Toxicologic Pathology Forum*: Opinion on the Future of Histopathology Using Whole Slide Images in Toxicologic Pathology of Preclinical Studies and Its Successful Implementation in Compliance With Good Laboratory Practice—Yes,We Are There!
Restricted accessResearch articleFirst published online October, 2025
Toxicologic Pathology Forum*: Opinion on the Future of Histopathology Using Whole Slide Images in Toxicologic Pathology of Preclinical Studies and Its Successful Implementation in Compliance With Good Laboratory Practice—Yes,We Are There!
Digital pathology (DP) for the purpose of primary reads has emerged as a transformative tool in the practice of histopathology and has already proved to be suitable, bringing numerous advantages over traditional light microscopy (LM). This position paper promotes the adoption of DP, particularly whole slide imaging (WSI), within toxicologic pathology, emphasizing its applicability in Good Laboratory Practice (GLP)-compliant nonclinical safety assessments. With established benefits such as efficiency, remote collaboration, data security, and compatibility with artificial intelligence AI-based tools, DP represents a reliable and advanced alternative. This paper offers a counterpoint to recent skepticism expressed in the literature on the readiness of DP including discussion of implementation strategies, technical requirements, and the growing body of validation evidence supporting DP’s utility in toxicologic pathology.
AbelsEPantanowitzLAeffnerF, et al. Computational pathology definitions, best practices, and recommendations for regulatory guidance: a white paper from the digital pathology association. J Pathol. 2019;249(3):286-294. doi:10.1002/path.5331.
2.
AeffnerFForestTSchumacherV, et al. Digital pathology and tissue image analysis. In: HaschekWMRousseauxCGWalligMABolonB, eds. Handbook of Toxicologic Pathology. 4th ed.vol 1. Cambridge, MA: Academic Press; 2022:395-421.
3.
AggarwalABharadwajSCorredorG, et al. Artificial intelligence in digital pathology — time for a reality check. Nat Rev Clin Oncol. 2025;22(4):283-291. doi:10.1038/s41571-025.
4.
Al-JanabiSHuismanAVan DiestPJ.Digital pathology: current status and future perspectives. Histopathology. 2012;61(1):1-9. doi:10.1111/j.1365-2559.2011.03814.x.
5.
Al SheikhyaqoobDOliveiraAFellaMLafertyDNiedobitekG. Polarised light scanner for digital pathology. Virchows Archiv. 2025;487:209-213. doi:10.1007/s00428-024.
6.
AzamASMiligyIMKimaniPKU, et al. Diagnostic concordance and discordance in digital pathology: a systematic review and meta-analysis. J Clin Pathol. 2021;74(7):448-455. doi:10.1136/jclinpath-2020-206764.
7.
BaidoshviliABucurAvan LeeuwenJ, et al. Evaluating the benefits of digital pathology implementation: time savings in laboratory logistics. Histopathology. 2018;73(5):784-794. doi:10.1111/his.13691.
8.
BertramCAStathonikosNDonovanTA, et al. Validation of digital microscopy: review of validation methods and sources of bias. Vet Pathol. 2022;59(1):26-38. doi:10.1177/03009858211040476.
9.
BorowskyADBishopJWDarrowMA, et al. Digital whole slide imaging compared with light microscopy for primary diagnosis in surgical pathology: a multicenter, double-blinded, randomized study of 2045 cases. Arch Pathol Lab Med. 2020;144(10):1245-1253. doi:10.5858/arpa.2019-0569.
10.
BoyceBF.An update on the validation of whole slide imaging systems following FDA approval of a system for a routine pathology diagnostic service in the United States. Biotech Histochem. 2017;92(6):381-389. doi:10.1080/10520295.2017.1355476.
11.
BradleyAJacobsenM.Toxicol pathol forum*: opinion on considerations for the use of whole slide images in GLP pathology peer review. Toxicol Pathol. 2019;47(7):100-107. doi:10.1177/0192623318818790.
12.
BradleyAECaryMGIsobeKNaylorSDrewS.Proof of concept: the use of whole-slide images (WSI) for peer review of tissues on routine regulatory toxicology studies. Toxicol Pathol. 2021;49(4):750-754. doi:10.1177/0192623320983252.
ClarkeEDohertyDRandellR, et al. Faster than light (microscopy): superiority of digital pathology over microscopy for assessment of immunohistochemistry. J Clin Pathol. 2021;76(5):333-338. doi:10.1136/jclinpath-2021.
15.
CrossSFFurnessPIgaliLSneadDTreanorD.Best Practice Recommendations for Implementing Digital Pathology. London, England: The Royal College of Pathologists, Special Advisory Committee on Cellular Pathology; 2018.
16.
ForestTAeffnerFBangariDS, et al. Scientific and regulatory policy committee brief communication: 2019 survey on use of digital histopathology systems in nonclinical toxicology studies. Toxicol Pathol. 2022;50(3):397-401. doi:10.1177/01926233221084621.
17.
GauthierBEGervaisFHammGO’SheaDPitonASchumacherVL.Toxicol pathol forum*: opinion on integrating innovative digital pathology tools in the regulatory framework. Toxicol Pathol. 2019;47(4):436-443. doi:10.1177/0192623319827485.
18.
GilbertsonJYagiY.Histology, imaging and new diagnostic work-flows in pathology. Diagn Pathol. 2008;3(1):1-3. doi:10.1186/1746-1596-3-S1-S14.
