Introduction: Thyroid cytology is a widely accepted tool in the clinical triaging of nodular lesions. Cell blocks (CBs) can help in the diagnosis of atypical lesions, namely, thyroid Bethesda category of Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS). Methods: In a series of 224 AUS/FLUS thyroid samples with CB, we studied CB cellularity and feasibility of 3 immunohistochemical markers (cytokeratin 19 [CK19], HBME-1, and galectin-3) apart and in combination. Results: The CBs were non-diagnostic in 34 cases. Twenty-four CBs contained <10 cells, 45 CBs 10–50 cells, and 121 CBs >50 cells. Notably, more cellularity was found in CBs performed by plasma-thrombin and in-house techniques (p < 0.001). The diagnostic accuracy to detect malignancy was 65.1% for CK19, 72.1% for HBME-1, and 70.3% for galectin-3. Conclusion: In conclusion, CB cellularity is essential for successful immunohistochemistry application and further diagnostic workup of AUS/FLUS cases.

1.
Kholová
I
,
Schalin-Jäntti
C
.
Thyroid fine needle aspiration cytology
. In:
Huhtaniemi
I
,
Martini
L
, editors.
Encyclopedia of endocrine diseases
. 2nd ed.
Oxford
:
Academic Press
;
2018
. p.
565
72
.
2.
Syed
AZ
,
Cibas
ES
.
The Bethesda system for reporting thyroid cytopathology: definitions, criteria and explanatory notes
. 1st ed.
New York, NY, USA
:
Springer
;
2010
.
3.
Straccia
P
,
Rossi
ED
,
Bizzarro
T
,
Brunelli
C
,
Cianfrini
F
,
Damiani
D
, et al
A meta-analytic review of the Bethesda system for reporting thyroid cytopathology: has the rate of malignancy in indeterminate lesions been underestimated?
Cancer Cytopathol
.
2015 Dec
;
123
(
12
):
713
22
. .
4.
Syed
AZ
,
Cibas
ES
.
The Bethesda system for reporting thyroid cytopathology: definitions, criteria, and explanatory notes
. 2nd ed.
Cham, Switzerland
:
Springer
;
2018
.
5.
Vuong
HG
,
Ngo
HTT
,
Bychkov
A
,
Jung
CK
,
Vu
TH
,
Lu
KB
, et al
Differences in surgical resection rate and risk of malignancy in thyroid cytopathology practice between Western and Asian countries: a systematic review and meta-analysis
.
Cancer Cytopathol
.
2020 Apr
;
128
(
4
):
238
49
. .
6.
Kholova
I
,
Ludvikova
M
.
Thyroid atypia of undetermined significance or follicular lesion of undetermined significance: an indispensable Bethesda 2010 diagnostic category or waste garbage?
Acta Cytol
.
2014
;
58
(
4
):
319
29
.
7.
Geramizadeh
B
,
Bos-Hagh
S
,
Maleki
Z
.
Cytomorphologic, imaging, molecular findings, and outcome in thyroid follicular lesion of undetermined significance/atypical cell of undetermined significance (AUS/FLUS): a mini-review
.
Acta Cytol
.
2019
;
63
(
1
):
1
9
. .
8.
Jain
D
,
Mathur
SR
,
Iyer
VK
.
Cell blocks in cytopathology: a review of preparative methods, utility in diagnosis and role in ancillary studies
.
Cytopathology
.
2014 Dec
;
25
(
6
):
356
71
. .
9.
Krogerus
L
,
Kholová
I
.
Cell block in cytological diagnostics: review of preparatory techniques
.
Acta Cytol
.
2018
;
62
(
4
):
237
43
. .
10.
Nambirajan
A
,
Jain
D
.
Cell blocks in cytopathology: an update
.
Cytopathology
.
2018 Dec
;
29
(
6
):
505
24
. .
11.
Shidham
VB
.
CellBlockistry: chemistry and art of cell-block making: a detailed review of various historical options with recent advances
.
Cytojournal
.
2019
;
16
:
12
. .
12.
Saqi
A
.
The state of cell blocks and ancillary testing: past, present, and future
.
Arch Pathol Lab Med
.
2016 Dec
;
140
(
12
):
1318
22
. .
