Towards Cellular-Scale Interpretability in Pathology Foundation Models for Biomarker Assessment

[Submitted on 7 Nov 2025 (v1), last revised 2 Jul 2026 (this version, v2)]

Authors:Jingsong Liu, Han Li, Zhengyang Xu, Franz-Leonard Klaus, Fabian Stögbauer, Shihui Zu, Weiwei Zhou, Atsuko Kasajima, Felix Schicktanz, Alexander Muckenhuber, Julius Shakhtour, Jiale Yu, Tiannan Zheng, Xun Ma, Maggie Wang, Christian Grashei, Bao Li, Guiyang Jiang, Hongming Xu, Shaohua Kevin Zhou, Nassir Navab, Peter J. Schüffler

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Abstract:Molecular biomarker testing in pathology is often costly and tissue-consuming, limiting scalable clinical deployment. Artificial intelligence applied to hematoxylin and eosin (HE)-stained histology could enable rapid biomarker screening, but clinical translation requires models that are both accurate and interpretable. Here we introduce Hireca, a biomarker-focused pathology foundation model pretrained on more than 80,000 whole-slide images spanning 38 organ types from three medical centers, together with CytoMap, an interpretability module that localizes cellular-scale evidence underlying predictions. Across 10 biomarker tasks encompassing morphological, molecular, genetic, and spatial-transcriptomic-proxy readouts, Hireca ranked first in five tasks and outperformed comparable models overall. In evaluation by eight pathologists from two countries, CytoMap was consistently preferred over alternative visualization approaches and revealed error patterns in difficult cases. These results position Hireca and CytoMap as a transparent framework for clinically reviewable biomarker assessment directly from routine HE histology.

Submission history

From: Jingsong Liu [view email]
[v1] Fri, 7 Nov 2025 11:05:36 UTC (454 KB)
[v2] Thu, 2 Jul 2026 15:10:58 UTC (31,368 KB)