19.
IkenbergHLiederSAhrAWilhelmMSchönCXhajaA.Comparison of the hologic genius digital diagnostics system with the ThinPrep imaging system-a retrospective assessment. Cancer Cytopathol. 2023;131:424-432. doi:10.1002/cncy.22695.
20.
International Society for Pharmaceutical Engeneering (ISPE). GAMP 5: A Risk-Based Approach to Compliant GxP Computerized Systems. 2nd ed.North Bethesda, MD: ISPE; 2022.
21.
JacobsenMLewisABailyJFraserARudmannDRyanS.Utilizing whole slide images for the primary evaluation and peer review of a GLP-compliant rodent toxicology study. Toxicol Pathol. 2021;49(6):1164-1173. doi:10.1177/01926233211017031.
KelleherMCollingRBrowningL, et al. Department-wide validation in digital pathology: experience from an academic teaching hospital using the UK Royal college of pathologists’ guidance. Diagnostics (Basel). 2023;13(13):2144.
24.
KumarNGuptaRGuptaS.Whole slide imaging (WSI) in pathology: current perspectives and future directions. J Digit Imaging. 2020;33(4):1034-1040. doi:10.1007/s10278-020.
25.
L’ImperioVBrambillaVCazzanigaGFerrarioFNebuloniMPagniF.Digital pathology for the routine diagnosis of renal diseases: a standard model. J Nephrol. 2021;34(3):681-688. doi:10.1007/s40620-020.
26.
La PerleKMD. Toxicologic pathology forum: opinion on digital primary read and peer review—diving head-first into the deep digital pool!Toxicol Pathol. 2024;53(2):1-3. doi:10.1177/01926233241303909.
27.
LemppCArmsSBertramCA, et al. A minimal approach to demonstrate concordance of digital and conventional microscopy in toxicologic pathology. Toxicol Pathol. 2024;52(5):251-257. doi:10.1177/01926233241255125.
28.
MalarkeyDEWillsonGAWillsonCJ, et al. Utilizing whole slide images for pathology peer review and working groups. Toxicol Pathol. 2015;43(8):1149-1157. doi:10.1177/0192623315605933.
29.
McGenityCClarkeELJenningsC, et al. Artificial intelligence in digital pathology: a systematic review and meta-analysis of diagnostic test accuracy. NPJ Digit Med. 2024;7(1):1-19. doi:10.1038/s41746-024.
30.
OECD. Digital Histopathology—is there any objection from the GLP compliance monitoring authorities to implement digital pathology in GLP studies? In: OECD good laboratory practice: frequently asked questions (FAQs). Published June 15, 2022. Accessed June 30, 2025. https://www.oecd.org/chemicalsafety/testing/glp-frequently-asked-questions.htm.
31.
OECD. Guidance Document on the GLP Requirements for Peer Review of Histopathology. OECD Series on Principles of Good Laboratory Practice and Compliance Monitoring. Paris, France: Organisation for Economic Co-operation and Development; 2022.
32.
PantanowitzLSharmaACarterABKurcTSussmanASaltzJ.Twenty years of digital pathology: an overview of the road travelled, what is on the horizon, and the emergence of vendor-neutral archives. J Pathol Inform. 2018;9(40):1-12. doi:10.4103/jpi.jpi_69_18.
33.
ParkSAnilVPRaymondDA, et al. The history of pathology informatics: a global perspective. J Pathol Inform. 2013;4(1):7. doi:10.4103/2153-3539.112689.
34.
RajaganesanSKumarRRaoV, et al. Comparative assessment of digital pathology systems for primary diagnosis. J Pathol Inform. 2021;12(1):25-25. doi:10.4103/jpi.jpi_94_20.
35.
SchaferKARaoDB.Toxicol pathol forum: opinion on digital primary read and peer review—are we there yet?Toxicol Pathol. 2025;53:210-214. doi:10.1177/01926233241303911.
36.
SchumacherVLAeffnerMBaraleE, et al. The application, challenges, and advancement toward regulatory acceptance of digital toxicologic pathology: results of the 7th ESTP international expert workshop (September 20-21, 2019). Toxicol Pathol. 2021;49(4):720-737. doi:10.1177/0192623320975841.
37.
StathonikosNNguyenTQvan DiestPJ.Rocky road to digital diagnostics: implementation issues and exhilarating experiences. J Clin Pathol. 2021;74(7):415-420. doi:10.1136/jclinpath-2020.
38.
US Food Drug Administration. Guidance for industry: use of whole slide imaging in nonclinical toxicology studies: questions and answers. Published May 23, 2023. Accessed August 4, 2025. https://www.fda.gov/media/168209/download.
39.
WeinsteinRSGrahamARLianF, et al. Reconciliation of diverse telepathology system designs. Historic issues and implications for emerging markets and new applications. APMIS. 2012;120(4):256-275. doi:10.1111/j.1600-0463.2011.02866.x.
40.
WilliamsBJTreanorD.Practical guide to training and validation for primary diagnosis with digital pathology. J Clin Pathol. 2020;73(7):418-422. doi:10.1136/jclinpath-2019.
41.
ZiaSYildiz-AktasIZZiaFParwaniAV.An update on applications of digital pathology: primary diagnosis; telepathology, education and research. Diagn Pathol. 2025;20(1):17. doi:10.1186/s13000-025.
