Disease

Whatisit?

Whatcausesit?(Pathogenesis)

Intrinsic/Acquired?

Morphology/Pathology

RenalAgenesis

Completelymissingrenal
tissue

Developmentalissue

Intrinsic

Unilateral(usuallyasympomatic) Uni 1in800livebirths,opposite

orBilateral
kidneyislarge(compense
hypertroph)
bilat lethal,
1in5000(PotterSyndr)

HorseshoeKidney

Kidneysdon'tseparateat Developmentalissue
lowerpolesduringdev,so
ascensionisstoppedby
inferiormesentericartery.

Intrinsic

???

EctopicKidney
Autosomal
Dominant(adult)
PolycysticKidney
Disease(ADPKD)

Locatedinthepelvis
Bilaterallyenlarged
multicystic kidneyswith
renalfailurehappeningin
adultlife

Autosomal
Recessive
(childhood)
PolycysticKidney
Disease(ARPKD)

mutationinPKHD1 geneleadingtoits Intrinsic(Congenital)

Cystictransformationof
collectingductsininfants; product,fibrocystin,tobedefective.
renalfailureininfancy(75% Mutationalsoleadstopancreatic
dieinperinatalperioddue cysts,hepaticbiliarydysgenesis,
topulm hypoplasiacaused fibrosis
byoligohydramnios (lowin ciliacentrosomecomplexoftubular
amnioticfluid)
epi cells Autosomal Recessive

Developmentalissue
Intrinsic
ciliacentrosomecomplexoftubular Intrinsic(Congenital)
epi cells Autosomal Dominant
85%muts inpolycystickidneydisease
genePKD1, 15%inPKD2
Geneproductspolycystin1 and
polycystin2 areinprimaryciliaof
tubularepi cells
Cystsshowupinsegmentsortubules
butaredisconnectedintubules

Glomerulonephritis Inflammation dueto

depositionofimmune
complexesorantibodies
reactinginsituwithin
glomeruli

Acute
Ex.ofProliferative
Poststreptococcal glomerulonephritis,
Glomerulonephritis nephriticsyndrome.Acute
Proliferative glomneph
Causedbydepositionof
immunecomplexesin
glomeruli

OccursafterinfectionwithgroupA(B Extrinsic
hemolytic)strep.Latentperiod914
daysafterinfection.Immune
complexesdepo'd fromcirculationor
forminsituasbacterialAgtrappedin
glomblindcirculatingantibodies.
Initiateinf byactivatingcomplement,
recruitofleukocytes,otherhumoral
andcellularinf mediators

ClinicalSignificance/Features

Misc.

Mightcompressvenacavaoraorta
andcauseUrinarytractobstruction

UniorBilat;
Pronetoinfectionorobstruction
Eachweighs1000g,upto4500g asymptomatictil 4thdecade
1in400to1000
(normalis100170g)
Renalfailureinadulthood(4th
births
Bilat enlargement(superlarge), decade)
10%ofcasesofCKD
lotsoffluidfilledcysts)
Flankpain
surfacesirregular,coveredwith Bilateralflankandabdominalmass
cystsofvaryingsizes,upto34cmSenseofheavinessinloins
india,scantnormalparenchyma Intermittentgrosshematuria
betweencysts
Hypertension(75%pts)
cystfluidisclear,turbid,or
UTI
hemorrhagic
Azotemia(^bloodureaN2)>
interveningparenchyma
uremia(clinicalrenalfailure) 1/2pts
subjectedtoischemicatrophy
overseveralyears
duetocystpressure
asymptomaticlivercysts=1/3of
pts
Bilateral
Externalsurfaceissmooth
Numeroussmallcystsin
cortex/medulla
cystsarefusiformdilationsof
corticalandmedullarycollecting
ducts,radialarrangement,lined
bycuboidalepi cells
interstitialfibrosis,tubular
atrophycommon
Liveraffectedbycongenital
hepaticfibrosis

Seriousmanifestationspresentat 1in20000livebirths
birth,maydiequicklyfromhepatic
orrenalfailure,pts whosurvive
infancydeveloplivercirrhosis
(congenitalhepaticfibrosis)

Proliferationofendothelial,
mesangial andepithelialcells,
glomerularnecrosis

NephriticSyndrome
Hematuria (acuteonset,maybe
grosslyvisible),proteinuria(mildto
moderate),Decreasedglomfiltraton
rate
ElevatedbloodureaN2,serum
creatinine,oliguria(scanty),saltand
waterretention,hypoalbuminemia,
edema,hypertension

Acutediffuseproliferative
glomerulonephritis
Diffuseglomerulienlargement
andhypercellularity
Proliferation ofendothelial,
mesangial andparietalcells
Infiltrationofneutr/monocytes
Subepithelial denseimmune
complexdeposits(isolated
humps,betweenoutersurfaceof
theGBMandthepodocytes)
Subendothelial depositsinthe
mesangium,betweenthe
endothelialcellsandtheGBM
Early:coarsely,granulardeposits
ofIgG andC3
(immunofluorescence)
Later:depositsofC3

90%kidsrecoverwithno
complications
Stilloneofmostcommonchildhood
renaldiseases
ShortlivedNephriticsyndrome
beginsabruptlywith oliguria,
azotemia,hematuria,hypertension,
facialedemaandproteinuriamay
persistforseveralmonths.Eventually
depositsclearoverperiodof2
months

Rapidprogressive Ex.ofGlomerulonephritis
withNecrosis.Clinicalentity
(Crescentic)
glomerulonephritis withfeaturesofnephritic
syndrome,rapidlossof
renalfunction.
Severeglominjuryw/
necrosis,inf,GBMbreak,
prolif ofparietalepi
(crescentsofbowman's
capsule)
AntiGlomerular
Basement
Membrane(TypeI)
Crescentic
Glomerulonephritis

autoantibodyagainstcomponentof Intrinsic
ExampleofRPGN.
GBMwithinglobularnoncollagenous
Aggressiveformof
glomneph occursasrate domainofa3typeofcollagenIV
limiteddiseaseorcombined reactswithbothGBMandpulm alv
withpulm hemorrhage
capbasementmembrane
(Goodpasture syndrome) 1/2pts pulm hemorr/hemoptysis
Goodpasture Syndrome bothlungs
andkidneysaffected
InjurymaybemediatedbyantiGBM
antibodies,antiGBMTcells,orboth
GeneticsusceptibilitytoantiGBM
diseasesassoc w/HLADR2genes

AcuteTubular
Necrosis(Acute
RenalInjury)

Ex.ofDiseasesofRenal
Tubules

IschemicAcute
TubularNecrosis

UrinaryTract
Infection

Ischemia
Acquired
ToxicInjuries(Ethyleneglycolaka
antifreeze,mercuricchloride,
therapeuticdrugssuchasgentamicin,
chems suchasCCl4)
Slough/necro ofepi cells>castform
>obstruction,^intraluminalpressure
>reducedglomfiltration.Afferent
arteriolarvasoconstriction.Causedby
tubuloglomerular feedback>
decreasedglomcapfiltratio pressure.
Tubularinjuryand^intraluminal
pressurecausefluidbackleakagefrom
lumenintointerstitium
Reducedrenalperfusion,assocw/
acquired
hypoperfinptsw/hypovolemicor
endotoxemiashockorcirculatory
collapseowingtopumpfailure(e.g.MI)

kidneysenlarged,pale,often
1020%ofRPGN
petechialhemorrages oncortical Presentswithrapidprogressive
surface
renalfail,nephriticsigns/symptoms
segmentalnecrosis,GBMbreaks Ifuntreated,pt diesfromrenalfail
prolif ofparietalepi cells,
withinperiodofweekstomonths
migratemonocytes/macrophages treatmentsincludeimmsuppressive
formcrescents,fillbowman's
therapyandplasmapheresis
Strongdiffuselinearstainingof (removespathogenicantibodiesfrom
GBMforIgG andC3with
circ)
immfluorescence.Depos notseen renaltransplant
underEM.Distinctrupturesin
GBM
Crescentseventuallyobliterate
Bowman'sspace,compressglom
Fibrinstrandsprominentbtwn
celllayersincrescent
Intimecrescentsundergo
scarring,glomeruloschlerosis devs
decreasedGFR

RelatedtoAcute
Kidneyinjury:
Variousinj>direct
damagetubs,>
decreaseGFRby
multiple
mechanisms,
promotes
vasoconstriction.
Someinjsthatcause
tubinjuryalso
directlydecGFRby
decreasingrenalflow

Tubinj ismostprominentin
ATN,whetherduetoisch ortoxicity
straightportionofproximaltubs isleadingcauseofacuterenal
andthicklimbsofloopofHenlein failure
outermedulla
rapidrisingserumcreatininelevel,
prox tubsdisplayfocalflattening decreasedurineoutput(oliguria)
ofepi,dilationoflumen,lossof Oliguriareversible,tubules
brushbordern
regenerate
proteinaceous casts indistal
Urinalysisshowsdegen epi cells,
tubs,collectingducts(madeof 'dirtybrown'granularcasts(tub
TammHorsfall proteinnormally prots andhemoglobin)
secreteintubepi,alongw/
Renalfunctioncanrecoverwithin
weeksormonthsifcauseofinjury
hemoglobinandotherplasma
removed
prots
Shortsegmentnecrosis.Absence
ofwidespreadnecrosis oftubular
epi cells
Indiv necro cellsshedintolumen,
areasofdenudationoftubular
basementmembrane
Vasarecta ofoutermedulla
congested,freq contain
mononuclearleukocytes
tubcellscanregen

conditionspredisposeascendingUTI: acquired
diagnosedclinicallyand
urinarystones,congenital
confirmedbyurinalysis
megaureter,strictures,pregnancy,
showingbac coloniesin
excessof100K/mL,presencetumors,vesicoureteral sphincter
ofWBCs
incompetence,chroniccystitis,BPH,
infectionroute
shorturethrainfemales,insertionof
hematogenous orascending catheter,instrumentationResults
frombacteremic spread.Most
commonisascendinginfection,
comboofurinarybladderinfect,
vesicouretal reflux,intrarenal reflux

AcutePyelonephritis ManifestationofUTI
Commonsuppurative
inflammationofkidney,
renalpelvis,causedbybac
infect

Gramneg bacteria,E.coli,Klebsiella, Acquired

Enterobacter,Proteus,Pseudomonas,
andSerratia etc
Predisposingconditions.Inabsence
ofinstrumentation,UTImost
commonlyaffectsfemales,outflow
obstruct,bladderdysfunc,genetic
factors,vesicoureteral reflux,
intrarenal reflux,seeabove

Smallwhiteabscesses onsubcap
surfaceandcutsurfaces
Pelvic/calyceal urothelium
hyperemic,purulentexudate
lesionsareoftenfocal,muchof
kidneyappearsnormal
parenchyma,esp cortex
extensivefocaldestructionbyinf
process,vesselsandglomeruli
preferentiallyspared
inf infilitrates neutrs,filltubs
andesp collectingducts
severecases necrosisof
papillarytipsmayoccuror
perinephric abscessmayform
Obstruction>pusfillingrenal
pelvis,calycesadureter
pyonephrosis

KidneyStones

UrinaryTractCalculi

riskfactors:concentratedurine,
hereditary,diet,assocdiseases
(sarcoidosis,infbowldisease,cancer)

Bothpossible

Stonesblcokingfloweverywhere

Wilms Tumor
(Nephroblastoma)

Malignantneoplasmmade
ofembryonal elementsw/
mixofblastemal,stromal,
epi tissue.

