Background: The advent of programmed cell death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors has revolutionized lung cancer treatment, necessitating accurate PD-L1 immunohistochemical (IHC) assessment. While standardized for formalin-fixed paraffin-embedded histological samples, PD-L1 testing on cytology remains challenging. This review aims to address the complexities of PD-L1 IHC in cytology, focusing on validation guidelines, quality assessment, cytohistological correlation, and interobserver variability. Summary: This review synthesizes current guidelines and research on PD-L1 IHC in cytology; in particular, recent College of American Pathologists (CAP) guidelines emphasize the necessity for rigorous validation, particularly for non-formalin-fixed specimens. As far as cytohistological concordance studies are concerned, the review of 48 original articles revealed significant variability in PD-L1 expression, with concordance rates ranging from 54 to 100% at the 1% cutoff and 82–100% at the 50% cutoff. Finally, interobserver variability, particularly in the 1–49% PD-L1 expression range, further complicates accurate assessment. The review also discusses the challenges associated with quality assessment in cytology, including the lack of standardized control materials and external quality assessment (EQA) programs specifically tailored for cytological samples. Key Messages: PD-L1 testing in cytology is feasible but faces substantial challenges compared to histological specimens. Validation of PD-L1 IHC protocols for cytological preparations, especially non-formalin-fixed samples, is essential. Concordance between cytological and histological PD-L1 expression is variable, highlighting the need for caution in interpretation. Interobserver variability, particularly in cases with intermediate PD-L1 expression (1–49%), affects diagnostic reproducibility. The development of standardized quality control materials and EQA programs for cytology is urgently needed to support consistent and reliable PD-L1 testing.

1.
Brahmer
J
,
Reckamp
KL
,
Baas
P
,
Crinò
L
,
Eberhardt
WEE
,
Poddubskaya
E
, et al
.
Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer
.
N Engl J Med
.
2015
;
373
(
2
):
123
35
.
2.
Borghaei
H
,
Paz-Ares
L
,
Horn
L
,
Spigel
DR
,
Steins
M
,
Ready
NE
, et al
.
Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer
.
N Engl J Med
.
2015
;
373
(
17
):
1627
39
.
3.
Hellmann
MD
,
Paz-Ares
L
,
Bernabe Caro
R
,
Zurawski
B
,
Kim
S-W
,
Carcereny Costa
E
, et al
.
Nivolumab plus ipilimumab in advanced non-small-cell lung cancer
.
N Engl J Med
.
2019
;
381
(
21
):
2020
31
.
4.
Reck
M
,
Rodríguez-Abreu
D
,
Robinson
AG
,
Hui
R
,
Csőszi
T
,
Fülöp
A
, et al
.
Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer
.
N Engl J Med
.
2016
;
375
(
19
):
1823
33
.
5.
Mok
TSK
,
Wu
Y-L
,
Kudaba
I
,
Kowalski
DM
,
Cho
BC
,
Turna
HZ
, et al
.
Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial
.
Lancet Lond Engl
.
2019
;
393
(
10183
):
1819
30
.
6.
Rittmeyer
A
,
Barlesi
F
,
Waterkamp
D
,
Park
K
,
Ciardiello
F
,
von Pawel
J
, et al
.
Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial
.
Lancet Lond Engl
.
2017
;
389
(
10066
):
255
65
.
7.
Herbst
RS
,
Giaccone
G
,
de Marinis
F
,
Reinmuth
N
,
Vergnenegre
A
,
Barrios
CH
, et al
.
Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC
.
N Engl J Med
.
2020
;
383
(
14
):
1328
39
.
8.
Liu
SV
,
Reck
M
,
Mansfield
AS
,
Mok
T
,
Scherpereel
A
,
Reinmuth
N
, et al
.
Updated overall survival and PD-L1 subgroup analysis of patients with extensive-stage small-cell lung cancer treated with atezolizumab, carboplatin, and etoposide (IMpower133)
.
J Clin Oncol
.
2021
;
39
(
6
):
619
30
.
9.
Senan
S
,
Özgüroğlu
M
,
Daniel
D
,
Villegas
A
,
Vicente
D
,
Murakami
S
, et al
.
Outcomes with durvalumab after chemoradiotherapy in stage IIIA-N2 non-small-cell lung cancer: an exploratory analysis from the PACIFIC trial
.
ESMO Open
.
2022
;
7
(
2
):
100410
.
10.
Goldman
JW
,
Dvorkin
M
,
Chen
Y
,
Reinmuth
N
,
Hotta
K
,
Trukhin
D
, et al
.
Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial
.
Lancet Oncol
.
2021
;
22
(
1
):
51
65
.
11.
Sezer
A
,
Kilickap
S
,
Gümüş
M
,
Bondarenko
I
,
Özgüroğlu
M
,
Gogishvili
M
, et al
.
Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial
.
Lancet Lond Engl
.
2021
;
397
(
10274
):
592
604
.
12.
Ni
L
,
Zhang
Z
,
Sun
D
,
Liu
Z
,
Liu
X
.
