EUS AND FNA IN INFLAMMATORY AND EUS AND FNA IN INFLAMMATORY AND CYSTIC PANCREATIC PATHOLOGY CYSTIC PANCREATIC PATHOLOGY

Enrique Enrique VVaazquezzquez--Sequeiros MD, PhDSequeiros MD, PhD

Gastroenterology Service. University Hospital RamGastroenterology Service. University Hospital Ramóón y Cajal. Madrid.n y Cajal. Madrid.

2nd European Meeting EGEUS European Group for Endos copic Ultrasonography

14th – 15th september, 2007 – Torino, Lingotto Congre ss Center

PERIGASTRIC REGION

Pancreas >

Stomach

PERIDUODENAL REGION

Ao

IVC >

Spine

< Pancreas

<< SMA/SMV

< Tail

< Body< Istm

< Head

ECOENDOSCOPESECOENDOSCOPESRadial Radial

DiagnDiagnosticosticLinear Linear FNAFNA

CYSTIC TUMORS OFCYSTIC TUMORS OF PANCREASPANCREAS

MUCINOUS

SEROUS

PSEUDOCYST

CLASSIFICATION PANCREAS CYSTSCLASSIFICATION PANCREAS CYSTS• PSEUDOCYSTS (70-90%)

• CYSTIC NEOPLASMS 10-15%

– SEROUS CYSTOADENOMA

– MUCINOUS CYSTIC NEOPLASMS– INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM (IPMN)

– SOLID PSEUDOPAPILAR NEOPLASM

– CYSTIC ENDOCRINE TUMOR – DUCTAL ADENOCARCINOMA WITH CYSTIC DEGENERATION

– CHORIOCARCINOMA, TERATOMA

• TRUE CYSTS

– POLYCYSTIC DISEASE– SIMPLE (RETENTION) CYST

– DERMOID CYST

• OTHERS: LYMPHOEPITELIAL CYST, ENDOMETRIOSIS CYSTS, MACROCYSTIC CYSTS IN CYSTIC FIBROSIS, PARASITIC CYSTS

Forsmark C. Sleisenger 2002

DifferentialDifferential Diagnosis Pancreas CystsDiagnosis Pancreas Cysts

1.Clinical presentation

2.Morphology (EUS)

3.Cyst aspirate analysis (EUS-FNA)

SEROSUS MUCINOUS PSEUDOCYST

SEROUS CYSTADENOMASEROUS CYSTADENOMA

Serous Cystadenoma

History/Demographics • 32-39% pancreas cysts. • Incidental finding; Female; >60 a.

Structure (Multilocular/Multiseptated/Calcified central scar: Honeycomb pattern)

• Microcystic*: (cysts < 1 cm) • Micro/macrocystic: (cysts < & > 1 cm) • Macrocystic: (cysts > 1 cm)

Wall • Thin (Cuboidal epitelium)

Solid Component • -

Comunicate with Wirsung • -

Cyst aspirate (EUS-FNA) • Content: Serous

• Amylase: -

• Mucin stain: -

Citology: • Cuboidal epitelium • Clear cytoplams PAS+.

• Dx in 50% • CEA: +/-

Prognosis • Benign**

BruggeBrugge WR. N WR. N EnglEngl J Med 2004. Gastroenterology 2004J Med 2004. Gastroenterology 2004

SEROUSSEROUS CYSTADENOMACYSTADENOMA

CYSTIC MUCINOUS TUMORCYSTIC MUCINOUS TUMOR

Mucinous Tumor: Mucinous Cystadenoma/CA

History/Demographics • 10-45% pancreas cysts. • Pancreatitis (+/-); Female; 40-50 y.o.

Structure (Uni*/Oligo/Multilocular/No central scar)

• Macrocystic*: (cysts > 1-2 cm. Mucin secreting cells. Thin septa)

Wall • Thick

Solid component • +/- (suggests malignancy)

Comunicates con Wirsung • +/-

Cyst aspirate (EUS-FNA) • Content: Mucinous, viscous

Citology: • Columnar Epitelium +/- atypia. • Mucin

• Dx in 50%.

