RANGER: Sparsely-Gated Mixture-of-Experts with Adaptive Retrieval Re-ranking for Pathology Report Generation

Pathology report generation remains a relatively under-explored downstream task, primarily due to the gigapixel scale and complex morphological heterogeneity of Whole Slide Images (WSIs). Existing pathology report generation frameworks typically employ transformer architectures, relying on a homogeneous decoder architecture and static knowledge retrieval integration. Such architectures limit generative specialization and may introduce noisy external guidance during the report generation process. To address these limitations, we propose RANGER, a sparsely-gated Mixture-of-Experts (MoE) framework with adaptive retrieval re-ranking for pathology report generation. Specifically, we integrate a sparsely gated MoE into the decoder, along with noisy top-$k$ routing and load-balancing regularization, to enable dynamic expert specialization across various diagnostic patterns. Additionally, we introduce an adaptive retrieval re-ranking module that selectively refines retrieved memory from a knowledge base before integration, reducing noise and improving semantic alignment based on visual feature representations. We perform extensive experiments on the PathText-BRCA dataset and demonstrate consistent improvements over existing approaches across standard natural language generation metrics. Our full RANGER model achieves optimal performance on PathText dataset, reaching BLEU-1 to BLEU-4 scores of 0.4598, 0.3044, 0.2036, and 0.1435, respectively, with METEOR of 0.1883, and ROUGE-L of 0.3038, validating the effectiveness of dynamic expert routing and adaptive knowledge refinement for semantically grounded pathology report generation.

HistoMet: A Pan-Cancer Deep Learning Framework for Prognostic Prediction of Metastatic Progression and Site Tropism from Primary Tumor Histopathology

Metastatic Progression remains the leading cause of cancer-related mortality, yet predicting whether a primary tumor will metastasize and where it will disseminate directly from histopathology remains a fundamental challenge. Although whole-slide images (WSIs) provide rich morphological information, prior computational pathology approaches typically address metastatic status or site prediction as isolated tasks, and do not explicitly model the clinically sequential decision process of metastatic risk assessment followed by downstream site-specific evaluation. To address this research gap, we present a decision-aware, concept-aligned MIL framework, HistoMet, for prognostic metastatic outcome prediction from primary tumor WSIs. Our proposed framework adopts a two-module prediction pipeline in which the likelihood of metastatic progression from the primary tumor is first estimated, followed by conditional prediction of metastatic site for high-risk cases. To guide representation learning and improve clinical interpretability, our framework integrates linguistically defined and data-adaptive metastatic concepts through a pretrained pathology vision-language model. We evaluate HistoMet on a multi-institutional pan-cancer cohort of 6504 patients with metastasis follow-up and site annotations. Under clinically relevant high-sensitivity screening settings (95 percent sensitivity), HistoMet significantly reduces downstream workload while maintaining high metastatic risk recall. Conditional on metastatic cases, HistoMet achieves a macro F1 of 74.6 with a standard deviation of 1.3 and a macro one-vs-rest AUC of 92.1. These results demonstrate that explicitly modeling clinical decision structure enables robust and deployable prognostic prediction of metastatic progression and site tropism directly from primary tumor histopathology.

Predicting Neo-Adjuvant Chemotherapy Response in Triple-Negative Breast Cancer Using Pre-Treatment Histopathologic Images

Triple-negative breast cancer (TNBC) is an aggressive subtype defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, resulting in limited targeted treatment options. Neoadjuvant chemotherapy (NACT) is the standard treatment for early-stage TNBC, with pathologic complete response (pCR) serving as a key prognostic marker; however, only 40-50% of patients with TNBC achieve pCR. Accurate prediction of NACT response is crucial to optimize therapy, avoid ineffective treatments, and improve patient outcomes. In this study, we developed a deep learning model to predict NACT response using pre-treatment hematoxylin and eosin (H&E)-stained biopsy images. Our model achieved promising results in five-fold cross-validation (accuracy: 82%, AUC: 0.86, F1-score: 0.84, sensitivity: 0.85, specificity: 0.81, precision: 0.80). Analysis of model attention maps in conjunction with multiplexed immunohistochemistry (mIHC) data revealed that regions of high predictive importance consistently colocalized with tumor areas showing elevated PD-L1 expression, CD8+ T-cell infiltration, and CD163+ macrophage density - all established biomarkers of treatment response. Our findings indicate that incorporating IHC-derived immune profiling data could substantially improve model interpretability and predictive performance. Furthermore, this approach may accelerate the discovery of novel histopathological biomarkers for NACT and advance the development of personalized treatment strategies for TNBC patients.

Cross-attention-based saliency inference for predicting cancer metastasis on whole slide images

Although multiple instance learning (MIL) methods are widely used for automatic tumor detection on whole slide images (WSI), they suffer from the extreme class imbalance within the small tumor WSIs. This occurs when the tumor comprises only a few isolated cells. For early detection, it is of utmost importance that MIL algorithms can identify small tumors, even when they are less than 1% of the size of the WSI. Existing studies have attempted to address this issue using attention-based architectures and instance selection-based methodologies, but have not yielded significant improvements. This paper proposes cross-attention-based salient instance inference MIL (CASiiMIL), which involves a novel saliency-informed attention mechanism, to identify breast cancer lymph node micro-metastasis on WSIs without the need for any annotations. Apart from this new attention mechanism, we introduce a negative representation learning algorithm to facilitate the learning of saliency-informed attention weights for improved sensitivity on tumor WSIs. The proposed model outperforms the state-of-the-art MIL methods on two popular tumor metastasis detection datasets, and demonstrates great cross-center generalizability. In addition, it exhibits excellent accuracy in classifying WSIs with small tumor lesions. Moreover, we show that the proposed model has excellent interpretability attributed to the saliency-informed attention weights. We strongly believe that the proposed method will pave the way for training algorithms for early tumor detection on large datasets where acquiring fine-grained annotations is practically impossible.

Attention2Minority: A salient instance inference-based multiple instance learning for classifying small lesions in whole slide images

Multiple instance learning (MIL) models have achieved remarkable success in analyzing whole slide images (WSIs) for disease classification problems. However, with regard to gigapixel WSI classification problems, current MIL models are often incapable of differentiating a WSI with extremely small tumor lesions. This minute tumor-to-normal area ratio in a MIL bag inhibits the attention mechanism from properly weighting the areas corresponding to minor tumor lesions. To overcome this challenge, we propose salient instance inference MIL (SiiMIL), a weakly-supervised MIL model for WSI classification. Our method initially learns representations of normal WSIs, and it then compares the normal WSIs representations with all the input patches to infer the salient instances of the input WSI. Finally, it employs attention-based MIL to perform the slide-level classification based on the selected patches of the WSI. Our experiments imply that SiiMIL can accurately identify tumor instances, which could only take up less than 1% of a WSI, so that the ratio of tumor to normal instances within a bag can increase by two to four times. It is worth mentioning that it performs equally well for large tumor lesions. As a result, SiiMIL achieves a significant improvement in performance over the state-of-the-art MIL methods.