Cytologia Ecoendoscopica Tracto Esofago-Gastro-Intestinal

Ricardo H. Bardales, MD

Outpatient Pathology Associates &

University of Minnesota

Indications for EUS-FNA

Imaging +/- sampling of any process not

adequately imaged or sampled by more

standard techniques, if it is seated in:

Mediastinum

Upper abdomen

Retroperitoneum

Pelvis

EUS-FNA Technique

Endoscopy: visualization of the gut surface.

Ecography: characterization of the GI wall, adjacent lymph nodes, pancreas, liver, spleen, and left adrenal gland.

FNA: sampling of lesions in various locations.

More cost effective than other modalities.

Higher sensitivity than CT.

EUS-FNA TECHNIQUE

EUS-FNA Lesion Sampling

Real time: there is no delay in the “eco”

transmission, capture, and conversion into

image by the computer.

Needle gauge: 19-25.

The thinner the better

Blood is the worse enemy

Cytology, cell block, and ancillary tests.

Sample collection and

processing

Material sprayed onto

a labeled slide

Air-dried for DQ

EtOH-fixed

Remaining material let

to clot for CB

Further sampling and

triage as needed

PAAF por Ecoendoscopia - Historia

En Donde Esta la Lesion? (1)

LESION LOCALIZACION FRECUENTE

GIST Estomago, intestino delgado

Neoplasias de musculo liso Esofago, estomago

Ca de celulas en anillo sello (difuso) Estomago, esofago

Gastroenteritis eosinofilica Intestino delgado, estomago

Quistes congenitos Esofago, estomago

Pancreas heterotopico Duodeno, estomago

Tumor celulas granulares & Schwanoma Esofago, estomago

Tumores endocrinos Recto, estomago, intestino delgado

Tumor glomus Estomago

Heterotopia - glandulas de Brunner Estomago

Hamartoma – glandulas de Brunner Duodenum

Linfoma Estomago, intestino delgado

En Donde Esta la Lesion? (2)

CAPA DE ORIGEN

Zona de Transicion

PAAF por Ecoendoscopia - Abordaje

Comenzar con aguja 25 g. Bloque celular with 19 g.

EE-PAAF y Patrones Citologicos

Masas Solidas (usualmente hipoecoicas)

Patron fusocelular

Patron epitelioide

Lesiones Quisticas (anecoicas)

Patron quistico

Pliegues Gastricos Engrosados

El Patron Fusocelular

GIST: Aspectos Generales

Fenotipo: celula intersticial de Cajal

Edad media: 60 a. Ligera predominancia mascul

Raro en ninos y neonatos

Localizacion:

Gastrica (65%), intestino delgado (25%),

esofago, recto, mesenterio, omento (10%).

EE: hipoecoico, adherido a la muscular propria

Conducta impredecible

Gastrico: 10% a 30% malignos

Otros: 50% malignos (omento, higado, peritoneo) Kirsch R. et al. Adv Anat Pathol 2007;14:261.

Fasciculos o remolinos cortos

GIST – Fusocelular (70%)

GIST – Fusocelular

Celulas uniformes – bordes indistintos – Fondo fibrilar

GIST – Fusocelular

Empalizada nuclear ~ Schwannoma

Nucleos – alargados, ovoides, hiperchromasia.

Vacuolas yuxtanucleares – GIST gastrico

GIST – Fusocelular

GIST - Inmunofenotipo

c-kit/CD117 membranoso

CD34

Leiomioma

Comun: esofago – Paucicelulares

Citoplasma eosinofilico - Nucleos blandos - raras mitosis

Stelow EB et al. A, J Clin Pathol 2003;119:703.

Leiomioma versus Normal

Leiomioma versus GIST

LEIOMIOMA GIST

GIST versus Leiomioma

GIST Leiomioma

Organo >estomago >esofago

Celularidad Mayor Menor

Ocasionales

celulas sueltas

Likely Unlikely

Ocasionales

nucleos sueltos

Probable Improbable

Atipia - mitosis Puede estar presente Ausente

Epithelioid cells Pueden estar presentes Ausente

Bloque cel - IHC Basofilico – CD117+ Eosinofilico – Actina+

Stelow EB et al. A, J Clin Pathol 2003;119:703.