90%casessporadic/unilateral
10%casesassoc w/defectsofWT1,
Wilms tumorgenelocatedonchrom
11(11p13)
WT1tumorsuppressorgenethat
regs transcriptionofseveralother
genes

Probsmostlyintrinsic

Largetumorwhendetected,
Presentsbtwn 1and3yrs age
Mostfreqabdom
bulging,paletan,cutsurface
98%beforeage10
solidtumorinkids,1
enclosedinthinrimofrenal
Palpableabdominalmass,pain,
in10000
intestinalobstruction,hypertension,
cortexandcapsule
containsstuffresembling
hematuria
normalfetaltissueincluding
Combinesurgical,chemo,radiation
metanephric blastema,immature tofavorableprognosis
stroma (mesenchymaltissue),
immatureepi elements

RenalCellcarcinoma Mostcommonprimary
cancerofkidney
Malignantneoplasmof
renaltubularorductalepi
cells
typicallyseeninmenbtwn
age50and70

TumorsofUrinary
Bladder

UrinaryBladder most
commonsiteofurinarytract
tumors.Mostoccurinolder
pts(medianage65),rarein
pplunder50s.Moreinmen
thanwomen3:1.Most
microscopicallyclassifiedas
urothelial(transitionalcell)
neoplasms).
Rare:squamcc,adenocarcs,
neuroendocarcs,sarcomas

Urothelial
Carcinoma
(TransitionalCell
Carcinoma)

Cancerrangesfrom
superficialpapillaryto
deply invasive
Can beanywherethathas
transitionalepithelium,
oftenmultifocal

mostsporadic,allsporadiccases
Bothpossible
assoc w/lossofheterozygosity of
tumorsuppressorgeneVHLonchrom
3p
Mut inVHLfound>1/2ofsporadic
RCCtumors
hereditory formsofRCC:autosomal
dom andVHLdiseaseassoc w/chrom
transloc involving3p,VHLdiseasehas
mut inVHLgeneitself.Hereditary
papillaryRCChasnoassoc w/VHL
gene

Fever,Chills,sweats,malaise,
frequency,dysuria,bacteriuria,
flankpain,leukocytosisand
neutrophilia common,presenceof
leukocytecastsinurine
(pathognomonic)

RCChasseveralvariants
Triadofpresentingfeatures:
80%ofallrenal
ClearcellRCC mostcommon
Hematuria(singlemostcommon
cancers,>30000
type,arisesfromproximal
presentingsign),FlankPain,
casesinUS
tubularepi cells
PalpableMass
Yelloworangemass,shows
Freq sourceofectopichormone
conspicuousfocalhemorrhage production,assoc w/feverand
paraneoplastic symptoms
andnecrosis
tumorssolidorfocallycystic
earlyhematogenous dissemination
clearcytoplasmofneoplastic
freq
cellsreflectsremovalofabundantTumorstage mostimportantprog
cytoplasmiclipidsandglycogen factor
duringtissueprocessing
5yr survivalis90%iftumorhasnot
Tumorcellsarrangedinroundor extendedbeyondrenalcapusle
elongatedcollectionsdemarcated 5yr survivalrateis30%orlessif
bynetworkofdelicatevessels
distantmetastasis(mostfreq lungs
littlecellularornuclear
andbones)
pleomorphism
mosttumorsmalignant,aggressive,
prognosisvaries,dpendingonclinical
stage,microscopicgrade.Tumors
oftenmultifocalandoccurinanypart
ofurinarytractlinedbytransitional
epithelium.Surgicaltreatmentoften
followedbyrecurrence

Cigsmokingismostimportantrisk
factor
Industrialexposuretoazo dyes
schistosomiasis
Drugs
Radiationtherapy

Acquired

stagedaccordingtoTNMclass
Variesfromsmall,delicate,low
gradepapillarylesionslimitedto
mucosalsurfaceorlarger,
highergrade solidinvasive
masses,oftenulcerated.
Papillaryandexophytic cancers
tendtobebetterdifferentiated;
infiltratingtumorsusuallymore
anaplastic
Classifiedaseitherloworhigh
gradepapillaryurothelial
carcinomas

Suddenhematuria
Dysuria
initialpresentation 85%confined
inurinarybladder,15%already
metastasized
Papillarylesionslimitedtomucosa
orlaminapropria commonlytreated
bytransurethralresection
Radicalcystectomydonewith
tumorsshowingmuscleinvasion
andoccasionallyforadvancedstage
tumors

Disease

Whatisit?

Whatcausesit?(Pathogenesis)

Intrinsic/Acquired?

Morphology/Pathology

Hyperthyroidismin
general

Thyrotoxicosis
Hyperfunction ofthyroidgland.
hypermetabolic state Alternatively,excessivereleaseof
duetotoomuch
preformedthyroidhormonesor
T3/T4
extrathyroidsource

Hypothyroidismin
general

Notenoughthyroid Anystructuralorfunctionalproblem
hormone
thatinterfereswithproductionof
adequatethyroidhormonelevels
Defectivethyroidhormonesynth
(goitrous hypothyroidism)
Inadequatethyroidparenchyma
function(thyroiditis)
InadequatesecretionofTSHby
pituitaryorTRHbyhypothalamus

Cretinism

Hypothyroidism
dietaryiodinedeficiency(endemicin Acquired
developingininfancy suchareas)
orearlychildhood

Myxedema

Hypothyroidism
developinginolder
childrenandadults

ChronicLymphocytic
Thyroiditis
(Hashimoto
Thyroiditis)

Autoimmunediseasewithgradual Intrinsic occurswith

Exampleof
destruction,failureofthyroidgland. increasedfreqin1st
Hypothyroidism
degreerelatives,but
mostcommoncause SensitizedCD4+helperTcellsto
thyroidAg>delayedtype
moreprevalentin
ofgoitrous
regionswithgreatest
hypothyroidismin hypersensitivityreaction(tissue
areasofworldwhere destructionfromtoxicproductsof intakeofiodine
iodinelevels
inf cells,Tcellmediatedcelldeath)
sufficient
orstimulatescytotoxicTcell
responses,helperBcells>auto
antibodysecretingplasmacells

ClinicalSignificance/Features

Intrinsic

ClinicalFeatures2
ClinicalFeatures1
Ocular wide,staringgaze,lidlag
skin soft,warm,flush;heat
presentb/cofsympathetic
intolerance/excesssweatingcommon
weightlosseventhoughmorehungry overstimulationoflevator palpebrae
superioris muscle
GI hypermobility,malabsorption,
Thyroidstorm abruptonsetofsevere
diarrhea
hyperthyroidism,probs duetoacute
Cardiac Palpitations,tachy
elevationincatecholaminelevels,might
Elderlymay>CHFbecauseof
beencounteredduringstress.MEDICAL
aggravatingpreexistingheartcond
Neuromusc nervous,tremor,irritable. EMERGENCY.candieofcardiac
50%dev proximalmuscleweakness
arrhythmia
(thyroidmyopathy)
Diagnosisbasedonclinicalfeats,lab
data.TSHlevelsmostusefulsingle
screeningtestbc TSHlevelsdecreasedin
earlieststagewhendiseasesis
subclinical
Diagnosis Measurementofserum
TSH.TSHincreasedinprimary
hypothyroidism,notincreasedin
personswithconditioncausedby
primaryhypothalamicorpituitary
disease.SerumT4decreasedin
individualswithhypothyroidismofany
origin

Misc.

Impairedskeletal+CNSdev,severe
'salary'
mentalretardation,shortstature,coarse
facialfeatures,protrudingtongue,
umbilicalhernia
generalizedapathyandmental
sluggishness
listless,coldintolerant,oftenobese
mucopolysacchariderichedemabuilds
upinskin,subcut.Tissue,visceralareas,
sobroader,coarserfacialfeatures,larger
tongue,deepervoice
Constipationfromdecreasedbowel
motility
pericardialeffusionscommon,later
stages,heartenlarged,heartfailure
supervenes
Glanddiffuselyenlarged,firm(60200g)
Cutsurfacepaletan,flashy,vaguely
nodularpattern
Capsuleintact
Parathyroidnotaffected
Conspicuousmononuclearinfiltrationof
lymphocytes,plasmacells
Destroyed,atrophyoffollicles
Acidophilicmetaplasiaoffollicularepi
cells(Hurthle oroxyphil cells)
Lymphoidfollicles,oftengerminal
centers,present)

painlessenlargementofthyroidassoc
w/hypothyroidism,devs slow
sometimesprecededbytransient
thyrotoxicosiscausedbydisruptionof
folliclesw/2ndryreleaseofthyroid
hormones.FreeT3/T4elevated,TSH
diminished,radioactiveiodineuptake
decr.
progressinghypothyroidism>T3T4
progressivelyfalls,TSHrises
oftenotherautoimm diseases,^riskof
dev ofBcellnonHodgkinlymphoma
Thyroidhormonegiventoalleviate
hypothyroidism,decreaseglandsize

mostprevalentbtwn
45&54yrsold.
Womenpredominant
overmen10:1
Foundinolder
women,majorcause
ofnonenedemic
goiterinkids

Diffuseand
Hypothyroidism
Dietaryiodinedeficiency.LowTH Acquired
Multinodular Goiter without
levelsleadtocompensatoryrisein
inflammationnot
serumTSH>hypertrophyand
causedbyneoplasm hyperplasiaofthyroidfolicular cells
inadequatesynthesis andenlargementofgland
ofthyroidhormone. Pts mostlynormalthyroidfunction,
somehypothyroid.
Endemicgoiter affects>10%pop,
lowiodine(areasofglaciation)
sporadicgoiter mostcauses
unknown
toxicgoiter hormonallyactive,
causesthyrotoxicosis

Diffuse diffuse,symmetric,enlargement
ofgland.Follicleslinedbycrowded
columnarcells,pileupandform
projections.
Ifdietaryiodineincreasedordemandsfor
hormonedecreased,follicularepi
involutestoformanenlargedcolloidrich
gland(colloidgoiter)
Multinodular recurrentepisodesof
hyperplasia,involutioncombineto
produceirrelgular enlargementofgland

GravesDisease

Mostcommonform
ofhyperthyroidism.
1)thyrotoxicosis
2)ophthalmopathy
3)dermopathy

Thyroidenlargedsymmetrically,35100g
Hyperplasticfolicularepi,highlyvasc
Epicellstall,columnar,arrangedas
papillaethatprojectintolumenof
follicles.Nofibrouscores.
Colloidappearsscalloped
lymphoidinfiltrates,mostT,someB&
plasma,germinalcenterscommon
Exophthalamos causedbyenlargement
oforbitalextraocularmusclesswollenby
mucinousedema,accumulationof
fibroblasts,lymphocyteinfiltration.
Proptosis increasedorbitalcontents
displaceeyeforward
Dermopathy dermisthickeningdueto
glycosaminoglycans,lymphocyteinfiltrate

commonmanifestationswith
Womenaffected7
thyrotoxicosis
timesmoreoften
diffusehyperplasiaofthyroid,
thanmen.Peak
ophthalmopathy,dermopathy
incidence2040yrs.
Diffuseenlargementofgland
Seenin1.52%of
Sympatheticoveractivity >wide,staringwomeninUS.
gaze,lidlag
skinlesionsslightlypigmentedpapules
ornodules,orangepeeltexture
ElevatedserumfreeT4/T3,decreaseTSH
Radioactiveiodineuptakeincreased,
diffuseduptakeimage

ThyroidAdenoma

Solitary,benign
clonalneoplasm
showingfollicular
differentiation.Most
nonfunctional,some
toxicadenomasthat
causethyrotoxicosis.

Usuallysolitary,circumscribednodule1
3cmindia,protrudesfromsurfaceof
thyroid,surroundedcompletelybywell
defined,fibrouscapsule,compresses
adjacentnonneoplasticthyroid
Hemorrhage,fibrosis,cysticchanges
common
neoplasticcellsdemarcatedfrom
adjacentparencbywelldefinedcapsule
neocellsarrangedinuniformfollicles
thatcontaincolloid
Folliculargrowthpatterninadenoma
distinctfromadjacentnonneoplastic
thyroid
neocellsuniform,welldefinedborders
papillarychangesnot typicalofadenoma
Hurthlecelladenomaw/oxyphils
behaveslikeadenoma
Hallmark presenceofintactwell
formedcapsaroundtumor

Mosttakeupradioactiveiodineless
avidlythannormalthyroidparenc,'cold
nodules',buttoxicones(active)are
'warm'or'hot'
10%'cold'eventuallymalignant.Most
'hot'practicallynever

Carcinomasofthe
Thyroid

DerivedfromThyroid
FollicularEpi
Papillarycarcs
(>85%)
Follicularcarcs(5
15%)
Anaplasticcarc(<5%)
Derivedfrom
parafollicularCcells
Medullarycarc(5%)

PapillaryThyroid
Carcinoma

Ex.ofThyroidCancer ActivationofMAPkinasepathway
featofmostpapillarycarcs
Mostcommon
thyroidcancerand somaticmuts rearrangementof
accountsforupto RETprotooncogeneonchrom10
90%ofsporadiccases(10q11.2)common
ofthyroidcancerin Iodineexcess
US
Radiation
Geneticfactors 4to10foldhigher
infirstdegreerelativesofpts

Autoimmunediseasemediatedby Acquired
antibodiestothyroidstimulating
hormone(TSH)receptors.Antibodies
boundtoTSHreceptorsstimulate
thyroidcellstosynthT4,thyroxine
Smokingincreasesrisk

Hyperparathyroidism

Primaryhyperparathyroidism char'd
byspontaneoushypersecretion of
parathyroidhormone(PTH)
Solidparathyroidadenomain85%
ofcases
Primaryhyperplasiaofallfour
parathyroidglandsin510%ofcases
Parathyroidcarcinomaseenin1%
ofcaes,char'd byinvasivegrowth
andmetastases

Hypercortisolism
Exampleof
(CushingSyndrome) Adrenocortical
Hyperfunction

exogenous administrationof
exogenoussteroids
Endogenous primary
adrenocorticalhyperplasia,
adrenocorticalneoplasia,
Adrenocorticotropichormone
(ACTH)secretingpituitaryadenomas
(Cushingdisease),EctopicACTH
secretingnonendocrineneoplasms
(e.g.smallcellcarcinomaoflungs)

Chronic
Exampleofadrenal
Adrenocortical
hypofunction
Insufficiency(Addison Deficient
Disease)
productionof
adrenalcortical
hormone
Fatalwasting
disorder

canresultfrom1)adrenalgland
Acquired
destruction,2)pituitaryor
hypothalamicdysfunctionw/
decreasedACTHproduction,3)
chroniccorticosteroidtherapy
Failureofadrenalstoproduce
glucocorticoids,mineralocorticoids,
androgens.
>90%duetofourdisorders
autoimmuneadrenalitis,
Tuberculosis,AIDS,metastaticcanc

