“Lymph node FNA: the multiparametric approach”

The XXXII International Academy of Pathology Congress

Dead Sea, Jordan, October 14-18, 2018

Mousa Al-Abbadi, MD, CPE, CPHQ, FCAP, FIACProfessor of Pathology & Cytopathology

University of Jordan

I declare No conflict of interest

Baig & Al-Abbadi..et al Cytojournal. 2006 Apr 9;3:12

FCM MP CG

CB

RPMI

SalineFormalinEthanol

C&SEM

Sensitivity & specificitySensitivity: 80-90%Specificity: 99-100%Our data:

- FNA performed by non-pathologists: 81% sensitivity and 99% specificity

- FNA by pathologist: 96% sense., 100% spec.

Al-Abbadi & Saleh, CAP annual meeting, Chicago Abstract 2006

Sensitivity & specificitySensitivity: 80-90%Specificity: 99-100%Our data:

- FNA performed by non-pathologists: 81% sensitivity and 99% specificity

- FNA by pathologist: 96% sense., 100% spec.

Al-Abbadi & Saleh, CAP annual meeting, Chicago Abstract 2006

IT IS OPERATOR

DEPENDENT

Diagnostic Possibilities

Benign

Lymph Node FNA

Lymphoid Neoplasm Metastasis

Unsatisfactory Not sure / ???

AM I IN A LYMPH NODE?

Tingible-body macrophage

Lymphoglandular bodies (LGB)

Benign Lesions• Reactive hyperplasia• Inflammatory…Infectious• Inflammatory…Non

Infectious• Benign lymphoid disorders

Reactive LN aspirate

“Granulomas”

Approach to Granulomatous lymphadenitis :

• Triage on site• Immediate smears evaluation• Smears for AFB and other stains• Material sent for culture and PCR• If AFB + ve…cancel PCR and keep

culture• If AFB –ve …proceed with PCR and

culture

Non Hodgkin lymphomaMONOTONY

MONOTONOUS

Ancillary studies help to:• Lymphoid vs non-lymphoid• Clonality (FCM)• Sub classification• Grading (s-phase, DNA, cell size)• Reed-Sternberg cells (IHC)• PCR, Southern Blot A, FISH,

Cytogenetic studies (T-cell)

SLL/CLL

CD19 APC (IgG1)

CD5

PerC

P-cy

5.5

100 101 102 103 104100

101

102

103

104

Anti-Lambda PE Dako

Anti-

Kap

pa F

ITC

Dako

100 101 102 103 104100

101

102

103

104

CD20 APC

CD23

PE

100 101 102 103 104100

101

102

103

104

CD19 FITC

CD5

PerC

P-C

y5.5

100 101 102 103 104100

101

102

103

104

ZAP 70 PE INTRA

Coun

t

100 101 102 103 1040

126

252

377

503

Almasri et al Am J Hematol 1992

Marginal Zone Lymphoma (MZL)

FOLLICULAR LYMPHOMA

FOLLICULAR LYMPHOMA

- Young et all 2006 Cancer

- Young et al 2004 Acta Cytol

- Sun & Caraway et al 2004 Acta Cytol

Mantle Cell Lymphoma

CD20 +

CD5 +

Cyclin D1

T(11;14)

CLL/SLL

FL

MCL

MZL/MALT

SLVL

DLBCL

Channels (FL3-A-FL3-A-DRAQ5)0 40 80 120 160C

ell n

umbe

r

DNA contentDNA content

G0/G1

G2/MS

Aneuploid

Tumor specific S-phase=20%

Acute Lymphoblastic Lymphoma (ALL)