Survival improvement of stage IV non-small cell lung cancer in the immunotherapy era: a retrospective cohort study in a US population
.
Adv Ther
.
2024
;
41
(
12
):
4591
600
.
13.
Hektoen
HH
,
Tsuruda
KM
,
Fjellbirkeland
L
,
Nilssen
Y
,
Brustugun
OT
,
Andreassen
BK
.
Real-world evidence for pembrolizumab in non-small cell lung cancer: a nationwide cohort study
.
Br J Cancer
.
2025
;
132
(
1
):
93
102
.
14.
Porte
M
,
Vaudron
A
,
Crequit
P
,
Vaugier
L
,
Chatellier
T
,
Fronteau
C
, et al
.
A multicenter study assessing the real-world use and effectiveness of first-line chemotherapy plus immunotherapy in advanced small-cell lung cancer (SCLC) patients
.
Clin Lung Cancer
.
2024
;
25
(
2
):
e101
11.e2
.
15.
Lantuejoul
S
,
Sound-Tsao
M
,
Cooper
WA
,
Girard
N
,
Hirsch
FR
,
Roden
AC
, et al
.
PD-L1 testing for lung cancer in 2019: perspective from the IASLC pathology committee
.
J Thorac Oncol
.
2020
;
15
(
4
):
499
519
.
16.
Koomen
BM
,
Badrising
SK
,
van den Heuvel
MM
,
Willems
SM
.
Comparability of PD-L1 immunohistochemistry assays for non-small-cell lung cancer: a systematic review
.
Histopathology
.
2020
;
76
(
6
):
793
802
.
17.
Buonocore
DJ
,
Konno
F
,
Jungbluth
AA
,
Frosina
D
,
Fayad
M
,
Edelweiss
M
, et al
.
CytoLyt fixation significantly inhibits MIB1 immunoreactivity whereas alternative Ki-67 clone 30-9 is not susceptible to the inhibition: critical diagnostic implications
.
Cancer Cytopathol
.
2019
;
127
(
10
):
643
9
.
18.
Sakabe
N
,
Maruyama
S
,
Ito
C
,
Shimoyama
Y
,
Komene
T
,
Oboshi
W
, et al
.
Immunocytochemical reactivity comparison between formalin-fixed and liquid-based cytology-fixed specimens
.
Acta Cytol
.
2023
;
67
(
1
):
38
45
.
19.
Mansour
MSI
,
Pettersson
L
,
Seidal
T
,
Strömberg
U
,
Mager
U
,
Ali
L
, et al
.
The impact of different fixatives on immunostaining of lung adenocarcinomas in pleural effusion cell blocks
.
Cancer Cytopathol
.
2024
;
132
(
9
):
569
79
.
20.
Sakakibara
R
,
Inamura
K
,
Tambo
Y
,
Ninomiya
H
,
Kitazono
S
,
Yanagitani
N
, et al
.
EBUS-TBNA as a promising method for the evaluation of tumor PD-L1 expression in lung cancer
.
Clin Lung Cancer
.
2017
;
18
(
5
):
527
34.e1
.
21.
Skov
BG
,
Skov
T
.
Paired comparison of PD-L1 expression on cytologic and histologic specimens from malignancies in the lung assessed with PD-L1 IHC 28-8pharmDx and PD-L1 IHC 22C3pharmDx
.
Appl Immunohistochem Mol Morphol
.
2017
;
25
(
7
):
453
9
.
22.
Torlakovic
EE
,
Cheung
CC
,
D’Arrigo
C
,
Dietel
M
,
Francis
GD
,
Gilks
CB
, et al
.
Evolution of quality assurance for clinical immunohistochemistry in the era of precision medicine: part 2 – immunohistochemistry test performance characteristics
.
Appl Immunohistochem Mol Morphol
.
2017
;
25
(
2
):
79
85
.
23.
Vyberg
M
,
Nielsen
S
.
Proficiency testing in immunohistochemistry: experiences from Nordic Immunohistochemical Quality Control (NordiQC)
.
Virchows Arch
.
2016
;
468
(
1
):
19
29
.
24.
Goldsmith
JD
,
Troxell
ML
,
Roy-Chowdhuri
S
,
Colasacco
CF
,
Edgerton
ME
,
Fitzgibbons
PL
, et al
.
Principles of analytic validation of immunohistochemical assays: guideline update
.
Arch Pathol Lab Med
.
2024
;
148
(
6
):
e111
53
.
25.
Bass
BP
,
Engel
KB
,
Greytak
SR
,
Moore
HM
.
A review of preanalytical factors affecting molecular, protein, and morphological analysis of formalin-fixed, paraffin-embedded (FFPE) tissue: how well do you know your FFPE specimen
.
Arch Pathol Lab Med
.
2014
;
138
(
11
):
1520
30
.
26.
Thunnissen
E
,
Allen
TC
,
Adam
J
,
Aisner
DL
,
Beasley
MB
,
Borczuk
AC
, et al
.