Pheochromocytoma Neoplasticdisorder mostsporadic

Mostacquired,some
ofadrenalmedulla smallamountinheritedaloneor intrinsic
Catecholamine
partofhereditarysyndromessuchas
secretingtumorsof MENtypes2Aand2B,VHLdisease,
chromaffin cellsof neurofibromatosistype1(NF1),RET,
adrenalmedulla
etc.
Presenting
Canbepartofmultipleendocrine
symptomsreflect
neoplasiasyndrome(MEN)
sustainedorepisodic
hypertension
Pallor,anxiety,
cardiacarrhytmias
Hyperpituitarism
Excessivesecretion Mostcommoncauseisadenoma
oftrophichormones arisinginanteriorlobe.
PituitaryAdenomas Class'd onbasisof Mostsinglecelltype,onepredom
hormonesproduced hormone
inneoplasticcells
mostcommonadenomasecretes
Canbefunctional, morethanonehormone,one
assoc w/hormonal secretesbothgrowthhormone,
excess,clinical
prolactin
manifest
canbesilent,w/o
clinicalmanifestof
hormonalexcess
(30%)

Prolactinomas

Mostcommontype
ofhyperfunctioning
pituitaryadenomas
(50%ofcases)

Maypresentsolitaryormultifocal
Mostfreqbtwnages
(PathologyContinued)
lesioninthyroid
Invaginationofcytoplasm>lookslike 20and50yrs,femto
Canbewellcircumscribed,
intranuclear inclusionsincrosssections, maleratio3:1
encapsulatedorcaninfiltrateadjacent 'pseudoinclusions'
parench w/illdefinedmargins
Papillaryarchitecturepresentinmany
Maycontainareasoffibrosis,
cases
calcification,andcystic
neoplasticpapillaedo havedense
Diag ofpapillarycarc basedonnuclear fibrovasc cores
features eveninabsenceofpapillary
Psammoma bodiesconcentricalkly
calcifiedstructs oftenpresentwithin
architecture
papillae
Nucleiofpapillarycarc cellscontain
veryfinelydispersedchromatin,imparts Metastasestoadjacentcervicallymph
opticallyclearappearance,designation nodesestimatedtooccurinabouthalf
cases
'groundglass'or'OrphanAnnieeye'
Survivalrate~85%at20yrs
nuclei
Secondaryhyperparathyroidism
Mostcommonmanifestationofprimary
Diffuseenlargementofallfourglandsin hyperparathyroidismincreaseinserum
responsetohypocalcemiasuchasseenin ionizedCa
endstagerenaldisease,malabsorption Primaryhyperthyroidismmostcommon
syndromes,VitDdeficiency
causeofclinicallysilenthypercalcemia
Tertiaryhyperparathyroidism
PTHelevated
Diffuseenlargementofallfourglands. Hypophosphatemia
AutonomoushypersecretionofPTH
Demineralizationofboneresultsin
followssecondaryhyperparathyroidsm, bonesoftening,painfulfractures
persistsevenaftercauseofhyperplasia (osteitis cystica fibrosa inprimary,renal
eliminated
osteodystrophy in2ndryhyperparathyr)
Hypercalciuria predisposestourinary
calculi
Constibation,pepticulcers,
pancreatitis,biliarystonessourcesof
abd pain
Mentalsymptoms lethargy,depression
CardiacArrhythmiasmaybepresent
Yellow,thickened,multinodulardueto Obesity gradualonsetofobesityof
hypertrophy,hyperplasiaoflipidrich
face(moonface),neck(buffalohump),
zonafasciculataandreticularis.
trunk,abdomen.Extremitiesnot
affectedorevenwasted
Skin atrophic,subcut.Fatdecreased,
stretchedwithstriae
Muscskel system osteoporosis,
proximalmusc wasting,weakness
Cardiovasc hypertension,possible
congestiveheartfailure
2ndrysexchars virilization acne,
oligomenorrhea inwomen,erectile
dysfunct inmen,decreaselibidoinboth
sexes
Glucoseintoleranceand
hyperinsulinemia,diabetesmellitusdevs
in15%ofpts
Psychochanges irritability,emotional
lability,depression,paranoia
(Autoimmune)
weakness,weightloss,GIsymptoms,
Autoimmuneadrenalitis accountsfor hypotension,electrolyteimbalance,
6070%ofcases
hyperpigmentation
autoimm destructionofsteroid
producingcells,autoantibodiestoseveral (Infections)
keysteroidogenic enzymes
ParticularlyTBandproducedbyfungi,
1/2ofcases,autoimm reactionrestricted alsoprimarychronicadrenocortical
toadrenals(isolatedautoimm Addison insufficiency
Tuberculous adrenalitis assoc w/
disease)
restofpts,otherimm diseasescoexist infectioninothersites
autoimm polyendocrinopathy syndrome AIDSpts atriskfordev'ing adrenal
insufficienciesfrominfections
Metastaticneoplasmssometimes
destroysufficientadrenalcortexto
producedegreeofadrenalinsufficiency
sporadic? 80%uni,10%bilat,10%in
Ifariseinextra
Boutsofparoxysmalhypertension,
extraadrenallocations
adrenalsites,called
headaches,sweating,tachycardia,
90%benign,10%malignant
paragangliomas
nervousness
Histologyhighlyvariable.Typically
>90%pts showhypertension(2/3rd
circumscribednestsofneoplasticcells
sustained,1/3rdepisodic)
present(Zellballen)
AnginaandMIinabsenceofcoronary
Tumorcellsrangefrompolyhedralto
arterydisease(catecholamine
fusiformw/granularamaphophilicor
cardiomyopathy)
basophiliccytoplasmandvesicularnuclei. Diagnosis increasedurinarylevelsof
Eosinophilicglobulesusuallyseenin
catecholaminemetabolites,particularly
cytoplasm
Vanillylmandelic acid

Macroadenoma:>1cmindia
Bitemporal Hemianopsia,reductionof
Microadenoma <1cmindia
fieldofvision
wellcircumscribedsoftlesion,maybe (Histopathology)
confinedbysella turcica,largerlesions Composedofrelativelyuniform,
extendsuperiorlythroughsellar
polygonalcellsarrayedinsheets,cords,
diaphragmintosuprasellar region,often papillae
compressopticchiasm,adjacentstructs SupportingCT(reticulin)issparse
Invasiveadenomas 30%ofcases,
Nucleiuniformorpleomorphic
adenomasgrosslynonencapsulated and Mitoticactivityscanty
infiltrateadjacentbone,dura,
cytoplasmofneoplasticcellsacidophilic,
uncommonlybrain
basophilic,chromophobic
functionalstatusofadenomacannot be
reliablypredictedfromhisto look
cellmonomorphism andabsenceof
significantreticulin networkdistinguish
pituitaryadenomasfromnonneoplastic
anteriorpituitaryparenchyma
Microtomacroadenomas
Prolactinpositivestaininginneocells

Hyperprolactinemia Amenorrhea,
galactorrhea,lossoflibido,infertilityin
women
decreasedlibidoandimpotencyinmen
moresymptomaticinyoungerwomen
Treatmentincludedbromocriptine
(dopamineagonist)toinhibitPRL
secretion
Largetumorsrequiresurgicalremoval

PersistenthypersecretionofGH
GrowthHormone
Somatotroph
ProducingAdenomas adenomas incl
stimulateshepaticsecretionof
thosethatproduce insulinlikegrowthfactorI
mixofgrowth
(somatomedinC)
hormoneandother
hormones(e.g.
prolactin) 2ndmost
commontypeof
functionalpituitary
adenoma)

Maybequitelargebytimeofdiscovery
Gigantism happensifadenomaoccurs
beforeepiphysescloess
Acromegaly ifepiphysesclosed.
Conspicuousgrowthinsofttissues,skin,
viscera,bonesofface,hands,feet.
Enlargejawresultsinprotrusion
(prognathism),broaderlowerface,
separationofteeth.
Mostcasesofgigantismare
accompaniedbyacromegaly
Othermanifestsincl.abnormglucose
tolerance,diabetesmellitus,generalized
muscleweakness,hypertension,arthritis,
osteoporosis,CHF

Adrenocorticotropic Most
HormoneProducing microadenomas.
Adenomas
Accumulationof
ACTHcontaining
granulesincells

Maybeclinicallysilent
Maycausehypercortisolism(Cushing
disease)
Nelsonsyndrome largeclinically
aggressivecorticotrophcelladenomas
developaftersurgicalremovalofadrenal
glandsfortreatmentofCushign
syndrome(w/oadrenals,
hypercortisolismdoesnotdevelop)
Hyperpigmentation ACTHcleavedfrom
POMC(Proopiomelanocortin)

Hypopituitarism

NotenoughsecretionPituitarytumors(>1/2
ofoneormore
hypopituitarisminadults),maybe
pituitaryhormones functionalornonfunctional,
lossof75%anterior symptomsoftenresultfrom
pituitarygland>
compressionofadjacenttissuesby
hypopituitarismlike mass
destructionof
Craniopharyngioma Benigntumor
hypothalamusor
originatingfromremnantsofrathke
hypothalamic
pouch,locatedinorabovesella
pituitarytract
turcica
(pituitarystalk)
Gliomas causesdestructionof
hypothalamiccenteronhypothalamic
pituitar tract

DiabetesInsipidus

PosteriorPituitary
Syndrome
Deficiit inADH
(arginine
vasopressin)>
uncrontrolled lossof
waterinurine,
hypernatremia
(concentrationof
sodiuminremaining
fluidvol)
PosteriorPituitary
Syndrome
ExcessADH >water
retention,dilutional
hyponatremia,
cerebraledema,
resultantneurologic
dysfunction

Syndromeof
InappropriateADH
Secretion(SIADH)

definitivediagonly
aftercareful
histologicexamof
resectedspec
excellentprognosis,
norecurrenceor
metastasizing

(causescontinued)
Trauma Headinjury,surgery,etc might
damagehypothalamicpituitarytract
SheehanSyndrome postpartum
ischemicpituitarynecrosis,oftendueto
severehypotensionfrompostpartum
hemorrhage
EmptySella Syndrome Congenital
defectorabsentdiaphragma sella,
permitstransmissino ofcerebrospinal
fluidpressureintosella.Sella enlarged,
containsthin,flattenedpituitaryatbase.
Looks'empty'.Endocrinedisturbances
generallyminor

dependsonextentofloss,specific
hormones,pt's age
Majorones Pituitarynecrosis,Pallor,
hypothyroidism,Failureoflactation,
adrenalinsufficiency,ovarianfailure
withamenorrhea

Causedbydestructionof
hypothalamusorposteriorpituitary
gland(centraldiabetesinsipidus)
1/4casesassoc w/braintumors,esp
craniopharyngioma,restofcases
idiopathic,trauma,,inf disordersof
hypothalamusandpituitary

Polyuria,thirst,polydipsia

EctopicADHsecretionbymalignant
neoplasms(e.g.smallcellcarcinoma
oflung(mostcommoncause)
Drugs somepsychotropicagents,
diuretics,cytostaticagents
Hypothalamichyperfunction

waterretention,dilutional
hyponatremia,cerebraledema,resultant
neurologicdysfunction

Disease

Whatisit?

Whatcausesit?(Pathogenesis)

AnemiaClassified
NormocyticnormochromicMicrocytichypochromicRBC
basedonmorphology RBC
Irondeficiencyanemia(anisocytosis),
ofRBC
Bloodloss,hemolytic
thalassemia(targetcells),anemiaof
anemia,aplasticanemia, chronicdisease(2030%ofcases)
anemiaofchronicdisease
(mostcases)

HemolyticAnemias

assoc w/accelerated
destruction

Intracorpuscular defects(intrinsic)
membraneabnormalities,enzyme
deficiencies,defectivehemoglobin
synthesis
Extracorpuscular defect(extrinsic)
Antibodymediated,mechanical
traumatoredcells,infections

Intrinsic/Acquired?

Morphology/Pathology

Macrocytichyperchromic Compensatorymechanisms
RBC
Hyperplasiaoferythroid precursorsin
large,lackcentralpallor, bonemarrow,extramedullary
VitaminB12orfolate
hematopoiesisinsecondaryhematopoietic
deficiency,alcoholism
organs(liver,spleen,lymphnodes)

ClinicalSignificance/Features

Misc.

dependsonseverity,speedofonset,
underlyingpathologicconditions
Acute SOB,organfail,shock
Pallor,fatigue,lassitude
hemolyticanemias hyperbilirubinemia,
jaundice,pigment
Ineffectivehematopoiesis ironoverload,
heartandendocrin failure
Congenitalabnormalities,cachexia

