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  • 50 ENCORE! Pancreas: Surgical Pathology and Cytopathology of Pancreatic Neoplasms

    N Adsay MD Michelle Reid MD

    2011 Annual Meeting Las Vegas, NV

    AMERICAN SOCIETY FOR CLINICAL PATHOLOGY 33 W. Monroe, Ste. 1600

    Chicago, IL 60603

  • 50 ENCORE! Pancreas: Surgical Pathology and Cytopathology of Pancreatic Neoplasms With recent advances in imaging and interventional techniques and a dramatic decline in mortality and morbidity of pancreatic operations pancreatic resection specimens are now seen more often by surgical pathologists. Endoscopic ultrasound-guided fine needle aspiration has significantly increased the number of preoperative cytologic specimens reviewed by cytopathologists. Changes in terminology and classifications add to the new information one must now absorb. This session will provide an overview of challenges and practical clues in the diagnosis of pancreatobiliary specimens, with an algorithmic approach to differential diagnosis. Discussions will include: Pancreatic adenocarcinoma and its distinction from its mimics; Differential diagnosis of solid cellular/fleshy tumors of the pancreas; Clinicopathologic characteristics and biologic behavior of cystic tumors of the pancreas; Cytopathologic diagnosis of solid and cystic pancreatic lesions.

    Accurately differentiate problematic cases in surgical pathology of the pancreas, including solid-scirrhous lesions, solid/fleshy circumscribed lesions and cystic and traductal pancreatic tumors.

    Recognize the most common solid and cystic pancreatic lesions/tumors encountered on pancreatic fine needle aspiration; Evaluate the usefulness of ancillary studies in their cytologic diagnosis; Recognize key gastrointestinal contaminants in endoscopic tultrasound-guided pancreatic fine needle aspiration, that may lead to misdiagnosis on cytology.

    Distinguish and diagnose tumors of the ampulla, gallbladder and extrahepatic bile duct; Describe the grossing of pancreatoduodenectomy specimens.

    FACULTY: N Adsay MD Michelle Reid MD Practicing Pathologists Surgical Pathology Surgical Pathology (GI, GU, Etc.) 3.0 CME/CMLE Credits Accreditation Statement: The American Society for Clinical Pathology (ASCP) is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education (CME) for physicians. This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME). Credit Designation: The ASCP designates this enduring material for a maximum of 3 AMA PRA Category 1 Credits. Physicians should only claim credit commensurate with the extent of their participation in the activity. ASCP continuing education activities are accepted by California, Florida, and many other states for relicensure of clinical laboratory personnel. ASCP designates these activities for the indicated number of Continuing Medical Laboratory Education (CMLE) credit hours. ASCP CMLE credit hours are acceptable to meet the continuing education requirements for the ASCP Board of Registry Certification Maintenance Program. All ASCP CMLE programs are conducted at intermediate to advanced levels of learning. Continuing medical education (CME) activities offered by ASCP are acceptable for the American Board of Pathologys Maintenance of Certification Program.

  • 1

    EUSGuidedFineNeedleAspirationand

    CytopathologyofCysticandSolidLesionsofthePancreas

    MichelleReid,MDDepartmentofPathologyEmoryUniversityHospital

    Atlanta,GA

    NEEDLEASPIRATIONOFTHEPANCREAS

    1.Percutaneousfineneedleaspiration(FNAB) Performedbyaradiologist

    2. Endoscopicultrasoundguided(EUS)FNAB(#1technique) Performedbyagastroenterologist

    Anechoendoscopeisplacedg

    A.Transabdominalultrasound

    B.CT guided Betterresolutionofsmallerlesions

    p pagainststomach/duodenum

    Highresolutionimageobtained

    INTRODUCTION

    Endoscopicultrasoundguided(EUS)FNAB Advantages:

    Mostcosteffectiveandsensitivediagnosticmodality

    Higherresolutionofsubcentimeter(0.5cm)lesionsthanCT

    Real time visualization of needle during FNA RealtimevisualizationofneedleduringFNA

    Simultaneouslydiagnoseandstagepatients

  • 2

    DIAGNOSISOFPANCREATICLESIONS

    Canbechallenging SOWHYDOIT? Becausecytologicdiagnosisaffectssurgicalmanagement

    Pseudocysts,serouscystadenoma,pancreatitisNOSURGERYREQUIRED

    Allotherlesions/neoplasmsSURGERYREQUIRED

    Initialassessmentofpancreaticlesionsisradiologic Lesionsareeithercystic,solidormixed