Immunohistochemistry of pulmonary biomarkers: a perspective from members of the pulmonary pathology society
.
Arch Pathol Lab Med
.
2018
;
142
(
3
):
408
19
.
27.
van Seijen
M
,
Brcic
L
,
Gonzales
AN
,
Sansano
I
,
Bendek
M
,
Brcic
I
, et al
.
Impact of delayed and prolonged fixation on the evaluation of immunohistochemical staining on lung carcinoma resection specimen
.
Virchows Arch
.
2019
;
475
(
2
):
191
9
.
28.
Brunnström
H
,
Johansson
A
,
Westbom-Fremer
S
,
Backman
M
,
Djureinovic
D
,
Patthey
A
, et al
.
PD-L1 immunohistochemistry in clinical diagnostics of lung cancer: inter-pathologist variability is higher than assay variability
.
Mod Pathol
.
2017
;
30
(
10
):
1411
21
.
29.
Roy-Chowdhuri
S
,
Dacic
S
,
Ghofrani
M
,
Illei
PB
,
Layfield
LJ
,
Lee
C
, et al
.
Collection and handling of thoracic small biopsy and cytology specimens for ancillary studies: guideline from the College of American Pathologists in Collaboration with the American College of Chest Physicians, Association for Molecular Pathology, American Society of Cytopathology, American Thoracic Society, Pulmonary Pathology Society, Papanicolaou Society of Cytopathology, Society of Interventional Radiology, and Society of Thoracic Radiology
.
Arch Pathol Lab Med
.
2020
;
144
(
8
):
933
58
.
30.
Hendriks
LE
,
Kerr
KM
,
Menis
J
,
Mok
TS
,
Nestle
U
,
Passaro
A
, et al
.
Non-oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
.
Ann Oncol
.
2023
;
34
(
4
):
358
76
.
31.
Jain
D
,
Nambirajan
A
,
Borczuk
A
,
Chen
G
,
Minami
Y
,
Moreira
AL
, et al
.
Immunocytochemistry for predictive biomarker testing in lung cancer cytology
.
Cancer Cytopathol
.
2019
;
127
(
5
):
325
39
.
32.
Sholl
LM
,
Awad
M
,
Basu Roy
U
,
Beasley
MB
,
Cartun
RW
,
Hwang
DM
, et al
.
Programmed death ligand-1 and tumor mutation burden testing of patients with lung cancer for selection of immune checkpoint inhibitor therapies: guideline from the College of American Pathologists, Association for Molecular Pathology, International Association for the Study of Lung Cancer, Pulmonary Pathology Society, and LUNGevity Foundation
.
Arch Pathol Lab Med
.
2024
;
148
(
7
):
757
74
.
33.
Fitzgibbons
PL
,
Bradley
LA
,
Fatheree
LA
,
Alsabeh
R
,
Fulton
RS
,
Goldsmith
JD
, et al
.
Principles of analytic validation of immunohistochemical assays: guideline from the College of American Pathologists Pathology and Laboratory Quality Center
.
Arch Pathol Lab Med
.
2014
;
138
(
11
):
1432
43
.
34.
Mansfield
AS
,
Aubry
MC
,
Moser
JC
,
Harrington
SM
,
Dronca
RS
,
Park
SS
, et al
.
Temporal and spatial discordance of programmed cell death-ligand 1 expression and lymphocyte tumor infiltration between paired primary lesions and brain metastases in lung cancer
.
Ann Oncol
.
2016
;
27
(
10
):
1953
8
.
35.
Elfving
H
,
Mattsson
JSM
,
Lindskog
C
,
Backman
M
,
Menzel
U
,
Micke
P
.
Programmed cell death ligand 1 immunohistochemistry: a concordance study between surgical specimen, biopsy, and tissue microarray
.
Clin Lung Cancer
.
2019
;
20
(
4
):
258
62.e1
.
36.
Nam
CH
,
Koh
J
,
Ock
C-Y
,
Kim
M
,
Keam
B
,
Kim
TM
, et al
.
Temporal evolution of programmed death-ligand 1 expression in patients with non-small cell lung cancer
.
Korean J Intern Med
.
2021
;
36
(
4
):
975
84
.
37.
Evans
M
,
O’Sullivan
B
,
Hughes
F
,
Mullis
T
,
Smith
M
,
Trim
N
, et al
.
The clinicopathological and molecular associations of PD-L1 expression in non-small cell lung cancer: analysis of a series of 10,005 cases tested with the 22C3 assay
.
Pathol Oncol Res
.
2020
;
26
(
1
):
79
89
.
38.
Velcheti
V
,
Patwardhan
PD
,
Liu
FX
,
Chen
X
,
Cao
X
,
Burke
T
.
Real-world PD-L1 testing and distribution of PD-L1 tumor expression by immunohistochemistry assay type among patients with metastatic non-small cell lung cancer in the United States
.
PLoS One
.
2018
;
13
(
11
):
e0206370
.
39.
