Background: The incorporation of digital pathology into routine pathology practice is becoming more widespread. Definite advantages exist with respect to the implementation of artificial intelligence (AI) and deep learning in pathology, including cytopathology. However, there are also unique challenges in this regard. Summary: This review discusses cytology-specific challenges, including the need to implement digital cytology prior to AI; the large file sizes and increased acquisition times for whole slide images in cytology; the routine use of multiple stains, such as Papanicolaou and Romanowsky stains; the lack of high-quality annotated datasets on which to train algorithms; and the considerable computer resources required, in terms of both computer infrastructure and skilled personnel, for computing and storage of data. Global concerns regarding AI that are certainly applicable to cytology include the need for model validation and continued quality assurance, ethical issues such as the use of patient data in developing algorithms, the need to develop regulatory frameworks regarding what type of data can be utilized and ensuring cybersecurity during data collection and storage, and algorithm development. Key Messages: While AI will likely play a role in cytology practice in the future, applying this technology to cytology poses a unique set of challenges. A broad understanding of digital pathology and algorithm development is desirable to guide the development of algorithms, as well as the need to be cognizant of potential pitfalls to avoid when incorporating the technology in practice.

1.
Salto-Tellez
M
,
Maxwell
P
,
Hamilton
P
.
Artificial intelligence: the third revolution in pathology
.
Histopathology
.
2019 Feb
[cited 2019 Mar 24];
74
(
3
):
372
6
.
Available from
: http://www.ncbi.nlm.nih.gov/pubmed/30270453. .
2.
Chollet
F
.
Deep learning with python
. 1st ed.
Greenwich, CT
:
Manning Publications Co.
;
2017
.
3.
Abels
E
,
Pantanowitz
L
,
Aeffner
F
,
Zarella
MD
,
vd Laak
J
,
Bui
MM
,
Computational pathology definitions, best practices, and recommendations for regulatory guidance: a white paper from the Digital Pathology Association
.
J Pathol
.
2019
;
249
(
3
):
286
94
.
4.
Géron
A
.
Hands-on machine learning with scikit-learn, keras & tensorFlow
. 2nd ed.
O’Reilly Media Inc.
;
2019
. p.
23
32
.
5.
Capitanio
A
,
Dina
RE
,
Treanor
D
.
Digital cytology: a short review of technical and methodological approaches and applications
.
Cytopathology
.
2018
;
29
(
4
):
317
25
. .
6.
Niazi
MKK
,
Parwani
AV
,
Gurcan
MN
.
Digital pathology and artificial intelligence
.
Lancet Oncol
.
2019
;
20
(
5
):
e253
61
.
Available from
: . .
7.
Gill
G
.
Cytopreparation: principles & practice
.
New York
:
Springer
;
2013
.
Vols. 143–188
; p.
217
43
.
8.
Levi
AW
,
Chhieng
DC
,
Schofield
K
,
Kowalski
D
,
Harigopal
M
.
Implementation of FocalPoint GS location-guided imaging system: experience in a clinical setting
.
Cancer Cytopathol
.
2012 Apr
;
120
(
2
):
126
33
. .
9.
Thrall
MJ
.
Automated screening of Papanicolaou tests: a review of the literature
.
Diagn Cytopathol
.
2019 Jan
;
47
(
1
):
20
7
. .
10.
Kitchener
HC
,
Blanks
R
,
Dunn
G
,
Gunn
L
,
Desai
M
,
Albrow
R
,
Automation-assisted versus manual reading of cervical cytology (MAVARIC): a randomised controlled trial
.
Lancet Oncol
.
2011 Jan
;
12
(
1
):
56
64
. .
11.
Levi
AW
,
Galullo
P
,
Gordy
K
,
Mikolaiski
N
,
Schofield
K
,
Elsheikh
TM
,
Increasing cytotechnologist workload above 100 slides per day using the BD focalpoint GS imaging system negatively affects screening performance
.
Am J Clin Pathol
.
2012 Dec
;
138
(
6
):
811
5
. .
12.
Aeffner
F
,
Adissu
HA
,
Boyle
MC
,
Cardiff
RD
,
Hagendorn
E
,
Hoenerhoff
MJ
,
Digital microscopy, image analysis, and virtual slide repository
.
ILAR J
.
2018
;
59
(
1
):
66
. .
13.
McAlpine
ED
,
Michelow
P
.
The cytopathologist’s role in developing and evaluating artificial intelligence in cytopathology practice
.
Cytopathology
.
Blackwell Publishing Ltd
;
2020
.
14.
Rubin
DL
.
Artificial intelligence in imaging: the radiologist’s role
.
J Am Coll Radiol
.
2019
;
16
(
9 Pt B
):
1309
17
.
Available from
: . .
15.
FDA. Proposed Regulatory Framework for Modifications to Artificial Intelligence/Machine Learning (AI/ML)-Based Software as a Medical Device (SaMD). 2019;1–20. Available from: https://www.fda.gov/downloads/MedicalDevices/DigitalHealth/SoftwareasaMedicalDevice/UCM635052.pdf
.
16.
Panesar
A
.
Machine learning and AI for healthcare: big data for improved health outcomes
.
Berkeley, CA
:
Apress
;
2019
.
17.
Casey
K
.
How to staff an AI team: 11 key roles [Internet]. The Enterprisers Project
.
2019
[cited 2019 Sep 13]. Available from:
https://enterprisersproject.com/article/2019/6/how-staff-ai-team-11-key-roles.
18.
Tizhoosh
HR
,
Pantanowitz
L
.
Artificial intelligence and digital pathology: challenges and opportunities
.
J Pathol Inform
.
