# Act Like a Pathologist: Tissue-Aware Whole Slide Image Reasoning

arXiv: https://arxiv.org/abs/2603.00667 · HTML: https://mlsanity.com/paper/2603.00667/

## Key facts

- Cited by 5 papers in the map (data through 14 Oct 2026).
- Placed in Clinical and biomedical applications, one of 17 directions in LLM reasoning.
- Builds on 47 of its 62 references that are in the map.
- First posted on arXiv 28 Feb 2026.

## Placed in

- LLM reasoning / [Clinical and biomedical applications](https://mlsanity.com/lr/clinical-and-biomedical-applications/)
- Multimodal LLMs / vision-language models / [Medical vision-language models](https://mlsanity.com/mllm/medical-vision-language-models/)

## Builds on (most cited first, 30 of 47)

- [BLIP-2: Bootstrapping Language-Image Pre-training with Frozen Image Encoders and Large Language Models](https://mlsanity.com/paper/2301.12597/) (2023)
- [Flamingo: a Visual Language Model for Few-Shot Learning](https://mlsanity.com/paper/2204.14198/) (2022)
- [Qwen2 Technical Report](https://mlsanity.com/paper/2407.10671/) (2024)
- [Estimating or Propagating Gradients Through Stochastic Neurons for Conditional Computation](https://mlsanity.com/paper/1308.3432/) (2013)
- [LLaVA-Med: Training a Large Language-and-Vision Assistant for Biomedicine in One Day](https://mlsanity.com/paper/2306.00890/) (2023)
- [Attention-based Deep Multiple Instance Learning](https://mlsanity.com/paper/1802.04712/) (2018)
- [Token Merging: Your ViT But Faster](https://mlsanity.com/paper/2210.09461/) (2022)
- [Deep Variational Information Bottleneck](https://mlsanity.com/paper/1612.00410/) (2016)
- [DynamicViT: Efficient Vision Transformers with Dynamic Token Sparsification](https://mlsanity.com/paper/2106.02034/) (2021)
- [Data Efficient and Weakly Supervised Computational Pathology on Whole Slide Images](https://mlsanity.com/paper/2004.09666/) (2020)
- [TransMIL: Transformer based Correlated Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2106.00908/) (2021)
- [Dual-stream Multiple Instance Learning Network for Whole Slide Image Classification with Self-supervised Contrastive Learning](https://mlsanity.com/paper/2011.08939/) (2020)
- [DTFD-MIL: Double-Tier Feature Distillation Multiple Instance Learning for Histopathology Whole Slide Image Classification](https://mlsanity.com/paper/2203.12081/) (2022)
- [LongNet: Scaling Transformers to 1,000,000,000 Tokens](https://mlsanity.com/paper/2307.02486/) (2023)
- [Quilt-1M: One Million Image-Text Pairs for Histopathology](https://mlsanity.com/paper/2306.11207/) (2023)
- [DivPrune: Diversity-based Visual Token Pruning for Large Multimodal Models](https://mlsanity.com/paper/2503.02175/) (2025)
- [Interventional Bag Multi-Instance Learning On Whole-Slide Pathological Images](https://mlsanity.com/paper/2303.06873/) (2023)
- [Deep Learning-based Computational Pathology Predicts Origins for Cancers of Unknown Primary](https://mlsanity.com/paper/2006.13932/) (2020)
- [Multimodal Optimal Transport-based Co-Attention Transformer with Global Structure Consistency for Survival Prediction](https://mlsanity.com/paper/2306.08330/) (2023)
- [Quilt-LLaVA: Visual Instruction Tuning by Extracting Localized Narratives from Open-Source Histopathology Videos](https://mlsanity.com/paper/2312.04746/) (2023)
- [Cross-Modal Translation and Alignment for Survival Analysis](https://mlsanity.com/paper/2309.12855/) (2023)
- [Attention-Challenging Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2311.07125/) (2023)
- [Multiple Instance Learning Framework with Masked Hard Instance Mining for Whole Slide Image Classification](https://mlsanity.com/paper/2307.15254/) (2023)
- [SlideChat: A Large Vision-Language Assistant for Whole-Slide Pathology Image Understanding](https://mlsanity.com/paper/2410.11761/) (2024)
- [Task-specific Fine-tuning via Variational Information Bottleneck for Weakly-supervised Pathology Whole Slide Image Classification](https://mlsanity.com/paper/2303.08446/) (2023)
- [Towards a Visual-Language Foundation Model for Computational Pathology](https://mlsanity.com/paper/2307.12914/) (2023)
- [Multimodal Prototyping for cancer survival prediction](https://mlsanity.com/paper/2407.00224/) (2024)
- [Predicting Axillary Lymph Node Metastasis in Early Breast Cancer Using Deep Learning on Primary Tumor Biopsy Slides](https://mlsanity.com/paper/2112.02222/) (2021)
- [Bi-directional Weakly Supervised Knowledge Distillation for Whole Slide Image Classification](https://mlsanity.com/paper/2210.03664/) (2022)
- [HistGen: Histopathology Report Generation via Local-Global Feature Encoding and Cross-modal Context Interaction](https://mlsanity.com/paper/2403.05396/) (2024)

## Built on by (most cited first, 5 of 5)

- [PathNavigate: A Training-Free Pathology Agent with Surprise-Guided Scan and Shared Slide Memory for Whole-Slide Image VQA](https://mlsanity.com/paper/2605.23559/) (2026)
- [SlideBank: A Persistent Hierarchical Evidence Bank for Consistent Whole-Slide Reasoning](https://mlsanity.com/paper/2609.00342/) (2026)
- [SLICEChat: Progressive In-Encoder Token Pruning for Whole-Slide Pathology Language Models](https://mlsanity.com/paper/2609.24894/) (2026)
- [Beyond Sparse Captions: Aligning Slide-Level Text and Patch-Level Vision in Pathology](https://mlsanity.com/paper/2610.17233/) (2026)
- [PlanPath: Exploration-Guided Orchestration for Patient-Level Pathology Reasoning](https://mlsanity.com/paper/2610.18664/) (2026)

## Abstract (arXiv)

Computational pathology has advanced rapidly in recent years, driven by domain-specific image encoders and growing interest in using vision-language models to answer natural-language questions about diseases. Yet, the core problem behind pathology question-answering remains unsolved, considering that a gigapixel slide contains far more information than necessary for a given question. Pathologists naturally navigate tissue and morphology complexity by scanning broadly, and zooming in selectively according to the clinical questions. Current models, in contrast, rely on uniform patch sampling or broad attention maps, often attending equally to irrelevant regions while overlooking key visual evidence. In this work, we try to bring models closer to how humans actually examine slides. We propose a question-guided, tissue-aware, and coarse-to-fine retrieval framework, HistoSelect, that consists of two key components: a group sampler that identifies question-relevant tissue regions, followed by a patch selector that retrieves the most informative patches within those regions. By selecting only the most informative patches, our method becomes significantly more efficient: reducing visual token usage by 70% on average, while improving accuracy across three pathology QA tasks. Evaluated on 356,000 question-answer pairs, our approach outperforms existing methods and produces answers grounded in interpretable, pathologist-consistent regions. Our results suggest that bringing human-like search and attention patterns into WSI reasoning is a promising direction for building practical and reliable pathology VLMs. Code is available at https://github.com/winston52/HistoSelect.