Torlakovic
EE
,
Nielsen
S
,
Vyberg
M
,
Taylor
CR
.
Getting controls under control: the time is now for immunohistochemistry
.
J Clin Pathol
.
2015
;
68
(
11
):
879
82
.
40.
Srebotnik Kirbiš
I
,
Rodrigues Roque
R
,
Bongiovanni
M
,
Strojan Fležar
M
,
Cochand-Priollet
B
.
Immunocytochemistry practices in European cytopathology laboratories-Review of European Federation of Cytology Societies (EFCS) online survey results with best practice recommendations
.
Cancer Cytopathol
.
2020
;
128
(
10
):
757
66
.
41.
Lozano
MD
,
Robledano
R
,
Argueta
A
.
Quality assurance in immunocytochemistry: a review and practical considerations
.
Acta Cytol
.
2025
;
69
(
1
):
60
8
.
42.
Overview of external quality assessment (EQA) [Internet]
[cited 2025 Mar 8]. Available from: https://www.who.int/publications/m/item/overview-of-external-quality-assessment-eqa
43.
PDL1 programme [Internet]
[cited 2025 Mar 12]. Available from: https://www.sekk.cz/PDL1/index.php
44.
Raab
SS
,
Grzybicki
DM
.
Cytologic-histologic correlation
.
Cancer Cytopathol
.
2011
;
119
(
5
):
293
309
.
45.
Crothers
BA
.
Cytologic-histologic correlation: where are we now, and where are we going
.
Cancer Cytopathol
.
2018
;
126
(
5
):
301
8
.
46.
Crothers
BA
,
Jones
BA
,
Cahill
LA
,
Moriarty
AT
,
Mody
DR
,
Tench
WD
, et al
.
Quality improvement opportunities in gynecologic cytologic-histologic correlations: findings from the College of American Pathologists Gynecologic Cytopathology Quality Consensus Conference working group 4
.
Arch Pathol Lab Med
.
2013
;
137
(
2
):
199
213
.
47.
Nguyen
LN
,
Crothers
BA
,
Davey
DD
,
Natale
KE
,
Nunez
AL
,
Harkcom
T
, et al
.
Current state of cytologic-histologic correlation implementation for North American and international laboratories: results of the College of American pathologists cytopathology committee laboratory practices in gynecologic cytology survey
.
Arch Pathol Lab Med
.
2023
;
147
(
1
):
52
61
.
48.
O’Conor
CJ
,
Dehan
LM
,
Ely
KA
.
Use of nongynecologic cytologic-histologic correlation to identify patterns of error: an institutional experience
.
Cancer Cytopathol
.
2023
;
131
(
9
):
581
5
.
49.
Gosney
JR
,
Boothman
A-M
,
Ratcliffe
M
,
Kerr
KM
.
Cytology for PD-L1 testing: a systematic review
.
Lung Cancer
.
2020
;
141
:
101
6
.
50.
Mansour
MSI
,
Lindquist
KE
,
Seidal
T
,
Mager
U
,
Mohlin
R
,
Tran
L
, et al
.
PD-L1 testing in cytological non-small cell lung cancer specimens: a comparison with biopsies and review of the literature
.
Acta Cytol
.
2021
;
65
(
6
):
501
9
.
51.
Satturwar
S
,
Girolami
I
,
Munari
E
,
Ciompi
F
,
Eccher
A
,
Pantanowitz
L
.
Program death ligand-1 immunocytochemistry in lung cancer cytological samples: a systematic review
.
Diagn Cytopathol
.
2022
;
50
(
6
):
313
23
.
52.
Tajarernmuang
P
,
Aliaga
F
,
Alwakeel
AJ
,
Tavaziva
G
,
Turner
K
,
Menzies
D
, et al
.
Accuracy of cytologic vs histologic specimens for assessment of programmed cell death ligand-1 expression in non-small cell lung cancer: a systematic review and meta-analysis
.
Chest
.
2024
;
165
(
2
):
461
74
.
53.
Heymann
JJ
,
Bulman
WA
,
Swinarski
D
,
Pagan
CA
,
Crapanzano
JP
,
Haghighi
M
, et al
.
PD-L1 expression in non-small cell lung carcinoma: comparison among cytology, small biopsy, and surgical resection specimens
.
Cancer Cytopathol
.
2017
;
125
(
12
):
896
907
.
54.
Stoy
SP
,
Rosen
L
,
Mueller
J
,
Murgu
S
.
Programmed death-ligand 1 testing of lung cancer cytology specimens obtained with bronchoscopy
.
Cancer Cytopathol
.
2018
;
126
(
2
):
122
8
.
55.
Russell-Goldman
E
,
Kravets
S
,
Dahlberg
SE
,
Sholl
LM
,
Vivero
M
.
Cytologic-histologic correlation of programmed death-ligand 1 immunohistochemistry in lung carcinomas
.
Cancer Cytopathol
.
2018
;
126
(
4
):
253
63
.
56.
