Cytology of the GI Cytology of the GI TractTract

Teresa Alasio, MDTeresa Alasio, MD

Clinical IndicationsClinical Indications

►Suspected malignancySuspected malignancy►Screening for dysplasiaScreening for dysplasia

Surveillance of dysplasia for patients at Surveillance of dysplasia for patients at increased risk of squamous or increased risk of squamous or adenocarcinoma of the esophagusadenocarcinoma of the esophagus

►Suspected infectionSuspected infection

Advantages to Cytology vs. Advantages to Cytology vs. BiopsyBiopsy

►Samples wider areaSamples wider area►Reaches deep organsReaches deep organs►Stenotic lesions more amenable to Stenotic lesions more amenable to

cytologycytology►Better recognition of lymphoid cellsBetter recognition of lymphoid cells►Less invasiveLess invasive

Better for patients with clotting abnormalities Better for patients with clotting abnormalities or very vascular tumorsor very vascular tumors

►Shorter turnaround timeShorter turnaround time

Advantages to CytologyAdvantages to Cytology

►Exfoliative cytologyExfoliative cytology Dysplastic and malignant cells have a lower Dysplastic and malignant cells have a lower

level of intercellular cohesion than normal level of intercellular cohesion than normal cells, allowing the endoscopic brush cells, allowing the endoscopic brush procedure to selectively sample these procedure to selectively sample these discohesive elementsdiscohesive elements

less traumatic and less expensiveless traumatic and less expensive

►FNAFNA Preferable to core biopsy because tumor Preferable to core biopsy because tumor

stroma is left intactstroma is left intact

Types of GI Cytology Types of GI Cytology SpecimensSpecimens

► BrushingsBrushings► Salvage cytologySalvage cytology

Processing material present on external biopsy Processing material present on external biopsy forceps after biopsy is takenforceps after biopsy is taken

► Transmucosal FNATransmucosal FNA Endoscopic Ultrasound (EUS) guidedEndoscopic Ultrasound (EUS) guided Better visualization of lesionsBetter visualization of lesions Allows lymph node samplingAllows lymph node sampling GI tract, liver, pancreas all amenable GI tract, liver, pancreas all amenable

► Balloon cytologyBalloon cytology Experimental procedure but results highly Experimental procedure but results highly

predictive of gastric-cardia cancer and esophageal predictive of gastric-cardia cancer and esophageal cancerscancers

Review of SmearsReview of Smears

► Low power featuresLow power features CellularityCellularity Cellular arrangementsCellular arrangements BackgroundBackground

► High power featuresHigh power features Cytoplasmic characteristicsCytoplasmic characteristics Nuclear detailsNuclear details

► LBPLBP Smaller cellsSmaller cells More single cellsMore single cells Less obvious gland formationLess obvious gland formation Tumor diathesis in small clumps of debrisTumor diathesis in small clumps of debris

EsophagusEsophagus

EsophagusEsophagus

► InfectionsInfections CandidaCandida HerpesHerpes CMVCMV

► RepairRepair► Barrett’sBarrett’s

Dysplasia (low grade, high grade)Dysplasia (low grade, high grade)

► AdenocarcinomaAdenocarcinoma► Squamous cell carcinomaSquamous cell carcinoma

Candida EsophagitisCandida Esophagitis

Herpes EsophagitisHerpes Esophagitis

Other InfectionsOther Infections

► CMVCMV►MucormycosesMucormycoses► IC PatientsIC Patients

Epithelial RepairEpithelial Repair

► Cohesive sheets with flowing or streaming Cohesive sheets with flowing or streaming pattern on direct smear (not seen on LBP)pattern on direct smear (not seen on LBP)

► Uniform nuclei withUniform nuclei with EnlargementEnlargement Smooth and thin nuclear bordersSmooth and thin nuclear borders Fine chromatinFine chromatin Prominent nucleoliProminent nucleoli

► Evident mitosesEvident mitoses► Background inflammationBackground inflammation► Atypical stromal cellsAtypical stromal cells

RepairRepair

Barrett’s EsophagusBarrett’s Esophagus

► Epithelial repairEpithelial repair►Goblet cellsGoblet cells

►DysplasiaDysplasia Background of Barrett’s epitheliumBackground of Barrett’s epithelium Scattered atypical cells with some but not all Scattered atypical cells with some but not all

features of adenocarcinomafeatures of adenocarcinoma Crowded groupsCrowded groups

►LG – stratified with mild atypia and pleomorphismLG – stratified with mild atypia and pleomorphism►HG – can be isolated, more atypia and pleomorphismHG – can be isolated, more atypia and pleomorphism

Barrett’sBarrett’s

DysplasiaDysplasia

Esophageal Adenocarcinoma - Esophageal Adenocarcinoma - FeaturesFeatures

► Increased cellularityIncreased cellularity► Abnormal cellular Abnormal cellular

arrangementarrangement Numerous isolated cellsNumerous isolated cells Feathering at edges of Feathering at edges of

cellular groupscellular groups Haphazard crowded Haphazard crowded

arrangementarrangement Gland formationGland formation

► Barrett’s epithelium Barrett’s epithelium may or may not be may or may not be presentpresent

