C2RM-Seg: Causal Counterfactual Reasoning with Structural-Semantic Priors for Weakly Supervised Histopathological Tissue Segmentation

Histopathological tissue segmentation is essential for computer-aided diagnosis, yet weakly supervised methods often suffer from noisy pseudo-labels generated by Class Activation Mapping (CAM). Existing CAM approaches tend to focus on staining-driven appearance cues rather than true causal tissue morphology, resulting in spurious localization and poor structural consistency. To address this issue, we propose C2RM-Seg, a two-stage framework that integrates causal pseudo-label refinement with structure-aware semantic enhancement. For classification, we introduce a Causal Counterfactual Reasoning Module (C2RM) that decomposes features into latent factors and performs counterfactual intervention via a learned causal structure matrix, suppressing confounding context and producing morphology-aligned CAMs. For segmentation, we design a Dual-Path Structural-Semantic Architecture that combines fine-grained structural features from ResNeSt with global semantic priors from a frozen DINOV3 foundation model. A cross-path gating mechanism adaptively regulates semantic injection using local structural cues to preserve boundary fidelity. To further mitigate residual pseudo-label noise, we propose an Uncertainty-Gated Margin (UGM) loss, which dynamically balances margin enforcement and confidence learning based on prediction uncertainty. Extensive experiments on two public histopathological tissue datasets show that C2RM-Seg achieves state-of-the-art performance.