Schwannoma

Mas comun: estomago, muscularis propria - Hipoecoico

Benigno. Puede ser grande y con mitosis (<5/HPF) Stelow EB et al. Diagn Cytopathol 2004;30:172. Miettinen M et al. Am J Surg Pathol 2001;25:846.

Schwannoma

Fusocelular/Epitelioide: 3/1 – Empalizada nuclear vaga – Carece

de cuerpos de Verrocay – linfocitos – Semeja al GIST

Duodenal LG-NET (21 x 18 mm)

Duodenal LG-NET (21 x 18 mm)

Synaptophysin

Spindle Cell Tumors of the Gut GIST Smooth

Muscle

Tumors

Schwannoma SFT Mesenteric

Fibromatosis

Neuroendocr

ine Tumor

c-kit/

CD117

+ diffuse

membran

- - - Variable weak

(Ab-depend)

-

CD34 + diffuse

(70%)

+ (10%) Rare focal + - -

SMA Variable

focal

+ - Variable focal

-

S-100

protein

+ (5%)

- + - -

Chromo

Synapto

- - - - - +

beta-

catenin

- + nuclear -

Yamaguchi U, et al. Virchows Archiv. 2004;445:142.

Montgomery E, et al. Am J Surg Pathol 2002;26:1296.

Abraham SC. Adv Anat Pathol 2007;14:178.

Fletcher CDM, et al. Hum Pathol 2002;33:459.

Greenson JK. Mod Pathol 2003;16:366.

Stelow EB, et al. Am J Clin Pathol 2008;129:219

Tumores Fusocelulares Raros? Tumor fibroso calcificante del estomago

(Agaimy AM et al. Am J Surg Pathol 2010;34:271)

Colageno estoriforme + Calcio + celulas inflamatorias

Cavidad abdominal y tejidos blandos

CD117, SMA, S100, h-caldesmon, PDGFRA (-)

Puede mostrar focal CD34+

Fibromixoma plexiforme

(Miettinen M et al. Am J Surg Pathol 2009;33:1624)

Todos en el antro gastrico

Elementos fibromixoides

Actina muscular (+), variable CD10

CD117, DOG1, CD34, desmin, proteina S100 (-)

MFH primario y metastatico

(Agaimy A et al. Virchows Arch 2007;451:949)

Actina and PDGFRA (+); CD117, CD34, S100 (-)

GIST del Colon (n=37)

Fusocelular/Epitelioide: 9/1. Edad promedio 67 a.

CD117(+) 76%; CD34(+) 59%. mutacion c-kit 36%

Diagnostico tardio: tipicamente transmural

4 casos: ≤1 cm – hallazgo incidental – no recurrencia

10 casos: ≥1 cm & mitosis ≤5/50 HPF – muerte 20%

23 casos: ≥1 cm & mitosis ≥5/50 HPF – muerte ~ 100%

Leiomiosarcomas (n=7): CD117(-), CD34(-), SMA(+), desmin (+), no mutacion gen c-kit .

GIST del colon mitoticamente activo (>5/50) parece ser mas letal que el leiomiosarcoma con similar

actividad mitotica. Miettinen M et al. Am J Surg Pathol 2000;24:1339

Leiomiosarcoma

SMA

GIST – Riesgo de Conducta Agresiva – Consenso*

Tamano (cm) Mitosis por 50 HPF

Riesgo muy bajo <2 <5

Riesgo bajo 2-5 <5

Riego intermedio <5

5-10

6-10

<5

Riesgo alto >5

>10

Cualquier tamano

>5

Cualquier cuenta mitotica

>10

* NIH – Abril 2001 Fletcher CDM, et al. Hum Pathol 2002;33:459. Blay J-Y, et al. Ann Oncol 2005;16:566.

GIST: Predictores de Malignidad

Tamano Proliferacion celular [Cuenta mitotica

Indices (Ki-67 >10%), p53]

*p16, *ezrin, apoptosis baja, telomerasa alta, marcadores de angiogenesis (MVD,

*VEGF)

Localizacion La gran mayoria de GISTs de riesgo muy bajo, bajo, e

intermedio se comportan de manera benigna.

Existe un subgrupo (~10%) que se comporta agresivamente. Corless CL. AJCP 2004;122:11. Wei Y-C, et al. Mod Pathol 2009;22:1351.

