Semantic-Guided Multimodal Preprocessing for Vision Transformer-Based Clear Cell Renal Cell Carcinoma Grading

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.