C2RM-Seg: Causal Counterfactual Reasoning with Structural-Semantic Priors for Weakly Supervised Histopathological Tissue Segmentation
Authors: Hualong Zhang, Siyang Feng, Zihan Huan, Yi Qian, Zhenbing Liu, Rushi Lan, Xipeng Pan
Abstract
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.
Existing weakly supervised semantic segmentation (WSSS) methods in computational pathology rely on a multi-stage paradigm: class activation map (CAM) generation, offline pseudo-mask refinement, and fully supervised retraining. While established, this decoupled approach presents fundamental limitations. The multi-stage process not only incurs high computational training costs but also suffers from error propagation: local texture biases in shallow CNN layers generate false-positive artifacts that subsequent refinement steps often fail to correct. To address these persistent challenges through a simple yet highly effective approach, we propose the Single-Stage Hierarchical Rectification (SSHR) framework. Rather than passively refining CAMs post-hoc, our method proactively purifies intermediate feature representations during the forward pass. We introduce a Hierarchical Feature Rectification Module (HFRM) that utilizes deep global semantic context to filter out local anomalies in shallow layers. This mechanism generates high-fidelity activation maps directly within a single training loop. Experiments on the LUAD-HistoSeg and BCSS datasets demonstrate that SSHR outperforms state-of-the-art multi-stage methods. Furthermore, SSHR reduces training duration by 2 to 5 times. This efficiency minimizes computational overhead and accelerates clinical translation for large-scale histopathology workflows. The code is available at: https://github.com/trongduc-nguyen/SSHR
Weakly supervised semantic segmentation enables histopathology tissue segmentation from image-level annotations, avoiding costly pixel-level labeling by expert pathologists. However, CAM-based methods often localize only highly discriminative regions and remain unreliable near tissue interfaces. We propose ProBAG, a stage-1 pseudo-mask generator that combines dataset-specific visual prototypes with pathology-aligned CONCH text prototypes over multi-scale frozen UNI features. ProBAG introduces two complementary mechanisms: class-wise power recalibration that reshapes inter-class competition while preserving the total foreground activation mass at each pixel, and one-step graph diffusion in which feature affinities are penalized by a late-transformer attention-context discrepancy used as a soft structural boundary cue. The resulting stage-1 pseudo-masks require neither CRF nor an external segmentation model; for complete two-stage comparison, they additionally supervise a downstream Phikon-FPN segmenter. Experiments on BCSS-WSSS and LUAD-HistoSeg show consistent gains over recent WSSS approaches, while ablations indicate that pathology-aligned text semantics provide the largest improvement and graph refinement provides a smaller complementary gain. The code is available at: https://github.com/wterrr/WSSS
Semi-supervised histopathology segmentation is challenging due to scarce annotations and unreliable pseudo-labels in ambiguous gland regions. To address this problem, we propose Confidence-Guided Diffusion Refinement (CoDiR), a semi-supervised framework that combines a Mean Teacher segmentation model with diffusion-based pseudo-label refinement. Given an unlabeled image, the teacher first produces a soft prediction, and only low-confidence regions are refined by a conditional diffusion model trained to capture plausible mask structures from labeled data. The refined mask is then fused with reliable teacher predictions and used to train the student with confidence weighting and consistency regularization. On the GlaS and CRAG datasets CoDiR reaches 88.09% and 89.83% mDice with 10% labeled data, and 89.19% and 90.29% mDice with 20%, matching or exceeding the strongest published method on seven of the eight benchmark metrics. Ablations attribute the largest single contribution to the refinement module, which adds +6.36% mDice over the Mean Teacher baseline. The implementation code is publicly available at: https://github.com/vongla345/codir