    ABRIDGEDCLASSIFICATIONOFSOLIDANDCYSTICPANCREATICNEOPLASMS

    GrossConfiguration Neoplasms %

    SolidNeoplasms

    DuctalAdenocarcinoma 85%

    PancreaticNeuroendocrineTumor 34%

    AcinarCellCarcinoma 12%

    (SolidPseudopapillaryNeoplasm) 12%

    Pancreatoblastoma

  • 3

    INTRODUCTIONAccuracyofFNAB

    ImmediatecytologicassessmentISAMUST Bestperformedbycytopathologistorcytotechnologist

    Reducesnumberofpasses

    Reducesinadequatesamples

    Savestimeandmoney

    AccuracyofPancreaticFNAB Sensitivityfordetectingmalignancy:

    86% 98%forpercutaneousFNAB 75% 94%forEUSFNAB

    Specificityforbothapproaches100% Falsenegativeandfalsepositiveresultsoccur False negative results more common Falsenegativeresultsmorecommon

    SAMPLEPREPARATION ANDEVALUATION

    1.PrepareairdriedandalcoholfixedslidesA. Airdriedslides

    StainwithaRomanowskistain DiffQuik

    Determineadequacy Triagespecimens

    Flow cytometry (if

    2.Collectneedlerinsesfor: Cellblocks(placespecimenin

    95%alcoholorformalin) Immunohistochemicalstains

    Flowcytometry(iflymphomaissuspected)

    Cystfluidcollectionforanalysis*

    B. Alcoholfixedslides Papanicolaouandhematoxylin

    andeosin(H&E)

  • 4

    PancreaticCystFluidAnalysis1.Enzymes PseudocystorNonNeoplasticCyst NeoplasticCyst

    amylase High low*

    lipase High low

    leukocyteesterase high low

    2.Viscosity NonMucinousCyst MucinousCyst

    viscosityserum

    3.TumorMarkers NonMucinousCyst MucinousCyst

    CEA Notelevated(200ng/mL)(200ng/mL)

    CA724 notelevated elevated

    CA199 notelevated elevated

    CA125 notelevated elevated

    CA153 notelevated elevated

    4.MolecularMarkers NegativeforKrasmutationNegativeforLOHmutationLowquantity/qualityDNA

    KrasmutationLOHmutationor

    Highquantity/qualityDNACEA,carcinoembryonicantigen;CA,cancerantigen;LOH,lossofheterozygosity.

    Modified from Weinstein L, Pancreas. In: Cytology. Diagnostic principles and clinical correlates. 3rd Ed. E. Cibas, B. Ducatman editors

    MolecularMarkersinPancreaticCystFluidAnalysis

    RedPathIntegratedPathologydevelopedacommerciallyavailablemolecular kitforpancreaticcystfluidandcellblockanalysis

    CalledPathFinderTG

    Includes3tests 1 k ras gene point mutation (on chromosome 12p12) 1.kras genepointmutation(onchromosome12p12)

    2.Lossofheterozygosity(LOH)analysisformutationsin 2of15genomicloci

    1and2areconsideredhighamplitudemutationsiftheyinvolves>75%oftotalDNAcontent

    3.MeasurementofDNAquantityandquality

    UseofImmunohistochemicalStainsinDiagnosisofPancreaticNeoplasms

    Table from Klimstra et al. Archives of Pathology and Laboratory Medicine 2009; 133(3):454-64.[14]

  • 5

    REPORTINGTERMINOLOGYSixdiagnosticcategories

    1)Nondiagnostic

    2)Negativeformalignancy

    3)Atypicalcellspresent

    4)Suspiciousformalignancy

    5)Positiveformalignantcells

    6)Neoplasticcellspresent

    DiagnosticCategories

    1. Nondiagnostic: Materialisunsatisfactory:

    Becauseoflowcellularity

    Becauseitdoesnotrepresentthesitebiopsied

    2.Negativeformalignancy: Benignpancreaticepithelium

    p

    DiagnosticCategories

    3.Atypicalcellspresent:

    Atypiaismild Backgroundpancreatitis

    common

    4.Suspiciousformalignancy:

    Atypiamoderate Worrisomeformalignancybut:

