renal pathology-week 2

8/14/2019 Renal Pathology-Week 2

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LG 2.3 Renal Embryology

Embryology

Week 2


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Around the third week the intermediate

mesoderm forms alongitudinal elevation

Urogenital Ridge

Part of the urogenitalridge turns into thenephrogenic rod

This leads to the Urinarysystem

Nephrogenic roddevelops into 3sequential nephricstructures:

Pronephros: a non-functional structure


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Pronephros Starts with the development of kidneys in the

4th week

It is the cranialmost nephric structure, is atransitory structure that regresses completelyby the fifth week, and is non-functional inhumans

Mesonephros In 4th week mesonephros tubules and

mesonephric duct derive form nephrogeniccord

The mesonephros tubules forms nephrons thatempty into this collecting duct (mesophrenicduct)this connects the nephrons to the

urogenital sinus The future urinary bladder

The tubules regress by 6th week Therefore functional for a short time

The mesonephric duct (wolfian) persists No wolffian duct In females

2ndmonththe mesonephros is an ovoid


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Metanephros it replaces the mesonephros as the

functional excretory organ and

develops into the adult kidney It develops from an outgrowth from

the caudal mesonephric duct calledthe Ureteric Bud and from theMetanephric Mesoderm (metanephricblastema)within the most caudalnephrogenic cord

At about week 5 begins third andfinal urinary organ, or permanentkidney

It will be functional in the fetus by week 10

initiated by the growth of the uretericbud off of the most caudal

mesonephric duct grows into the mesonephric mesoderm and

induces development of the kidney frommesoderm which condenses around it

Two separate components Collecting System: arise from the Ureteric

Bud, an outgrowth from the mesonephric

duct.


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The ureteric bud grows out, contacts and eventuallypenetrates the metanephric mesoderm

Upon contact, the UB expands and branches out The branching will form the renal pelvis, the major and minor

calyces and collecting tubules

Lengthening of the proximal end of each ureteric bud forms theUreter.

Collecting tubule has MetanephricTissue Cap which itinduces to form nephrons

This tissue forms renal vesicles which differentiate into excretorytubules


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At the proximal end,

capillaries willgrow into theGlomeruli andenter into eachBowmans Capsule,completing the

Nephron The kidneys develop

from two sources: Ureteric Bud-

gives rise to thecollecting system

MetanephricMesoderm-provides theexcretory units(nephrons) which


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Fetal nephrons are formed until birth

At birth, the kidneys have alobulated appearance thatdisappear during infancy

Urine production begins by the 10thweek

The kidneys ascend cranially toachieve their final position inthe lower lumbar area (T-12-L3)

Between the 6th and 9th week

The ascent is caused more bydifferential growth; the kidneysstay in position

Abnormal ascent

Sometimes a kidney fails toascend to the lumbar area,creating a Pelvic Kidney

the inferior poles may fusetogether during the initialascent, creating a HorseshoeKidney

When this type of kidneystarts to ascend, it is

Pelvic


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During normalascent, there is a

90 degree rotation In horseshoe

kidney, there isno rotation the

hilum continues toface ventrally ureters take an

abnormal courseacross the bridge of

renal tissue whichcan lead to partialurinary tractobstruction,


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Bladder

Functioning of the fetal kidneys

begins in the 12th

week. Amniotic fluid is swallowed by

the fetus, absorbed from the gutinto the bloodstream, filtered bythe nephrons,

The urinary bladder is derivedfrom the superior anterior region

of the cloaca (most caudal end ofthe hindgut) called theUrogenital Sinus

the mesonephric (wolffian) ductenters into the urogenital sinusduring kidney development and

the allantois also joins theurogenital sinus

The Allantois is part of thedeveloping umbilical cord whichcollects the waste

The Urorectal Septum in the5th week:

separates the cloaca into


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Three parts of theurinogenital sinus Urinary Bladder: The

upper and largest partthat is continuous with

the allantois Pelvic Portion: a narrow

canal which in the maleforms the prostatic andmembranous parts ofthe urethra

Phallic Portion: The lastpart, forms the penileurethra in the male

urogenital sinus portionsdevelopment differsreatl between the two


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Anomalies of the

Urorectal fistula: The hindgut empties

directly into theurethra below theurinary bladder in the

male Cause: Incomplete

separation of theurogenital sinus andanorectal area by theurorectal septum

Rectovaginal fistula: due to the same

incomplete separationin a female that resultsin hindgut emptyingdirectly into the vagina