Ilie
M
,
Juco
J
,
Huang
L
,
Hofman
V
,
Khambata-Ford
S
,
Hofman
P
.
Use of the 22C3 anti-programmed death-ligand 1 antibody to determine programmed death-ligand 1 expression in cytology samples obtained from non-small cell lung cancer patients
.
Cancer Cytopathol
.
2018
;
126
(
4
):
264
74
.
57.
Noll
B
,
Wang
W-L
,
Gong
Y
,
Zhao
J
,
Kalhor
N
,
Prieto
V
, et al
.
Programmed death ligand 1 testing in non-small cell lung carcinoma cytology cell block and aspirate smear preparations
.
Cancer Cytopathol
.
2018
;
126
(
5
):
342
52
.
58.
Wang
H
,
Agulnik
J
,
Kasymjanova
G
,
Wang
A
,
Jiménez
P
,
Cohen
V
, et al
.
Cytology cell blocks are suitable for immunohistochemical testing for PD-L1 in lung cancer
.
Ann Oncol
.
2018
;
29
(
6
):
1417
22
.
59.
Jain
D
,
Sukumar
S
,
Mohan
A
,
Iyer
VK
.
Programmed death-ligand 1 immunoexpression in matched biopsy and liquid-based cytology samples of advanced stage non-small cell lung carcinomas
.
Cytopathology
.
2018
;
29
(
6
):
550
7
.
60.
Xu
J
,
Han
X
,
Liu
C
,
Gao
N
,
Zhao
J
,
Zhang
X
, et al
.
PD-L1 expression in pleural effusions of pulmonary adenocarcinoma and survival prediction: a controlled study by pleural biopsy
.
Sci Rep
.
2018
;
8
(
1
):
11206
.
61.
Sakata
KK
,
Midthun
DE
,
Mullon
JJ
,
Kern
RM
,
Nelson
DR
,
Edell
ES
, et al
.
Comparison of programmed death ligand-1 immunohistochemical staining between endobronchial ultrasound transbronchial needle aspiration and resected lung cancer specimens
.
Chest
.
2018
;
154
(
4
):
827
37
.
62.
Munari
E
,
Zamboni
G
,
Sighele
G
,
Marconi
M
,
Sommaggio
M
,
Lunardi
G
, et al
.
Expression of programmed cell death ligand 1 in non-small cell lung cancer: comparison between cytologic smears, core biopsies, and whole sections using the SP263 assay
.
Cancer Cytopathol
.
2019
;
127
(
1
):
52
61
.
63.
Capizzi
E
,
Ricci
C
,
Giunchi
F
,
Zagnoni
S
,
Ceccarelli
C
,
Gómez
BUÁ
, et al
.
Validation of the immunohistochemical expression of programmed death ligand 1 (PD-L1) on cytological smears in advanced non small cell lung cancer
.
Lung Cancer
.
2018
;
126
:
9
14
.
64.
Hernandez
A
,
Brandler
TC
,
Zhou
F
,
Moreira
AL
,
Schatz-Siemers
N
,
Simsir
A
.
Assessment of programmed death-ligand 1 (PD-L1) immunohistochemical expression on cytology specimens in non-small cell lung carcinoma
.
Am J Clin Pathol
.
2019
;
151
(
4
):
403
15
.
65.
Xu
H
,
Bratton
L
,
Nead
M
,
Russell
D
,
Zhou
Z
.
Comparison of programmed death-ligand 1 (PD-L1) immunostain for nonsmall cell lung carcinoma between paired cytological and surgical specimens
.
CytoJournal
.
2018
;
15
:
29
.
66.
Arriola
AGP
,
Bashover
E
,
Joseph
C
,
Staerkel
G
,
Wang
W-L
,
Roy-Chowdhuri
S
.
The usefulness of various cytologic specimen preparations for PD-L1 immunostaining in non-small cell lung carcinoma
.
J Am Soc Cytopathol
.
2018
;
7
(
6
):
324
32
.
67.
Grosu
HB
,
Arriola
A
,
Stewart
J
,
Ma
J
,
Bassett
R
,
Hernandez
M
, et al
.
PD-L1 detection in histology specimens and matched pleural fluid cell blocks of patients with NSCLC
.
Respirology
.
2019
;
24
(
12
):
1198
203
.
68.
Pak
MG
,
Roh
MS
.
Cell-blocks are suitable material for programmed cell death ligand-1 immunohistochemistry: comparison of cell-blocks and matched surgical resection specimens in lung cancer
.
Cytopathology
.
2019
;
30
(
6
):
578
85
.
69.
Lozano
MD
,
Abengozar-Muela
M
,
Echeveste
JI
,
Subtil
JC
,
Bertó
J
,
Gúrpide
A
, et al
.
Programmed death-ligand 1 expression on direct Pap-stained cytology smears from non-small cell lung cancer: comparison with cell blocks and surgical resection specimens
.
Cancer Cytopathol
.
2019
;
127
(
7
):
470
80
.
70.