    Qualitatively insufficientcommon

    ACOMMENTshouldbeadded

    Qualitativelyinsufficient

    Quantitativelyinsufficient

    foradefinitediagnosisofmalignancy

  • 6

    DiagnosticCategories

    5.Positiveformalignantcells Cells shows obvious malignant

    features

    6.Neoplasticcellspresent: When the cells are obviously

    neoplastic but not definitely benign or malignant

    e.g. Mucinous cystse.g. Mucinous cysts

    ContaminantsinPancreaticFNAB EUSFNABintroducesgastrointestinal(GI)tractcontaminants

    GItractcontaminantsinclude: 1.Duodenalepithelium

    2.Gastricepithelium

    3.GItractmucin

    DistinguishingGIcontaminantsfrompancreaticductaladenocarcinomaandneoplasticmucinouscystscanbechallenging

    CONTAMINANTSINPANCREATICFNAB

    Mustknowlocationoflesiontodeterminelikelycontaminant

    Lesionsinheadanduncinateprocessduodenalepithelialpcontaminants

    Lesionsinbody/tailgastricepithelialcontaminants

  • 7

    1.DuodenalEpithelialContaminants

    Formflathoneycombsheetswithinterspersedgobletcells

    Tissueedgeshavedistinctbrush border best seen atbrushborderbestseenatveryhighpower

    Distinctionfromwelldifferentiatedductalcarcinomaoraneoplasticmucinouscystcan bedifficult

    WellDifferentiatedDuctalAdenocarcinomavs

    DuodenalContaminants

    Welldifferentiatedductalcarcinoma notepleomorphism,overlappingcellsandabsenceofbrushborder

    Duodenalepitheliumnoteblanduniformcellswith2dimensionalarrangementandbrushborderatedgeofsheet

    DuodenalContaminantsvsMucinousNeoplasm

    Goblet cells

    Duodenalepitheliumhas2dimensionalhoneycombsheetswithisolatedgobletcellsinterspersedbetweenbenigncolumnarcellsThishelpstodistinguishduodenalcontaminantsfromaneoplasticmucinouscystwhichhasapurepopulationofmucinfilledcellswhichareoften

    crowdedtogetherandoverlapping

    Duodenal epithelium Neoplastic mucinous cyst

  • 8

    2.GastricEpithelialContaminants

    Gastricepithelialmucindoesnotfilltheentirecellbutisconfinedtothesuperficial1/3rdofthecellwhereitformsadistinctmucincup

    Gastric epithelium on cell block

    2.GastricEpithelialContaminants

    ItisevenmorechallengingtodistinguishgastricepitheliumfrommucinouscysticlesionsNotethedistinctmucincupsinsuperficial1/3rd ofcell(ontheleft)

    3.GITractMucin

    GItractmucinmayalsobeseeninEUSFNAB

    Thin,wateryandscant

    Notabundantorthicklikemucin in cystic mucinous

    Thin watery GI tract mucin

    mucinincysticmucinousneoplasms

    Neoplasticmucinmayhavetumorcellsadmixed

    Thick colloid-like mucin in mucinous neoplasm

  • 9

    NormalExocrinePancreas AcinarCells

    Cellsformacinarstructureswithoutdistinctlumens Cellsarebland,pyramidal/triangularwithlowN/Cratio,granular(zymogenrich)cytoplasm,roundnuclei,inconspicuousorprominentnucleoli

    CYTOLOGYOFTHENORMALEXOCRINE

    PANCREAS

    Ductalcells Formmonolayersheets

    Cellsareevenlydispersed

    Welldefinedcellborders

    Round nuclei with fine Roundnucleiwithfinechromatin

    Inconspicuousorabsentnucleoli

    Ductalcellsinhoneycombsheet

    CYTOLOGYOFTHE

    NORMALPANCREAS

    Endocrinepancreas Isletcells

    RarelysampledonaFNA

    Formlooseaggregateswithilldefined cell bordersdefinedcellborders

    Wispycytoplasm

    Roundnuclei

    Finechromatin

    Nucleoliareabsentorinconspicuous

    Endocrinecellsaresmall,monotonouswithlowN/Cratioandblandnuclei

  • 10

    CYSTICPANCREATICLESIONS

    CYSTICPANCREATICLESIONS Themajorityarenonneoplasticorbenign

    Pancreaticpseudocystsaccountforthemajority(75%)