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Urachal Fistula: maycause urine to drainfrom the umbilicus.

Urachal Cyst: If only alocal area of the

allantois persistsbetween the ligaments,this will result in aresulting in a epithelial-lined dilated cyst.

Urachal Sinus: Occurs

when the lumen of theupper part persistsonly.

All 3 are due to a failureof the Allantois(Urachus) and its lumen


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Bladder

The mesonephric ductsare absorbed into the wallof the urinary bladder atthe same time that theureters come to separatelyopen directly into the

bladder as developmentproceeds

Caudally, the mesonephricducts move closer togetherto enter the prostaticportion of the urethra

where they form theejaculatory ducts andseminal vesiclesin themale

Mesonephric ducts in

femal


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Urethra

At the end of the third month, cells inthe urethral epithelium differentiateinto the

prostate gland

seminal vesicles

ductus deferens

urogenital sinus gives rise to the

penile urethra.

In females: the distal portion of the


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Congenital Anomalies


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LG 2.4 Congenital Anomalies

Potter Syndrome

The Potter (Oligohydramnios)

Syndrome syndrome of abnormalities that are

caused by markedly reducedintrauterine urine production

>>less amniotic fluid which cushionsfetus

With less fluid, the fetus is

compressed by the uterus, causingspecific abnormalities

Physical Appearance infraorbital folds, low-set ears,

a small receding chin, aflattened nose, redundant skinfolds of the hands, club feet(varus deformity)

Pulmonary hypoplasiaincomplete development oflungs

caused by compression of thechest by the uterus

Infraorbit

al

Pulmonary

hypoplasia

Bilateral renal


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Other anomalies

Unilateral Agenesis: relativelycommon usually they are unaware of its

presence as long as the singlekidney functions normally.

Compensatory hyperthrophy Renal Hypoplasia: the

kidneys do not develop tonormal size.

Horseshoe Kidney: fusion ofthe kidney at the midline.

Usually causes no problemunless there is an associateddefect that favors obstructionto renal flow


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Renal Cystic

Characterized by the presenceof multiple cysts of varyingsize in the kidney and theabsence of a normalpelvocaliceal system

Results from abnormal

differentiation of the renalstructures during theembryonic period Occurs unilateral

No association with malignancy

Most common cause of anabdominal mass in newborns

The bilateral form causesoligohydramnios and resultantPotter Sequence withpulmonary hypoplasia

Clinically


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Adult Polycistic Kidney

Characterized by multipleserous or purulent-filledcysts of both kidneys thatdestroys the interveningparenchyma

An autosomal dominant

disorder The cysts are derived from

obstructed tubules

Renal failure usually in the 30sor 40s

Cyst appear to arise from anypart of the nephron Pressure from cysts may lead to

ischemic atrophy Can lead to hemorrhage, HTN

and infection

Elevated BUN

HTN in 75% of the patients


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Childhood Polycistic KidneyDi Autosomal recessive disease

enlarged bilateral kidneys Resembles sponges

In utero, there isoligohydramnios (Pottersequence)

Results in pulmonary

hypoplasia Associated with:

Congenital hepatic fibrosis.