Yoshimura
K
,
Inoue
Y
,
Karayama
M
,
Tsuchiya
K
,
Mori
K
,
Suzuki
Y
, et al
.
Heterogeneity analysis of PD-L1 expression and copy number status in EBUS-TBNA biopsy specimens of non-small cell lung cancer: comparative assessment of primary and metastatic sites
.
Lung Cancer
.
2019
;
134
:
202
9
.
71.
Kuempers
C
,
van der Linde
LIS
,
Reischl
M
,
Vogel
W
,
Stellmacher
F
,
Reck
M
, et al
.
Comparison of PD-L1 expression between paired cytologic and histologic specimens from non-small cell lung cancer patients
.
Virchows Arch
.
2020
;
476
(
2
):
261
71
.
72.
Wang
G
,
Ionescu
DN
,
Lee
C-H
,
Hiruki
T
,
Myers
R
,
Shaipanich
T
, et al
.
PD-L1 testing on the EBUS-FNA cytology specimens of non-small cell lung cancer
.
Lung Cancer
.
2019
;
136
:
1
5
.
73.
Smith
A
,
Wang
H
,
Zerbo
A
,
Beaudoin
S
,
Ofiara
L
,
Fiset
P-O
, et al
.
Programmed death ligand 1 testing of endobronchial ultrasound-guided transbronchial needle aspiration samples acquired for the diagnosis and staging of non-small cell lung cancer
.
J Bronchol Interv Pulmonol
.
2020
;
27
(
1
):
50
7
.
74.
Hendry
S
,
Byrne
DJ
,
Christie
M
,
Steinfort
DP
,
Irving
LB
,
Wagner
C-A
, et al
.
Adequate tumour cellularity is essential for accurate PD-L1 immunohistochemistry assessment on cytology cell-block specimens
.
Cytopathology
.
2020
;
31
(
2
):
90
5
.
75.
Song
SG
,
Lee
J
,
Koh
J
,
Kim
S
,
Chung
DH
,
Jeon
YK
.
Utility of PD-L1 immunocytochemistry using body-fluid cell blocks in patients with non-small-cell lung cancer
.
Diagn Cytopathol
.
2020
;
48
(
4
):
291
9
.
76.
Dong
Z
,
Liu
Y
,
Jiang
T
,
Hou
L
,
Wu
F
,
Gao
G
, et al
.
Cell block as a surrogate for programmed death-ligand 1 staining testing in patients of non-small cell lung cancer
.
J Cancer
.
2020
;
11
(
3
):
551
8
.
77.
Bortolotto
C
,
Maglia
C
,
Ciuffreda
A
,
Coretti
M
,
Catania
R
,
Antonacci
F
, et al
.
The growth of non-solid neoplastic lung nodules is associated with low PD L1 expression, irrespective of sampling technique
.
J Transl Med
.
2020
;
18
(
1
):
54
.
78.
Bozzetti
C
,
Squadrilli
A
,
Nizzoli
R
,
Lagrasta
C
,
Gasparro
D
,
Majori
M
, et al
.
Optimizing PD-L1 evaluation on cytological samples from advanced non-small-cell lung cancer
.
Immunotherapy
.
2020
;
12
(
3
):
183
93
.
79.
Zou
Y
,
Xu
L
,
Tang
Q
,
You
Q
,
Wang
X
,
Ding
W
, et al
.
Cytology cell blocks from malignant pleural effusion are good candidates for PD-L1 detection in advanced NSCLC compared with matched histology samples
.
BMC Cancer
.
2020
;
20
(
1
):
344
.
80.
Jug
R
,
Giovacchini
CX
,
Liu
B
,
Green
CL
,
Clarke
JM
,
Mahmood
K
, et al
.
EBUS-FNA cytologic-histologic correlation of PD-L1 immunohistochemistry in non-small cell lung cancer
.
J Am Soc Cytopathol
.
2020
;
9
(
6
):
485
93
.
81.
Song
Z
,
Cheng
G
,
Zhang
Y
.
PD-L1 expression in malignant pleural effusion samples and its correlation with oncogene mutations in non-small cell lung cancer
.
J Thorac Dis
.
2020
;
12
(
4
):
1385
92
.
82.
Daverio
M
,
Patrucco
F
,
Gavelli
F
,
Airoldi
C
,
Sciortino
G
,
Chiaramonte
C
, et al
.
Comparative analysis of programmed death ligand 1 expression in paired cytologic and histologic specimens of non-small cell lung cancer
.
Cancer Cytopathol
.
2020
;
128
(
8
):
580
8
.
83.
Gagné
A
,
Orain
M
,
Ionescu
D
,
Tsao
M-S
,
Joubert
D
,
Joubert
P
.
Comprehensive assessment of PD-L1 immunohistochemistry on paired tissue and cytology specimens from non-small cell lung cancer
.
Lung Cancer
.
2020
;
146
:
276
84
.
84.
Lou
SK
,
Ko
HM
,
Kinoshita
T
,
MacDonald
S
,
Weiss
J
,
Czarnecka-Kujawa
K
, et al
.