    Lymphoepithelialcysts

    Serouscystadenoma

    M i ti l Mucinouscysticneoplasm

    Intraductalpapillarymucinousneoplasm

    Solidneoplasmswithcysticdegeneration

    ABRIDGEDCLASSIFICATIONOFSOLIDANDCYSTICPANCREATICNEOPLASMS

    GrossConfiguration Neoplasms %

    SolidNeoplasms

    DuctalAdenocarcinoma 85%

    PancreaticNeuroendocrineTumor 34%

    AcinarCellCarcinoma 12%

    (SolidPseudopapillaryNeoplasm) 12%

    Pancreatoblastoma

  • 11

    Serous cystadenoma

    Solidpseudopapillaryneoplasm

    Mucinous CysticNeoplasm

    Intraductal

    CYSTICPANCREATICLESIONS

    Pseudocyst

    papillarymucinous neoplasm

    TheprimarygoalofFNABofcysticlesionsistodistinguishlowfrom

    highriskpancreaticcystsg p y

    Lowriskpancreaticcysts Lesslikelytoharbormalignancy

    Resectedonlyif: Symptomatic

    Whendefinitivediagnosis

    Highriskpancreaticcysts Haveahigherriskofhigh

    gradedysplasiaormalignancy Managedsurgicallywith

    partial/totalpancreatectomy

    impossible

    Lowriskpancreaticcysts Pancreaticpseudocysts

    Serouscystadenomas

    Lymphoepithelialcysts

    Highriskpancreaticcysts Intraductalpapillarymucinous

    neoplasm(IPMN) 30%harborcarcinoma

    Mucinouscysticneoplasm(MCN)

  • 12

    CYSTICLESIONSOFTHEPANCREASSerous cystadenoma

    Solidpseudopapillaryneoplasm

    Mucinous CysticNeoplasm

    Intraductal

    LOW-RISK PANCREATIC CYSTS

    Pseudocyst

    papillarymucinous neoplasm

    PancreaticPseudocyst FNA

    Collectionofamylaserichsecretions,debrisandblood

    Lacksatrueepitheliallining

    i ll l i h l d b i Paucicellularsmearswithgranulardebris,macrophages,yellowbile/hematoidinpigmentandfatnecrosis

    PancreaticPseudocyst

    Fluid is turbid/necrotic NOT mucinous or gelatinous Granular background debris Inflammatory cells Pigment is important for

    diagnosisY ll i t

    Cell blocks Yellow pigment =

    bile/hematoidin Brown pigment =

    hemosiderin

  • 13

    PancreaticPseudocystsvsMucinousCysticLesions

    Pancreatic Pseudocysts Fluid is turbid or necrotic Mucicarmine negative Amylase

    MucinousCysticLesions

    Fluid is gelatinous Mucicarmine positive Amylase y

    High (>250ng/mL) CEA

    Low ( 200ng/mL)

    Serous cystadenoma

    Solidpseudopapillaryneoplasm

    Mucinous CysticNeoplasm

    Intraductal

    LOW-RISK PANCREATIC CYSTS

    Pseudocyst

    papillarymucinous neoplasm

    SerousCystadenoma

    Cystic spaces lined by bland cuboidal or low columnar clear epithelial cells

  • 14

    SerousCystadenoma FNA

    Cystfluidisusuallythinandclear

    Aspiratesareoftenhypocellular

    AE1/AE3andCA19.9are+,EMAisfocally+

    Amylase and CEA levels are low AmylaseandCEAlevelsarelow

    Mucicarminenegative

    Accuracyofdiagnosisbyimaging,cytologyandchemicalanalysisisONLY20%**

    SerousCystadenoma

    Sheets and clusters of cells with clear cytoplasm, defined borders, PAS+ cytoplasm

    LOW-RISK PANCREATIC CYSTS

    Lymphoepithelial cyst

  • 15

    LymphoepithelialCyst FNA

    Hasthick,white,cheesyfluid Linedbymaturesquamousepithelium Surroundedbydenselymphoidinfiltrate+/ follicles Smearshave:

    Nucleated/anucleated squames Nucleated/anucleatedsquames Keratinousdebris Lymphocytes,histiocytes,giantcells

    AspiratesareusuallyDIAGNOSTIC AccurateFNAdiagnosisobviatestheneedforradicalsurgery CystfluidhashighCEAandamylaselevels

