Recent advances in multi-instance learning (MIL) have witnessed impressive performance in whole slide image (WSI) analysis. However, the inherent sparsity of tumors and their morphological diversity lead to obvious heterogeneity across regions, posing significant challenges in aggregating high-quality and discriminative representations. To address this, we introduce a novel concept of anchor instance (AI), a compact subset of instances that are representative within their regions (local) and discriminative at the bag (global) level. These AIs act as semantic references to guide interactions across regions, correcting non-discriminative patterns while preserving regional diversity. Specifically, we propose a dual-level anchor mining (DAM) module to select AIs from massive instances, where the most informative AI in each region is extracted by assessing its similarity to both local and global embeddings. Furthermore, to ensure completeness and diversity, we devise an anchor-guided region correction (ARC) module that explores the complementary information from all regions to correct each regional representation. Building upon DAM and ARC, we develop a concise yet effective framework, AINet, which employs a simple predictor and surpasses state-of-the-art methods with substantially fewer FLOPs and parameters. Moreover, both DAM and ARC are modular and can be seamlessly integrated into existing MIL frameworks, consistently improving their performance.
Figures & tables
Figure 1: Comparison results of FLOPs (G), parameters (M), and average accuracy with representative MIL methods on TCGA-ESCA, TCGA-BRCA, and BRACS datasets. AINet delivers superior performance with improved efficiency.
Figure 2: (a) Regional heterogeneity within a WSI originates from tumor sparsity and morphological diversity. (b) Previous MIL methods often neglect this heterogeneity, resulting in suboptimal feature aggregation. (c) The proposed AINet alleviates this limitation via DAM and ARC modules, yielding more discriminative representations and improved predictive accuracy.
Figure 3: Overview of the proposed AINet for WSI classification. Each bag is first divided into multiple spatial regions. The dual-level anchor mining (DAM) module identifies a compact set of anchor instances (AIs), which are then incorporated by the anchor-guided region correction (ARC) module into regional representations to guide the aggregation of heterogeneous features.
Methods
TCGA-BRCA
TCGA-ESCA
Accuracy
AUC
F1
Accuracy
AUC
F1
ResNet18
ABMIL [ 15 ]
0.862 ± 0.025
0.882 ± 0.033
0.915 ± 0.015
0.815 ± 0.129
0.882 ± 0.126
0.852 ± 0.101
DSMIL [ 2 ]
0.823 ± 0.021
0.820 ± 0.033
0.892 ± 0.014
0.712 ± 0.085
0.823 ± 0.078
0.773 ± 0.074
CLAM [ 25 ]
0.865 ± 0.020
0.890 ± 0.029
0.917 ± 0.014
0.821 ± 0.091
0.916 ± 0.052
0.844 ± 0.085
TransMIL [ 31 ]
0.847 ± 0.021
0.846 ± 0.036
0.905 ± 0.013
0.815 ± 0.081
0.878 ± 0.086
0.847 ± 0.065
DTFD-MaxM [ 46 ]
0.816 ± 0.023
0.810 ± 0.033
0.885 ± 0.013
0.821 ± 0.067
0.914 ± 0.075
0.851 ± 0.057
Table 1: Quantitative results of AINet compared with representative MIL baselines on TCGA-BRCA and TCGA-ESCA datasets.
Methods
ResNet18
PLIP
Accuracy
AUC
F1
Accuracy
AUC
F1
ABMIL [ 15 ]
0.691 ± 0.041
0.816 ± 0.020
0.604 ± 0.055
0.754 ± 0.042
0.875 ± 0.036
0.705 ± 0.044
DSMIL [ 2 ]
0.657 ± 0.026
0.795 ± 0.021
0.555 ± 0.016
0.717 ± 0.044
0.847 ± 0.039
0.629 ± 0.041
CLAM [ 25 ]
0.689 ± 0.036
0.830 ± 0.028
0.601 ± 0.024
0.742 ± 0.054
0.871 ± 0.023
0.692 ± 0.043
TransMIL [ 31 ]
0.706 ± 0.044
0.799 ± 0.035
0.596 ± 0.036
0.709 ± 0.032
0.851 ± 0.022
0.640 ± 0.059
DTFD-MaxM [ 46 ]
0.698 ± 0.030
0.815 ± 0.062
0.610 ± 0.044
0.724 ± 0.054
0.838 ± 0.063
0.617 ± 0.075
Table 2: Quantitative results of AINet compared with representative MIL baselines on the BRACS dataset.
