risk factor?image. What is the most likely risk factor?

1 2 3 4 5

0% 0% 0%

100%

0%

1. Bladder calculi2. Chronic HPV infection3. Diabetes mellitus4. Exposure to Azo dyes5. Previous catheterization.

68y male, Image shows prostate biopsy. What is the 68y male, Image shows prostate biopsy. What is the most likely most likely complication complication of this lesionof this lesion??

1 2 3 4 5

20%

50%

9%

0%

21%

1. Destructive vertebral lesions.

2. Bladder hypertrophy.

3. Calcium oxalate nephrolithiasis.

4. Gram negative septicaemia.

5. Lead to Prostatic carcinoma

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?

1 2 3 4 5

6% 4%

89%

0%2%

1. Basal cell hyperplasia

2. Chronic prostatitis

3. Obstructive uropathy

4. Nodular BPH

5. PIN.

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

1 2 3 4 5

84%

6%2%0%

8%

1. Adenocarcinoma

2. Nodular BPH

3. PIN-3

4. Squamous Carcinoma

5. Transitional Carcinoma

68y male, Image shows prostate biopsy. What is 68y male, Image shows prostate biopsy. What is the most likely complication?the most likely complication?

1 2 3 4 5

7%

83%

0%2%7%

1. Destructive vertebral lesions.2. Bladder hypertrophy.3. Calcium oxalate nephrolithiasis.4. Gram negative septicemia.5. Infertility.

68y male, Image shows Bladder & prostate. What 68y male, Image shows Bladder & prostate. What complication is complication is notnot shown? shown?

1 2 3 4 5

4% 4% 5%

76%

11%

1. Invasive bladder cancer.

2. BPH.

3. Ball valve obstruction.

4. Bladder diverticula.

5. Tumor necrosis & hemorrhage.

Today is the First Day, Today is the First Day,

of Rest of Your Life...!of Rest of Your Life...!

CPC-4.3– KFP Questions: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.

Referral - if >5 mm or has not passed after two weeks.

US X-Rayno contrast Helical CT

Management

70y male70y 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.

70y male70y 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?

Prostatic neoplasms: OverviewProstatic neoplasms: Overview

Condition Incidence Location in gland

Morphology Serum acid phosphatase

Metastases

Benign nodular hyperplasia

75% of men >70 years

Peri-urethral zone

Nodular hyperplasia of glands and stroma

Normal None

Clinical (symptomatic) carcinoma

Common tumour; peak 60-85 years

Posterior subcapsular zone

Infiltrating adenocarcinoma

Raised in approximately 60% of cases

BoneLymph nodeLungLiver

Latent (incidental) carcinoma

Commoner than clinical carcinoma; 80% of glands over 75 years

Any site Microscopic focus of adenocarcinoma

Normal Rare