Implementation of PD-L1 22C3 IHC pharmDxTM in cell block preparations of lung cancer: concordance with surgical resections and technical validation of CytoLyt® prefixation
.
Acta Cytol
.
2020
;
64
(
6
):
577
87
.
85.
Bubendorf
L
,
Conde
E
,
Cappuzzo
F
,
Langfort
R
,
Schildhaus
H-U
,
Votruba
J
, et al
.
A noninterventional, multinational study to assess PD-L1 expression in cytological and histological lung cancer specimens
.
Cancer Cytopathol
.
2020
;
128
(
12
):
928
38
.
86.
Lin
Y-Y
,
Lin
L-Y
,
Hang
J-F
,
Lin
C-H
,
Ho
H-L
,
Chou
T-Y
.
Programmed death-ligand 1 (PD-L1)/thyroid transcription factor-1 double immunohistochemical staining facilitates scoring of tumor PD-L1 expression in cytopathology specimens from lung adenocarcinoma patients
.
Cancer Cytopathol
.
2021
;
129
(
2
):
148
55
.
87.
Ambrosini-Spaltro
A
,
Dubini
A
,
Pieri
F
,
Ravaglia
C
,
Delmonte
A
,
Poletti
V
.
PD-L1 expression in NSCLC: role of cell blocks and concordance between samples
.
Diagn Cytopathol
.
2021
;
49
(
2
):
303
10
.
88.
Koomen
BM
,
van der Starre-Gaal
J
,
Vonk
JM
,
von der Thüsen
JH
,
van der Meij
JJC
,
Monkhorst
K
, et al
.
Formalin fixation for optimal concordance of programmed death-ligand 1 immunostaining between cytologic and histologic specimens from patients with non-small cell lung cancer
.
Cancer Cytopathol
.
2021
;
129
(
4
):
304
17
.
89.
Chauhan
A
,
Siegel
L
,
Freese
R
,
Racila
E
,
Stewart
J
,
Amin
K
.
Performance of Ventana SP263 PD-L1 assay in endobronchial ultrasound guided-fine-needle aspiration derived non-small-cell lung carcinoma samples
.
Diagn Cytopathol
.
2021
;
49
(
3
):
355
62
.
90.
Ricci
C
,
Capizzi
E
,
Giunchi
F
,
Casolari
L
,
Gelsomino
F
,
Rihawi
K
, et al
.
Reliability of programmed death ligand 1 (PD-L1) tumor proportion score (TPS) on cytological smears in advanced non-small cell lung cancer: a prospective validation study
.
Ther Adv Med Oncol
.
2020
;
12
:
1758835920954802
.
91.
Hagmeyer
L
,
Schäfer
S
,
Engels
M
,
Pietzke-Calcagnile
A
,
Treml
M
,
Herkenrath
S-D
, et al
.
High sensitivity of PD-L1 analysis from pleural effusion in nonsmall cell lung cancer
.
ERJ Open Res
.
2021
;
7
(
1
):
00787-2020
.
92.
Martin-Deleon
R
,
Teixido
C
,
Lucena
CM
,
Martinez
D
,
Fontana
A
,
Reyes
R
, et al
.
EBUS-TBNA cytological samples for comprehensive molecular testing in non-small cell lung cancer
.
Cancers
.
2021
;
13
(
9
):
2084
.
93.
Mansour
MSI
,
Hejny
K
,
Johansson
F
,
Mufti
J
,
Vidis
A
,
Mager
U
, et al
.
Factors influencing concordance of PD-L1 expression between biopsies and cytological specimens in non-small cell lung cancer
.
Diagn Basel Switz
.
2021
;
11
(
10
):
1927
.
94.
Mahajan
S
,
Nambirajan
A
,
Gupta
I
,
Gupta
N
,
Gupta
P
,
Jain
D
.
Malignant pleural effusion cell blocks are reliable resources for PD-L1 analysis in advanced lung adenocarcinomas: a concordance study with matched histologic samples
.
J Am Soc Cytopathol
.
2022
;
11
(
5
):
253
63
.
95.
Abdo
M
,
Belloum
Y
,
Heigener
D
,
Welker
L
,
von Weihe
S
,
Schmidt
M
, et al
.
Comparative evaluation of PD-L1 expression in cytology imprints, circulating tumour cells and tumour tissue in non-small cell lung cancer patients
.
Mol Oncol
.
2023
;
17
(
5
):
737
46
.
96.
Polanco
D
,
Pinilla
L
,
Gracia-Lavedan
E
,
Gatius
S
,
Zuil
M
,
Pardina
M
, et al
.
Performance of endobronchial ultrasound transbronchial needle aspiration as the first nodal staging procedure for the determination of programmed death ligand-1 expression in non-small cell lung cancer patients
.
J Cancer Res Clin Oncol
.
2023
;
149
(
13
):
12459
68
.
97.
Sun
Z
,
Xiao
X
,
Liang
S
,
Ma
H
,
Sun
Y
,
Zhao
L
, et al
.