Fletcher CDM, et al. Hum Pathol 2002;33:459. Steigen SE at al. Mod Pathol 2008;21:46. Wang Q et al. World J Gastroenterol 2007;13:2626. McAuliffe JCA et al. Clin Cancer Res 2007;13:6727.

Mercado de Pisac – Cerca a Cuzco - Peru

Patron Epitelioide de Celulas Grandes

Anisocitosis y anisonucleosis

Raras mitosis

GIST – Epitelioide (20%)

GIST - Epitelioide

Nucleos uniformes ovoides a redondos – cromatina vesicular

Celulas redondas – citoplasma variable eosinofilico o claro

GIST – Epitelioide

GIST - Epitelioide

c-kit/CD117

Inmunomarcadores del GIST

CD117, CD34

*CD171 (L1): molecula de adhesion celular

*DOG1: proteina de funcion desconocida

*Expresados independientemente de c-kit or PDGFRA y

Son utiles en el diagnostico de CD117(-) GISTs

Rosai, J. Int J Surg Pathol 2010 (supl) 18;79S-87S Lee C-H et al. Adv Anat Pathol 2010;17:222

Tumor de Celulas Granulares

Mas comun: esofago distal, submucosa – Mayormente

benigno - EE: hipoecoico Stelow EB et al. Diagn Cytopathol 2004;30:172.

Tumor de Celulas Granulares

PAS(+), S100 protein(+), CD117(-), CD34(-), actina(-)

TUMOR de CELULAS

GRANULARES CELULAS PARIETALES

Pancreas Heterotopico

Estomago & duodeno

Esofago: t18, t13

Endoscopia: nodulo umbilicado

EE-PAAF: rara aspiracion

Celulas ductales y acinares

Quistico: celulas ductales (adenomioma) citodiagnostico es dificil

Rodriguez FJ et al. Diagn Cytopathol 2004;31:175

Linfomas del Tracto GI

Primarios: raros

Estomago:

H=M. Tercera edad

Bx forceps: no es Dx.

PAAF-EE: 25 g

Examenes especiales

DLBL = PAAF-EE Dx

EMZL = Biopsia

Kolve ME et al. Recent Results Cancer Res 2000;156:63.

Janssen J. Best Pract Res Clin Gastroenterol 2009;23:671.

Hiper o hipoecoico

Engrosamiento de capas 3, 4 o ambas

Linfoma a Celulas Grandes

Cancer Gastric Difuso (CGD)

Incidencia mundial de CG es menor. CGD esta aumentando

La expression de E-cadherina es el principal discriminador entre GCI y CGD.

CDH1 codifica E-cadherin, una glicoproteina transmembrane, critica para la adhesion intercelular.

La mayoria del CGD esporadico y hereditario no expresan E-cadherina

Perdida de E-cadherin = invasividad = metastasis

CGDH tiene mutaciones en el genCDH1

Autosomico dominante. Pacientes jovenes. Gastrectomia profilactica

Tumores No-primarios

LOBULAR CA RCC

MELANOMA AMMoL

Tumores Epitelioides Raros?

PEComa (benigno y maligno)

Estomago, duodeno, colon

Celulas epitelioides eosinofilicas

HMB45+, Actina+, desmin+, vimentin+, Melan A variable

Proteina S100 (-)

Puede ocurrir en pacientes con esclerosis tuberosa

Sarcoma sinovial

Esofago, estomago, duodeno

Monofasico o bifasico (epitelioide & fusocelular)

Epitelioide: CK+, EMA-. Fusocelular: Vimentina+, CD10+.

Ambos: CD117-, CD34-, S100-, Actina muscular-, Desmina-

Citogenetica: translocacion X;18.

Mitteldorf CA et al. World J Gastroenterol 2010;16:522. Makhlouf HR et al. Am J Surg Pathol 2008;32:275.

