prostatic carcinoma, usual variant
TRANSCRIPT
PROSTATIC CARCINOMA, USUAL VARIANT
Definition• Acinaradenocarcinomaoftheprostateglandisthe
mostfrequentlydiagnosedformofcancerintheUnitedStates.TheNationalCancerInstituteestimatesthatalmost200,000newcaseswilldevelopin2010.
Clinical featuresEpidemiology• Prostatecanceristhethirdleadingcauseofcancer-
relateddeathinmenindevelopingcountries.• Multiplegeneticandenvironmentalfactorsare
involvedinprostatecarcinogenesis.• Age,familyhistory,andracearedefinitiveriskfactors.• Thedegreeofriskisrelatedtotheageandthenumber
oftheaffectedrelatives,withthegreatestriskconferredbyafatherorbrother,withanonsetbefore40yearsofage.
• Racialbackground,withAmericanblackshavinghigherincidence,highergrade,andmoreextensivecancer,mayberelatedtodifferentgeneticandenvi-ronmentalfactors.
• Dietaryfatandsexhormonelevelsareprobableriskfactorsforprostatecarcinoma.
• Manysusceptibilitylociandseveralcandidategeneshavebeenidentifiedforhereditaryprostatecancer.
• Linkageanalysishasidentifiedfewcandidatelociforhereditaryprostatecancer.Ofthem,threegeneshavebeenclonedasRNaseLon1q24-25,HPC2on17p,andMSR1on8p22-23.
Presentation• Mostprostatecarcinomaisasymptomatic.• Approximately70%ofprostatecarcinomaarisein
theperipheralzone,andsomecanresultinabnormalfindingsondigitalrectalexamination.
• Rarely,prostatecarcinomacanleadtourinaryobstructionwhenalargetumorarisesinthetransi-tionzoneorextendsintothetransitionzonefromtheperipheralzoneorinvadesthebladderneck.
• Locallyaggressiveprostatecarcinomainvolvesthebladderandrectumandcancausehematuria,rectalbleeding,orobstruction.
• Rarely,patientsexhibitsymptomsandsignsthatarerelatedtometastaticprostatecarcinomatodifferentanatomicsites,mostcommonlybone,regionallymphnodes,lung,andbrain.
• Currently,mostprostatecarcinomasareclinicallydetectedbyserumPSAscreeninganddigitalrectalexamination.
Prognosis and treatment• Treatmentforprostatecancerdependsonthestageof
thediseaseandthegradeofthetumor;otherimpor-tantfactorsinplanningtreatmentaretheman’sageandgeneralhealthandhisfeelingsaboutthetreat-mentsandtheirpossiblesideeffects.
• Prostatecancercanbemanagedinanumberofways: • Activesurveillance(watchfulwaiting) • Surgery(radicalprostatectomy)
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• Radiationtherapy(externalbeamradiotherapyorimplantationofradioactiveseeds[brachytherapy])
• Hormonaltherapy(surgicalcastration[orchiec-tomy]orpharmacologicblockadeofandrogeneffectwithlutenizinghormone–releasinghormoneanalogsorantiandrogencompounds)
• Cryotherapy• Radicalprostatectomyisconsideredtobethemostreli-
ablemethodoferadicationoflocalizedprostatecancer.• Locallyadvancedprostatecarcinomaisfrequently
managedbyacombinationofradiationandhormonalablation.
• Theprognosisforpatientswithprostatecarcinomaishighlyvariableanddependsonavarietyofhost,tumor,andtreatmentparameters:
• Forprostatecancer,limitedtotheprostate(stagesIorII)andwellormoderatelydifferentiated(Glea-sonscore3+4=7orless),the5-yearoutcomeisconsideredtobeexcellent.
• Biochemicalrecurrenceoccursinapproximately11%to13%ofpatientswithclinicallylocalizedprostatecancertreatedwithradicalprostatectomy.
• TheoverallPSArecurrence-freesurvivalratesare84%and83%at3and5years,respectively.
• Theactuarialprobabilityofremainingprogression-freeat5and8yearspostoperativelyis78%and71%,respectively.
• Whenstratifiedbypathologicstage,5-yearfreedomfromprogressionofdiseaseafterRPwas83%and69%forpT2andpT3,node-negativeprostatecancer,respectively.
