Background: Clear cell renal cell carcinoma (ccRCC) exhibits substantial clinical heterogeneity, and accurate grade assessment is essential for risk stratification and treatment planning. However, conventional grading requires invasive tissue sampling. We developed RCC-Align, a cross-modal contrastive learning framework that leverages paired histopathology and computed tomography (CT) data during training to improve noninvasive CT-based ccRCC grade prediction. Methods: RCC-Align aligns paired whole-slide histopathology images (WSIs) and CT scans through contrastive cross-modal objectives, transferring grade-discriminative information from microscopic tissue morphology to macroscopic radiologic representations. The framework was trained and evaluated on paired TCGA and CPTAC cohorts using patient-level five-fold cross-validation. Performance for low- versus high-grade ccRCC classification was compared against CT-only baselines (DINOv2-Base and DINOv2-Finetuned) and a WSI-based reference model (GigaPath-Finetuned). Cross-modal alignment was assessed using cosine similarity analysis. Results: RCC-Align achieved an AUC of 0.601 (95% CI, 0.524-0.673) and AUPRC of 0.599 (95% CI, 0.541-0.676), outperforming DINOv2-Finetuned (AUC 0.545; AUPRC 0.543) with significantly improved low-grade prediction (p = 0.004). RCC-Align also demonstrated stronger paired WSI-CT embedding alignment compared with baselines. The WSI-based GigaPath reference achieved an AUC of 0.719. Conclusion: Pathology-guided contrastive learning improves CT-based ccRCC grading while requiring only CT at inference. This approach may complement tissue diagnosis when biopsy is unsafe, infeasible, or limited by intratumoral heterogeneity. Validation in larger, multi-institutional cohorts with external testing is needed before clinical translation.
Clear cell renal cell carcinoma (CCRCC) grading is essential for treatment planning, yet existing approaches either analyze patch-level images directly or focus solely on nuclei-level classification, without linking to final tumor grading. We propose a semantic-guided multimodal preprocessing method that integrates nuclei classification maps from existing pre-trained models with RGB histopathology images for Vision Transformer (ViT)-based CCRCC grading. Our approach employs classification map channel concatenation and multiplicative modulation, with optimized overlays to leverage nuclei grading information, while preserving RGB textural features. Evaluation of multiple preprocessing strategies demonstrates that semantic-guided enhancement achieves 0.916 balanced accuracy, outperforming RGB-only baseline (0.707) and max-voting aggregation from prior studies (0.427). Sensitivity analysis reveals that this 21 percentage point improvement over baseline persists even under simulated perturbation at rates matching current state-of-the-art nuclei classification model error thresholds, suggesting both effective semantic utilization and practical robustness. These findings show that preprocessing-based multimodal fusion can leverage the diagnostic potential of existing imperfect nuclei classifiers, effectively bridging previously isolated fine-grained nuclear-level analysis with coarse-grained ViT-based patch classification. Per-class recall was consistent across grades (0.93, 0.91, 0.91), indicating that gains are not concentrated in the majority class. Because the sensitivity analysis perturbs ground-truth maps rather than predictions from an actual nuclei model, this result characterizes robustness under simulated error rather than deployment with a real upstream model, which remains for future work.
Accurate preoperative subtype classification of renal cell carcinoma (RCC) from contrast-enhanced computed tomography remains clinically challenging. Radiomics provides structured tumour descriptors, whereas foundation representations offer transferable image features. However, it remains unclear whether radiomics still adds value beyond pretrained representations, and how 2D and 3D MedVAE encoders compare in this setting. We compared handcrafted radiomics, 2D MedVAE, 3D MedVAE, and their fusion for binary clear-cell RCC versus non-clear-cell RCC classification on KiTS23 under a unified preprocessing pipeline. Concatenation, cross-attention, and gated fusion were evaluated as representative integration strategies, and radiomics feature importance was analysed to support decision-centric interpretability. Fusion consistently improved discrimination over image-only MedVAE branches. The best overall performance was achieved by 3D gated fusion, with an AUC of 82.7%, outperforming the best 2D fusion model (79.6%), the radiomics baseline (74.4%), and the single-modality MedVAE branches. Ablation analysis further showed clear gains of the full fusion model over both image-only and radiomics-only variants, indicating complementary contributions from radiomics and image representations. These findings suggest that radiomics remains relevant for RCC CT classification in the presence of foundation representations, and that its integration with MedVAE is more effective in the 3D setting. More broadly, the study supports a complementary role for radiomics and foundation representations in clinically meaningful imaging decision support.
Yuan Liang, Sourav Bhattacharjee, Abraham Campbell
Radiomics provides quantitative descriptions of tumour appearance that may complement disease-specific foundation models in small labelled cohorts. We investigate this complementarity for computed tomography-based classification of clear cell renal cell carcinoma. Our framework uses radiomics to modulate RenalCLIP features through feature-wise linear modulation (FiLM), while retaining a direct radiomics contribution. Internal testing and external validation compare it with conventional fusion strategies and reference classifiers. The FiLM model achieves an area under the receiver operating characteristic curve (AUC) of 0.804 internally and 0.854 externally, with the highest mean AUC among the evaluated RenalCLIP fusion strategies in both cohorts. Pathway ablations examine the contributions of conditional modulation and the direct radiomics residual, while feature permutation highlights the role of tumour texture. These findings support radiomics as a useful complement to RenalCLIP in a small labelled cohort and identify FiLM as an effective approach to integrating their representations for robust renal tumour classification.
Yuan Liang, Sourav Bhattacharjee, Abraham Campbell