    LymphoepithelialCyst FNA

    Anucleated squames Mature lymphocytes

    Keratinous debris Cell block with gastric contaminants

    HIGHRISKPANCREATICCYSTSNEOPLASTICMUCINOUSCYSTS

    MucinousCysticNeoplasmIntraductal

    illpapillarymucinousneoplasm

  • 16

    NEOPLASTICMUCINOUSCYSTS

    Mucinouscysticneoplasm(MCN) Primarymucinproducingcysticneoplasm Linedbyblandmucinfilledcolumnarcells HasclassicalsubepithelialovariantypeER+,PR+stroma

    Intraductalpapillarymucinousneoplasm(IPMN) Primarymucinproducingcysticneoplasm Arisesfromthemainorbranchpancreaticducts Linedbypapillarymucinousepitheliumwithvariableatypia

    KeyDifferencesBetweentheTwoCysts

    MCN Large,circumscribed,solitarycystic

    lesion Notconnectedtothemainpancreatic

    duct oritsbranches Becausetheyarenotconnectedtothe

    mainpancreaticduct/branchesamylaselevelsareusuallylow

    >90%ariseinthetail

    IPMN Diffuseectasiainvolvingthemain

    and/orbranchpancreaticducts Alwaysconnectedtothemain

    pancreaticduct orbranches Becausetheyareconnectedtomain

    pancreaticductamylaselevels arehighincystfluid

    >80%ariseinthehead ofthepancreas Mostpatientsareperimenopausal

    females between4050yrs F:M20:1 Hassubepithelialovariantypefibrous

    stroma Malignantfeaturesinclude:

    Size>3cm Thickwall,peripheralcalcifications Intramuralmass/nodules

    Mostpatientsareolderadults,overtheageof60

    M=Forareslight>females Nosubepithelialovariantypestroma

    present Malignantfeaturesinclude:

    Size>3cm Dilatedmainpancreaticduct Intramuralmass/nodules

    CytologicSimilarities

    BothIPMNandMCNhaveabundantthickmucin

    Difficulttoexpressfromneedle

    Difficulttospreadontheslide

    Smear cellularity is variable

    Abundant thick colloid-like mucin

    DiffQuikstainSmearcellularityisvariable

    Higherthegradeofdysplasia,thegreaterthecellularity

    PsammomatouscalcificationsmaybeseeninIPMN

    Papstain

  • 17

    SimilaritiesBetweenMCNandIPMN

    Bothcontainsheetsandclustersofcolumnarcellswithabundantintracytoplasmicmucin

    SimilaritiesbetweenMCNandIPMN

    Themucinfillstheentirecytoplasmanddisplacesthenucleusperipherally Notelimitednuclearatypiainthisexample.

    NEOPLASTICMUCINOUSCYSTS

    Nuclei are slightly pleomorphic with

    Mucin +

    coarse chromatin and prominent nucleoli

    Macrophages may be present

  • 18

    NEOPLASTICMUCINOUSCYSTS

    PapillaryclustersmaybeseeninIPMNbutarenottypicalinMCN

    NuclearandarchitecturalatypiacanbeseeninbothIPMNandMCN Includeshypercellularity

    Nuclearcrowding

    Lossofpolarity

    PapillarystructureinanIPMN

    NotenuclearatypiawithnuclearCrowding and hyperchromasiap y

    Hyperchromasia,pleomorphism

    HighN/Cratioandnucleoli

    Singleepithelialcellsinmucin

    NuclearatypiaismoreoftenseeninIPMNthanMCN

    Crowdingandhyperchromasia

    PancreaticNeoplasticMucinousCystwithHighGradeDysplasia

    Interesting Case - Pancreatic Tail Cyst

  • 19

    Diagnosis? Adenocarcinoma(atleastinsitu)possiblyarisinginaneoplasticmucinouscyst

    NEOPLASTICMUCINOUSCYSTS Necrosis,inflammationand

    signetringcellsmorecommoninhighgradedysplasia/carcinoma

    Note background mucin and necrosisy p /

    Bestcorrelateofinvasioninpancreaticmucinouscystsisnecrosis

    Singlehighlyatypicalcellsarealsosuggestiveofmalignancy

    Signetringcells Singleatypicalcells

    KeyPointInDailyPractice

    Thick gelatinous mucin is DIAGNOSTIC of a l ti i t ifneoplastic mucinous cyst even if

    diagnostic cells are not identified.- Correlation with imaging is required.

  • 20

    PANCREATICMUCINPRODUCINGCYSTS

    DefinitivecytologicdistinctionbetweenMCNandIPMNisdiscouraged

    The best diagnosis for such lesions is: Thebestdiagnosisforsuchlesionsis: Neoplasticcellspresent.