PathologyHistology• Threehistologicfeaturesarediagnostic(cancer-
specific)ofprostatecarcinoma,becausetheyhavenotbeendescribedinbenignglands:
• Mucinousfibroplasia(collagenousmicronodules)occursasdelicatefibroustissuewithingrowthoffibroblastswithinoradjacenttocancerglands.
• Glomeruloidformationiscreatedbyintraluminalcribriformproliferationofmalignantcellsandoftensurroundedbyacrescenticspace,resemblingarenalglomerulus.
• Perineuralinvasionwithcancerglandsencirclingtheentirecircumferenceofanerveispathogno-monicofprostatecarcinoma.(Benignglandscanoccasionallybefoundtoabutanerve;however,circumferentialextensionofbenignglandsentirelyaroundanervehasnotbeendescribed.)
• Prostatecarcinomahasaconstellationofarchitec-tural,cytoplasmic,nuclear,andintraluminalfeatures:
• Architecture • Gland-formingprostatecarcinomasaremore
crowdedthanbenignglandsandtypicallyexhibithaphazardgrowthpatternandinfiltrativegrowthpattern,withmalignantglandssituatedbetweenorflankingbenignglands.
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• Incontrasttobenignglandswithirregularandundulatingluminalborders,prostatecarcinomaglandsaresmallerandhavestraightluminalborders.
• Whenprostatecarcinomabecomeslessdifferenti-ated,itlosesglandulardifferentiationandformscribriformstructures,fusedglands,poorlydelin-eatedglands,solidsheetsorcords,orevensingletumorcells.
• Cytoplasm • Prostatecarcinomaglandsmayhaveamphophilic
cytoplasm. • Low-gradeprostatecarcinomaoftenhaspale,
clearcytoplasm,indistinctfrombenignglands. • Prostatecarcinomatypicallylackslipofuscinpig-
ment. • Nuclei • Typically,prostatecarcinomadisplaysenlarged
nucleiandprominentnucleoli. • Someprostatecarcinomaslackprominentnucle-
oliyethaveenlargedandhyperchromaticnuclei. • Cancernuclei,eveninpoorlydifferentiatedones,
showlittlevariationinsizeandshape. • Mitosesandapoptoticbodiesaremorecommon
inprostatecarcinomaandrarelyfoundinbenignglands.
• Lumina • Crystalloidsaredense,eosinophilic,crystal-like
structurescommonlyfoundwithintheglandularlumensofcancerglands.
• Intraluminal,pink,acellular,densesecretionsandblue-tingedmucinareadditionalfindingsseenpreferentiallyinprostatecarcinoma.
• Corporaamylaceaarecommoninbenignglandsandareseenrarelyinprostatecarcinoma.
• Stroma • Ordinaryprostatecarcinomadoesnotelicita
prominentstromalinflammatoryordesmoplasticresponse.
Immunopathology (including immunohistochemistry)• ThemajorityofprostatecarcinomasexpressPSA,
althoughthereisconsiderableintratumoralandinter-tumoralheterogeneity,andtheexpressionisdecreasedinaminorityofhigh-gradeprostatecarcinoma.
• Prostate-specificacidphosphatase(PSAP)hasadiag-nosticutilitysimilartoPSA,althoughitisingeneralmoresensitiveandlessspecificthanthelatter.
• Prostatecancercanoccasionallyshownegativestain-ingforcytokeratin(CK)7,whichcanbeusefultodifferentiateprostatecarcinomafromurothelialcarci-noma,whichistypicallypositive.
• Prostatecarcinomauniformlylacksabasalcelllayerandthereforeisnegativeforhigh-molecular-weightcytokeratin(HMWCK).However,prostatecarcinomacanoccasionallycontainsparsetumorcellspositiveforHMWCK,yetnotinabasalcelldistribution,espe-ciallyafterradiationorhormonaltherapy.
• p63isanuclearproteinexpressedinbasalcellsofpseudostratifiedepithelia,includingtheprostate.p63isnegativeinprostatecancer.
• AMACRisanenzymeinvolvedinthemetabolismofbranchedchainfattyacidsandbileacidintermediates;itisoverexpressedinapproximately80%ofprostatecarcinomainneedlebiopsyspecimens.AMACRisnotentirelyspecificforprostatecarcinoma,asitispres-entinhigh-gradeprostaticintraepithelialneoplasia(>90%),adenosis(17.5%),partiallyatrophicglands,
andoccasionallymorphologicallybenignglands.AMACRcanbeusedasaconfirmatorystaining,inconjunctionwithH&Ehistologyandbasalcellmark-ers,forprostatecarcinoma.