► Atypical nuclear Atypical nuclear featuresfeatures EnlargementEnlargement HyperchromasiaHyperchromasia Uneven and irregular Uneven and irregular

nuclear membranenuclear membrane PleomorphismPleomorphism

► Various amounts of Various amounts of vacuolated cytoplasmvacuolated cytoplasm

► Tumor diathesesTumor diatheses

AdenocarcinomaAdenocarcinoma

Esophageal SCCEsophageal SCC

► Well differentiatedWell differentiated Hyperchromatic pyknotic Hyperchromatic pyknotic

nucleinuclei Completely obscured Completely obscured

chromatinchromatin Variable cell shapesVariable cell shapes Irregular angulated Irregular angulated

nucleinuclei Keratinized cytoplasmKeratinized cytoplasm Sharp cytoplasmic Sharp cytoplasmic

borderborder Prominent tumor Prominent tumor

diatheses and necrosisdiatheses and necrosis

► Poorly differentiatedPoorly differentiated Less keratinization, Less keratinization,

nuclear angularity and nuclear angularity and pyknosispyknosis

Indistinct cell bordersIndistinct cell borders Coarsely textured Coarsely textured

chromatinchromatin Prominent nucleoliProminent nucleoli

SCCSCC

Uncommon Tumors of the Uncommon Tumors of the EsophagusEsophagus

► Verrucous carcinomaVerrucous carcinoma Pushing rather than infiltrative margins, need to Pushing rather than infiltrative margins, need to

examine the base of the tumorexamine the base of the tumor

► Adenosquamous carcinomaAdenosquamous carcinoma►MECMEC► Basaloid carcinomaBasaloid carcinoma► Adenoid cystic carcinomaAdenoid cystic carcinoma► Small cell carcinomaSmall cell carcinoma

Mimic lymphocytesMimic lymphocytes

StomachStomach

Normal StomachNormal StomachHoneycomb configuration - normal Intestinal metaplasia

StomachStomach

► InfectionsInfections Same as for esophagusSame as for esophagus H. pyloriH. pylori GiardiaGiardia

► RepairRepair►DysplasiaDysplasia► AdenocarcinomaAdenocarcinoma► Endocrine tumorEndocrine tumor►NHLNHL►GISTGIST

H. pyloriH. pylori

► Faintly basophilic s-Faintly basophilic s-shaped rods entrapped shaped rods entrapped in mucus (pap)in mucus (pap)

► Imprint and brushing Imprint and brushing cytology specimens are cytology specimens are equivalent to H&E equivalent to H&E sections in sensitivity sections in sensitivity (88%) and specificity (88%) and specificity (61%)(61%) Rapid resultsRapid results Inexpensive compared Inexpensive compared

with biopsywith biopsy

Dysplasia and Gastric Dysplasia and Gastric AdenomasAdenomas

► Similar appearanceSimilar appearance► Precursor lesions to carcinomaPrecursor lesions to carcinoma► ““dysplasia” = flat, “adenoma” = polypoiddysplasia” = flat, “adenoma” = polypoid► Both are rare in USBoth are rare in US► Features:Features:

Cohesive 3D clustersCohesive 3D clusters Uniformly enlarged nucleiUniformly enlarged nuclei Increased NC ratioIncreased NC ratio Crowded but regular nuclear spacingCrowded but regular nuclear spacing Absent or inconspicuous nucleoliAbsent or inconspicuous nucleoli

AdenocarcinomaAdenocarcinoma

► Cellularity and dyshesion more than dysplasiaCellularity and dyshesion more than dysplasia► Intestinal typeIntestinal type

Resembles typical colorectal and esophageal Resembles typical colorectal and esophageal adenocarcinomasadenocarcinomas

► Diffuse (signet ring cell type)Diffuse (signet ring cell type) Difficult to sample with brush unless ulceration is Difficult to sample with brush unless ulceration is

present because of infiltrative behaviorpresent because of infiltrative behavior►Reactive atypia will be present and may complicate Reactive atypia will be present and may complicate

diagnosisdiagnosis

Signet ring cells can look bland and be confused Signet ring cells can look bland and be confused with histiocyteswith histiocytes

Gastric AdenocarcinomaGastric AdenocarcinomaIntestinal TypeIntestinal Type

► Large cancer cellsLarge cancer cells► Cuboidal or columnar Cuboidal or columnar

configurationconfiguration► Loosely structuredLoosely structured► 3D clusters3D clusters► Enlarged pale nucleiEnlarged pale nuclei► Irregular nuclear Irregular nuclear

membranemembrane► HyperchromasiaHyperchromasia► Coarse chromatinCoarse chromatin

Gastric AdenocarcinomaGastric AdenocarcinomaDiffuse TypeDiffuse Type

► Small inconspicuous Small inconspicuous cellscells

► Large nucleiLarge nuclei►HyperchromaticHyperchromatic► Conspicuous Conspicuous

nucleolinucleoli► Scanty cytoplasmScanty cytoplasm

Gastric AdenocarcinomaGastric AdenocarcinomaSignet Ring Cell TypeSignet Ring Cell Type