    Neoplasticmucinouscyst

    Acommentshouldbemaderegardingthepresenceandgradeofcytologicatypia/dysplasia

    SOLIDPANCREATICLESIONS

    ABRIDGEDCLASSIFICATIONOFSOLIDANDCYSTICPANCREATICNEOPLASMS

    GrossConfiguration Neoplasms %

    SolidNeoplasms

    DuctalAdenocarcinoma 85%

    PancreaticNeuroendocrineTumor 34%

    AcinarCellCarcinoma 12%

    (SolidPseudopapillaryNeoplasm) 12%

    Pancreatoblastoma

  • 21

    DuctalAdenocarcinoma

    60% 70%occurinthepancreatichead

    Well poorlydifferentiated

    Poorlydifferentiatedcarcinomaisstraightforward

    Well and moderately differentiated carcinoma mayWellandmoderatelydifferentiatedcarcinomamaybedifficulttodistinguishfromreactiveductalcellsandGItractcontaminants

    PoorlyDifferentiatedDuctalCarcinoma

    PoorlyDifferentiatedDuctalCarcinoma

    Notadiagnosticchallenge 3dimensionalgroups 4foldanisonucleosisis

    characteristic

    Irregularnuclei HighN/Cratio Macronucleoli Abnormalmitoses Necrosis Singleintacttumorcellsare

    critical

  • 22

    PoorlyDifferentiatedDuctalAdenocarcinoma

    3-D crowded groups 4-fold anisonucleosis

    Disorganized sheets with hyperchromatic cells with irregular nuclei

    MALIGNANT BENIGN

    PoorlyDifferentiatedDuctalAdenocarcinoma

    WellDifferentiatedDuctalCarcinoma

    Disorganizedsheets similartonormalductalcells

    Slightnuclearcrowding

    Drunkenhoneycombsheets

    Mild nuclear enlargement Mildnuclearenlargement

    N/Cratiomayremainlow

    Anisonucleosisnotaspronounced

    Normalpancreaticaciniandendocrinecellsareraretoabsent

  • 23

    InterestingCase FNABPancreaticMass

    Slightly drunken honeycomb sheet and cellular dissociation

    Irregular nuclear contours, hypochromasiaand prominent nucleoli

    An extremely bland-appearing well differentiated adenocarcinoma with voluminous foamy cytoplasm

    Cells have abundant mucinous vacuoles and very bland almost benign cytologic appearance

    Closer examination revealed single intact malignant cells with nuclear irregularity

    Diagnosis?

    FoamyGlandVariantofWellDifferentiatedDuctalAdenocarcinoma

  • 24

    FoamyGlandDuctalAdenocarcinoma

    DuctalAdenocarcinoma Immunohistochemicalmarkers:

    CK7,CK8,CK18,CK19

    CA125

    DUPAN2(pancreaticcancerassociatedantigen)

    Mucinglycoproteinsarevariablyexpressed MUC1,3,4andMUC5AC

    Molecularmarkers: Krasmutation

    Lossofheterozygosity(LOH)mutation

    p53mutation

    OtherVariantsofDuctalCarcinomaCarcinoma

  • 25

    SquamousCellCarcinomaofPancreas

    Extremelyrarevariantofpancreaticcarcinoma Incidencerangesfrom0.5% 5%

    Onlydiagnoseaftermetastasishasbeenexcludedandafteraglandularcomponenthasbeenexcluded(i.e.adenosquamouscarcinoma)

    Similarbiologicbehaviortoductaladenocarcinomag

    SquamousCellCarcinomaofPancreas

    Malignant squamous cells are admixed with benign pancreatic ductal cellsThis was a case of primary pancreatic squamous cell carcinoma

    SquamousCellCarcinomaofPancreas

    Mostcasesrepresentmetastases Fromthelung,followedby

    cervixthenesophagus

    Correlationwithclinicalinformationisparamounttoaccuratediagnosis

  • 26

    Osteoclastic GiantCellCarcinomaofPancreas Extremelyrareprimarymalignantpancreatictumor

    Associatedwithductaladenocarcinoma(40%ofcases) Maybefocalorpredominant

    Prognosisiscontroversial: Somesaynotasdismalasductalcarcinoma

    Others say more aggressive than ductal carcinoma Otherssaymoreaggressivethanductalcarcinoma

