Images in Obstetrics
org
The Placenta Pathology Tool: an online application
for understanding histopathologic lesions
Rini Lukose, MHSc, BSc; Maria Mazaharally, MHSc, BSc; Raymond W. Redline, MD; Brian J. Cox, PhD, MSc, BSc
Introduction
Placental pathology can play an important role in helping to
determine the etiology of pregnancy complications, guiding the
immediate and future care of patients including the prediction
of recurrence risks, helping patients and doctors to come to
terms with why adverse outcomes have occurred, and generally
advancing the scientific underpinnings of obstetrical diseases.1
However, pathology in general and placental pathology in
particular can be difficult for nonpathologists to grasp. One of
the barriers to understanding is a failure to appreciate the
relatively simple overall hierarchical structure of placental
pathology. In brief, maternal and fetal vascular disorders can be
separated into subcategories of maldevelopment, malperfu-
sion, and loss of integrity; inflammatory disorders can be
separated into infectious and idiopathic subcategories; and
structural abnormalities can be separated into malformations,
deformations, disruptions, and underlying genomic abnor-
malities. Each subcategory includes several diagnostic headings
under which the actual diagnostic lesions fall themselves.
Taken out of context, these lesions can be confusing and
obscure, but when considered within this hierarchical struc-
ture, they are easier to understand.
It seems obvious that placental pathology is of little use if not
readily comprehensible to the clinicians who actually manage
patients. However, this aspect of placental pathology has been
underemphasized, and there is an urgent need to address this
deficiency. Although subject reviews and continuing medical
education courses can contribute, it would be particularly
helpful to have a real-time, online resource that allows the busy
clinician to rapidly interpret and understand lesions that
appear in the placenta report.
This report introduces the Placental Pathology Tool, a com-
prehensive online guide for understanding histopathologic
From the Department of Physiology, University of Toronto, Toronto,
Ontario, Canada (Mses Lukose and Mazaharally and Dr Cox); Departments
of Pathology and Reproductive Biology, Case Western Reserve University
School of Medicine, Cleveland, OH (Dr Redline); and Department of
Obstetrics and Gynecology, University of Toronto, Toronto, Ontario,
Canada (Dr Cox).
Received July 14, 2023; accepted July 26, 2023.
The authors report no conflict of interest.
Corresponding authors: Brian J. Cox, PhD, MSc, BSc. b.cox@utoronto.ca
Raymond W. Redline, MD. raymond.redline@uhhospitals.org
0002-9378
ª 2023 The Authors. Published by Elsevier Inc. This is an open access article under
the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
https://doi.org/10.1016/j.ajog.2023.07.051
264 American Journal of Obstetrics & Gynecology FEBRUARY 2024
ajog.
lesions. As described in detail below, this application is hierar-
chically structured with each branch of the tree fully explained
and related to the underlying pathophysiology and clinical
context with selected references. Descriptions of individual le-
sions are paired with color illustrations, and the application is
fully searchable for diagnostic terms, synonyms, and key words.
We anticipate that the Placental Pathology Tool will be of value
to clinicians who are reading placenta reports and anyone
who wishes to better familiarize themselves with the clinical and
biologic significance of placental lesions.
Methods
The Placental Pathology Tool was originally developed as part
of a larger initiative, the Placental Atlas Tool, that included 2
of the authors of this study (R.W.R. and B.J.C.). This project
sought to create a comprehensive online resource for all types
of biologic data related to the placenta.2 Sponsored by the
Human Placenta Project and initially funded by the National
Institutes of Health, this resource did not receive long-term
financial support and is no longer accessible. We therefore
decided to revise and relaunch the pathology component as a
freely available resource to make terminology, images, and
diagnostic criteria accessible to the community. The inter-
active web application was built using the R shiny platform
(R Studio, R Core Team, Vienna, Austria), which can run on
a variety of computer operating systems and web browsers,
including mobile devices. Placental pathology annotation text
files were hierarchically organized using the R yaml package
(version 2.3.5). The yaml text file was read into R as an
interactive tree structure using the R data.tree package
(version 1.0.0) that can be expanded and collapsed. The data
tree, associated pathology images and descriptions, and
hyperlinked citations were then attached to the annotation
terms. Data were displayed in a web application using the R
shiny package and hosted at shiny.io. The code for the pa-
thology tool is available through a GitHub repository
(https://github.com/rLukose99/Placenta-Pathology-Tool.git).
The application can be accessed through https://placenta.
shinyapps.io/placenta_pathology_app/.
Description
The Placental Pathology Tool contains 156 hierarchically
structured classification terms based on the 2016 Amsterdam
consensus diagnostic terminology as defined in the original
manuscript and a subsequent, more comprehensive text-
book.3,4 Pathophysiological categories 1 and 2 describe ab-
normalities related to maternal and fetal vasculature.
Category 3 describes patterns of placental inflammation
elicited by infectious organisms, innate inflammatory
ajog.org Images in Obstetrics

