Title: Tissue Microenvironment as an Additional Prior for Visual Representation Learning in Histopathology
Primary area: applications to physical sciences (physics, chemistry, biology, etc.)
Keywords: Representation Learning, Unsupervised Segmentation, Data-Augmentation, Histopathology, Mutation Prediction

Abstract: Self-supervised learning has transformed histopathology by enabling foundation models to learn from vast unlabeled image archives, with methods developed using natural images, such as DINOv2, establishing powerful baselines. We propose augmenting these approaches by incorporating tissue microenvironment structure as an additional prior through semantic masking. We train adversarial mask generators adapted from ADIOS with perceptual reconstruction losses to identify tissue structures, then integrate these semantic masks as augmentations within DINOv2 self-supervised learning pipelines. Using a set of 55 million TCGA histopathology tiles of 224$\times$224 pixels at a resolution of 0.5 $\mu$m/pixel, we pre-train vision transformers to evaluate three augmentation strategies: standard DINOv2 augmentations, mixed (combining standard and semantic masking), and semantic masking only. The mixed augmentation strategy, when used in DINOv2, demonstrates consistent improvements over baseline across four patch-level classification benchmarks (PCam, MiDOG, MHIST, BRACS) and on two slide-level mutation prediction tasks (EGFR in LUAD, FGFR3 in BLCA). Qualitative PCA visualization of patch tokens shows that semantic masks combined with standard augmentations enable a better decomposition of tissue into biologically interpretable components without supervision, with DINOv2-mixed achieving clear separation of cellular structures, vasculature, and stromal elements. Therefore, incorporating domain-specific tissue priors through semantic masking enhances representation learning in self-supervised frameworks, alongside standard augmentations.

TL;DR: Integrating semantically segmented tissue images into DINOv2 builds microenvironment priors in the encoder, enhancing downstream task performance. Demonstrated via benchmarking and PCA analysis.