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

arXiv: https://arxiv.org/abs/2606.25508 · HTML: https://mlsanity.com/paper/2606.25508/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 8 of its 31 references that are in the map.
- First posted on arXiv 24 Jun 2026.

## Builds on (most cited first, 8 of 8)

- [Segment Anything](https://mlsanity.com/paper/2304.02643/) (2023)
- [SAM 2: Segment Anything in Images and Videos](https://mlsanity.com/paper/2408.00714/) (2024)
- [DINOv3](https://mlsanity.com/paper/2508.10104/) (2025)
- [ResNeSt: Split-Attention Networks](https://mlsanity.com/paper/2004.08955/) (2020)
- [Self-supervised Image-specific Prototype Exploration for Weakly Supervised Semantic Segmentation](https://mlsanity.com/paper/2203.02909/) (2022)
- [Multi-Layer Pseudo-Supervision for Histopathology Tissue Semantic Segmentation using Patch-level Classification Labels](https://mlsanity.com/paper/2110.08048/) (2021)
- [Prototype-Based Image Prompting for Weakly Supervised Histopathological Image Segmentation](https://mlsanity.com/paper/2503.12068/) (2025)
- [Online Easy Example Mining for Weakly-supervised Gland Segmentation from Histology Images](https://mlsanity.com/paper/2206.06665/) (2022)

## Abstract (arXiv)

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.