• Amylase: +/- • Mucin stain: ++ • CEA: ++ (accuracy: 79%)

Pronosis • Premalignant/Malignant**

BruggeBrugge WR. N WR. N EnglEngl J Med 2004. Gastroenterology 2004J Med 2004. Gastroenterology 2004

CYSTIC MUCINOUS TUMORCYSTIC MUCINOUS TUMOR

INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM

IPMN

History/Demographics • 10-21% pancreas cysts. • Relapsing pancreatitis; Female/Male.

• ¨Ductal epitelium formed by mucin producing cells¨.

• ¨Cystic dilatation of ducts due to obstructing mucin plug¨

Structure • Difuse vs localized.

• Main branch type: (Wirsung: Dilated) Side branch type: (Wirsung: normal;

Side braches: Dilated)

Endoscopy/ERCP/MRI • Mucin protuding from the ampulla • Filling defects in Wirsung:

mucin +/- parietal nodules

Solid component • +/- (suggests malignization)

Comunicates with Wirsung • Arises from Wirsung or side branches

Cyst aspirate (EUS-FNA) • Content: Mucinous

(Cytology: ~ Mucinous cystoadenoma. Dx in 50-60%)

• Mucin stain: ++

Prognosis • Premalignant/Malignant** • Side branch type: better prognosis

INTRADUCTAL PAPILLARY MUCINOUS NEOPLASMINTRADUCTAL PAPILLARY MUCINOUS NEOPLASM

BruggeBrugge WR. N WR. N EnglEngl J Med 2004. Gastroenterology 2004J Med 2004. Gastroenterology 2004

Mucin

Mucin

Wirsung

Papillary projection

INTRADUCTAL PAPILLARY MUCINOUS NEOPLASMINTRADUCTAL PAPILLARY MUCINOUS NEOPLASM (IPMN)(IPMN)

Pseudocyst

History/Demographics • 32-39% pancreas cysts. • History of pancreatitis; Male; 50-60 y.o.

Structure • Unilocular*: (large size cysts) • Septated (+/-)

Wall • Thin (except chronic)

Solid component • +/-

Comunicates with Wirsung • +

Cyst aspirate(EUS-FNA) • Content: Turbid (brown)

Citology:

• Inflammatory cells; no mucin, no epitelial cells.

• Amylase: ++++

• Mucin stain: -

• CEA: +/-

Prognosis • Benign*

INFLAMMATORY CYSTIC LESION: PSEUDOCYSTINFLAMMATORY CYSTIC LESION: PSEUDOCYST

BruggeBrugge WR. N WR. N EnglEngl J Med 2004. Gastroenterology 2004J Med 2004. Gastroenterology 2004

Seudoquistesimple

Simple Pseudocyst

Wirsung >

Stone

Complex Pseudocyst >

Detritus < Varices

<

INFLAMMATORY CYSTIC LESION: PSEUDOCYSTINFLAMMATORY CYSTIC LESION: PSEUDOCYST

Mucinous Serous Pseudocyst

History Pancreatitis (+/-) Incidental Hx Pancreatitis (+)

Demographics 40-50 y.o. Female >60 y.o. Anyone

Structure Unilocular Multilocular Multiseptated

Unilocular

Wall Thick Thin Thin

Solid component +/- - +/-

Comunictes with MPD

+/- - +

Content Mucoid Serous Turbid

Amylase +/- - ++++

Mucin stain ++ - -

CEA* ++ +/- +/-

Diagnostic accuracyDiagnostic accuracy:: 8080--90%.90%. Vazquez Sequeiros E, et al. Curr Gastroenterol 2000

SUMMARYSUMMARY CYSTIC TUMORSCYSTIC TUMORS PANCREASPANCREASH

IST

OR

YM

OR

PH

OLO

GY

CY

ST

AS

PIR

AT

E

van van derder waijwaij LA. LA. GastrointestGastrointest EndoscEndosc 20052005

Systematic RevSystematic Rev

12 12 studies studies

450 450 patientspatients

MANAGEMENT ALGORITHMMANAGEMENT ALGORITHM

Pancreas cyst

History/CT/MRIEUS-FNA

SEROUS CYST MUCINOUS CYST PSEUDOCYST

BENIGN(Tumor)

BENIGN(No tumor)

PREMALIGNANTMALIGNANT

•SURGERY*•FOLLOW-UP: if

•< 3 cm•Poor surg candidate

•THERAPY*•X-Ray

•Endoscopy/EUS•SURG

•FOLLOW-UP*•SURG: if symptoms

•Pancreatitis•Jaundice

Diagnostic accuracyDiagnostic accuracy:: 8080--90%90%

Risk/BenefitRisk/Benefit Risk/BenefitRisk/Benefit

Observe?Observe?