Intrinsic,usuallyinherited allhemolyticanemias char'd by

orextrinsic,usually
1)^rateRBCdestructinspleen/liver
acquireddependingon 2)Reticulocytosis whichreflects
defect
compensatoryincreaseinerythropoiesis
3)retentionbybodyofproductsofredcell
destruction(includingFe)
leadsto>
4)Markederythroid hyperplasiainbone
marrow
5)^reticulocytecountinperipheralblood
6)Extramedullary hematopoiesisdevs in
spleen,liver,LN

normalRBClifespan
120days

Membranestabilityaffected,redcellslose splenectomycorrectsanemiccondition
withoutaffectinghereditarydefectand
membranefragmentsuntilcellsbecome
spherocytosis.However,procedure
spherical(spherocytes)
increasesriskforinfections
Spherocytes havelimiteddeformability;
sequesteredinspleen,destroyedby
ClinicalCourse
macrophages
ReducedlifespanofRBSfrom120dto10
muts affectintegrityofmembrane
20d
cytoskeleton,erythrocytelosesmembrane Anemia usuallymderate inseverity,
fragments>sphere.Lessdeformable,so acuteaplasticcrisismaybetriggeredby
trappedinspleniccords,phagocytosed by parvovirusinfectionwhichkillsredcell
macrophages.GP,glycophorin
progenitorcells,reticulocytosis
Erythrostasis >decreaseglucose,pHwhich Splenomegaly fromcongestionfromRBC
leadstomoremembraneloss
andincreasednumberofmacrophages
Bloodsmearshowsanisocytosis,dark
Jaundice,pigmentstones,systemic
appearing(hyperchromatic)spherocytes,no hemosiderosis fromdegradationof
centralpallor.HowellJollybodies(small
excessiveamountsofhemoglobin
darknuclearremnants)present
SickleCellAnemia
Structurallyabnormal
MutationinthegenecodingforB
ClinicalCourse
(clinicalcoursecontinued Upondeoxygenation,HbS molecules
~8%ofAfrican
globinchain,singleaminoacid
globinsynthesis
Chronichemolyticanemiaand
2)
Americansare
undrgo polymerization(akagelation,
hemolyticanemia,
substitution(valine forglutamicacidat2)Acutechestsyndrome crystallation)
microvascularobstructionsarethetwo heterozygousofthis
intracorpuscular anemia the6thposition),leadstoformationofwithpulmonary
majorconsequences
hemoglobinopathy,
RBCsdistorted,assumeanelongated
causedbyincreasedRBC sicklehemoglobin(hemoglobinS,HbS) dysfunction,
homozygousdiseasesurfacesafterthe
about1in600have
crescentic,orsickle,shape
destruction
NormaladultRBCS:96^HbA,3^HbA2, systemichypoxemia,
Sicklingofredcellsinitiallyreversibleupon sixthmonthoflifewithHbF beingreplaced sicklecellanemia
1%fetalHbF
sickling,vasoocclusion reoxygenation
byHbS.Anemiasevere,hematocrit1830% Conditionmayoffer
Homozygotessicklecellanemiaall
3)CNSstroke
(normalis3545%) meanlifespanofRBC somedegreeof
Repeatedsicklingcausesmembrane
HbA replacedbyHbS
Conditions2and3are damage,eventuallycellsaccumulate
now20days(1/6ofnormal)
protectioninAfrica
Heterozygotessicklecellanemia,
twoleadingcausesof
calcium,losepotassiumandwater,become HeterozygotesforHemoglobinS(sicklecell againstMalaria
about40%replacedbyHbS
ischemiarelateddeath irreversiblysickled,rapidlyhemolyzed
trait)donotdevelopredcellsickling,
Hypoxyurea canreduce Sicklecells,anisocytosis (considerable
clinicallynormal
(ClinicalCoursecontinued1)
paincrisesandreduce variationinsizeofcellsthatarenormally Reticulocytosis andhyperbilirubinemia
hemosiderosis andgallstoneare
anemia increaseslevel uniform),Poikilocytosis (RBCofirregular
duetochronichemolysis
common
ofHbF,antiinf effects, shape),targetcells
Compensatoryhyperplasiaoferythroid
Vasoocclusiveorpaincrisis(pl.crises) increasesmeancell
progenitorcellsinbonemarrow,vascular
1)hypoxicinjuryandinfarctionin
congestion,thrombosisandinfarctioncan
volume,producesNO,a (Clinicalcoursecontinued3)
manysitesleadingtopain,esp inthe potentvasodilatorand Aplasticcrisis temporarycessationof
affectanyorganavascularnecrosisin
erythropoiesis
bonemarrow,canprog toinfarction inhibitorofplatelet
bone
pts pronetoinfections
andnecrosis
Autosplenectomy inadultstartsas
aggregation
splenomegalyintheyoung
G6PDhelpsrecyclereducedglutathione,
mostprevalentinareas
Glucose6Phosphate Enzymedefect
Xlinkedrecessivedisorderwithred
drugswhichcanleadtosymptoms
deficiencyrendersRBCssusceptibleto
wheremaleariais
Dehydrogenase
(deficiency) Hemolytic cellsensitivitytooxidativestress
includeantimalarials,someantibiotics
oxidativestress,conditionsaccentuatedby (sulfonamides,nitrofurantoin),some
historicallyendemic
Deficiency
Anemia,intracorpuscular manifestedashemolyticanemia form
ofhereditarynonspherocytic anemia
infections,somedrugs.
(Afircanandpartsof
anemiacausedby
analgesics(phenacetin,aspirininlarge
Oxidationofhemoglobincaues
Mediterranean)
increasedRBCdestruction
doses),VitK derivatives
precipitationincytoplasmasHeinzbodies, Favism favabeaningestionmayleadto appearstoprovide
increasedcellregidity,ultimately
someprotection
fatalhemolysis
hemolysis
againstmalaria
Naphthalenesensitivity(mothballs)
afterpassingthroughspleen,cellsmay
Infections phagocytosisw/freeradical A varientmaybe
havepartofmembraneremoved(bite
seenin1015%of
production
cells)
Drughemolysisacute,variableseverity, Americanblacks,assoc
Inertredcellsprecipitatedenaturedglobinlage of23days
withreducedenzyme
(Heinzbodies),splenicmacrophagespluck Avoidsubstanceswhichmaytrigger
activity(10%norm)due
hemolyticreaction
todecreasedhalflifeof
outinclusions,'bite'cellsproduced
enzyme
Bloodtransfusioninacutephaseof
hemolysis
Prompttreatmentofinfections
Folicacidsupplement
Thalassemia
Deficientglobinsynthesis OverallconcentrationofnormalHbA
Hyperplasiaoferythroid progenitors with particularlycommon
TypesofThalassemia
Hemolyticanemia
reduced
amongmediterranean,
BThalassemia mostcommon,mutationof ashifttowardearlyforms
intracorpuscular Anemia AbnormalratioofachainstoBchains
african,asian
oneorbothgenesthatcodeBglobin.Red Cachexia
causedbyincreased
resultsinintracellulardeposits,
populations
cellhemolysisresultsfromunbalancedratesSkeletaldeformities duetomarrow
destructionofRBC
producingcharacteristic'targetcells'
ofBglobinandaglobinchainsynth
expansion(ex.inslideisnewbone
Groupofinherited
pronetohemolysis
>unpairedaglobinchainsformaggregates formationproducingperpendicular
disorderscausedbymuts
thatdamageredcellprecursorsandimpair radiationsresemblingcrewcut)
thatdecreaserateof
erythropoiesis
Splenomegaly,hepatomegaly,
synthesisofaorBglobin
lymphadenopathy
Thalassemiamajor (Cooleyanemia)
chains(normalisHbA a2b2
Ironoverload canleadtosevere
Homozygotesdevelophemolysis,
Reducedhemoglobin
splenomegaly,bonemarrow,hyperplasia, hemosiderosis
synthesis,microcytic,
BThalassemiamajorappearsinchildren
bonedeformities
hypochromicanemia
Thalassemiaminor (trait) mildanemiain asHbF decreases,growthisretarded,
repeatedtransfusionneeded
heterozygotes
aThalassemia deletionofoneormoreof BThalassemiaminorisusedonlyamild
microcytichypochromicanemiawith
thefouraglobingenes.Severormild
dependsonnumberofgenesdeleted
normallifeexpectancy
BThalassemiamajor Failuretothrive,
repeatedbloodtransfusionhelps,systemic
ironoverload
IrondeficiencyAnemia DeficientHeme synthesis Chronicbloodloss(mostimportant
Microcytichypochromicanemiawith
Lowbonemarrowironstores
Irondefismost
anemias ofdiminished causeinWesternworld)
anisocytosis (i.e.pencilorcigarshaped
Lowserumiron
commonformof
erythropoiesis
Inadequateironuptake;dietary
cells)
Lowferritinlevels
nutritionaldeficiency
deficiency(mostimportantin
Hypochromicmicrocyticaniemia ofiron Lowtransferrinsaturation
mostcommonformof
developingworld)
deficiency smallredcellscontaining
Hightotalironbindingcapacity(TIBC)
anemia
Inadequateironabsorption;
narrowrimofperipheralhemoglobin.
Noregulatedpathway
achlorhydria,celiacdisease
forironexcretion.Iron
Excessiveironloss;menstruation,
balancemaintainedby
chronicGIbleeding
regulatingabsorption
Increasedirondemand;pregnancy,
ofdietaryiron
lactation,infancy
Perniciousanemia causedbyvit b12
Pallor,easyfatigability
AnemiaduetoVitamin DeficienciesinDNA
Macrocytichyperchromatic RBCs
B12andFolate
synthesis Anemiadueto def (autoimm attackongatric mucosa
whichsecretesintrinsicfactor a
Hypersegmented neutrophils
Deficiency
decreasedRBC
Bonemarrowwithnumerous
production.SynthofDNA substancecriticalinabsorptionofvit
B12
megaloblasts (ie immatureRBCprecursors
inhematopoieticcells
Malabsoprtion ofBitB12ingastritis,
thataremuchlargerthannormoblasts)
affected,soisthe
Crohn disease,GIparasiticinfection
Lowplateletcount
maturationofbone
marrowprecursorsof
Inadequateintakeoffolicacid,in
Serumvit B12orfolatelevelslow
bloodcells
malnutrition,alcoholism
atrophyofgastricfundic glands(PA)
increaseddemandoffolicacidin
CNSlesionswithdemylelination ofdorsal
pregnancy
andlateraltractsofthespinalcord(PA),
Drugtherapy interferewith
maynotresolveevenwithB12
absorptionoractasfoliateantagonist
supplementation
(e.g.methotrexate)
NeurologicabnormalitiesdoNOToccurin
folatedeficiencyanemia
Hereditary
Spherocytosis

intrinsic
Membraneabnormalities Transmittedmostcommonlyasan
HemolyticAnemia,
autosomaldominanttrait:about25&
Intracorpuscular Anemia ofcasesasautonomal recessiveand
causedbyincreasedRBC moresevereformofthedisease muts
instructuralproteinsimportantin
Destruction
maintainingspheroidcellshapes(e.g.
spectrin,ankyrin,band3prot involved
RBCsbecomespheres
inverticalinteractionsbtwn
membraneskeletonandintrinsic
membraneprots)

AplasticAnemia

Disturbanceof
proliferationand
differentiationofstem
cells.Anemiadueto
deficiencyinRedand
WhiteCellproduction

Polycythemia
(Erythrocytosis)

Leukopenia:
Neutropenia/
Agranulocytosis

Multipotentmyeloidstemcells
suppressed>marrowfailureand
pancytopenia
mosttimescauseisunknown
(idiopathic)
Canbeduetodrugtherapy,toxins,
radiation,viralinfection
AutoreactiveTcellsplayimportantrole
(geneticallyalteredstemcellsproduce
newantigens>Tcellresponse)
(immunosuppressivetherapyuseful)
IncreaseinRBCmass
Relative hemoconcentration dueto
abnormallyhighredblood decreasedplasmavol (e.g.water
cellcount,usually
deprivationdehydration,prolonged
correspondingincreasein vomitingordiarrheaorexcessive
hemoglobinlevel
diureticusew/normalredcellmass
Absolute actualincreaseintotalRCM
splitintoprimaryor2ndary
Primary NormalorLower
erythropoietininsystem
1)Polychtehmia vera,a
myeloproliferative disorderw/
autonomous,erythropoietin
independentgrowthofredcell
progenitors
2)Rareinheritederythrpopoietin
receptormutationswitherythrpoietin
independentreceptoractivation
(primaryfamilialpolycythemia)
Nonneoplasticdisorder *decreasedproduction:irradiation,
ofWBC Neutropeniais druginduced,viralinfects,congenital
absoluteneutrophilcount*ineffectiveproduction:
<1600/uL
megaloblastic anemia,myelodysplastic
syndrome
*generalizedmarrowfailure
Increaseddestruction:autoimmune
related,idiopathic,infections

Leukopenia:Reactive Nonneoplasticdisorder commonreactiontovarietyofinf

(inflammatory)
ofWBC Increasein
states.Dependsonsizeofmyeloidand
Proliferation
numberofwhiteblood lymphoidprecursorpools inbone
marrow,thymus,circulation,
cells(nonneoplastic
peripheraltissues,rateofrelease of
disorderofWBC
cellsfromstoragepoolsinto
circulation,marginalpool ofcells
adheringtovesselwalls,rateof
extravasation ofcellsfrombloodinto
thetissues
Lymphadentitis
Reactive(inflammatory) Infections,nonmicrobialinfstimulinot
proliferationoflymph
onlycauseleukocytosis,alsoacton
nodes(nonneoplastic
lymphnodes>enlarged
disorderofWBC)
(lymphadenopathy)

Neoplastic
Leukemias tumors
Lymphomas tumorsproducemassesinLymphoidneos non
ProliferationsofWhite primarilyinvolvebone
involvedlymphnodes,spleen,
Hodgkinlymphomas,
cells
marroww/spillageofneo extranodaltissues
HodgkinLymphomas,
cellsintoperipheralblood
lymphocyticleukemia,

plasmacelldyscrasias

AcuteMyelogenous
Leukemia(AML)

Myeloidneoplasm clonal blockedatsomeearlystageofmyeloid

prolif ofimmaturemyeloidcelldev ;noterminaldiff
cells(blasts)inbone
(commitment).
marroww/subsequent maystartdenovo,orendstageof
appearanceinblood&
chronicmyelkogenous leukemiaand
tissues
myelofibrosis
assoc w/acquiredmuts intx facs that
inhibitnormalmyeloiddiff(noterminal
diff,nocommitment)

AcutePromyelocytic
Leukemia

exampleofAML

Mut ingenesencodingTx facs req'd for

normalmyeloidcelldiff.Onemut
involvest(15;17)transloc inacute
promyelocyte leukemia >formationof
abnormalPML/RARAfusionprot >
blocksmyeloiddiffatpromyelocytic
stage.RARA=retinoicacidreceptor
alpha(geneon17)PML(geneon15).
Assoc w/radiation,cytotoxicchemo,
benzeneexposure,andinthecaseof
cigsmokingdoublesrisk
Disorderassocw/activatingmutsin
ChronicMyelogenous Myeloidneoplasm,
Leukemia(CML)
clonalstemcelldisorder. tyrosinekinases,generateconstitutive
signalsmimickingthosenormally
Oneofthe
producedinresponsetohematopoietic
myeloproliferative
disorders.Char'd by
growthfactors
hyperprolif ofneo
myeloidprogenitorsthat
retaincapacityfor
terminaldiff >increase
oneormoreformed
elementsofperipheral
blood.