If survives, may results inportal hypertension

Splenomegaly

the kidneys are markedlyenlarged and tend to fill the entireretroperitoneum and displace theabdominal contents

numerous small uniform cysts inthe cortex and medulla

Leads to renal failure after

Enlarged


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Medullary Sponge Kidney

A congenital conditionwithout a definedinheritance pattern

Often bilateral

Symptomatic inadolescence or earlyadulthood withhematuria and/or UTIs Due to renal stones

which develops in 65% ofpatients

Eventual pyelonephritisbut without RF

Polycistic changes withdialysis

Policystic changes

with dialysis


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Simple Renal Cysts

Cysts found in overhalf of patients over50 yoa Rarely produce

clinical symptoms Solitary or multiple

fluid-filled cysts foundin the outer cortex

Duplication of ureters Single or multiple

ureters may beduplicated on the sideof the fetal urinarybladder

May be unilateral orDuplication of


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Congenital Hydroureter

AKA congenitalmegaureter

May be due toobstruction at theuretal orifice intothe bladder

May be unilateral orbilateral

If dilation involvesrenal pelvis Can cause

Congenital Hydroureter withResultant Hydronephrosis


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Congenital Diverticuli

Sac-like outpouchingsof the bladder wallrelated to incompleteformation of themuscle layers May be solitary or

multiple Urine is retained

inside the diverticuliand can cause

infections With time it can lead

to urinary stones(complication)

Diverticuli may also

Acquired Bladder

Congenital DiverticuliUrinary Bladder


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Urachal Cyst

A cyst occurring inthe remnants of theumbilicus and theurinary bladderpresenting as aextraperitonealmass in theumbilical region Caused by

incomplete

involution Presents with

abdominal pain andfever if infected,possible leading to


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LG 2.5 Pathology of Renal Tumors

Benign and Malignant

Tumors


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Renal Adenomas

A renal epithelialneoplasm

Less than 3 cm Composed ofsmall

cuboidal cells with round,regular nuclei, arranged inclosely packed tubules orpapillary configurations

Most are located in theouter cortex

Increase in frequency withage

Found in over 40% of

Renal cortical


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Medullary FibromaAKA Renomedullary Interstitial Cell Tumors

Small, pale white,well-circumscribedbenign tumors

located in themidportion of themedullary pyramid

Composed of small,

stellate to polygonalcells lying in a loosestroma


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Angiomyolipomas

Benign lesions that exhibit anadmixture of: well-differentiated adipose

tissue,

smooth muscle and

thick-walled blood vessels

Tumors are yellow andbosselated

Resemble renalcarcinoma BUT this one is always

encapsulated withoutareas of necrosis

Associated with tuberoussclerosis A disease characterized by


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Congenital Mesoblastic

A congenital benigntumor usually discoveredin the first three monthsof life because of anabdominal mass

Gross Grossly, the tumor is

usually solitary andunilateral with tan fleshyill-defined borders

Histology Monomorphic spindle-

shaped cells resemblingfibroblasts with scantinterstitial collagen withminimal compression


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Oncocytoma

Grossly resembles a renalcell carcinoma but tends tobe more uniform tan tobrown color

Made of oncocytesEpithelial cell

characterized by anexcessive amount ofmitochondria, resulting inan abundant acidophilic,granular cytoplasm.

Accounts for 5-15% of

renal neoplasms Good prognosis because it

typically acts in a benignfashion, and is notassociated with aparaneoplastic syndrome.


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Malignant Tumors

Renal Cell Carcinoma comprise 85% of allkidney tumors.

Transitional Cell Carcinoma of the renal pelvis

comprise another 10% Wilms Tumor, a pediatric tumor, comprises

5%.