Treat?Treat?TreatTreatCHRONIC PcystCHRONIC Pcyst

((>> 6 6 weeks)weeks)

ObserveObserveTreatTreatACUTE PcystACUTE Pcyst(< 6 (< 6 weeks)weeks)

AsymptomaticAsymptomaticSymptomaticSymptomatic

TECHNIQUE PSEUDOCYST DRAINAGETECHNIQUE PSEUDOCYST DRAINAGE

TTéécnicacnica DrenajeDrenaje PseudoquistePseudoquiste

SURGSURG????Complete stenosisComplete stenosis

Stenosis DilatatioStenosis Dilatationn

++

Endoscopy/EUS/Endoscopy/EUS/

PercutPercutaneousaneous

YesYesPartial stenosisPartial stenosis

Endoscopy/EUS/Endoscopy/EUS/

PercutPercutaneousaneousYesYesNormalNormal

Drainage Drainage ComunicatesComunicates PcystPcystWirsungWirsung

Baron TH. N. Engl. J. Med. 1999Baron TH. N. Engl. J. Med. 1999

TECHNIQUETECHNIQUE PSEUDOCYST DRAINAGEPSEUDOCYST DRAINAGE

PSEUDOCYST DRAINAGEPSEUDOCYST DRAINAGE

• : Gastrointest Endosc. 2005 Sep;62(3):383-9.Links– Comment in:

• Gastrointest Endosc. 2005 Sep;62(3):390-1.

– Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions: a pooled analysis.– van der Waaij LA, van Dullemen HM, Porte RJ.– Department of Gastroenterology, Martini Ziekenhuis, Groningen, The Netherlands.– BACKGROUND: Pancreatic cystic tumors commonly include serous cystadenoma (SCA), mucinous

cystadenoma (MCA), and mucinous cystadenocarcinoma (MCAC). A differential diagnosis with pseudocysts(PC) can be difficult. Radiologic criteria are not reliable. The objective of the study is to investigate the valueof cyst fluid analysis in the differential diagnosis of benign (SCA, PC) vs. premalignant or malignant (MCA, MCAC) lesions. METHODS: A search in PubMed was performed with the search terms cyst, pancrea, andfluid. Articles about cyst fluid analysis of pancreatic lesions that contained the individual data of at least 7 patients were included in the study. Data of all individual patients were combined and were plotted in scattergrams. Cutoff levels were determined. RESULTS: Twelve studies were included, which comprised data of 450 patients. Cysts with an amylase concentration <250 U/L were SCA, MCA, or MCAC (sensitivity 44%, specificity 98%) and, thus, virtually excluded PC. A carcinoembryonic antigen (CEA) <5 ng/mL suggested a SCA or PC (sensitivity 50%, specificity 95%). A CEA >800 ng/mL strongly suggested MCA or MCAC (sensitivity 48%, specificity 98%). A carbohydrate-associated antigen (CA) 19-9 <37 U/mL strongly suggestedPC or SCA (sensitivity 19%, specificity 98%). Cytologic examination revealed malignant cells in 48% ofMCAC (n = 111). DISCUSSION: Most pancreatic cystic tumors should be resected without the need for cystfluid analysis. However, in asymptomatic patients, in patients with an increased surgical risk, and, in patients in whom there is a diagnostic uncertainty about the presence of a PC, cyst fluid analysis helps to determine theoptimal therapeutic strategy.

