Automated Detection of Kaposi Sarcoma–Associated Herpesvirus–Infected Cells in Immunohistochemical Images of Skin Biopsies

PURPOSEImmunohistochemical staining for the antigen of Kaposi sarcoma (KS)–associated herpesvirus, latency-associated nuclear antigen (LANA), is helpful in diagnosing KS. A challenge lies in distinguishing anti–LANA-positive cells from morphologically similar brown counterparts. This work aims to de...

Full description

Saved in:
Bibliographic Details
Main Authors: Iftak Hussain, Juan Boza, Robert Lukande, Racheal Ayanga, Aggrey Semeere, Ethel Cesarman, Jeffrey Martin, Toby Maurer, David Erickson
Format: Article
Language:English
Published: American Society of Clinical Oncology 2025-04-01
Series:JCO Global Oncology
Online Access:https://ascopubs.org/doi/10.1200/GO-24-00536
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849725483261886464
author Iftak Hussain
Juan Boza
Robert Lukande
Racheal Ayanga
Aggrey Semeere
Ethel Cesarman
Jeffrey Martin
Toby Maurer
David Erickson
author_facet Iftak Hussain
Juan Boza
Robert Lukande
Racheal Ayanga
Aggrey Semeere
Ethel Cesarman
Jeffrey Martin
Toby Maurer
David Erickson
author_sort Iftak Hussain
collection DOAJ
description PURPOSEImmunohistochemical staining for the antigen of Kaposi sarcoma (KS)–associated herpesvirus, latency-associated nuclear antigen (LANA), is helpful in diagnosing KS. A challenge lies in distinguishing anti–LANA-positive cells from morphologically similar brown counterparts. This work aims to develop an automated framework for localization and quantification of LANA positivity in whole-slide images (WSI) of skin biopsies.METHODSThe proposed framework leverages weakly supervised multiple-instance learning (MIL) to reduce false-positive predictions. A novel morphology-based slide aggregation method is introduced to improve accuracy. The framework generates interpretable heatmaps for cell localization and provides quantitative values for the percentage of positive tiles. The framework was trained and tested with a KS pathology data set prepared from skin biopsies of KS-suspected patients in Uganda.RESULTSThe developed MIL framework achieved an area under the receiver operating characteristic curve of 0.99, with a sensitivity of 98.15% and specificity of 96.00% in predicting anti–LANA-positive WSIs in a test data set.CONCLUSIONThe framework shows promise for the automated detection of LANA in skin biopsies, offering a reliable and accurate tool for identifying anti–LANA-positive cells. This method may be especially impactful in resource-limited areas that lack trained pathologists, potentially improving diagnostic capabilities in settings with limited access to expert analysis.
format Article
id doaj-art-9afcfe0a6e9d4cc38b3fd69a4f4fc81b
institution DOAJ
issn 2687-8941
language English
publishDate 2025-04-01
publisher American Society of Clinical Oncology
record_format Article
series JCO Global Oncology
spelling doaj-art-9afcfe0a6e9d4cc38b3fd69a4f4fc81b2025-08-20T03:10:27ZengAmerican Society of Clinical OncologyJCO Global Oncology2687-89412025-04-011110.1200/GO-24-00536Automated Detection of Kaposi Sarcoma–Associated Herpesvirus–Infected Cells in Immunohistochemical Images of Skin BiopsiesIftak Hussain0Juan Boza1Robert Lukande2Racheal Ayanga3Aggrey Semeere4Ethel Cesarman5Jeffrey Martin6Toby Maurer7David Erickson8Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NYMeinig School of Biomedical Engineering, Cornell University, Ithaca, NYDepartment of Pathology, Makerere University College of Health Sciences, Kampala, UgandaInfectious Diseases Institute, Makerere University College of Health Sciences, Kampala, UgandaInfectious Diseases Institute, Makerere University College of Health Sciences, Kampala, UgandaPathology and Laboratory Medicine, Weill Cornell Medical College, New York, NYDepartment of Epidemiology and Biostatistics, University of California, San Francisco, CADepartment of Dermatology, Indiana