PEComa

Patron Epitelioide a Celulas Grandes

GIST Linfoma Carcinoma Tumor Celulas

Granular

Melanoma

Citologia Componente fusocelular

variable

Disociacion celular

Agregados & celulas sueltas

Citoplasma granular

Pleomorfico

CD117 + - - - +

CD34 + - - - -

CD45 - + - - -

Keratin - - + - -

Proteina S100

- - - + +

HMB45 - - - - +

Macchu Picchu – Cuzco - Peru

Patron Epitelioide a Celulas Pequenas

Tumores Endocrinos GI

Submucosos

Comunes en el intestino distal

Somatostatinomas, gastrinomas, carcinoide

Hipoecoicos

Gastrinoma

Rosetas – celulas redondas/ovales – plasmacitoides,

cromatina “sal y pimienta” – nucleolos inconspicuos

GI LG-NETs: Location

Ileum 31%

Rectum 21%

Appendix 18%

Colon 12%

Stomach 6%

Duodenum 4%

Jejunum 3%

Turaga KK and Kvols LK. CA Cancer J Clin 2011:61:113-132.

Recommendations WHO based on ENETS

Endocrine and neuroendocrine terms can be used interchangeably

All WD-NENs be termed NETs (Ns = Ts)

The term NECa is reserved to poorly differentiated neoplasms (HG small and large cell NE neoplasms)

Nomenclature for GI-NETs (WHO,ENETS)

LOW GRADE Neuroendocrine tumor grade 1 (G1)

INTERMEDIATE GRADE

Neuroendocrine tumor grade 2 (G2)

HIGH GRADE Neuroendocrine carcinoma grade 3 (G3)

GI-NETs, gastrointestinal neuroendocrine tumors; WHO, World Health Organization; ENETS, European Neuroendocrine Tumor Society

Kilmstra DS. Semin Oncol 2013; 40:23-36.

GI-NETs Grading System (WHO,ENETS)

LOW <2 mitoses/10 hpf, AND Ki67 index <3%

INTERMEDIATE 2-20 mitoses/10hpf, OR Ki67 index 3%-20%

HIGH >20 mitoses/hpf OR Ki67 index >20%

WD

PD

WD, well-differentiated; PD, poorly-differentiated; GI-NETs gastrointestinal neuroendocrine tumors; WHO, World Health Organization; ENETS, European Neuroendocrine Tumor Society

Kilmstra DS. Semin Oncol 2013; 40:23-36.

Antro gastrico

Tercera edad

Benigno, solitario

Celulas de musculo liso modificadas del cuerpo glomico

Debol SM et al. Diagn Cytopathol 2003;28:316.

Gu M et al. Diagn Cytopathol 2002;46:560.

Vinette-Leduc D et al. Diagn Cytopathol 2001;24:340.

Tumor Glomus

Tumor Glomus

Celulas pequenas, nucleo uniforme, no mitosis

Tumor Glomus

IHQ: SMA (+), Desmina (-), vimentina (+), keratina (-)

Linfoma MALT

Reactivo

Patron Epitelioide a Celulas

Pequenas TUMOR

ENDOCRINO

GIST

EPITELIOIDE

TUMOR

GLOMUS

LINFOMA

Agregados y celulas

sueltas (usualmente

pequenas). Rosetas.

Moderado

citoplasma.

Cromatina

sal/pimienta

Agregados y

celulas sueltas

(usualmente

grandes).

Cromatina

gruesa. Cytopl

abundante.

Agregados y

celulas sueltas

(usualmente

pequenas).

Nucleos

homogeneos e

hipercromaticos.

Predominan

celulas sueltas

irregulares

monomorphic

(usualmente

grandes).

Cromogranina (+)

Sinaptofisina (+)

NSE (+). Keratin (+)

CD117 (+)

CD34 (+)

CD117(-). Actina

(+), Calponina

(+), H-

caldesmon (+),

Vimentina (+)

Marcadores de

celulas B & T

Debol SM et al. Diagn Cytopathol 2003;28:316. Miettinen M et al. Am J Surg Pathol 2002;26:301.

El Patron Quistico

Quistes/Duplicaciones Congenitos

Ectopia del intestino anterior o posterior

EE: anecoico

Esofagico: tercio distal, intramural o extrinsico

Gastrico: curvatura mayor > menor, piloro

Ponder TB et al. Acta Cytol 2001;47:201.

Van Dam J et al. Am J Gastroenterol 1992;87:762.

Eloubeidi MA et al. Cancer 2004;102:253.

Quiste por Duplicacion del Intestino

Anterior

Raro – Semeja neoplasia – A menudo asintomatico

Epitelio: escamoso, ciliado, columnar

Distincion del quiste bronquial puede ser dificil

Imagen: a lo largo del arbol TB posterior a la carina.