Table 4 . Suggested management forasymptomatic patients and for patients with anincreased surgical risk with a pancreatic cysticlesion Cyst fluid analysisDiagnosisSuggestedmanagement Cytology: malignantcellsMalignancyConsider resectionCEA > 800 ng/mLMCA, MCACConsider resectionCEA < 5 ng/mLSCA, PCNo resection neededCA 19-9 < 37 U/mLSCA, PCNo resection neededAmylase < 250 U/LNo pseudocystNo endoscopic cystdrainageCEA, Carcinoembryonic antigen; MCA,mucinous cystadenoma; MCAC, mucinouscystadenocarcinoma; SCA, serous cystadenoma;

Líquido del quiste

acuosoviscosoviscosoacuosoFLUIDO

Macrófagos/ cell

inflamatorias/histiocitos

mucinaMg,mucina

Cell cuboideCITOLOGÍA

⇑⇑⇑⇑⇑⇑⇑⇑⇓⇓⇓⇓⇓⇓⇓⇓AMILASA

⇓⇓⇓⇓⇓⇓⇓⇓⇑⇑⇑⇑⇓⇓⇓⇓CA 15.3

⇓⇓⇓⇓⇓⇓⇓⇓≈⇓⇓⇓⇓CA 125

⇑⇑⇑⇑≈≈≈CA 19.9

⇓⇓⇓⇓Ó≈⇑⇑⇑⇑⇑⇑⇑⇑⇓⇓⇓⇓CA 72.4

⇓⇓⇓⇓Ó≈⇑⇑⇑⇑⇑⇑⇑⇑⇓⇓⇓⇓CEA

Seudoquiste

TIMPNQMCaseroso

DrenajeDrenaje PseudoquistesPseudoquistes

221 (2?)1 (2?)NNúúmeromero prpróótesistesis

SSííNo (?)No (?)IrrigaciIrrigacióónn PQPQ

SSííNo (?)No (?)DrenajeDrenaje nasoqunasoquíísticostico

10 Fr10 Fr77--10 Fr10 FrTamaTamaññoo prpróótesistesis

PQ PQ Complejo Complejo

Material Material NecrNecróóticoticoPQ SimplePQ Simple

Baron TH. N. Engl. J. Med. 1999Baron TH. N. Engl. J. Med. 1999

Algoritmo de manejo

TAC ó RMN

Riesgo/beneficio tto quirúrgico

Riesgo ⇓Beneficio⇑

Riesgo ≈Beneficio ≈

Riesgo ⇑Beneficio ⇓

RESECCIÓNQUIRÚRGICA

SEGUIMIENTOTAC/USE

REEVALUAR USE + PAAF

Brugge .N Engl J Med2004

TTéécnicascnicas DrenajeDrenaje PseudoquistePseudoquiste

+++++/+/--++SeguridadSeguridad

++

++++

+/+/--

+/+/--

PercutPercutááneoneo

++++++++EfectividadEfectividad

----FFíístulasstulas CutCutááneasneas

++--VisualizaciVisualizacióónnVasosVasos

++--DcoDco DiferencialDiferencialQuistesQuistes

USEUSEEndoscopiaEndoscopia

EPIDEMIOLOGÍA Y CARACTERÍSTICAS BIOLÓGICAS

= sólidos

Muy Frecuente

<160-70sMCistoadeCAcell-acinar

Muy Frecuente

<160-70sMadeCa.ductalquístico

= sólidos<1050-60s=N.Endocrina quística

Raro<1040sFN.Pseudopapilar sólida

Frecuente21-3360-70s=TIPM

Frecuente10-4550sFNQM

Raro32-3970sFC.Seroso

MALIGNO%EDADSEXOTIPO

Brugge. N Engl J Med2004

Límites marcadores

100?48MCACCitologíamaligna

38949819SCA

PC

CA19.9<37U/mL

75949848MCAMCAC

CEA>800ng/mL

55949550SCA

PC

CEA<5ng/mL

53989844SCA,MCA,MCAC

Amilasa<250U/L

VPN(%)VPP(%)E(%)S(%)DxPto corte

van der Waaij. GastrointestEndosc 2005.