BAcuteLymphoblastic Malignancyofprecursor
Leukemia/Lymphoma Lymphocytes
(ALL/LBL)
Immature(precursorB
lymphoblastsmalignant
cellsinBALL/LBL

Blymphoblasticleukemia(BALL)
precurosrBcellmalignancyinvolving
primarilybonemarrow,peripheral
blood
Blymphoblasticlymphoma(LBL)
precursorBcellmalignancyinvolving
lymphnodes

Mature(peripheral)B Neoplasmoflymphoid
CellLymphomas
cells
Lymphomas tumors
thatproducemassesin
involvedlymphnodes,
spleen,extranodal
tissues.Mostcommon
typeinwesternworld

derviedfromclonalproliferationof
peripheralBcells.MostcommonBcell
lymphomasfollicularlymphomas
(22.1%),diffusedlargecelllymphomas
(30.6%).

DiffuseLargeBCell
Lymphoma

PeripheralBCell
heterogeneousgroupofaggressive,
Neoplasm.Most
potentiallycurableBcellneoplasms.All
importanttypeof
agesbutmostly6070yrs age
lymphomainadults.50%
ofalladultnonHodgkin
lymphomas

Burkitt Lymphoma(BL) PeripheralBcell

neoplasm.oneofmost
rapidgrowingmalig
chrom transloc involving
8q24whichharborsMYC
oncogene

Ariseassinglenodeorchainofnodes,
spreadanatomicallycontinguous
lymphoidtissues.Stagingimportant

HodgkinLymphoma
(HL)

ClonalneoplasmsofB
lymphocytes

MultipleMyeloma

Plasmacellneo
DysregulationofDcyclin and
terminallydiff'dB
chromosomaltranslocationsare
lymphocytes(plasma
cmommon inmultimyelo
cells),multimyeloma(akaRiskfactors:Genedisposition
plasmacellmyeloma)is (increasedincidenceofmultimyelo in
mostcommon(90%of
firstdegreerelativesofplasmacell
cases).
neoplasia,higherfreq inblacks(2x)),
ionizingradiation,chronicantigenic
stimulation,age freq increaseswith
age,meanageatdiag is65yrs

Splenomegaly

Largespleen.Commonin
varietyofunrelated
functional,infectious,
infiltrativeprocesses

Thymomas

Neoplasmofthymic
corticalormedullaryepi
cells

Markedhypocellularmarrowcontains
anemia,leukopenia,thrombocytopenia
mainlyfatcells(hematopoieticcellsinbone Hemorrhages,infections
marrowreplacedbyfat)
repeatedtransfusionscanleadto
hemosiderosis

Absolutecontinued
Absolutecontinued
Secondary Higherythropoietininsystem Bloodviscous,cardiacfunctionand
Compensatory:lungdisease,highaltitude peripheralbloodflowmaybeimpaired.
living,cyanoticheartdisease
Skinandmucosaappeardarkred
Paraneo:erythropoietinsecretingtumors Blooddoping autologoustransfusion,
(renalcellcarcinoma,hepatocellular
homologoustransfusion,EPOinjections
carcinoma,cerebralhemangioblastoma)
HemoglobinmutationswithhighO2
affinity
inheriteddefectsthatincreasestabilityof
HIF1a(hypoxiainducedfactor)leadingto
^EP
Chuvashpolychtemia (homozygous VHL
muts)
Prolyl hydroxylasemuts

hematocrit:normal
4252%M,3747%F
Polycythemia:52%M,
>47%F

(causescontinued)
Malaise,chills,fever,markedweakness,
Marrowhypercellularity increasein#of fatigability
ulcerating,necrotizinglesionsonmucous
granulocyticprecursorsb/cexcess
destructionofmatureneutrophils,
membranes
ineffectivegranulocytopoiesis
infectionssometimeswithmassive
Marrowhypocellularity w/decreasein growthofmicroorganisms
controlinfection,treatwithgranulocyte
maturinggranulocyticprecursors seen
colonystimulatingfactor
whendrugswhichsuppress
granulocytopoiesis areused
withmyelotoxic drugs,bothRBCandWBC
productionareaffected

Leukopenia decrease
inWBC,mainly
granulocytes,total
WBCcount<4300uL
absoluteneutrophil
counte<1000/uL>
vulnerabletomicrobe
infect
absolutecountbelow
500/uL
(agranulocytosis)>
seriousriskinfect

' Hemoglobin:normal
13.216.7g/dLM
11.915.0g/dLinF
Polycythemiain>18.5
M,>16.5inF

Neutrophilscontaincoarsepurple
cytoplasmicgranules(toxicgranulations),
bluecytoplasmicpatchesofdilated
endoplasmicreticulum

(causescontinued)
Somecauses
acutebacterialinfects neutrophilia
Allergicdisorders,parasiticinfections
(eosinophilia)
chronicinfects,bacterialendocarditis
monocytosis
Chronicimm stim suchasTB,epstein
Barr,CMVetc lymphocytosis(eg in
infectiousmononucleosis)
swollen,greyred,engorged.
Acutenonspecificlymphadenitis may
histopathnonspecificw/largegerminal containabscessincenteroffollicles;
centers w/numerousmitoticfigures
neutrophilicinfiltratesseenw/pyogenic
Germcentersoffolliclescontainlarger
organisms
lymphocytes.Morepronouncedreactive
Chronicnonspecificlymphadenitis
changefeatureslargerfollicleinlymphnodeFollicularhyperplasiaassocw/infections
andgerminalcenterscontaining
orinfprocesses,activateBcells,create
macrophages
folliculargermcenterreaction(in
rheumatoidarthritis,toxoplasmosis,early
HIVinfect)
Paracorticalhyperplasia reactivechanges
intcellregionsofnodew/largeprolif
immunoblasts(viralinfects(EBV),certain
vaccinations(e.g.smallpox),certaindrugs
(e.g.phenytoin/Dilantinforseizures))
Myeloidneoplasms arisefromstemcells Histiocyticneoplasms
thatnormallygiverisetoformedelements (Leukemias)
ofblood:granulocytes,redcells,platelets. Leukemias arisefrommutsthatblockdiff
Monoclonalprolifsreplacebonemarrow atearlystagesofwhitecelldev,enhance
cells Acutemyeloblasticleukemia(AML), selfrenewal,incgrowthandsurvival.
Important:BCRABL(breakpoint
chronicmyeloproliferativedisorders,
chromosomeregionAbelsonkinasefusion
myelodysplasticsyndromes
gene),MLL(mixedlineageleukemiagene),
PMLRARa,promyelocyticleukemiaretinoic
acidreceptorafusiongene
Blasts,whichcanexhibitevidenceof
Fatigue,pallor,fever,infections(esp
granulocytic,erythroid,monocytic,or
opportunisticorganisms)common,
accountsfor80%of
megakaryocyticdiffaccumulateinmarrow, abnormalbleeding(cutaneousbleedand acuteleukemiasin
replacingnormalelements,freqcirculatein serosalhemorrhagesoverviscera)
adults,medianageof
peripheralblood
60atonset
chemoleadstoremissionin>50%pts,
progaccuminbonemarrowofimmature overall5yrsurvival<30%
cellsthatlackpotentialforfurtherdiffand bonemarrowtransplantcommonmodeof
maturation >suppressnormal
treatment
hematopoiesis,granulocytopenia,
thrombocytopenia,anemia(bonemarrow
failure)
neopromyelocytes w/abnormalcoarse treatmentw/alltrans retinoicacid
andnumerousazurophilic granules.Other overcomesblock,immaturecellsundergo
findings>presenceofseveralcells,bilobed terminaldiffintoneutrosanddie
nuclei,cellincenteroffieldcontains
retinoicacid+chemo>excellentprog
multipleneedlelikeAuerrods(lysosomes)

philadelphiachrom(t(0:22)(q34:q11)
CMLcurablebyallogenic bonemarrow
BCR(breakpointclusterregion)gene
transplantearlyindsease.Drugimantinib
chrom22fusedtoABLgeneonchrom9> mesylate (gleevec)blocksATPbindingsite
fusionprotp2190.Dimerized>constitutive onBCr/ABLTyrkin(inactivates).Untreated
Tyrkinactivity>PO4'sprots,activates
>blastcriss resemblingAMLor
multipledownstreampaths>drivegrowth lymphoblasticleukemia
factorindependentprolif,survivalofbone
marrowprogenitors.BCRBCLdoesnot
interferew/differentiation,sonet^in
matureelementsinperipheralblood,esp
granulocytesandplatelets
Hypercellularbonemarrowduetoincrease
ingranulocyteprecursors,mature
granulocytes,megakaryocytes.Numerous
granulocytesatvariousdevstages
Malignantlymphoblasts 20%ofbone
tumorcellsinmarrow>masseffectw/
marrowcellularity.Smallmediumsizecells, painandarthralgias
increasednuccytoratio,delicatechromatin, ChildhoodBALLtreatedw/chemo,
inconspicuousnucleoli.
excellentprognosis,completeremission
BALLfeatsnumerousaberrations,
rateof>90%
chromosomaltranslocs,incl,Philadelphia
chrom(w/p190)
Leukemiccellsdisplacenormalmarrow
elements,>anemia,thrombocytopenia,
neutropenia
lymphoblastsw/condensednucchromatin,
smallnucleoli,scantagranularcytoplasm

1520%ofall
leukemias.Mostly
adults2560yrs age.
Presenceof
philadelphia chrom
(t(0:22)(q34:q11)by
conventional
cytogenetics,FISH,mol
demonstrationof
BCR/ABLfusiongene
req'd fordiagnosis.
95%ofCMLcases

Mostcommon
childhoodleukemia,
75%caseschildren
underage6

Mostoccurin6th7th
decades.Uncommon
inchildren exceptfor
Burkitt lymphoma,
largecellBcell
lymphoma

involveslymphnodes,extranodal locations. aggressiveandrapidlyfatalifuntreated.

Neocellsresembleimmunoblasts w/nuclei, Goodresultsw/intensivecombochemo,
exhibitprominentcentralnucleoli.Cells
completeremissinoin6080%ofpts,about
large,34xsizeofrestinglymphocytes.
50%oftheseremainfreeofdiseasefor
exhibitBcellantigens
severalyears
BCL6,BCL2generearrangesseen
Assoc w/imm def,pos forEBV
Rapidevolving,multifocal,nodal,
extranodal tumormanifestsseenattimeof
presentation
isolatedmasstypical.Prominentnuclei,
openchromatin,prominentnucleoli
Mostcommonmalig in
extranodal tumors,highriskofCNS
ClassicpresentationforendemicBLis
centralafrica,peak
involvement
destructivetumorinjaws,otherfacial
incidenceage37.
Highnumberofmitoticfigures.
bones.Ptsw/sporadicBL abdominal
SporadicBLaffects
Macrophagesw/apoptotictumorcells,
masses.Mostptspresentw/bulky
kids,youngadultsin
extranodaltumorsthatemergeinshort
'starryskymacrophages'
westernworld(12%of
time,respondtoaggrochemo,both
endemicandsporadicBLcurableupto90% alllymphomas).
ofpts
Increasedrateinppl w/
HIV.EBVpresentin
nearlyallcasesof
endemicBL,seenin
lessthan30%of
sporadictypes
Largeatypicalmononuc/multinuc tumor lymphadenopathyw/cervicaland
Mostcommonmali of
cells(HodgkinandReedSternbergcells) mediastinal nodesaffectedinmorethan Americansbtwn 1030
arehallmark.Largeinclusionlikenucleoli, halfofcases.Involveslymphnodes,spleen yrs.Bimodal
abundantcytoplasmsurroundedby
(1/3cases),liver(2/3),bonemarrow(rare), distributino w/peakat
lymphocytes,macrophages,eosinophils
lungs(1/2),epiduralspreadfreq neuro
late20s,gradincrease
complication.Prognosisdependsmainlyonafterage50
pt's age,anatomicextentofdisease(stage
andhisto class)
Bonemarrowcontainsmultifocalinfiltrate Effectsofplasmacellgrowthintissuesesp
bymali plasmacells
bone:Bonedestructduetoprog tumor
Multipledestructive(lytic)lesions,diffuse growth,secreteosteoclastactivatingfactor,
demineralizationofbone
boneresorp freq >pathologicfractures,
tumorcellssecretesinglehomogenous, chron pain,hypercalcemia,andanemia
complete,orpartialimmglob molecule,M Productionofexcessiveimmunoglobulins
componentorparaprot,mostcommonly Humoralimm def,Recurrentbac inf,Renal
IgG orIgAlightchain(BenJonesprot)
failure(Bence Jonesproteinuria,excreted
Monoclonalgammopathies
lightchainstoxictorenaltubularepi cells),
Punchedoutlesionsinskull,normal
Lightchain(AL)amyloidosis
marrowreplacedbyplasmacells,incl forms Incurabledisease,meansurvivalrateof6
monthsinuntreatedpt,3yrs w/chemo.
w/multinuclei,prominentnucleoli,cyto
Deathduetoinf orrenalfail
dropletsw/Ig

Infections(acute,subacute,chron)
Immunologicinfldisorder SLE,
amyloidosis
Hemolyticanemias
Immunethrombocytopenia
Splenicveinhypertension(rightside
heartfailure)
Primaryormetastaticneoplasm
StoragediseaselikeGaucher's
Benignthymomas wellencapsulated,
irregularlyshapedmasses,firm,grayto
yellowtumors,dividedintolobulesby
fibroussepta
Malignantthymoma w/localinvasion
Bothbenign/malignantthymomas assoc w/
paraneo syndromes(myastheniagravis,
graves,cushing)

Almostalwaysoccurin
adultlife,most(80%)
benign

Disease

Whatisit?