Histologia: pared con doble capa de musculo liso. Sato MA et al. J Clin Ultrasound 2007

Wang B et al. Acta Cytol 2009;53:219

Pliegues Gastricos Gruesos

Diagnostico Diferencial:

Malignidad: Linitis plastica, linfoma zona marginal

Granulomatosos: Crohn’s, sarcoidosis, sifilis

Hiperplasia epithelial: gastropatias (Menetrier, Zollinger-Ellison)

Gastroenteritis eosinofilica

Linitis Plastica

EE: engrosamiento de la capa 3 y a menudo capa 4

Estomago (comun), recto, esofago distal

Primario o metastatico (mama, prostata, vejiga)

Compromiso locoregional frecuente:

EE mejor que CT

EE paracentesis

Gleeson FC et al. Gastrointest Endosc 2008;68:591.

Carter JE et al. Acta Cytol 2008;52:725.

DeWitt J et al. Clin Gastroenterol Hepatol 2007;5:609.

Linitis Plastica

Hipocelular, pequenos grupos – celulas en anillo de sello

Sobrevida: pobre - Cirugia: raramente curativa

Carcinomatosis Peritoneal en

Linitis Plastica Gastrica Lavado peritoneal al momento de la

laparotomia.

47 pacientes: candidatos para una reseccion curativa.

Carcinomatosis peritoneal Diagnostico citologico

Diagnostico molecular: quantificacion del CEA mRNA por RT-PCR

Curso clinico: carcinomatosis peritoneal en la laparotomia o seguimiento clinico.

RT-PCR muestra compromiso de la cavidad abdominal en ~80% pacientes.

Los resultados explican poque la cirugia es raramente curativa en pacientes con linitis plastica gastrica

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

Peritoneal

involvement

Cytology

CEAmRNA

Clinicalcourse

Kodera Y et al. Jap J Clin Oncol 2004;34:525.

20

39 36

EE-PAAF versus Biopsia Forceps

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

Diagnostic Accuracy

Forceps Biopsy

EUS-FNA

Masas Intramurales del Tracto GI Lesions

Vander Noot MR et al. Cancer 2004;102:157.

Polkowski M et al. Gastrointest Clin N Am 2005;15:33.

Hoda KM et al. Gastrointest Endosc 2009;69:1218.

60%

89%

Cytologia Ecoendoscopica Mediastino y Estadiaje Tumoral

Ricardo H. Bardales, MD

Outpatient Pathology Associates &

University of Minnesota

LN EUS-FNA: Sample Triage

SAMPLE NON-DIAGNOSTIC DIAGNOSTIC

INFECTIOUS LYMPHOID NON LYMPHOID

CULTURES

c/w KNOWN 1

STOP

NOT c/w KNOWN 1

UNKNOWN 1

CELL BLOCK

FOR IHC

FLOW CYTOMETRY

CYTOGENETICS

OTHER Stelow EB et al. Diagn Cytopathol 2004;30:301.

EUS-FNA & Mediastinal

Adenopathy of Unknown Etiology

Common isolated mediastinal abnormalities: Benign: sarcoid, TB, histoplasmosis Malignant: metastatic cancer, lymphoma

EUS-FNA is safe, accurate, and the most cost effective non surgical technique. Alters the w/u & therapy in 75% of patients

Mediastinoscopy and transtracheal biopsy Better access to the upper and anterior

mediastinum

Infectious Lymphadenopathy

Geography dependent. At HCMC TB and histoplasmosis.

Fungal and Mycobaterial stains.

Histoplasmosis

Infectious Lymphadenopathy

CRYPTOCOCCUS TUBERCULOSIS

EUS-FNA & Sarcoidosis

5% mediastinal LNs

Scant cellularity

“Tight” granulomas

Damaged cells

Often lacks necrosis

Always send cultures

Sensitivity 94%

Specificity 100%

Mishra G et al. Endoscopy 1999;31:377.

Fritscher Ravens A et al. Chest 2000;118:928.

EUS-FNA & Lymphoma

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

EUS-FNA only EUS-FNA + Ancillary

Tests

Sensitivity

Specificity

Accuracy

74%

93%

81%

44%

90%

68%

Ribeiro A et al. Gastrointest Endosc 2001;53:485.