    Meansurvival12months relatedtoquantityofductalcarcinoma

    Osteoclastic GiantCellCarcinomaofPancreas

    3celltypes: 1.Benignappearingosteoclast

    likegiantcells CD68+,Cytokeratin

    2 Pleomorphic giant carcinoma

    3

    2.Pleomorphicgiantcarcinomacells

    CD68,Cytokeratin 3.Smallovoidspindlehistiocyte

    likecarcinomacells CD68+ Cytokeratin+/,EMA+/

    P53+,ki67+

    1 2

    OsteoclasticGiantCellCarcinomaofPancreas

    Conventionalductaladenocarcinomasamecase Cellblockwithbenigngiantcells

    BenignosteoclastlikegiantcellsAll3celltypesarerepresented

  • 27

    MucinousColloidCarcinomaofPancreas

    Accountsfor

  • 28

    ChronicPancreatitis Atypicalreactiveductalcellscanbeconfusedwithductalcarcinoma

    Distinctionbetweenthe Reactive ductal cells2mayrequireimmunohistochemistry

    Reactive ductal cells

    FNA:AtypicalCellsPresentReactiveDuctalCellsvs.DuctalCarcinoma

    Notethesheetlikearrangement,roundnuclearcontoursandsimilaritybetweencells.

    Thisismarkedreactiveatypia

    Benign ductal cells in honeycomb sheets

    DrunkenHoneycombSheet

    Well differentiated ductal carcinomaAbnormal mitosis

    Reactive ductal cells in honeycomb sheetsWell differentiated ductal carcinoma

  • 29

    ImmunohistochemicalDistinctionbetweenAdenocarcinoma,

    ChronicPancreatitisandGITractContaminants

    AtypicalDuctalCells

    SMAD4 p53 CDX2

    DuctalAdenocarcinoma + Chronicpancreatitis + GItractcontaminants + +SMAD4: Belongs to the SMAD family of cell signaling proteins: It is a homologue of the Drosophila protein: Mothers against decapentaplegic and is also known as DPC4 (Deletion target in pancreatic carcinoma 4); CDX-2, caudal-related homeobox 2 .

    KeyPointInDailyPractice

    Ifatypicalglandularcellsarepresentandonecannotdeterminewhethertheyareneoplasticorreactivethebestdiagnosisis:

    AtypicalcellspresentwithCOMMENT Correlateclinicallyandradiologically

    AutoimmunePancreatitis

    Lymphoplasmacyticsclerosingpancreatitis

    Canproduceamasseffectinpancreas

    Associated with RA IBDAssociatedwithRA,IBD,primarysclerosingcholangitis

    serumIgG4antibody Antinuclearantibody(ANA)+

    Rheumatoidfactor+

  • 30

    AutoimmunePancreatitis(AIP)

    Fewreportsoncytologicfeatures

    Rangefrompaucicellulartohypercellularaspirates

    Contain stromal fragments Containstromalfragments,lymphoplasmacyticinfiltrate,eosinophils

    Minimalductalepithelium

    IgG4immunostainispositiveinplasmacells

    PancreaticNeuroendocrineTumors Rangefromwell poorlydifferentiated

    Welldifferentiatedpancreaticneuroendocrinetumor(PanNET)isthemostcommon

    Poorly differentiated neuroendocrine carcinomaPoorlydifferentiatedneuroendocrinecarcinoma(PanNEC)isextremelyrare

    Smallcellcarcinoma

    Largecellneuroendocrinecarcinoma

    WellDifferentiatedPancreaticNeuroendocrineTumor Hypercellularsmears

    Uniform,dyscohesivecells

    Fragile,easilystrippedcytoplasm

    Oftenhaveeccentricnucleiplasmacytoidappearance

    WelldifferentiatedNET

    Plasmacytoid cells Mayresemblelymphocytes

    ClassicalsaltnpepperchromatinonPap/H&Estain

    Indistinctnucleoliusually

    Mayhaveprominentnucleoli Variablenuclearatypia

    Plasmacytoid cells

    NETwithprominentnucleoli

  • 31

    WellDifferentiatedPancreaticNeuroendocrineTumor

    D

    Plasmacytoid cells

    Pseudorosettes on cell block

    Salt-n-pepper chromatin, small nucleoli

    Prominent nucleoli and pseudoacini

    WellDifferentiatedPancreaticNET

    Pseudorosettes are visible both on smear and cell block

    Well Differentiated Pancreatic Neuroendocrine Tumor - Pleomorphic Variant

    Single plasmacytoid cells and cells with focal degenerative endocrine atypia

  • 32

    PancreaticNeuroendocrineTumor Immunohistochemistry

    Positiveforneuroendocrinemarkers

    Synaptophysin,chromogranin,CD56,

    CD57

    Positiveforkeratin,CAM5.2

    PoorlyDifferentiatedPancreaticNeuroendocrineCarcinoma(NEC)