Congenital
Anormalities

Malformationof
urethralgrooveand
urethralcanal>
abnormalopenings

Phimosis

Openingofprepuce Congenitalanomalyorresults
toosmalltopermit
fromscarringofprepuceasresult
normalretraction
ofpreviousinf
Balanitis glanspenis
Balanoposthitis glans
penisandprepuce
Bacteria,fungi

Inflammation

Condyloma
acuminatum

Benignsexually
transmittedtumor
(genitalwarts)

CancerofthePenis originatesmostly
fromsquam mucosa
ofglansand
contiguousurethral
meatusorprepuce
andskincovering
penileshaft
BowenDisease

Whatcausesit?(Pathogenesis)

Intrinsic/Acquired?

Morphology/Pathology

ClinicalSignificance/Features

hypospadias ventralsurface,more
common,1in250livebirths
'epispadias urethralorificeondorsal
surface

Openingmaybeconstricted,trac
obstruction,increasedriskof
ascendinginfections
Mayaffectfertility(hypospadias)
Maybeassocw/bladderexstrophy
(epispadias)
Interfereswithcleanliness,increased
risksofinfection,possiblycancer

HPVassoc w/type6,lessw/
type11
mayoccuronanymoist
mucocutaneous surfaceof
externalgenitalsineithersex
inmale,mostoftenabout
coronalsulcusandinnersurface
ofprepuce

Single/multiplesessileor
pedunculated,redpapillary
outgrowth,1mmtoseveralmmin
dia
Branching,villous,papillary
connectivestroma coveredbyepi
thatmayhaveconsiderable
superficialhyperkeratosisand
thickeningofunderlyingepidermis
(acanthosis)
orderlymaturation ofepi is
preserved
koilocytosis,cytoplasmic
vacuolizationofsquam cellscharof
HPVinfect,notedinlesions
lesionstendtorecur,rarely
progressintoinsituorinvasive
cancer

Gardasilvaccine,preventivemustbe
inoculatedbeforestartofsexuallife

mostptsuncircumsizedandolder
than40yrs
Prolongedcontactbtwnsmegma
andpenileepimayplayrole
HPV16/18mayplayarole

Penilecarcinomaoccursni a
preinvasive form(carcinomainsitu)
andaninvasivevariety

Carcinomainsituof strongassoc w/HPV,esp type16

thePenis

Bowenoidpapulosis Carcinomainsituof
thePenis

Misc.

notcommoninUS
(<0.5%),more
commoninAfrica
andAsia(>10%)of
allcancersinmen

genitalregion,usu >35yr old

skinofshaftofpenisandscrotum
solitary,thickened,graywhite
opaqueplaque
Epidermisshowsproliferationw/
numerousmitosis,someatypical
Cellsmarkedlydysplasticw/large
hyperchromatic nuclei,lackorderly
maturation
Dermalepidermalbordersharply
delineatedbyintactBM
maytransformintoSCCin10%or
more
Erythroplasia ofQueyrat presents
aserythematouspatchonglans
penis

strongassocw/HPV,esptype16,
occursinyoung,sexuallyactive
males

Multiplelesions,reddishbrown
papule
HistologicallyidenticaltoBowen
disease
Virtuallyneverdevelopsintoinvasive
carcandmanycaesspontaneously
regress
Gray,crustedpapular lesion
infiltratesunderlyingconnective
tissuetoproduceindurated,
ulceratedlesionw/irregularmargins
Histologicalappearance
keratinizingSCCw/infiltrating
margins
Indolent,locallyinfiltrativelesions
Regionalmetastasisininguinal
nodes~25%ofcasesattimeofdiag
Estensive destructionofpenile
tissueinneglectedcases
Overall5yrsurvivalis70%

SquamousCell
usuallyinvolvesglans
Carcinomaofthe orprepuce
Penis

Cryptorchidism

UndescendedTestis Congenitalabnormality
unilateralorbilateral

Testicular
Neoplasms

Mostimportantcause inAdults,95%arisefromgerm
offirm,painless
cells,allofthesemalignant.
enlargementoftestis Cryptorchidismassocw/35fold
increaseinriskofcancer

Germcelltumorsinclude:seminoma,
embryonalcarcinoma,yoksactumor,
choriocarcinoma,teratoma
nongermcelltumorsinclude:Leydig
Celltumors,SertoliCelltumors

Seminoma

Ex.ofGermcelltumor
oftestis.Most
commontesticular
cancer,40%ofall
germcelltumors.

presentsassolid,rubberyfirm,
Growsasprogressivescrotalmass Peakincidence30
lumpymasses
Diag'd whilecanbecuredby
40years
Cutsurfaceshowslobulation,
orchiectomyw/orw/oabdominal
homogeneouslytanorgrayish
lymphnodedissection
yellow
highlyradiosensitive
singlepopulationofuniform
Thoseinadvancedstagesof
polygonalcellsw/centrallylocated disseminationaretreatedw/
vesicularnuclei
additionalchemo
Cytoplasmcontainslargeamountof Curerateis>90%
glycogen&lipid,paleand
eosinophilic orclearinsections
Tumorcellsarrangedasnestsor
sheetsw/interveningfibroussepta
Lymphocyticinfiltrateusually
present.
25%ofcases cellstainpositivefor
hCG

Prostatitis

Inflammationof
Prostate

CanbeBacterialorchronic.

Intrinsic

Acquired

Maybearrestedatanypointfrom Assoc w/35foldhigherriskof

abd cavitytoupperscrotum
testicularcancer,evenaftersurgical
Arresteddev ofgermcellsassoc w/ correction
markedhyalinzation/thickeningof
BMofsemin.Tubs
Leydig cellsappearprominent
Progressiveatrophy,cryptorchid
testissmallinsize,firmfromfibrosis
Selfexamimportant
forearlydetection.
Seenin5per
100,000males.Peak
incidence2035yrs

Dysuria,Urinaryfrequency,lower
AcuteBacteriaProstatitis
backpain,poorlylocalized
UTIbacteria,e.g.E.colietc.
Acuteneutr inf infiltrate,congestion, suprapubicorpelvicpain,prostate
maybeenlargedandtender,esp.in
stromaledema,
Neutrophilsfirstinglands,theninto acuteprostatitis,chroniccasesmay
besymptomaticorsilent.Important
stroma >microabscesses
causeofrecurrentUTIinmales.PSA
ChronicProstatitis
Varia amountoflymphoidinfiltrate, maybeelevated
evidenceofglandinj
Concomitantacute/chronicinf
evidenceoftissuedestruct,
fibroblastprolif,presenceofotherinf
cellsreq'd forhisto diag
olderindividuals,abacterial
prostatitis:negaative culture,
>10WBCperhighfield

Nodular
BPH,benignProstatic Mosthyperplasticlesionsarise
Hyperplasiaofthe Hyperplasia,nodular fromtransitionalandcentralzone
Prostate
hyperplasia.Beginsto
appearinmenafter
age40,prog inc w/
age,90%ineighth
decade

Prolif ofepi andstromalelements.

Glandenlarged,maycauseurinary
obstruction
Cutsurfacecontainsmanyfairly
wellcircumscribednodulesthat
bulgefromcutsurface.
Cysticspacesrepresentdilated
glandularelements
Urethrausuallycompressed
Nodulescomposedofproliferating
glandularelements,fibromusc
stroma
Hyperplasticglandslinedbytall,
columnarepi cells,peripheralbasal
cells
Prolif ofstromalelements
Areasofinfarc fairlycommoninadv
cases,freq accom byfociofsquam
metaplasiainadjacentglands

Cancerofthe
Prostate

Blacks>Caucasians>
Arisesfromperipheralzone,maybe Mostlocalcancersareclinically
silent,detectedbyroutinely
orientals
palpableviadigitalrectalexam
monitoringPSAinoldermen
adenoarc w/variable
advancedcancerspresentw/
differentiationandanaplasia
Neoplasticglandslinedbysingle metastasis,freq tobones
layerofcells.Basalreservecellsnot SerumPSAlevelsunder4ng/mL
present
considerednormal.Valuesover10
Gradingofprostatecancerby
ng/mLsuggestiveofcancer
Gleasonsystemcorrelatesw/
Anatomicalstagingofextentof
anatomicalstageandprognosis
diseasehasimportantrolein
evaluationandtreatment
Prostatecanc isstagedbyclinical
exam,surgicalexploration,
radiographicimagingtechs,andin
somesystems,histologicgradeof
tumorandlevelsoftumormarkers
Treatw/surgery,radiation,
hormones

Commoncancerof
oldermenbtwn65
and75yrsofage.

PSAandProstate PSA Serineprotease Ifelevated,meansProstatitis,

Cancer:ToTestor madebyprostaticepi BPH,ProstateCa
nottoTest?
cells

Shouldeverybody
whythecontroversy?
BestuseofPSA?
Whatis'waitand
over50getaPSA
Overdiagnosis,unpredictablecancer Monitortumorrecurrenceafter
see'approachto
test?
biology,seriouscomplicationsassoc treatment
prostatecancer?
race,age,family
w/someuntreatmentmodalities
'Biggestchallengeforprostatecancer0Ptmaydieof
history,recsfromprof
diagnosis?
othercausesin
organizations
Nogoodwaytotellifcancer(seen spiteofhaving
inbiopsy)goingtobeslowgrowing prostatecancer
oraggressive

Disease

Whatisit?

Whatcausesit?(Pathogenesis)

Intrinsic/Acquired?

Vulvitis

Acquired
moisthairbearingskin mostimportantSTD inNorth
anddelicatemembrane America:
Contactisintrinsic
ofvulvaarevulnerable Chlamydia,mostcommon
humanpapillomavirus (HPV),
tomanynonspecific
microbeinducedinfand producingcondylomaacuminataand
dermatologicdisorders vulvarintraepithelialneoplasia
herpes genitalis (herpessimplex
(HSV1or2),causingvesicular
eruption
gonococcal suppurativeinfectionof
thevulvovaginalglands
syphillis,withitsprimarychanceat
thesiteofinoculation
candidalvulvitis

Morphology/Pathology

ClinicalSignificance/Features

Misc.

ContactDermatitis
Irritantdermatitis,reactiveinfto
exogenousstimulus
Allergicdermatitis,reactiveinfto
allergen
BartholinCystand
Abscess

PairedBartholin'sglands
(greatervestibular
glands)produceclear
mucoidsecretionthat
continuouslylubricates
vestibularsurface Ducts
pronetoobstructionand
consequentcyst
formation
Autoimmune
LichenSchlerosus of nonneoplasticepi
theVulva
disorder
inf diseaseassoc w/
autoimm disorders(e.g.
vilitigo,pernicious
anemia,thyroiditis)
characterizied by
atrophicepi,usuallyw/
dermalfibrosis

Condyloma
Acuminatum

Cystinfectionleadstoabscess
Bartholinductcysts
formation
relativelycommon,
acuteinfwithingland(adenitis)and
occuratallages
mayresultinabscess
Gonorrhea,Staphylococci,Chlamydia,
anaerobesfrequentlyinvolved
Treatmentsincludeincision,drainage,
marsupialization,antibiotics
intrinsic

Benignlesion benign CausedbyHPV,assoc w/type6,

sexuallytransmitted
lessfreq w/type11
tumor,anogenital warts Mayoccuronanymoist
mucocutaneous surfaceofthe
externalgenitalsineithersex
onthevulvatheyrangefromfew
mmtomanycmindia

VulvarIntraepithelialCarcinomaofthevulva
Neoplasmand
represents3%ofall
VulvarCarcinoma
genitaltractcancersin
women,2/3inwomen
olderthan60
90%ofvulva
carcinomasare
squamouscell
carcinomas
10%are
adenocarcinomas,
melanomas,orbasal
cellcarcinomas
Basaloid andWarty AssociatedwithHPV HPV16,18assoc vulvarcancer,30%
Carcinomas
ofscc cases
Developfromprecancerousinsitu
lesioncalledvulvarintraepithelial
neoplasia (VIN)
Includes'carcinomainsitu'and
Bowendisease