13.
da Cunha Santos
G
,
Saieg
MA
.
Preanalytic specimen triage: smears, cell blocks, cytospin preparations, transport media, and cytobanking
.
Cancer
.
2017 Jun
;
125
(
S6
):
455
64
. .
14.
Kholova
I
,
Ryska
A
,
Ludvikova
M
,
Cap
J
,
Pecen
L
.
Dipeptidyl peptidase IV expression in thyroid cytology: retrospective histologically confirmed study
.
Cytopathology
.
2003 Feb
;
14
(
1
):
27
31
.
15.
Cochand-Priollet
B
,
Dahan
H
,
Laloi-Michelin
M
,
Polivka
M
,
Saada
M
,
Herman
P
, et al
Immunocytochemistry with cytokeratin 19 and anti-human mesothelial cell antibody (HBME1) increases the diagnostic accuracy of thyroid fine-needle aspirations: preliminary report of 150 liquid-based fine-needle aspirations with histological control
.
Thyroid
.
2011 Oct
;
21
(
10
):
1067
73
. .
16.
Kalfert
D
,
Ludvikova
M
,
Kholova
I
,
Ludvik
J
,
Topolocan
O
,
Plzak
J
.
Combined use of galectin-3 and thyroid peroxidase improves the differential diagnosis of thyroid tumors
.
Neoplasma
.
2020 Jan
;
67
(
1
):
164
70
. .
17.
Pusztaszeri
MP
,
Sadow
PM
,
Faquin
WC
.
CD117: a novel ancillary marker for papillary thyroid carcinoma in fine-needle aspiration biopsies
.
Cancer Cytopathol
.
2014 Aug
;
122
(
8
):
596
603
. .
18.
Abdou
AG
,
Abdelwahed
M
,
Said
A
,
Taie
DM
,
Fahmy
S
.
Evaluation of the diagnostic value of Emerin and CD56 in papillary thyroid carcinoma: an immunohistochemical study
.
J Immunoassay Immunochem
.
2018
;
39
(
5
):
521
37
. .
19.
Sadowski
SM
,
Petrenko
V
,
Meyer
P
,
Pusztaszeri
M
,
Brulhart-Meynet
MC
,
Heddad Masson
M
, et al
Validation of molecular biomarkers for preoperative diagnostics of human papillary thyroid carcinoma in fine needle aspirates
.
Gland Surg
.
2019 Aug
;
8
(
Suppl 2
):
S62
76
. .
20.
Maleki
Z
,
Abram
M
,
Dell'Aquila
M
,
Kilic
I
,
Lu
R
,
Musarra
T
, et al
Insulinoma-associated protein 1 (INSM-1) expression in medullary thyroid carcinoma FNA: a multi-institutional study
.
J Am Soc Cytopathol
.
2020 May–Jun
;
9
(
3
):
185
90
. .
21.
Huhtamella
R
,
Kholová
I
.
Thyroid Bethesda category AUS/FLUS in our microscopes: three-year-experience and cyto-histological correlation
.
Cancers
.
2019 Oct 28
;
11
(
11
):
1670
. .
22.
Hakso-Makinen
H
,
Kholova
I
.
New cell block method to enhance the cellular yield in mucous and/or bloody samples
.
Acta Cytol
.
2020
;
64
(
3
):
265
9
.
23.
Haugen
BR
.
2015 American Thyroid Association Management Guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: what is new and what has changed?
Cancer
.
2017 Feb 1
;
123
(
3
):
372
81
. .
24.
Srebotnik Kirbis
I
,
Rodrigues Roque
R
,
Bongiovanni
M
,
Strojan Flezar
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 Oct
;
128
(
10
):
757
66
.
25.
Fischer
AH
,
Schwartz
MR
,
Moriarty
AT
,
Wilbur
DC
,
Souers
R
,
Fatheree
L
, et al
Immunohistochemistry practices of cytopathology laboratories: a survey of participants in the College of American Pathologists nongynecologic cytopathology education program
.
Arch Pathol Lab Med
.
2014 Sept
;
138
(
9
):
1167
72
. .
26.
Herbert
A
.
Cell blocks are not a substitute for cytology: why pathologists should understand cytopathology particularly in their chosen speciality
.