    Extremelyrare

    IncludesmallcellandlargecellNEC

    Ruleoutmetastasisbeforemakingthisdiagnosis

    Smallcellcarcinomaresemblessmallcellcarcinomaofthelung Molding,saltandpepperchromatin,

    crushartifact

    LargecellNEC Resemblespoorlydifferentiatedcarcinoma

    Expressesneuroendocrinemarkers

    Small cell carcinoma

    AcinarCellCarcinoma

    Hypercellular smears Acinar formation and naked nuclei

    Abundant granular cytoplasmCells have basophilic cytoplasm,Nuclei with fine to coarse chromatin,inconspicuous nucleoli

    Normal pancreatic acini

  • 33

    AcinarCellCarcinoma

    Prominent nucleoli may be seen Cell block with acinar groups and trabeculae

    AcinarCellCarcinoma Tumorcellsstainpositivelyfor:

    Pancytokeratin

    Pancreaticenzymes: Lipase,trypsin,chymotrypsin,1antichymotrypsin,elastaseandh h li A2phospholipaseA2

    Donotconfusetrypsinwith1antitrypsin

    1 antitrypsinisnotaveryusefulstainforacinarcells

    Becauseitalsostainssolidpseudopapillaryneoplasmandpancreaticneuroendocrinetumors

    Trypsin

    SolidPseudopapillaryNeoplasm

    Tumor cells form vague clefts or spaces lined by bland epithelial cells with intervening myxoid stroma, thin-walled vessels and vesicular, grooved nuclei

  • 34

    SolidPseudopapillaryNeoplasm

    Rarelow gradesolidandcysticpancreatic

    Usuallyarisesinthepancreatictail

    Almostexclusivelyinwomen(F:M9:1)

    Thirddecade(meanage28years)oradolescence

    Cytologicfeaturesaredistinctive

    Accuratediagnosisoftenmadebeforeresection

    SolidPseudopapillaryNeoplasm

    Monomorphic small cells with high N/C Complex branching papillae gratio, fine chromatin, nuclear grooves

    g

    Papillary fronds with central myxoid stroma (on Diff Quik stain) and blood vessel (H&E)

    Solid-Pseudopapillary Neoplasm

    Fibrovascular core

    Vesicular nuclei with open, fine, powdery chromatin

    Nuclear grooves

  • 35

    SolidPseudopapillaryNeoplasm

    Immunohistochemistryischaracteristicanddiagnostic Positiveforvimentin: Frequentlynegativeforcytokeratin Positivefor:

    Neuronspecificenolase

    CD56(variable)

    CD10

    catenin(nuclear)

    Progesteronereceptor

    1 antitrypsinisnothelpfulbecauseitispositiveinSPN,acinarcellcarcinomaandpancreaticNETs

    PancreaticNeuroendocrineTumor(NET)vsSolidPseudopapillaryNeoplasm(SPN)

    NET SPN

    Fine, open chromatinFibrovascular core Salt-n-pepper chromatin

    SecondaryPancreaticNeoplasms Varioustumorsmaymetastasizetothepancreas

    Lung(smallcellandsquamouscellcarcinoma)

    Breast

    Kidney

    L h Lymphoma

    Lesscommonly: Ovary,colonandstomach

    Historyofpreviousmalignancyandimmunohistochemistryarehelpfulindiagnosis

  • 36

    SUMMARY PANCREATICFNAB

    Cytologicevaluationofpancreaticlesionsiscomplex

    Knowledgeoftypesandlocationofthemostcommonsolidandcysticlesionsishelpfulindiagnosis

    Correlationwithclinical,imagingdataisparamount

    Cytopathologist/cytotechnologistspresenceduringimmediateevaluationimprovesadequacyanddiagnosticyield

    BemindfulthatchronicpancreatitisandGItractcontaminants(inEUSFNAB)maysimulatecarcinoma

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    evaluationwithemphasisonadequacyassessment,diagnosticcriteriaandcontaminationfromthegastrointestinaltract.Cytopathology2006;17(1):3441.

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    QUESTIONS?

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