Validation of Whole-Slide Foundation Models for Image Retrieval in TCGA Data

Fuente: arXiv
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Autori principali: Lei, Tianhao, Esmaeilkhani, Parsa, Alfasly, Saghir, Uegami, Wataru, Boughey, Judy C., Goetz, Matthew P., Kalari, Krishna R., Tizhoosh, H. R.
Natura: Preprint
Pubblicazione: 2026
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author Lei, Tianhao
Esmaeilkhani, Parsa
Alfasly, Saghir
Uegami, Wataru
Boughey, Judy C.
Goetz, Matthew P.
Kalari, Krishna R.
Tizhoosh, H. R.
author_facet Lei, Tianhao
Esmaeilkhani, Parsa
Alfasly, Saghir
Uegami, Wataru
Boughey, Judy C.
Goetz, Matthew P.
Kalari, Krishna R.
Tizhoosh, H. R.
contents Foundation models are reshaping computational histopathology, yet their value for whole-slide image retrieval relative to strong patch-based and supervised aggregation baselines remains unclear. We benchmarked ten pipelines on 9,387 diagnostic slides spanning 17 organs and 60 diagnoses from The Cancer Genome Atlas (TCGA) using patient-level leave-one-patient-out evaluation. Methods included four pre-trained slide foundation models, a supervised attention-based multiple instance learning (ABMIL) aggregator on patch embeddings, and patch-level retrieval across five sampling densities. Performance varied more across organs and diagnoses than across architectures. Although the slide foundation model TITAN achieved the strongest overall results, its advantage was modest; ABMIL and patch-based methods reached comparable Top-1 and Top-3 accuracy, with no model consistently dominant. Morphologically distinctive entities approached ceiling performance, while rare, heterogeneous, and closely related subtypes remained challenging. Misclassifications aligned with organs exhibiting known inter-observer variability, suggesting an intrinsic ceiling for morphology-only retrieval. Performance was driven primarily by patch-level feature representations, with limited benefit from slide-level aggregation, indicating aggregation may be unnecessary in many settings. These findings argue against a universally optimal architecture and instead support organ-resolved benchmarking, diagnosis-aware or ensemble strategies, stronger feature representations, and multimodal retrieval frameworks. Notably, even the best model achieved only $\approx 68\% \pm 21\%$ retrieval accuracy on TCGA, and some subtypes showed $0\%$ accuracy across all methods, highlighting fundamental limitations of morphology-based representations and the need for substantial progress before reliable clinical deployment.
format Preprint
id arxiv_https___arxiv_org_abs_2605_00902
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle Validation of Whole-Slide Foundation Models for Image Retrieval in TCGA Data
Lei, Tianhao
Esmaeilkhani, Parsa
Alfasly, Saghir
Uegami, Wataru
Boughey, Judy C.
Goetz, Matthew P.
Kalari, Krishna R.
Tizhoosh, H. R.
Computer Vision and Pattern Recognition
Information Retrieval
Foundation models are reshaping computational histopathology, yet their value for whole-slide image retrieval relative to strong patch-based and supervised aggregation baselines remains unclear. We benchmarked ten pipelines on 9,387 diagnostic slides spanning 17 organs and 60 diagnoses from The Cancer Genome Atlas (TCGA) using patient-level leave-one-patient-out evaluation. Methods included four pre-trained slide foundation models, a supervised attention-based multiple instance learning (ABMIL) aggregator on patch embeddings, and patch-level retrieval across five sampling densities. Performance varied more across organs and diagnoses than across architectures. Although the slide foundation model TITAN achieved the strongest overall results, its advantage was modest; ABMIL and patch-based methods reached comparable Top-1 and Top-3 accuracy, with no model consistently dominant. Morphologically distinctive entities approached ceiling performance, while rare, heterogeneous, and closely related subtypes remained challenging. Misclassifications aligned with organs exhibiting known inter-observer variability, suggesting an intrinsic ceiling for morphology-only retrieval. Performance was driven primarily by patch-level feature representations, with limited benefit from slide-level aggregation, indicating aggregation may be unnecessary in many settings. These findings argue against a universally optimal architecture and instead support organ-resolved benchmarking, diagnosis-aware or ensemble strategies, stronger feature representations, and multimodal retrieval frameworks. Notably, even the best model achieved only $\approx 68\% \pm 21\%$ retrieval accuracy on TCGA, and some subtypes showed $0\%$ accuracy across all methods, highlighting fundamental limitations of morphology-based representations and the need for substantial progress before reliable clinical deployment.
title Validation of Whole-Slide Foundation Models for Image Retrieval in TCGA Data
topic Computer Vision and Pattern Recognition
Information Retrieval
url https://arxiv.org/abs/2605.00902