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Renal Cell Carcinomas

It is more common in males than in females Ages 50-70

Higher incidence in cigarette smokers

Gross Appear as nodules or masses

They arise from either the upper or lower poles of the kidneys

Originates in the renal tubules

Histology composed of cuboidal cells reminiscent of renal tubules that have

either clear or granular cytoplasm, filled with glycogen and lipids(adenocarcinoma)

Metabolic Paraneoplastic findings, such as hypercalcemia andpolycythemia may present but it is rare


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Transitional Cell Carcinoma

Papillary neoplasmsof the renal pelvisthat resemble

carcinomas of theurinary bladder

Most tumors presentwith hematuria or

urinary obstructionearly in the course


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Wilms Tumor The most common of all the solidabdominal tumors in infants andchildren

Tumordevelops from remnants of theimmature kidney (nephrogenic elements)

Presents with a large solitary or multi-nodularpalpable abdominal mass thatreplaces the kidney

In 5-7%, the tumor arises in thecontext ofthree different

congenital syndromes Children complain of abdominal

pain, intestinal obstruction,hematuria, hypertension, andfever

Patients < 2 yoa have a better prognosis

than older children due to increasedanaplasia of the tumor


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Wilms Tumor Congenital Syndromes

WAGR Syndrome

WilmsTumor,

Aniridia (absence of an iris),

Genitourinary Anomalies, and Mental

Retardation. Due to a deletion of the shortarm of chromosome 11

Denys-Drashsyndrome (DDS): Wilms Tumor,and Glomerulopathy. Due to mutations of WT1

Beckwith-Weidmann Syndrome (BWS)

Wilms Tumor, Gigantism withVisceromegaly, and Macroglossia. Due todeletion of WT2. (both WT1 and WT2 areconsidered tumor suppressor genes)

Fetal Tissues Metanephric Blastema (immature

kidneys): consisting of small ovoidcells growing in nests

Immature mesenchymal stroma:loose spindle cells resemblingfibroblasts with possible foci ofskeletal or smooth muscle, fat, orbone

Immature epithelial elements:small tubular structures andimmature glomeruli

Wilms Tumor withBlastema and Stroma

Primitive Glomerular and TubularStructures of Wilms Tumor


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Metastatic Tumors to the

Lymphomas arethe most commonmalignancies thatmetastasize to the

kidneys Also leukemias,

lung, colon andmalignantmelanomas

Usually small,asymptomatic, andoccasionally cause


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XanthogranulomatousP l n hriti

An uncommon formofchronicpyelonephritis,often caused by a

Proteus (gramneg.) infection

There are nodulesof yellow within the

renal parenchymawhich arenumerous lipid-laden macrophages


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Urothelial tumors, more than 90% aretransitional cell carcinomas. Squamous cellcarcinoma (7%)--exposure toSchistosoma

Urothelium consists of a 3- to 7-cellmucosal layer within the muscular bladder

Transitional cell papilloma Benign tumor

Painless hematuria People >50 yoa

Two types Exophytic Papillomas

single lesions mostly, 2-5 cm indiameter

Inverted Papillomas typically present as nodular mucosal

lesions covered by normal urotheliumfrom which cords of transitionalepithelium descend into the laminapropria

Transitional cell carcinoma in-

situ -

Inverted

Exophytic

Transitional cell


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Cancer of the urinar bladder Most common urinary tract neoplasm

2-3x more common than renal cell

cancer Tumors are often multifocal

can occur in any part of the urinary tractlined by transitional epithelium, from therenal pelvis to the urethra.

Higher incidence in Egypt, Sudan andother A. Countries due to the

Schistosomiasis, which increasesfrequency of squamous cell carcinoma

Higher incidence in the US amongurban white people and lowerincidence among blacks

Risk Factors cigarette smoking

Azo dyes and chemicals used in the rubberindustry, and textile printing

They are conjugated in the liver andmetabolites excreted in the urine(arylamines), which is acidic and leads tothe production of reactive arylnitrenium ions carginogenic to bladder mucosal cells

Infection with Schistosoma haematobium

(parasite)in Egypt primarily Cyclophosphamide

MucinousAdenocarcinoma of the

Sarcoma botryoides of the


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Bladder Cancer The exophytic type arises most

frequently from the lateral walls of

the bladder Histologically, they are classified into

three grades of increasing severityand invasiveness

Grades Grade 1 (Low Grade): Papillary

projections lined by neoplastic

transitional cells with minimalpleomorphism, mitotic activity,resting on long papillae

Grade 2 (Intermediate Grade): Similarhistologic features, but more severenuclear and cytoplasmic changes.