Consistency analysis of programmed death ligand 1 expression in non-small cell lung cancer between pleural effusion and matched primary lung cancer tissues by immunohistochemical double staining
.
Lab Invest
.
2024
;
104
(
6
):
102058
.
98.
Li
C
,
Huang
C
,
Mok
TS
,
Zhuang
W
,
Xu
H
,
Miao
Q
, et al
.
Comparison of 22C3 PD-L1 expression between surgically resected specimens and paired tissue microarrays in non-small cell lung cancer
.
J Thorac Oncol
.
2017
;
12
(
10
):
1536
43
.
99.
Koomen
BM
,
Voorham
QJM
,
Epskamp-Kuijpers
CCHJ
,
van Dooijeweert
C
,
van Lindert
ASR
,
Deckers
IAG
, et al
.
Considerable interlaboratory variation in PD-L1 positivity in a nationwide cohort of non-small cell lung cancer patients
.
Lung Cancer
.
2021
;
159
:
117
26
.
100.
Gosney
JR
,
Peake
MD
,
Kerr
KM
.
Improving practice in PD-L1 testing of non-small cell lung cancer in the UK: current problems and potential solutions
.
J Clin Pathol
.
2024
;
77
(
2
):
135
9
.
101.
Tsao
MS
,
Kerr
KM
,
Kockx
M
,
Beasley
M-B
,
Borczuk
AC
,
Botling
J
, et al
.
PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of Blueprint phase 2 project
.
J Thorac Oncol
.
2018
;
13
(
9
):
1302
11
.
102.
Sinclair
W
,
Kobalka
P
,
Ren
R
,
Beshai
B
,
Lott Limbach
AA
,
Wei
L
, et al
.
Interobserver agreement in programmed cell death-ligand 1 immunohistochemistry scoring in nonsmall cell lung carcinoma cytologic specimens
.
Diagn Cytopathol
.
2021
;
49
(
2
):
219
25
.
103.
Kravtsov
O
,
Hartley
CP
,
Sheinin
Y
,
Hunt
BC
,
Felix
JC
,
Giorgadze
T
.
Utility of PD-L1 testing on non-small cell lung cancer cytology specimens: an institutional experience with interobserver variability analysis
.
Ann Diagn Pathol
.
2020
;
48
:
151602
.
104.
Acanfora
G
,
Iaccarino
A
,
Cerbelli
B
,
Di Cristofano
C
,
Bellevicine
C
,
Barberis
M
, et al
.
InterobServer AgreeMent in Pd-l1 evaLuatIoN on cytoloGical samples-SAMPLING project: a multi-institutional, international study
.
Cancer Cytopathol
.
2025
;
133
(
3
):
e70003
.
105.
Butter
R
,
Hondelink
LM
,
van Elswijk
L
,
Blaauwgeers
JLG
,
Bloemena
E
,
Britstra
R
, et al
.
The impact of a pathologist’s personality on the interobserver variability and diagnostic accuracy of predictive PD-L1 immunohistochemistry in lung cancer
.
Lung Cancer
.
2022
;
166
:
143
9
.
106.
Hondelink
LM
,
Hüyük
M
,
Postmus
PE
,
Smit
VTHBM
,
Blom
S
,
von der Thüsen
JH
, et al
.
Development and validation of a supervised deep learning algorithm for automated whole-slide programmed death-ligand 1 tumour proportion score assessment in non-small cell lung cancer
.
Histopathology
.
2022
;
80
(
4
):
635
47
.
107.
Davri
A
,
Birbas
E
,
Kanavos
T
,
Ntritsos
G
,
Giannakeas
N
,
Tzallas
AT
, et al
.
Deep learning for lung cancer diagnosis, prognosis and prediction using histological and cytological images: a systematic review
.
Cancers
.
2023
;
15
(
15
):
3981
.
108.
Wu
J
,
Liu
C
,
Liu
X
,
Sun
W
,
Li
L
,
Gao
N
, et al
.
Artificial intelligence-assisted system for precision diagnosis of PD-L1 expression in non-small cell lung cancer
.
Mod Pathol
.
2022
;
35
(
3
):
403
11
.
109.
Kim
D
,
Sundling
KE
,
Virk
R
,
Thrall
MJ
,
Alperstein
S
,
Bui
MM
, et al
.
Digital cytology part 1: digital cytology implementation for practice: a concept paper with review and recommendations from the American Society of Cytopathology Digital Cytology Task Force
.
J Am Soc Cytopathol
.
2024
;
13
(
2
):
86
96
.
110.
Kim
D
,
Sundling
KE
,
Virk
R
,
Thrall
MJ
,
Alperstein
S
,
Bui
MM
, et al
.
Digital cytology part 2: artificial intelligence in cytology: a concept paper with review and recommendations from the American Society of Cytopathology Digital Cytology Task Force
.
J Am Soc Cytopathol
.
2024
;
13
(
2
):
97
110
.
You do not currently have access to this content.