Main differential diagnosis• Partialatrophy• Postatrophichyperplasia• Adenosis• Sclerosingadenosis• Basalcellhyperplasia• Seminalvesicle–ejaculatoryducttissue• Verumontanummucosalglandhyperplasia• Cowperglands• Paraganglia• Mesonephricremnants• Nonspecificgranulomatousprostatitis• Benignprostatichyperplasia• High-gradeprostaticintraepithelialhyperplasia• Radiationeffect
Fig 1. Mucinousfibroplasia(collagenousmicronodules)consistsof delicate loose fibrous tissue with an ingrowth of fibroblastswithinoradjacenttocancerglands.
Fig 2. Perineural invasion with cancer glands encircling theentire circumference of a nerve is pathognomonic of prostatecarcinoma.
59Neoplastic Disease of the Prostate
A
B
Fig 3. A,Glomeruloidformationiscreatedbyintraluminalpro-liferationofmalignant cells.B,Glomeruloid structure isoftensurroundedbyacrescenticspaceresemblingarenalglomerulus.
Fig 4. Benignprostaticglandscanoccasionallybefoundtoabuta nerve; however, circumferential extension of benign glandsentirelyaroundanervehasnotbeendescribed.
Fig 5. Architecturally, gland-forming prostate carcinomas aremorecrowdedthanbenignglands.
Fig 6. Typically, prostate cancer glands exhibit an infiltrativegrowth pattern, with malignant glands situated between orflankingbenignglands.
Fig 7. Incontrasttobenignglandswithirregularandundulat-ingluminalborders,prostatecarcinomaglandsaresmallerandhavestraightluminalborders.
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Fig 8. Whenprostatecarcinomabecomeslessdifferentiated,itlosesglandulardifferentiationandformspoorlydelineatedfusedglands,cords,orevensingletumorcells.
Fig 9. Prostatecarcinomaglandsmayhaveamphophiliccyto-plasm.Notice the intensecytoplasmic stainingcomparedwiththesurroundingbenignglands.
Fig 10. Gleasonscore6mayhavepale-clearcytoplasm, indis-tinctfrombenignglands.
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B
Fig 11. Typically, prostate carcinoma displays nucleomegaly(A)andprominentnucleoli(B).
Fig 12. Poorlydifferentiatedprostatecancershowinglittlevari-ationinnuclearsizeandshape.
61Neoplastic Disease of the Prostate
Fig 14. Intraluminalpinkacellulardensesecretionsarefindingsseenpreferentiallyinprostatecarcinoma.
Fig 15. Blue-tinged mucin can be seen within the lumen ofprostatecarcinomaglands.
Fig 13. Crystalloidsaredenseeosinophiliccrystal-likestructurescommonlyfoundwithintheglandularlumensofcancerglands.
Fig 16. Corpora amylacea are common in benign glands andonlyrarelyseen(asinthiscase)inprostatecarcinoma.
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B
Fig 17. A, Small glands of prostate carcinoma infiltratingbetween larger benign glands. B, Prostate cancer glands uni-formly lack a basal cell layer and therefore are negative forHMWCK; in contrast, benign glands show strong cytoplasmicstaininginthebasalcells.
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B
C
Fig 18. A,Smallfocusofprostatecanceronneedlebiopsy(top).B, p63 nuclear staining is expressed in basal cells of benignprostaticglands,but isnegative inprostatecancer.C,Prostatecarcinoma shows strong cytoplasmic staining with AMACR.p63nuclearstainingispositiveinbasalcellsofadjacentbenignglands,butnegativeinneoplasticglands(p63/AMACRcocktail).
A
B
Fig 19. High-gradeprostatecancer.PSAP(A)hasadiagnosticutilitysimilartoPSA(B),althoughitisingeneralmoresensitiveandlessspecificthanPSA.
Fig 20. High-grade prostate cancer. Notice that most of thetumorcellsshownegativestainingforCK7.CK7cansometimesbeusefultodifferentiateprostatecarcinomafromurothelialcar-cinoma,whichistypicallydiffuselypositiveforCK7.
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Fig 21. ThemajorityofprostatecarcinomasexpressPSAalthoughthereisconsiderableintratumoralheterogeneity.Thereisvariableintensityofstainingintwodifferentareasofthesametumor.