REACTIVE LYMPHOMA

Mediastinal Large Cell B-Cell NHL

F>M 2nd to 3rd decade - Monomorphic large cells: single, clusters

– less cells and damaged if sclerosis

~ epithelial malignancy - ~ HD, syncytial variant – less cellular

EUS-FNA - Ancillary studies – Definitive diagnosis

Mediastinal Hodgkin Lymphoma

Nodular sclerosing variant

Scant cellularity; cell degeneration

~ reactive hyperplasia

~ granulomatous infection

~ germ cell tumor – more cellular

~ anaplastic lymphoma – more cellular

Syncytial variant

~ metastasis

Hodgkin Lymphoma: SV

Mediastinal Masses

Other Mediastinal Masses

Thymoma – anterosuperior

Thymic cyst – anterosuperior

Thyroid/parathyroid –anterosuperior

Germ cell – anterior, middle

Foregut cyst – middle

Neurogenic – posterior

Paraganglioma – posterior

Mesenchymal – posterior

Metastasis – anterior, middle

Nodal Staging by EUS

N0 N1

<1 cm Size >1cm

Less hypoechoic Echogenicity Hypoechoic

Oval, flat Shape Round

Poor Demarcation Sharp

EUS-FNA & Mediastinal Adenopathy

Probability of Malignancy

Patients with history of extrathoracic primary

Diagnostic sensitivity is slightly better

Metastasis from such a source is likely

Patients without history of malignancy

Benign or malignant diagnosis equal proportion

If malignant diagnosis: lung primary is diagnosed in >80% cases

Kramer H et al. Eur J Cancer 2004;40:559.

Fritscher-Ravens A et al. Am J Gastroenterol 2000;95:2278.

NSCLC

Subcarinal Lymph Node

Lung Cancer Staging

N1

Ipsilateral peribronchial

and/or hilar

N2 Ipsilateral mediastinal

and/or subcarinal

N3 Contralateral

Cervical, supraclavicular

CA

STAGE

IIIB

IIIA

NSCLC: Mediastinal LN Staging

COST

EUS+FNA = $1,975

Mediastinoscopy = $7,759

Thoracotomy = $26,028

0%

50%

100%

Accuracy

EUS

CT

EUS-FNA

Gress F et al. Ann Intern Med 1997;127:604.

Tournoy KG et al. Am J Respir Crit Care Med 2007

Micames CG et al. Chest 2007;131:539.

84

49

96

High diagnostic yield and accuracy,

detects occult metastasis, avoids

unnecessary surgery, has less

complications, and cost effective.

EUS-FNA in NSCLC Staging

N=40 patients in whom mediastinal exploration was required. Randomized to have EUS-FNA (n=19) or surgical staging (SS) (n=21).

Sensitivity:

EUS-FNA: 93%. Surgical staging: 73%

Complications: 0% EUS-FNA vs 5% SS.

Hospital stay: 0 EUS-FNA vs 2 nights SS.

“EUS-FNA reduces the need for SS in patients with lung cancer in need for mediastinal exploration.”

Tournoy KG et al. Am J Respir Crit Care Med. 2007.

EUS-FNA, CT & PET in NSCLC

Staging

113 patients with NSCLC

Diagnostic accuracy EUS-FNA CT PET

Mediastinal LNs 93% 81% 83%

Distant Metastasis 97% 89%

Celiac LN (n=11) 100% 50%

•EUS-FNA as first test has high diagnostic yield and accuracy for detecting

lung cancer metastasis to mediastinum and distant sites.

•EUS-FNA able to detect <1 cm metastasis often missed by CT.

•EUS-FNA avoided thoracotomy in 14% cases.

Singh, P. Am J Respir Crit Care Med. 2007;175:345.

EUS-FNA in NSCLC Staging

Medline, CINAHL, and citation indexing

Metaanalysis to estimate pooled sensitivity and specificity.

Patients with…. Sensitivity Especificity

Mediastinal LNs (18 studies) 83% 97%

Mediastinal LNs + by CT (8 studies) 90% 97%

Mediastinal LNs – by CT (4 studies) 58%

•Minor complications in 10 cases (0.8%).

•EUS-FNA is highly sensitive to confirm metastasis to mediastinal

LNs seen by CT.

•Potential to prevent unnecessary surgery in cases with (-) CT scan.

Micames CG et al. Chest 2007;131:539.