University School of Medicine, Indianapolis, INSibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NYPURPOSEImmunohistochemical staining for the antigen of Kaposi sarcoma (KS)–associated herpesvirus, latency-associated nuclear antigen (LANA), is helpful in diagnosing KS. A challenge lies in distinguishing anti–LANA-positive cells from morphologically similar brown counterparts. This work aims to develop an automated framework for localization and quantification of LANA positivity in whole-slide images (WSI) of skin biopsies.METHODSThe proposed framework leverages weakly supervised multiple-instance learning (MIL) to reduce false-positive predictions. A novel morphology-based slide aggregation method is introduced to improve accuracy. The framework generates interpretable heatmaps for cell localization and provides quantitative values for the percentage of positive tiles. The framework was trained and tested with a KS pathology data set prepared from skin biopsies of KS-suspected patients in Uganda.RESULTSThe developed MIL framework achieved an area under the receiver operating characteristic curve of 0.99, with a sensitivity of 98.15% and specificity of 96.00% in predicting anti–LANA-positive WSIs in a test data set.CONCLUSIONThe framework shows promise for the automated detection of LANA in skin biopsies, offering a reliable and accurate tool for identifying anti–LANA-positive cells. This method may be especially impactful in resource-limited areas that lack trained pathologists, potentially improving diagnostic capabilities in settings with limited access to expert analysis.https://ascopubs.org/doi/10.1200/GO-24-00536
spellingShingle Iftak Hussain
Juan Boza
Robert Lukande
Racheal Ayanga
Aggrey Semeere
Ethel Cesarman
Jeffrey Martin
Toby Maurer
David Erickson
Automated Detection of Kaposi Sarcoma–Associated Herpesvirus–Infected Cells in Immunohistochemical Images of Skin Biopsies
JCO Global Oncology
title Automated Detection of Kaposi Sarcoma–Associated Herpesvirus–Infected Cells in Immunohistochemical Images of Skin Biopsies
title_full Automated Detection of Kaposi Sarcoma–Associated Herpesvirus–Infected Cells in Immunohistochemical Images of Skin Biopsies
title_fullStr Automated Detection of Kaposi Sarcoma–Associated Herpesvirus–Infected Cells in Immunohistochemical Images of Skin Biopsies
title_full_unstemmed Automated Detection of Kaposi Sarcoma–Associated Herpesvirus–Infected Cells in Immunohistochemical Images of Skin Biopsies
title_short Automated Detection of Kaposi Sarcoma–Associated Herpesvirus–Infected Cells in Immunohistochemical Images of Skin Biopsies
title_sort automated detection of kaposi sarcoma associated herpesvirus infected cells in immunohistochemical images of skin biopsies
url https://ascopubs.org/doi/10.1200/GO-24-00536
work_keys_str_mv AT iftakhussain automateddetectionofkaposisarcomaassociatedherpesvirusinfectedcellsinimmunohistochemicalimagesofskinbiopsies
AT juanboza automateddetectionofkaposisarcomaassociatedherpesvirusinfectedcellsinimmunohistochemicalimagesofskinbiopsies
AT robertlukande automateddetectionofkaposisarcomaassociatedherpesvirusinfectedcellsinimmunohistochemicalimagesofskinbiopsies
AT rachealayanga automateddetectionofkaposisarcomaassociatedherpesvirusinfectedcellsinimmunohistochemicalimagesofskinbiopsies
AT aggreysemeere automateddetectionofkaposisarcomaassociatedherpesvirusinfectedcellsinimmunohistochemicalimagesofskinbiopsies
AT ethelcesarman automateddetectionofkaposisarcomaassociatedherpesvirusinfectedcellsinimmunohistochemicalimagesofskinbiopsies
AT jeffreymartin automateddetectionofkaposisarcomaassociatedherpesvirusinfectedcellsinimmunohistochemicalimagesofskinbiopsies
AT tobymaurer automateddetectionofkaposisarcomaassociatedherpesvirusinfectedcellsinimmunohistochemicalimagesofskinbiopsies
AT daviderickson automateddetectionofkaposisarcomaassociatedherpesvirusinfectedcellsinimmunohistochemicalimagesofskinbiopsies