Burkitt Lymphoma

KI-67

Burkitt Lymphoma

Burkitt

SSC-Height0 256 512 768 1024

FSC

-Hei

ght

0

200

400

600

800

1000

CD19 APC010 110 210 310 410

CD

10 P

E

010

110

210

310

CD19 APC (IgG1)010 110 210 310 410

CD

5 FI

TC

010

110

210

310

CD22 PE010 110 210 310 410

FSC

-Hei

ght

0

200

400

600

800

1000

CD20 FITC010 110 210 310 410

FSC

-Hei

ght

0

200

400

600

800

1000

Anti-Kappa FITC DAKO010 110 210 310 410

Cou

nt

500

400

300

200

100

0

Anti-Lambda FITC DAKO010 110 210 310 410

Cou

nt

500

400

300

200

100

0

Abnormal B cells

DLBCL

LL

ALCL

SLLExt

CLL/SLL

HCL SLCVL MALT FL MCL MZL Burk.L ALCL WM DLCL

CD5 - + - - - - + - - +/- - -

CD19 + + + + + + + + + - +/- +

CD20 +weak

+weak

+ + + + + + + - +/- +

S ig + + + + + + + + + - +/- +/-

C ig - - - - - - - - - - +/- -

CD22 + + + + + + + + + - +/- +

CD10 - * - - +/- + +/- - + - - +/-

CD21 + + - - + +/- - +/- - - +/-

CD23 - + - - - - - - - -

CD25 - - + +/- - - - - - +/- +/-

CD38 - - +/- - +/- - - - - + +

CD11cBly7

- + +/- - - - - - - NS -

Cytogen t (14;19)tri (12)

+ Del 7 t (14;18)Cyclin D1+

t (11;14)Cyclin D1+

Cyclin D1-tri (3)

t(11;18)

t (8;14) t (2;5) t(3;14)

CD43 +/- + - +/- - + +/- - -

HLA-DR + + + +

24 year old male with cervical node

Reed-Sternberg Cell

CD 30 CD 15

LCA

CD 20 CD 3

LCA L26 UCHL-1 CD15 (LEU M1) CD30 EMA

N-LP + + - - - +

D-LP +/- +/- - +/- +/- +/-

NS - +/- - + + -

MC - +/- - + + -

LD - +/- - + + -

WHO Classification of Hodgkin Lymphoma

N-LP: Nodular lymphocytic predominanceD-LP: Diffuse lymphocytic predominanceNS: Nodular sclerosisMC: Mixed cellularityLD: Lymphocytic depletion

Cytologic Mimickers of Reed-Sternberg Cells

• Immunoblasts• Megakaryocytes• Dendritic cells• Reactive mesothelial cells• Large cell lymphoma & ALCL cells• Melanoma• Plasmablast (myeloma cells)• Pleomorphic sarcoma & large cell

carcinoma

Plasma Cell

63 years old male with scalp mass for 2 months

LAMBDA KAPPA

DX: Plasma Cell Neoplasm

71-year-F- cervical node

Metastatic Small Cell Carcinoma

Chromogranin CK+

AE1/3CG

Squamous cell carcinomaKeratinizing

Basaloid P63, CK5/6

Melanoma

Breast Endometrium

Final message:• Lymph node FNA is the preferred

initial diagnostic procedure; though controversial

• In experienced hands; diagnostic accuracy, sensitivity and specificity are high (operator dependent)

• Proper sampling is key for better sampling and enough material for immunophenotyping and other needed studies

• Benign lesions and non Hodgkin’s lymphomas can be accurately diagnosed by FNA in most cases…whether newly diagnosed or as a follow up

• Cl. Hodgkin’s lymphoma diagnosis can be made provided a negative FCM and available CB with confirmatory IHC.

• FNA as a follow up for a previously diagnosed case of Hodgkin’s lymphoma can be done…if negative, excisional biopsy is recommended

• Metastatic tumors should not pose any diagnostic challenges provided cell block material is obtained for IHC

Problems of the FNA approach:

• Benign lymphoid lesions…no specific diagnosis

• Hodgkin’s lymphoma• T-cell rich B-cell Lymphoma• T-cell lymphomas• Necrotic/cystic tumors• Grading of some lymphomas• Some rare and mixed lymphomas

Young N 2006 Cancer Feb.

Persistent Lymphadenopathy

Epith. & non-lymphoid cells Granulomas Polymorphous

cell populationMonotonous

cell population

RS or RS-likecells present

No definite RS or RS-like Cells

Clinical suspicionfor Lymphoma

is very low

High clinicalsuspicion for lymphoma

Reactive,Clinical follow up FCM, CG, GR

FCM + CB

(-) FCM, ConfirmHD by IHC

AFB, Fluorescent AFB, PCR-TB,C&S, CB -stains

B-9, InclusionsMetastaticcarcinoma /melanoma

Confirm by IHC on CB

FNA with IE&T

FCM:Flowcytometry

CG: Cytegenetic analysis

GR: Gene re-arrangement studies

CB: Cell block

IHC: Immunohistochemistry Mousa Al-Abbadi, MD. 4-21-05

+/- =DX

Multiple Approach

Alquran, Al-Abbadi, Braylan: Arch Pathol Lab Med. 2004 Nov;128(11):1309

In hematopathology, love is every where

“The Sydney System 2019”

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