Grade 3 (High Grade): Significantnuclear pleomorphism, frequent mitoses

with fusion of the papillae. Invasion is more common with this grade.

Metastasis extension of the tumor into the muscle

layers of the bladder and into theadjacent pelvic organs

Initially found in the pelvic and periaortic

Transitional CellCancer of the BladderExophytic Tumor inthe Bladder Neck

Transitional CellCarcinoma-BladderPapillary, Solid, andNecrotic

Grade 1Resting on long

Grade 2

Transitional cell


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Prostate Gland It is about the size of a chestnut, and

secretes an alkaline fluid and

constitutes 13-33% of semen Contains 30-50 individual compound

tubuloalveolar glands, each gland having its own duct that

delivers the secretory product to theprostatic urethra

Lined by a simple to pseudostratifiedcolumnar epithelium

Lumen of these glands frequently houseround to oval prostatic concretions(corpora amylacea), composed ofcalcified glycoproteins and whosenumbers increase with age

Prostatitis inflammation of the prostate gland that

can occur as either an acute or chronicform

Usually caused by E.coli or others such as,chlamydia, trichomonas or mycoplasma.Histoplasma capsulatum can causegranulomatous prostatis

Acute Commonly caused by E.coli

PMNs are seen

Intense discomfort on urination and is

Acute bacterial prostatitiswith PMNs

Acute Prostatitis-Neutrophils within aLarge Gland and Surrounding Stroma


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Chronic Prostatitis May be preceded

by an episode ofacute prostatitis

lymphocytes,plasma cells, andmacrophages areseen

Suprapubic,

perineal, and lowback pain andexperience dysuriaand nocturia. The

Chronic Prostatitis-Mononuclear Cellswithin the Stroma

Chronic


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Benign Prostatic Reactive, benign hyperplastic lesion that

may obstruct the flow of urine, relatedto male hormonal changes thatoccurs with aging

Occurs in the periurethral portion of theprostate

a part of the prostate located at the neck ofthe urinary bladder

The enlargement impedes urination

Central located hyperplastic nodulescompresses and expands the peripheraltissue

Higher among U.S. blacks than whitesand the disease peaks at about 70 years

75% of men over 80 years of age havesome degree of BPH

Testosterone may play a crucial role sinceprostate develops in puberty only in thepresence testosterone

Proliferated glands may dilate cystically,and accumulate prostatic secretions

This may predispose the affected individualto infection

BPH causes distortion and elongation

Bladder MucosalTrabeculations due toObstructive Uropathy


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BPH Contd.

ComplicationsThe increased pressure

of urine in the bladdermay cause reflux ofurine into the ureters

Dilation of the ureter(hydroureter)

Dilation of the renalcollecting system(hydronephrosis)

May lead to end-stagerenal disease

Treated surgically witha TransurethralResection of theProstate (TURP)

Renal calculus due toobstruction Hydronephrosis


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Prostate Carcinoma The most common diagnosed cancer in

men

3rd most common cause of cancer relateddeaths in males

75% are 60-80 years of age

The highest frequencies for prostate cancerare seen in the U.S. and the Scandinaviancountries

The lowest are seen in Mexico,Japan and

Greece American blacks exhibit a rate twice as

high as that of American whites

Intake of yellow and green vegetablesappears to have a protective effect and adiet high in fat contributes to anincreased incidence

It is believed that testosterone stimulates

the growth of prostatic carcinoma Castration of carcinoma patients is

thought to retard the tumor growth

Testosterone receptors have beendemonstrated on prostatic cancer cells

No evidence that prostate carcinomaoriginates from hyperplastic nodules (BPH)

Prostate intrae ithelial Neo lasia (PIN)

PI

i f h


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Carcinoma of thePr t t

Presence of PIN in prostatecancer Many patients with PIN have been shown

on subsequent follow-up biopsies monthslater to have invasive cancer

Peripheral location for both lesions

The cytological similarity of high-gradePIN to invasive carcinoma and the close

proximity of both lesions in the samebiopsy when present

98% of prostate cancers areAdenocarcinomas

Pathology Grossly they are multicentric (or

sometimes a single nodule) lesions

located in the peripheral zones ofthe prostate. (posterior lobes)

irregular, yellow-white, firm andbosselated subcapsular nodules.