FIGURE
Illustration of Placental Pathology Tool features

A, Tab 1 Home Page: describes the overall purpose and structure of the application; a classification tree, fully browsable with expandable features
and a hierarchical organization. B, Tab 3 Classification tree: partially expanded to show only the 7 major pathophysiologic groups. C, Tab 3 Classification

FEBRUARY 2024 American Journal of Obstetrics & Gynecology 265

 Images in Obstetrics ajog.org

activators, autoantigens, and maternal or fetal alloantigens. Summary

Categories 4 and 5 on malformations or deformations and
disruptions use nomenclature developed for classifying fetal
congenital anomalies to organize disorders of placental
structure. Categories 6 and 7 describe the phenotypic ex-
pressions of specific placental, genomic, and epigenomic
abnormalities.
The application is organized into 5 tabs. The Home tab
provides an overview of the hierarchical application structure
and its branching architecture (Figure, A). The Getting
Started tab provides a brief instructional video and a detailed
user guide. The Classification Tree tab is the main access
point for the application. It can be directly searched for in-
dividual diagnostic terms. Alternatively, it can be serially
expanded to reveal the 7 major pathophysiological groups
(Figure, B), followed by subcategories, diagnostic headers,
and individual lesions. These elements are further annotated
with preferred nomenclature, synonyms and alternative
names, definition and current understanding, key words
indicating clinical and pathophysiological relationships,
hyperlinked references, and gross or microscopic images.
Many of the images were reproduced with permission from a
recent textbook by one of the authors (R.W.R.) that can be
consulted for further details.5 A representative example of
this annotation with an image is shown in Figure, C for the
placental lesion known as chorangiosis. The Can’t Find A
Term tab is a fully searchable lookup table showing the entire
classification tree. A key word search of this table for the term
infarction is illustrated in Figure, D. The final Contact tab
provides an email address for any additional questions
regarding the use of the application.
The Placental Pathology Tool is an easy-to-use, interactive
resource for users to directly access and learn more about
specific placental lesions with the goal of improving perinatal
care. The open R shiny code enables future updates to the
database, including classifications and images. More broadly,
through promoting an interdisciplinary approach of data sci-
ence and clinical knowledge, we hope to build on the Placenta
Pathology Tool platform to provide community resources
related to the placenta and reproductive biology. -
ACKNOWLEDGMENTS
The authors thank Geetu Tuteja, PhD, for critical feedback on the appli-
cation. B.J.C. was supported, in part, by a Canadian Research Chair Tier II
program.
REFERENCES
1. Redline RW, Roberts DJ, Parast MM, et al. Placental pathology is
necessary to understand common pregnancy complications and achieve
an improved taxonomy of obstetrical disease. Am J Obstet Gynecol
2023;228:187–202.
2. Ilekis JV, Keller M, Shlionskaya A, et al. The Placental Atlas Tool (PAT): A
collaborative research and discovery platform for the placental research
community. Placenta 2019;80:42–8.
3. Khong TY, Mooney EE, Ariel I, et al. Sampling and Definitions of
Placental Lesions: Amsterdam Placental Workshop Group Consensus
Statement. Arch Pathol Lab Med 2016;140:698–713.
4. Khong P, Mooney Y, Gordijn E, Nikkels S, Morgan T, eds. Pathology of
the singleton third trimester placenta. Berlin, Germany: Springer; 2019:
395.
5. Redline RW, Boyd TK, Roberts DJ In: Cohen MC, Scheimberg I, eds.
Placental and gestational pathology. Placental and Gestational Pathology.
1st ed. Cambridge, England: Cambridge University Press; 2018:1–356.

=
tree: fully expanded to show all data related to the placental lesion known as chorangiosis. The full expansion demonstrates antecedent headers. The
image shows a diagnostic increase of more than 10 capillary cross sections per terminal villus. The additional information provides preferred terminology,
synonyms or alternative terms, definition, current understanding, key words for clinical associations and pathophysiology, and hyperlinked references.
D, Tab 4 Can’t Find a Term: this lookup table can be searched to view all items containing any term or key word of interest. Illustrated is the result of a
search for the term infarction demonstrating the wide variety of placental processes that include tissue infarction in their pathogenesis.
Lukose. The Placenta Pathology Tool. Am J Obstet Gynecol 2024.

266 American Journal of Obstetrics & Gynecology FEBRUARY 2024