CARACTERÍTICAS MORFOLÓGICAS

Aspirado cell c/ estructuras

papilares, cellblanda núcleo

redondo, glóbulos PAS+, estroma

mixoide,

Detritus necróticosMixta:sólido/fuido/hemorragia

Neoplasia pseudopapilar sólida

Mucina/cellsvariables/ep.columnar atipia variable

Viscoso/claro/mucina

Macro/microquistes, dilatación

TIPM

Mucina/cellsvariables/ep.columnar atipia variable

Viscoso/claro/mucina

Macroquiste,mg: pared

gruesa/septos

Neoplasia quísticamucinosa

Ep.cuboideassimple, citop.claro

PAS+

Diluido/claro/no mucinoso/hemorra

gico

Microquiste/panal

C.seroso

CITOLOGÍAFLUIDOECO/TACCARACTERÍSTICAS

CITOLOGÍAFLUIDOECO/TACCARACTERÍSTICAS

Cellinflamatorias

(PMN/ macrófagos) sin

Diluido, oscuro, opaco, no mucinoso

Unilocular, gruesa pared,

datos pancreatitis

Pseudoquiste

Cilíndrico o cuboidal con gránulos de zimógeno

Diluido/claroMicro/macroCistoadeCa acinar

Celladenocarcinomatosas variadas

Diluido, hemorrágico

Masa con localización adyacente a

colección

AdenoCa ductalquística

Cell pequeñas citoplasma

escaso, núcleo monomorfo

cromatina sal y pimienta

No mucinosoVariableNeoplasia quísticaendocrina

TRATAMIENTO DOLOR VISCERALTRATAMIENTO DOLOR VISCERAL

SNCSNC

SNPSNP

NEUROLISIS PLEXO CELNEUROLISIS PLEXO CELIIACOACOAlcohol/Alcohol/TriamcinolonaTriamcinolona

Gunaratnam NT et al. Gastrointest Endosc 2001Gunaratnam NT et al. Gastrointest Endosc 2001

1

2

3

4

5

6

7

0 2 4 8 12 16 20 24

Time (weeks)

Mea

n P

ain

S

core

s p<0.0005

n = 58n = 58

VASVAS

NEUROLISIS PLEXO CELNEUROLISIS PLEXO CELIIACOACOCCarciarcinoma Pnoma Pááncreasncreas

HIPERTENSION PORTAL

Colaterales >

<

<

<< Pliegues Gástricos

Pseudoquiste

EfectividadEfectividad DrenajeDrenaje PseudoquistesPseudoquistes

USEUSEUSEUSEEndoscopiaEndoscopiaTTéécnicacnica

0%0%InfecciInfeccióónn 48%48%20%20%ComplicacionesComplicaciones((sangrado/infeccisangrado/infeccióónn))

94%94%78%78%90%90%ResoluciResolucióónn PQPQ

91%91%89%89%94%94%ExitoExito ttéécnicocnico

8.5 Fr8.5 Fr7 Fr7 Fr10 Fr10 FrPrPróótesistesis

8 cm8 cm11 cm11 cm10 cm10 cmTamaTamaññoo

35352727437437PacientesPacientes

GiovanniniGiovannini 0101BinmoellerBinmoeller 9595Baron 98Baron 98

Efectividad Drenaje Pseudoquistes

USEEndoscopiaTécnica

0%20%Complicaciones(sangrado/infección)

94%90%Resolución PQ

91%94%Exito técnico

8.5 Fr10 FrPrótesis

8 cm10 cmTamaño

35437Pacientes

Giovannini 01Baron 98

PPááncreas/Benignancreas/Benigna:: Pseudoquiste Pseudoquiste

PSEUDOQUISTEPSEUDOQUISTE

Pseudoquiste simple

Wirsung >

Litiasis

Pseudoquiste > complejo

Detritus

DRENAJE PSEUDOQUISTEDRENAJE PSEUDOQUISTEUSEUSEEndoscopiaEndoscopiaTTéécnicacnica

0%0%20%20%ComplicacionesComplicaciones((sangrado/infeccisangrado/infeccióónn))

94%94%90%90%ResoluciResolucióónn PQPQ

91%91%94%94%ExitoExito ttéécnicocnico

8.5 Fr8.5 Fr10 Fr10 FrPrPróótesistesis

8 cm8 cm10 cm10 cmTamaTamaññoo

3535437437PacientesPacientes

GiovanniniGiovannini 0101Baron 98Baron 98

USE vs CPRE: = efectividad. > Seguridad/< complicaciones

USE: Pacientes con hipertensión portal y/o no compresión de la pared