Keratinizing
SquamousCell
Carcinomasofthe
Vulva

Notassociatedwith
HPV

Ariseinindividualwithlong
standinglichenschlerosus or
squamouscellhyperplasia

Cervical
Intraepithelial
neoplasia(CIN)and
SquamousCell
Carcinoma

Mosttumorsofcervix NearlyallinvasivecervicalSCCs
areofepi origin,assoc arisefromprecursorepi changes
w/oncogenicstrainsof referredtoasCIN
HPV
However,notallcasesofCIN
Cervicalcancerranked progresstoinvasivecancer
13thincancerdeathin
US,lowrankingmainly CIN,dysplasia,SIL(squamous
duetopapsmear
intraepitheliallesion)used
Conversely,incidenceof interchangeably
precursorCINincreased,
mainlyduetoPap
smear

Lowgrade
Squamous
Intraepithelial
Lesions(LSIL),CINI
HighGrade
Squamous
intraepithelial
Lesion,HSIL,CINII
andIII
Carcinomasofthe
Cervix

CIN,lowgradedysplasia
assocw/productive
HPVinfection
CIN,moderate,severe, 80%HSILdevfromLSIL,20%ofHSIL
carcinomainsitu
devdenovo
Progressive
deregulationofcell
cyclebyHPV
HSILisimmediateprecursor
75%cervicalcancers
SCC,20%adenocarcs,
mixedadenosquamous
carcs,5%misc.Allassoc
w/highriskHPV

Whiteplaques(leukoplakia),atrophic Features
skin,parchmentlikeorcrinkled
occursinallagegroupsbutmost
appearance
commoninpostmenopausalwomen
thinning ofepidermisand
Pruritis/Itchingisthemostcommon
disappearanceofretepegs,hydropic
symptom
degenerationofthebasalcells,
Dyspareunia(painduringintercourse)
superficialhyperkeratosis,dermal
Implications
fibrosis
Womenw/symptomaticlichen
Scantperivascular,mononuclearinf cellsclerosus,1%5%developSCCofvulva
infiltrate(includingactivatedTcells) Biopsytodifferentiatefromother
bandlike
lesionswithwhiteplaques
Branching,villous,papillaryconnective
stroma coveredbyepi thatmayhave
considerablesuperficialhyperkeratosis
andthickeningoftheunderlying
epidermis(acanthosis)
Theorderlymaturationoftheepi cells
preserved
Koilocytosis,perinuclear cytoplasmic
vacuolizationofthesquamouscells,
characteristicHPVinfectionnotedin
theselesions
Lesionstendtorecur
Maycoexistw/lowgradevulvar
intraepithelialneoplasia(VIN)butonly
rarelyprogressintoinsitu orinvasive
cancers
TwoForms:Basaloid andWarty
CarcinomasandKeratinizingSquamous
Cellcarcinomasofthevulva

VINshowsnuclearatypia,increased
mitosis,lackofcellularmaturation,
nuclearcrowding
Precursor:VIN.Progressesto:
SquamousCellCarcinoma
Infiltratingtumorcharacterizedby
nestsandcordsofsmall,tightlypacked
malignantsquamouscellslacking
maturationthatresembleimmature
cellsfromthebasallayerofthenormal
epithelium
Thetumormayhavefociofcentral
necrosis
Wartycarcinomacharacterizedby
exophytic papillaryarchitectureand
prominentkoilocytic atypia
Immediateprematurelesioniscalled
differentiatedvulvarintraepielial
neoplasia (differentiatedVIN)
Markedatypiaofthebasallayerofthe
squamousepithelium
Normalepithelialmaturationand
differentiationinthesuperficiallayers
Hyperkeratosis
Etiologyunknown
Progressto:
Keratinizingsquamouscellcarcinomaof
thevulva infiltratingtumor
characterizedbynestsandtonguesof
malignantsquamousepitheliumwith
prominentcentralkeratinpearls

meanageis76yrs
Pruritis/itchingoflongdurationis
commonlythefirstsymptom
Ulceration,bleeding,secondary
infectionmaydevelop
Tumorsgrowslowlyandthenextend
tothecontiguousskin,vagina,rectum
Metastaize tosuperficialinguinalthen
deepinguinalfemoralandpelviclymph
nodes
Lymphohematogenous dissemination
tothelungs,liverandotherinternal
organsmayoccur
Pts w/lesions<2cmindia have6080%
5yrsurvivalaftertreatmentwith
vulvectomy andlymphadenectomy
Pts withlargerlesionswithlymph
nodeinvolvementhave5yrsurvival
rateof<10%
DiagnosisbasedonIDofnuclearatypia >80%LSILand100%HSILassoc w/
withnuclearenlargement,
oncogenicriskHPVs(HSILoccurs:80%
hyperchromasia,presenceofcoarse
LSIL,20%denovo)HPV16singlemost
chromatingranules,variationofnuclear commonHPVtypedetectedinboth
riskdev'ing precancer andcancer
sizesandshapes
conferredonlyinpart byHPVtypeand
Koilocytic atypia
GradingintoloworhighSILbasedon dependsalsoonimmunestatusand
environmentalfactors.Infectionwitha
expansionoftheimmaturecelllayer
highriskHPVtypeitselfisnot
fromitsnormal,basallocation
LSIL:immaturesquamouscellsconfinedsufficienttocausecancer,asvast
tolower1/3ofepi
majorityofwomenw/HPVinfections
HSIL:immaturesquamouscellsexpand donot navecancer
to2/3ofepi thickness
Vaccinespresentlybeingusedare
effectiveagainst4typesofHPV
(6,11,16,18)anddonotaffordsame
degreeofprotectionforblackwomen
asforwhitewomen(inclusionof
33,35,58,68subtye willgivebroader
rangeofprotection)
Progressionintoinvasivecarcinoma
whenithappensmaytakeplaceina
fewmonthstomorethanadecade,
thusscreeningandearlydetectionare
important
mayregressspontaneously
donotprogressdirectlytoinvasive
carcinoma
Oftenfollowedconservatively
Increasedcellularprolif,
10%willprogresstocarcinoma,usually
decreased/arrestedepimaturation,
within210yrs
lowerrateofviralreplication
Treatedaccordingtoextentofdisease
1/10thascommonasLSIL
SquamousCellCarcinoma Nestsand
tonguesofmalignantsquamousepi,
eitherkeratinizingornonkeratinizing,
invadingtheunderlyingcervicalstroma
Nestbreakingthroughbasement
membraneofHSILformicroinvasion
Adenocarc/Endocervicaladenocarc
15%ofcervicalcancer,devsfrom
adenocarcinsitu
Assocw/highoncogenicriskHPVs
Proliferationofglandularepicomposed
ofmalignantendocervicalcellswith
large,hyperchromaticnucleiand
relativelymucindepletedcytoplasm,
resultingindarkappearanceofglands

Electrocautery,conization,cryosurgery,
hysterectomy,lymphnodedissection,
irradiation
Prognosisandsurvivalforinvasive
cancerdependslargelyonthestage at
whichthecancerisfirstdetectedandto
somedegreeonthecelltype

Endometriosis

Presenceofbenign
RegurgitationTheory Menstrual
endometrialglandsand endometriumfragmentsrefluxed
stroma outside the
throughthefallopiantubesto
ectopicsites
uterus
Seenin510%of
MetaplasticTheory Endometrial
womeninreproage
tissuearisingdirectlyfromcoelomic
Regressesafternatural epi(mesotheliumofpelvisor
orartificialmenopause abdomen)
(tissuehormone
Vascular/LymphaticDissemination
Theory
responsive)
Theoriesarenotmutuallyexclusive

Severedysmenorrhea
Variableincolor.Yellowredstains
Dyspareunia(painwithintercourse)
reflectbreakdownofbloodproducts
Redlesionsreflectearlyformofdisease Pelvicpainduetointrapelvic bleeding
Withrepeatcyclesofhemorrhageand Malignancyoccursinabout12%of
onsetoffibrosis,affectedsurfacemay cases
showscarringandtakeongrossly
Complicationsincludeadhesions,
browndiscoloration("powderburns") infertility(3040%ofpts),ectopic
Inextensivedisease,maybeextensive pregnancy
fibrousadhesions
Sitesincludeovaries(>60%),other
Chocolatecystsinovaryfromrepeated uterineadnexa(uterineligaments,
hemorrhage
rectovaginal septum,pouchofdouglas),
Ectopicendometrialglandsand stroma,andthepelvicperitoneumcoveringthe
withorwithoutthepresenceof
uterus,fallopiantubes,rectosigmoid
hemosiderin
colon,andthebladderandevenlymph
Theendometriotic tissueisnotjust
nodes,lungs,heart,skeletalmuscleor
misplacedbutisalsoabnormal
bones
Tissueexhibitsanumberofchanges
whichenhancesurvivalandpersistence
ofthetissuewithinaforeignlocation

Endometrial
Carcinoma

4thmostfrequenttype
ofcancerinAmerican
womenandmostfreq
canceroccuring in
femalegenitaltract

Twotypes:TypeIEndometrial
adenocarcinomaandTypeIINon
endometroidadenocarcinoma

Endometrial
Adenocarcinoma
(TypeI)

Assoc w/endometrial Majorformofendometrialcancer,

intraepi neoplasia(EIN) 80%ofcases
precursors,prior
Linkedtoprolongedestrogen
exposrure toestrogens, stimulationoftheendometrium
slowclinicalcourse
Obesity,hypertension,diabetes
Mutationinthemismatchrepair
genesandthePTENtumor
suppressorgenefoundin3080%of
cases
Precursoriscomplexendometrial
hyperplasiawithatypia

Localizedpolyploid tumorordiffuse
tumorinvolvingtheendometrialsurface
Glandpatternsresemblenormal
endometriumepithelium
Variesfromwelldifferentiated(Grade
1),witheasilyrecognizableglandular
patterns;
tomoderatelydifferentiated(Grade2),
showingwellformedglandsmixedwith
solidsheetsofmalignantcells
topoorlydifferentiated(Grade3),
characterizedbysolidsheetsofcells
withbarelyrecognizableglandsanda
greta degreeofnuclearatypia and
mitoticactivity

Nonendometroid
Adenocarcinoma
(TypeII)

Notassoc w/estrogen,
emergewithout
warning,havehigher
fatalityrates

Lesscommon,generallyoccurin
womenadecadelaterthantypeI
carcinoma,usuallyariseinthe
settingofendometrialatrophy,not
associatedwithestrogenexposure,
poorlydifferentiated

SerousCarcinomaof Nonendometroid
theEndometrium
endometrial
Adenocarcinoma(Type
II)

Leiomyoma

Benigntumorthat
arisesfromsmooth
musclecellsin
myometrium.
Colloquiallyknownas
"myoma"or"fibroid"

Leiomyosarcoma

Malignanttumorofthe
myometriumwhich
arisesdenovo fromthe
mesenchymalcellsof
themyometrium,not
frompreexisting
leiomyomas
Much,muchlessfreq
thanleiomyomas
Malignanttumors
solitaryandusually
larger(1015cmvs35
cm)

Estrogenpromotestheirgrowth,
althoughitdoesnotinitiatethem.
Postmenopausalshrinkage
Althoughoftenmultiple,eachtumor
ismonoclonal
Nonrandomchromosomal
abnormalitiesseenin40%oftumors

Abnormaluterinebleeding
Mayspreaddirectlytoparaaortic
lymphnodes
Prognosisdependsheavilyonthe
clinicalstageofthediseasewhenitis
discovered
Highlevelsofestrogenand
progesteronereceptorsinthetumor
andlowlevelsofproliferativeactivity
correlatewithabetterdiagnosis
Endometroid carcinomahavebetter
prognosisthannonendometroid
carcinomasuchasserouscarcinoma
SeeEndometrialadenocarc

SeeEndometrialadenocarc

SeeEndometrialadenocarc
Allnonendometroidadenocarcs
classifiedasGrade3irrespectiveof
histologicpattern,cellswithmarked
cytologicatypia,mutatinoinp53tumor
suppressorgeneseenin90%ofserous
endometrialadenocarcinoma
Firm,palegray,sharplycircumscribed, Canbeclinicallysilent
whorledmasseswithoutencapsulation Menorrhagiaisthemostfrequent
Sizesrangefrom1mmto>30cmindia manifestation,withexcessively
Someintramural,othersdirectly
prolongedorprofusemenses
beneaththeendometrium(submucosal), Metrorhagiamaybepresent,irregular,
ordirectlybeneaththeserosa
acyclicbleedingbtwnperiods
(subserosal)
Rarelytransformsintosarcomas
Whorlingbundlesofsmoothmuscle
cells
Focioffibrosis,calcification,ischemic
necrosis,cysticdegeneration,
hemorrhagemaybepresent
Appearancevariablefrombulkymassto Recurrenceafterremovalcommon
polypoidlesionsprojectingintothe
Manymetastasizetolungs
uterinecavityorstructurethatresembles5yrsurvivalrateisabout40%
benignleiomyoma
Soft,hemorrhagic,necrotic
Widerangeofdifferentiationfromthose
thatcloselyresembleleiomyomato
wildlyanaplastictumors
Mitosisactivity,cellularatypia,and
geographicalnecrosisarethebest
diagnosticcriteria

Mostcommonbenign
tumorinfemales,
foundin3050%of
womenduringrepro
life

Accountsfor~2%of
uterin malignancies
Ageofappearance
onaveragemorethan
adecade(ageabove
50yrs)thanthose
withleiomyomas

Disease

Whatisit?

Whatcausesit?(Pathogenesis)

Intrinsic/Acquired?