2018
;
9
(
1
):
38
.
Available from:
http://www.jpathinformatics.org/text.asp?2018/9/1/38/245402. .
19.
Mazer
BL
,
Paulson
N
,
Sinard
JH
.
Protecting the pathology commons in the digital era
.
Arch Pathol Lab Med
.
2020 Jun
;
144
(
9
):
1037
40
.
20.
Marée
R
.
The need for careful data collection for pattern recognition in digital pathology
.
J Pathol Inform
.
2017
[cited 2018 Dec 2];
8
:
19
.
Available from:
http://www.jpathinformatics.org/text.asp?2017/8/1/19/204200. .
21.
Barkan
GA
,
Wojcik
EM
,
Nayar
R
,
Savic-Prince
S
,
Quek
ML
,
Kurtycz
DF
,
The Paris System for reporting urinary cytology: the quest to develop a standardized terminology
.
Acta Cytol
.
2016
[cited 2018 Dec 2];
60
(
3
):
185
97
.
Available from
: http://www.ncbi.nlm.nih.gov/pubmed/27318895. .
22.
Sanghvi
AB
,
Allen
EZ
,
Callenberg
KM
,
Pantanowitz
L
.
Performance of an artificial intelligence algorithm for reporting urine cytopathology
.
Cancer Cytopathol
.
2019 Oct 1
;
127
(
10
):
658
66
. .
23.
Panesar
A
.
Machine learning and AI for healthcare: big data for improved health outcomes
.
Berkeley, CA
:
Apress
;
2019
.
24.
Japkowicz N. Why Question Machine Learning Evaluation Methods? (An illustrative review of the shortcomings of current methods). In: The AAAI Conference on Artificial Intelligence [Internet]. 2006. p. 6–11. Available from: https://aaai.org/
.
25.
Landau
MS
,
Pantanowitz
L
.
Artificial intelligence in cytopathology: a review of the literature and overview of commercial landscape
.
J Am Soc Cytopathol
.
2019
;
8
(
4
):
230
41
.
Available from
: . .
26.
Ngiam
KY
,
Khor
IW
.
Big data and machine learning algorithms for health-care delivery
.
Lancet Oncol
.
2019
;
20
(
5
):
e262
73
. .
27.
Griffin
J
,
Treanor
D
.
Digital pathology in clinical use: where are we now and what is holding us back?
Histopathology
.
Blackwell Publishing Ltd
;
2017
.
Vol. 70
; p.
134
45
.
28.
Araújo
ALD
,
Arboleda
LPA
,
Palmier
NR
,
Fonsêca
JM
,
de Pauli Paglioni
M
,
Gomes-Silva
W
,
The performance of digital microscopy for primary diagnosis in human pathology: a systematic review
.
Virchows archiv
.
Springer Verlag
;
2019
.
Vol. 474
; p.
269
87
.
29.
IMDRF SaMD Working Group
.
Software as a Medical Device (SaMD): clinical evaluation
.
Int Med Device Regul Forum
.
2017 Sep
:
4
8
.
30.
Kim
DW
,
Jang
HY
,
Kim
KW
,
Shin
Y
,
Park
SH
.
Design characteristics of studies reporting the performance of artificial intelligence algorithms for diagnostic analysis of medical images: results from recently published papers
.
Korean J Radiol
.
2019 Mar
;
20
(
3
):
405
10
. .
31.
Park
SH
,
Han
K
.
Methodologic guide for evaluating clinical performance and effect of artificial intelligence technology for medical diagnosis and prediction
.
Radiology
.
Radiological Society of North America Inc.
;
2018
.
Vol. 286
; p.
800
9
.
32.
Williams
BJ
,
Knowles
C
,
Treanor
D
.
Maintaining quality diagnosis with digital pathology: a practical guide to ISO 15189 accreditation
.
J Clin Pathol
.
2019 Oct
[cited 2019 Oct 22];
72
(
10
):
663
8
.
Available from:
http://jcp.bmj.com/lookup/doi/10.1136/jclinpath-2019-205944. .
33.
Davies
TG
,
Rahman
IA
,
Lautenschlager
S
,
Cunningham
JA
,
Asher
RJ
,
Barrett
PM
,
Open data and digital morphology
.
Proc Biol Sci
.
2017 Apr
;
284
(
1852
):
20170194
. .
34.
Prabhu
SP
.
Ethical challenges of machine learning and deep learning algorithms
.
The lancet oncology
.
Lancet Publishing Group
;
2019
.
Vol. 20
; p.
621
2
.
35.
Turnquist
C
,
Roberts-Gant
S
,
Hemsworth
H
,
White
K
,
Browning
L
,
Rees
G
,
On the edge of a digital pathology transformation: views from a cellular pathology laboratory focus group
.
J Pathol Inform
.
2019 Jan 1
;
10
(
1
):
37
. .
36.
Jaremko
JL
,
Azar
M
,
Bromwich
R
,
Lum
A
,
Alicia Cheong
LH
,
Gibert
M
,
Canadian Association of Radiologists white paper on ethical and legal issues related to artificial intelligence in radiology
.
Canadian Association of Radiologists Journal
.
Canadian Medical Association
;
2019
.
Vol. 70
; p.
107
18
.
37.
Huss
R
,
Coupland
SE
.
Software‐assisted decision support in digital histopathology
.
J Pathol
.
2020 Feb 25
;
250
(
5
):
685
92
.
38.
Brewster
DH
,
Fraser
LA
,
Harris
V
,
Black
RJ
.
Rising incidence of prostate cancer in Scotland: increased risk or increased detection?
BJU Int
.
2000
;
85
(
4
):
463
3
. .
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