Cytopathology
.
2014 Dec
;
25
(
6
):
351
5
. .
27.
Mais
DD
,
Crothers
BA
,
Davey
DD
,
Natale
KE
,
Nayar
R
,
Souers
RJ
, et al
Trends in thyroid fine-needle aspiration cytology practices: results from a College of American Pathologists 2016 practice survey
.
Arch Pathol Lab Med
.
2019 Nov
;
143
(
11
):
1364
72
. .
28.
VanderLaan
PA
,
Marqusee
E
,
Krane
JF
.
Clinical outcome for atypia of undetermined significance in thyroid fine-needle aspirations: should repeated fna be the preferred initial approach?
Am J Clin Pathol
.
2011 May
;
135
(
5
):
770
5
. .
29.
Cristo
AP
,
Goldstein
HF
,
Faccin
CS
,
Maia
AL
,
Graudenz
MS
.
Increasing diagnostic effectiveness of thyroid nodule evaluation by implementation of cell block preparation in routine US-FNA analysis
.
Arch Endocrinol Metab
.
2016 Aug
;
60
(
4
):
367
73
. .
30.
Abu-Sinna
E
,
Hasan
MY
,
El-Deftar
MM
,
Amer
SA
,
Abdelsalam
LO
,
Nakhla
JA
.
Galectin-3 and HBME-1 expression on agarose cell blocks from fine-needle aspirates of follicular cell-derived thyroid tumors
.
J Cytol
.
2018 Jan–Mar
;
35
(
1
):
27
32
. .
31.
Desai
KM
,
Angadi
PV
,
Kale
AD
,
Hallikerimath
S
.
Assessment of cell block technique in head and neck pathology diagnoses: a preliminary study
.
Diagn Cytopathol
.
2019 May
;
47
(
5
):
445
51
. .
32.
de Matos
LL
,
Del Giglio
AB
,
Matsubayashi
CO
,
de Lima Farah
M
,
Del Giglio
A
,
da Silva Pinhal
MA
.
Expression of CK-19, galectin-3 and HBME-1 in the differentiation of thyroid lesions: systematic review and diagnostic meta-analysis
.
Diagn Pathol
.
2012 Aug 13
;
7
:
97
. .
33.
Ratour
J
,
Polivka
M
,
Dahan
H
,
Hamzi
L
,
Kania
R
,
Dumuis
ML
, et al
Diagnosis of follicular lesions of undetermined significance in fine-needle aspirations of thyroid nodules
.
J Thyroid Res
.
2013
;
2013
:
250347
. .
34.
Fadda
G
,
Rossi
ED
,
Raffaelli
M
,
Pontecorvi
A
,
Sioletic
S
,
Morassi
F
, et al
Follicular thyroid neoplasms can be classified as low- and high-risk according to HBME-1 and Galectin-3 expression on liquid-based fine-needle cytology
.
Eur J Endocrinol
.
2011 Sept
;
165
(
3
):
447
53
. .
35.
Margari
N
,
Giovannopoulos
I
,
Pouliakis
A
,
Mastorakis
E
,
Gouloumi
AR
,
Panayiotides
IG
, et al
Application of immunocytochemistry on cell block sections for the investigation of thyroid lesions
.
Acta Cytol
.
2018
;
62
(
2
):
137
44
. .
36.
Rossi
ED
,
Fadda
G
,
Schmitt
F
.
The nightmare of indeterminate follicular proliferations: when liquid-based cytology and ancillary techniques are not a moon landing but a realistic plan
.
Acta Cytol
.
2014
;
58
(
6
):
543
51
. .
37.
Cochand-Priollet
B
,
Schmitt
FC
,
Totsch
M
,
Vielh
P
;
European Federation of Cytology Societies’ Scientific C
.
The Bethesda terminology for reporting thyroid cytopathology: from theory to practice in Europe
.
Acta Cytol
.
2011
;
55
(
6
):
507
11
.
38.
Satturwar
S
,
Malenie
R
,
Sutton
A
,
Dai
D
,
Aly
FZ
.
Validation of immunohistochemical tests performed on cytology cell block material: practical application of the College of American Pathologists’ guidelines
.
Cytojournal
.
2019
;
16
:
6
. .
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