Methods
ResNet18
PLIP
FLOPs (G)
#Param. (M)
Accuracy
AUC
F1
Accuracy
AUC
F1
TransMIL [ 31 ]
0.815 ± 0.081
0.878 ± 0.086
0.847 ± 0.065
0.904 ± 0.062
0.988 ± 0.018
0.920 ± 0.051
84.22
0.68
+AINet
0.822 ± 0.121 (0.7)
0.889 ± 0.116 (1.1)
0.8438 ± 0.108 (0.4)
0.916 ± 0.054 (1.2)
0.993 ± 0.006 (0.5)
0.923 ± 0.052 (0.3)
22.30 (61.92)
0.19 (0.49)
ILRA [ 41 ]
0.803 ± 0.136
0.896 ± 0.097
0.838 ± 0.116
0.892 ± 0.105
0.965 ± 0.057
0.900 ± 0.103
123.05
1.85
+AINet
0.866 ± 0.098 (6.3)
0.915 ± 0.091 (1.9)
0.882 ± 0.090 (4.4)
0.905 ± 0.099 (1.3)
0.967 ± 0.054 (0.2)
0.918 ± 0.083 (1.8)
21.86 (101.19)
0.19 (1.66)
WIKG [ 18 ]
0.770 ± 0.131
0.874 ± 0.106
0.793 ± 0.121
0.892 ± 0.093
0.949 ± 0.063
0.900 ± 0.093
49.80
0.43
Table 3: Validation on the TCGA-ESCA dataset. The red denotes performance improvement, while green indicates reduced complexity.
Model
DAM
ACF
ARC
TCGA-ESCA
BRACS
Accuracy
AUC
F1
Accuracy
AUC
F1
Baseline
✗
✗
✗
0.777 ± 0.134
0.866 ± 0.095
0.808 ± 0.114
0.691 ± 0.056
0.809 ± 0.054
0.602 ± 0.073
w DAM
✓
✗
✗
0.809 ± 0.117
0.886 ± 0.128
0.841 ± 0.095
0.713 ± 0.047
0.835 ± 0.040
0.594 ± 0.061
w DAM+MHA
✓
✗
✗
0.839 ± 0.088
0.935 ± 0.064
0.867 ± 0.069
0.719 ± 0.061
0.845 ± 0.041
0.624 ± 0.063
w DAM+ACF
✓
✓
✗
0.840 ± 0.108
0.938 ± 0.073
0.868 ± 0.083
0.732 ± 0.039
0.844 ± 0.036
0.631 ± 0.045
w DAM+ARC (AINet)
✓
✓
✓
0.873 ± 0.098
0.946 ± 0.046
0.894 ± 0.080
0.737 ± 0.025
0.854 ± 0.046
0.638 ± 0.040
Table 4: Ablation study of the key components on the TCGA-ESCA and BRACS datasets with ResNet18 features. The gray highlights our results. We set L=4 regions, select the top k=20% instances as AIs, and apply a masking ratio of r=90% within each region.
Model
Bag-level
Region-level
TCGA-ESCA
BRACS
Accuracy
AUC
F1
Accuracy
AUC
F1
Baseline
✗
✗
0.777 ± 0.134
0.866 ± 0.095
0.808 ± 0.114
0.691 ± 0.056
0.809 ± 0.054
0.602 ± 0.073
w Attention
✗
✗
0.816 ± 0.156
0.890 ± 0.109
0.839 ± 0.131
0.713 ± 0.043
0.837 ± 0.041
0.638 ± 0.054
w Max-pooling
✗
✗
0.808 ± 0.093
0.918 ± 0.093
0.842 ± 0.067
0.681 ± 0.040
0.820 ± 0.058
0.593 ± 0.057
w Bag-similar
✓
✗
0.828 ± 0.133
0.923 ± 0.075
0.862 ± 0.099
0.687 ± 0.048
0.816 ± 0.040
0.575 ± 0.051
w Region-similar
✗
✓
0.834 ± 0.140
0.920 ± 0.069
0.869 ± 0.107
0.728 ± 0.044
0.835 ± 0.047
0.619 ± 0.059
Table 5: Ablation study of the proposed DAM on the TCGA-ESCA and BRACS datasets using ResNet18 features. We set L=4 regions, select the top k=20% instances as AIs, and apply a masking ratio of r=90% within each region.
Figure 4: Hyperparameter effects on the TCGA-ESCA dataset.
USTC, Anhui, China · Anhui Province Key Laboratory of Biomedical Imaging and Intelligent Processing, Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Anhui, China · SCNU, Guangdong, China +2