Salpingitis

Inflammationofthe
fallopiantubes

typicallyduetoinfectionascending Acquired
fromthelowergenitaltract
E.coli,Chlamydia,Mycoplasma,
Neisseriagonorrhea

OvarianNeoplasms Secondmostfreqwuent
gynecological
malignancyafter
endometrialcancer.
Carrieshighermortality
ratethanallother
femalegenitalcancers
combined
SurfaceEpithelial
Twoofthemostimportantrisk
StromalCellTumors
factorsarenulliparity(para0)
[neverhavinggivenbirth]and
familyhistory
510%ofovariancancersfamilial.
Majorityofcasesofhereditary
ovariancancershasmutsinBRCA
genewithlifetimeriskof3%in
BRCA1carriersandsomewhat
lowerinBRCA2carriers
MutsinBRCAgenesonlyabout
10%insporadiccancers
OverexpressionofHER2/NEUassoc
w/poorprognosis
SerousTumorsof SurfaceEpithelial
theOvary
stromalCellTumor
Mostfreqofovarian
tumors(6070%)
Benignlesionsusually
cisticencounteredbtwn
ages3040;
cystadenoma
Malignantlesions
morecommonlyseen
btwn4565yrsofage
cystadenocarcinoma
Combined,borderline
andmalignantserous
tumorsmostcommon
malignantovarian
tumors,accountfor
about60^ofallovarian
cancers
SerousOvarian
SurfaceEpithelial
Tumors
stromalCellTumor
usuallylarge,spherical
toovoidcystic
structuresandcan
reach3040cmindia
25%ofbenignforms
bilateral

MalignantEpithelial
StromalTumorsof
theOvary

CanceroftheBreast Mostcommon
Poorlyunderstoodprocessandrisk
malignancyofwomen factorsarecomplex
intheUS mortality
Cancersexhibitdiverse
ratefromthisdisease histopathology,molecularfeatures,
secondonlytothatof overallptoutcomes
lungcancer
Thus,canbeviewedasamultifaced
1in8American
andcomplexepimalignancy
womenmaybe
expectedtodevelop
breastcancer,1/4of
whomwilldieofthe
disease
45xmorefreq in
Westernindustrialized
countriesthanin
dev'ing countries
CanceroftheBreast Strongestassoc w/
BreastCancerGenes
Hereditary
increasedriskforbreastBRCA1(breastcancer1)
cancerisfam history, Tumorsuppressorgeneonchroms
specificallybreasat
17(17q21)
cancerinfirstdegree Implicatedinpathogenesisof
relatives(mother,
hereditarybreastandovarian
sister,daughter)
cancers,maybeprostateandcolon
Riskisgreaterwhen catoo
relativedevs diseaseat Mutationsthoughttobepresentin
1in200to400ppl inUS
youngageorw/
bilateralbreastcancer Germline pointmuts anddels in
BRCA1confer60%to85%lifetime
riskforbreastcancer,withmore
thanhalfofthetumorsdeveloping
before50yrs ofage
MutatedBRCA1ispropbs
responsiblefor20%ofallinherited
breastcancer,responsibleforabout
3%ofallbreastcancers
somaticmuts inBRCA1infreq
detectedinsporadic breastcancers
CanceroftheBreast MakeuptheMajority RiskFactors:
NonHereditary
ofthecases
Hormones:stronglinkbtwn breast
Mostbreastcancers cancerandhormonalstatusof
not assoc w/hereditary woman
factors
Nulliparouswomenorthosew/
1stpregnancyafterage35havea
2xhigherriskforbreastcancerthan
thosewhosefirstpregnancy
occurredbeforeage25
Radiation therapeuticdoses
increaserisk
Previouscancerofthebreast 10x
increasedriskofdevelopinga
secondprimarybreastinthesame
orinthecontralateralbreast
Fibrocysticchange womenwith
proliferativefibrocysticchange
(esp.withatypicalhyperplasiaare
atanincreasedriskforcancer
DuctalCarcinomain Mostcommonformof
situ
insitubreastcarcinoma
Arosefromterminal
ductlobularunit
Malignantepi cells
havenot penetrated
theBM

ComedoDCIS

Highgradesubtypeof
DCIS

LobularCarcinoma Secondmostcommon
insitu
formofinsitubreast
carcinoma
Arosewithinterminal
ductallobularnits
Malignantepi cells
havenot penetrated
BM

InvasiveDuctal
Carcinoma

PrognosisforBreast
Cancers

"nototherwise
About2/3expressestrogenor
specified"
progesteronereceptors
Termusedforallcarcs About1/3overexpressedHER2/NEU
thatcan'tbeclass'd
intooneofthe
specializedsubtypes
Majority(7080%)of
cancersfallintothis
category
Usuallyassoc w/DCIS

1.The size oftheprimary

carcinoma
Invasivecasmallerthan1cmhave
excellentprognosisinabsenceof
lymphnodemetastasis
2.Lymphnodeinvolvementandthe
numberoflymphnodesinvolvedby
themetastases
Withnoaxillarynodeinvolvement,
5yrsurvivalrateiscloseto90%
Survivalratedecreaestolessthan
50%withmorethanadozennodes
involved
Sentinellymphnodeimportantin
predictingpresenceorabsenceof
metastaticcaintheremaining
lymphnodes

Morphology/Pathology

ClinicalSignificance/Features

Misc.

Acuteinf phase markedinfiltrationbyAcuteepisode,esp.w/Chlamydia,

polys,pronouncededema,congestion maybeasymptomatic
Reinfectionscommon
ofmucosalfolds
chronicsalpingitis infiltrateconsists Usuallycomponentofpelvicinf
oflymphocytes,plasmacells.Edema disease
Adhesionmaydevelop;formationof
andcongestiontendtobeminimal
Latestages,tubesmaybesealedand tuboovarian abscess
Damagecausedbychronicsalpingitis
becomedistendedwithpus
mayimpairtubalmotilityandthe
(pyosalpinx)oratransudate
passageofsperm,leadingtoinfertility
(hydrosalpinx)
Tubesallowaccesstotheperitoneal Chronicsalpingitis commoncauseof
cavitybymicroorganisms,leadingto ectopicpregnancy
peritonitisandPID
Infiltrationwithnumerousneutrophils

Singlelayeroftallcolumnarepi that
linescystorcysts
frankcarcs liningcellsdisplay
anaplasia nad invasionofstroma
subtypeintermediatebtwn benignand
invasivecancer('borderline'),the
'tumorsoflowmalignantpotential'
canreachgreatsize(100+kg)
Spreadtoregionallymphnodebut
distantmetastasisisinfreq forthistype
oftumor
CA125,antibodytocancerantigenin
serumdetectshalfofepitumors
confinedtoovary,90%thathave
alreadyspread
Ovarianmassesrarelycausesymptoms
untilalreadylarge
Masseffects pain,pelvicpressure,or
compressionofregionalorgans
Bythetimeofdiagnosis,mayhave
metastasized(implanted)tothesurface
ofthepelvis,abdominalorgans,
bladder,diaphragm,paracolicgutter,or
omentum
Survivalw/malignantovariancancer
generallypoor 5yrrateis35%dueto
latedetection
Chiefformsofcarcinomasinthebreast "Lumpiness"orothersymptoms(1%of
A.Noninvasive
theseptshavecancer)
1.Fromtheterminalductlobularunit Pain(5%oftheseptshavecancer)
2.Ductalcarcinomainsitu(DCIS;
Nippledischarge(7%ofptshave
intraductalcarcinoma)
cancer)
3.Lobularcarcinomainsitu(LCIS)
Palpablemass(12%oftheseptshave
B.Invasive(Infiltrating)
cancer)
1.Invasiveductalcarcinoma("not
otherwisespecified")/scirrhous
carcinoma,mostcommon
2.Invasivelobularcarcinoma
3.Medullarycarcinoma
4.Colloidcarcinoma(mucinous
carcinoma)
5.TubularCarcinoma
6.Othertypes
MoreBreastCancerGenes
BRCA2(Breastcancer2)
Geneislocatedonchrom 13q12
Implicatedinabout20%ofhereditary
breastcancers
CarrierofonecopyofBRCA2genehas
3040%lifetimechanceofdev'ing breast
cancerandincreasedriskforovarian
cancer
Mut esp.commoninAshkenaziJewish
women
Men withthismutationareatincreased
riskofbreastcancer
P53
MutatedinLiFraumeni syndrome.
Breastcancerwilldev inalmostall
youngwomenwiththisdisease
Germline (inheritedmuts inp53
accountfor1%ofbreastcanceramong
womenunderageof40yrs
Geneticchanges
Mutationsaffectingprotooncogenes
andtumorsuppressorgenesinbreast
epi contributetotheoncogenic
transformationprocess
OverexpressionofHER2/NEU proto
oncogenehasbeenfoundinupto30%
ofinvasivebreastcancers
Geneismemberofepidermalgrowth
factorreceptorfamilyanditsover
expressionisassoc w/poorprognosis
EnvironmentalFactors

Tendstofill,distort,unfoldinvolved W/earlyscreening,DCISonlyrarely
lobules,thusappearstoinvolve
presentsasapalpableorradiologically
ductlike spaces
detectablemass
Histologicappearancevariesandare Ifdetectionisdelayed,apalpable
oftenmixed,includingsolid,comedo, massornippledischargemaydevelop
cribiform,papillary,micropapillary
PrognosisforDCIsisexcellentwith
typesetc.
over97%longtermsurvivalafter
Nuc appearanceusuallyuniformina simplemastectomy
givencaseandrangesfromblandand Atleast1/3ofwomenwithsmall
monotonous(lowgrade)to
areasofuntreatedlownucleargrade
pleomorphic(highgrade)
DCISwilleventuallydevelopinvasive
Necrosisisminimal
carcinoma
Calcificationsarefreq assoc w/DCIS Wheninvasivecancerdoesdevelop,it
andimportantindetectionofthese
isusuallyinthesame breastand
lesionsduringscreening
quadrantasteh earlierDCIs
Cellsinbetterdiff'dDCISexpress
Surgery,radiation,antiestrogens
estrogenand,lessoften,progesterone
receptors
Noncomedo subtypelesslikelyto
incitedesmoplastic response
Solidpatternw/neocellsfilledand
expandductlumina,stillwithinducts
andhavenotbrokenthroughBMinto
adjacentstroma.
Composedofverylarge,pleomorphic
epi cellsw/abundantcytoplasm,
irregularnuclei,oftenprominent
heterogenous nucleoli
Cancercellsgrowrapidlywithinducts
andfreq showintraductal necrosis
Gross:lesionoftenshowsdistended
ductlikestructurescontainingwhite,
necroticmaterialresemblingcomedos,
whichoftenundergoesdystrophic
calcification;thisresultsinmultiple,
microscopiccalcifiedbodiesvisibleona
mammogram(seenecroticmaterials
w/calcification)
Mayincitechronicinnf,
neovascularization,desmoplastic
response(fibroblastproliferationand
subsequentfibrosis)inaperitubular
distribution
Cellstendtobesmallerandmore
Virtuallyalwaysanincidentalfinding
monotonousthanDCIS,round,regular Doesnotformmassesandisonly
nucleiandminutenucleoli
rarelyassoc w/calcifications
Malignantcellsappearassolidclusters 1/3ofwomenwithLCISwill
thatpackanddistendterminalducts eventuallydev invasivecarcinoma
butnottotheextentofDCIS
Withthislesion,subsequentinvasive
Intracellularmucin vacuoles(signet
carcinomasariseineitherbreastat
ringcells)common
significantfrequency
LCISisbothamarkerofincreased
chanceofdevelopingbreastcancerin
either breastand adirectprecursorof
somecancers
Mostproducedesmoplastic response, 1.Nodules smallnoduels maybe
whichreplacesnormalbreastfat
detectedonpalpation
(resultinginamammographicdensity) nodulesof23cmdia usuallyinvolve
regionallymphnodesinabout50%of
andformsahard,palpablemass
Invasionisdefinedbythepresenceof cases
tumorcellsoutside oftheductlobular Nodulesaround1cmdia hadnodal
unitsandextendingintothestroma
metastasisinabout15%ofcases
(importanceofscreening!)
Histopathologyofinvasiveductal
carcinomaisheterogenous andranges 2.Nippleretraction,nippledischarge.
fromwelldev'd tubuleformationand Breastinf importantsignsifpresent
lowgradenucleitotumorsconsisting 3.Lymphnodeenlargement maybe
ofsheetsofanaplasticcells
firstsignofdisease
tumormarginsusuallyirregular
4.Paraneoplastic syndromee.g.
invasionoflymphvascularspacesor hypercalcemia
alongnervescanbeseen
5.Metastasis
Advancedcancersmaycausedimpling
oftheskin
3.DistantMetastasis
7.theProliferativerateofthecancer
Poorprognosisincaseofhetaogenous Mitoticcountsareincludedaspartof
spread(lungs,liver,ovary,brain,
thegradingsystem
adrenalglands)
Highprofileratesareassociatedwith
4.Gradeofthecarcinoma
apoorerprognosis
Moredifferentiatedcahavebetter
8.Aneuploidy
prognosisthanpoorlydifferentiated CarcinomaswithanabnormalDNA
ones
conten t(aneuploidy)haveaslightly
5.Histologictypeofcarcinoma
worseprognosisascomparedto
Allspecializedtypesofbreast
carcinomaswithaDNAcontentsimilar
carcinomashaveasomewhatbetter tonormalcells
prognosisthancarcinomasofnospecial9.OverexpressionofHER2/NEU
type("Ductalcarcinomas")
Overexpressionofthisgeneis
associatedwithapoorerprognosis
Antitumorantibody,Herceptin,
againstthegeneproduct