EUS-FNA & EBUS-TBNA in

Mediastinal Lymph Nodes

EUS-FNA (Posterior Mediast)

EBUS-TBNA (Anterior Mediast)

Both

Sensitivity >90% >90% 100%

Specificity 100% 100% 100%

Accuracy

In other study: EUS-FNA had 82% sensitivity and 80% specificity. When combined with EBUS-TBNA: accuracy was 100%.

Both techniques are complementary and may replace more invasive methods for diagnosing and staging NSCLC.

Vilmann P et al. Endoscopy 2005;37:833.

Vilmann P & Puri R. Minerva Med 2007:98:331.

Guidelines & New Proposed Classification of Lung ACA

Term NSCLC in not acceptable

Either ACA or SqCC… we need

Cytologic or tissue (CB) diagnosis and

Molecular characterization: EGFR and ALK

To provide targeted therapy

EGFR mut = ACA = Tx TKI (gefitinib, erlotinib)

ALK rearrang = ACA = Tx crizotinib

Travis WD et al. J Thorac Oncol 2011;6:244-285.

EGFR & ALK Alterations Detection Cytologic material … IHC as screening; if (-) do

PCR for EGFR or FISH for ALK….. PROMISING

Molecular testing: expensive and complex

Immunohistochemistry: cheap, widely used, easily available in a laboratory

Abs to EGFR exons: 19 deletion and 21 mutation. 92% sensitivity and 99% specificity

Abs to ALK rearrangements…

Moreira AL and Hasanovic A. Acta Cytol 2012;56:603

Esophageal Cancer Staging

T1 T2 T3 T4

T: EUS is the only imaging modality that can image wall layers

N: Majority of nodal regions visualized

M: Limited (cannot assess bone, lung, and lateral 1/3 liver)

Esophageal Nodal Staging

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Regional Celiac

EUS sensitivity

EUS-FNA accuracy

CT sensitivity

Vasquez-Sequeiros E et al. Gastrointest Endosc 2001;53:751.

Eloubeidi MA et al. Gastrointest Endosc 2001;54:714.

63%

93%

54%

77%

100%

54%

Subcarinal Lymph Node

ER

EUS-TCB & EUS-FNA in Thoracic Lesions

EUS-FNA EUS-TCB FNA + TCB

Adequacy 63% - 96% 89% 97%

Accuracy 74% - 79% 68% - 79% 98%

Complications 0.6%

EUS-FNA/TCB improves adequacy of sampling and accuracy compared with either technique alone and it is safe.

TCB appears to be better in benign conditions.

EUS-FNA & TCB are complementary and may prevent unnecessary invasive procedures.

Wittmann, J et al. Cytopathology 2006;17:27.

Storch I et al. Surg Endosc 2008;22:86.

How Many “Passes”?

Diagnostic Material 80% in the first pass, “100%” in 3 passes

Wallace et al, DDW 2000

Lymph node involvement can be focal

Hamada, et al. Br J Radiol 1997

EUS-FNA & LN Metastasis

Sensitivity 90%, specificity 100%.

Suction: ↑cellularity but not accuracy

LN site (edge vs center) doesn’t ↑accuracy

Excess blood when <25 g needle

Cytospin or CB add little diagnostic info (except for IHC)

On-site cytologic assessment and sample triage are of paramount importance.

Stelow EB et al. Diagn Cytopathol 2004;30:301.

Wallace MB et al. Gastrointest Endosc 2001;54:441.

EUS-FNA NODAL SAMPLING

EUS visualizes most mediastinal, superior abdominal, and retroperitoneal lymph nodes.

Sonographic criteria are good EUS-FNA increases accuracy and specificity.

Lymph node sampling ( 3 passes): Flow cytometry.

Cytogenetics.

Microbiology.

Serious complications: not reported.

Gastrointest Endosc 2003; 58:819-821

EUS-FNA Lymph Nodes:

Complications

Author N Comp

Wiersema (1995) 192 0

Vilmann (1995) 14 0

Bhutani (1997) 35 0

Gress (1997) 24 0

Fritscher-Ravens (2000) 153 0

O’Toole (2001) 62 0

Overall 480 0

Gracias!!!

Cytology Michael W. Stanley, M.D. HCMC Cytology Gastroenterology Shawn Mallery, M.D. Rebecca Lai, M.D

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AERIAL VIEW