The initial tumor is limited to the glands,bounded by the basement membrane(PIN)

Later may give rise to locally invasive


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Carcinoma of the Prostate Histologic findings

Most feature small to medium-sized glands that lackorganization and infiltrate thesurrounding fibromuscular stroma

The well-differentiated neoplasticglands are lined by a single layerof cuboidal epithelium

Loss of differentiation is seen with

increased variability of glandsize and shape, papillary andsolid cords of tumor cells withlittle gland formation, or

solid sheets of neoplastic cellswith no gland formation

Cytologic Features Usually there is marked

pleomorphism andovercrowding of cells withhyperchromatic nuclei

one or two prominentnucleoli, in a slightly eosinophilicor vacuolated cytoplasm

cribriform arrangement of theglands in the mid-grade lesions toa more solid appearances in the

P.D. Carcinoma

with no Glands,Cellular Cords andAbundant Stroma

Solid P. D.Adenocarcinoma

of the Prostatewith no Gland

Prostate Carcinomawith ProminentNucleoli and

With Small Backto Back Glands


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Gleason Grading System

Gleason grading system Five histologic patterns of

tumor gland formation andinfiltration

the Gleason score is the sumof the grades, numbered 1-5for

(1) the most prominentpattern and a (2)secondscoring for the minoritypattern

1 being the best or welldifferentiated

5 being the poorestdifferentiated

Best differentiated tumors willhave a total Gleason score of 2(1+1).

Most poorly-differentiatedcancers will have a totalGleason score of 10 (5+5)

When combined with the

Pattern 2 withUniform Round

Pattern 3 withCrowded Glands andProminent Nucleoli

Gleason Pattern 4with Cords and of

Back to Back

Pattern 5 with SolidSheet of


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Clinical Features Asymptomatic and is found incidentally

after a digital exam, PSA, or biopsy forBPH

When clinical features are present , thetumor has often expanded beyond thecapsule or into the urethra, obstructing it,

causing urinary frequency, urgency, andincontinence (symptoms of BPH)

Bone pain and pathologic fractures areseen in metastatic disease

Screening If the serum PSA is elevated, the diagnosis

is confirmed by needle biopsies of theprostate

Both malignant and normal prostaticcells express a specific antigen calledProstate Specific Antigen

Tumor cells release this antigen intothe circulation

osteoblastic metastases will cause of theserum alkaline phos-phatase levels

Originates in the peripheral parts of theprostate

Therefore no compression of the urethra orurinary problems until late in the course ofthe disease.

Prostatic cells normally produce ProstaticAcid Phosphatase (PAP)

the tumor cells, which are not organizedinto normal glands, release PAP into the

immunoperoxidase

Treatment and Prognosis


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Treatment and Prognosis Early tumors that are limited to the prostate are

the only forms of cancer amenable to successful

tx Tumor extension into the surrounding organs

usually are associated with pain, due toperineural invasion

Early prostate cancer is best treated surgically,(Radical Prostatectomy) but extensive tumors(T3) are usually treated with radiation therapy

Staging of Prostate Cancer The staging is based on the TMN system and

there are 4 subtypes of T for primary tumor T1: A clinically inapparent tumor not palpable or visible

by imaging. T2: The tumor is confined to the prostate. T3: The tumor extends through the prostate capsule. T4: The tumor is fixed or invades adjacent structures.

renal pathology-week 2

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