► Large sizeLarge size► Large cytoplasmic Large cytoplasmic

vacuoles push nuclei vacuoles push nuclei to peripheryto periphery

► Large hyperchromatic Large hyperchromatic nucleinuclei

► Irregularly shaped Irregularly shaped nuclear membranenuclear membrane

► Large irregular Large irregular nucleolinucleoli

Endocrine Tumors Endocrine Tumors (including carcinoid)(including carcinoid)

►Derived from diffuse endocrine system Derived from diffuse endocrine system of GI tractof GI tract

►Used to be called “neuroendocrine” Used to be called “neuroendocrine” because of presumed derivation from because of presumed derivation from neural crest cellsneural crest cells Found not to be true, now called Found not to be true, now called

“endocrine” instead of “neuroendocrine”“endocrine” instead of “neuroendocrine”

GI Endocrine Tumors – GI Endocrine Tumors – WHO ClassificationWHO Classification

►Well-differentiated endocrine tumorsWell-differentiated endocrine tumors►Well-differentiated endocrine carcinomasWell-differentiated endocrine carcinomas

Size, site, local invasion, angioinvasion, Size, site, local invasion, angioinvasion, metastasesmetastases

► Poorly differentiated endocrine (small cell) Poorly differentiated endocrine (small cell) carcinomascarcinomas

► Found in the appendix, ileum, rectum and Found in the appendix, ileum, rectum and stomach stomach

► 1% of all gasstric malignancies1% of all gasstric malignancies► Cytologic specimens rarely obtained from Cytologic specimens rarely obtained from

ileum, rectum and appendixileum, rectum and appendix

Lymphomas of GI TractLymphomas of GI Tract

►NHL second most common malignancy NHL second most common malignancy of stomachof stomach 5% of all gastric malignancies5% of all gastric malignancies

►MALTMALT Low grade, high grade (transformed from Low grade, high grade (transformed from

LG)LG)

►Large cell lymphomasLarge cell lymphomas►Small cell lymphomasSmall cell lymphomas

Stomach - GISTStomach - GIST

►Submucosal locationSubmucosal location Accessible via EUS FNAAccessible via EUS FNA

►Ddx includes leiomyoma and Ddx includes leiomyoma and leiomyosarcomaleiomyosarcoma

►C-kit needed on cell blockC-kit needed on cell block

GISTGIST

► Cellular specimensCellular specimens► Irregularly outlined clusters of cellsIrregularly outlined clusters of cells► Spindle shaped or epithelioidSpindle shaped or epithelioid► Wispy cytoplasm with long extensionsWispy cytoplasm with long extensions► Mitoses, necrosis (occasionally)Mitoses, necrosis (occasionally)

DuodenumDuodenum

DuodenumDuodenum

► InfectionsInfections GiardiaGiardia MicrosporidiaMicrosporidia CryptosporidiaCryptosporidia

►AdenomaAdenoma►adenocarcinomaadenocarcinoma

InfectionsInfectionsGiardia Cryptosporidia

Microsporidia

Extrahepatic Biliary TractExtrahepatic Biliary Tract

Extrahepatic Biliary TractExtrahepatic Biliary TractTypes of SpecimensTypes of Specimens

►Washings and brushingsWashings and brushings►Exfoliated bileExfoliated bile►Rinses from biliary stentsRinses from biliary stents

►ERCPERCP►PTCPTC

More sensitiveMore sensitive

Extrahepatic Biliary TractExtrahepatic Biliary TractIndicationsIndications

►Biliary strictureBiliary stricture► Identification of infectious agentsIdentification of infectious agents

AFBAFB MicrosporidiaMicrosporidia GiardiaGiardia

►PSC vs. neoplasmPSC vs. neoplasm

Normal Normal Honeycomb arrangement Reactive/Inflammatory atypia

Features of MalignancyFeatures of Malignancy

► Increased N/C ratioIncreased N/C ratio► Chromatin clumpingChromatin clumping►Nuclear molding, Nuclear molding,

loss of loss of honeycombinghoneycombing

ColonColon

Colon CytologyColon Cytology

►Not commonNot common►Colonoscopy with biopsy has replaced Colonoscopy with biopsy has replaced

brushings for diagnosis of IBD and brushings for diagnosis of IBD and colitiscolitis

►Diagnosis of dysplasia is controversial Diagnosis of dysplasia is controversial on cytologyon cytology

►Cannot tell behavior of lesion on Cannot tell behavior of lesion on cytology (invasive vs. superficial)cytology (invasive vs. superficial)

Which is benign?Which is benign?A B

C D