# Investigating Zero-Shot Diagnostic Pathology in Vision-Language Models with Efficient Prompt Design

arXiv: https://arxiv.org/abs/2505.00134 · HTML: https://mlsanity.com/paper/2505.00134/

## Key facts

- Cited by 3 papers in the map (data through 14 Oct 2026).
- Placed in Medical vision-language models, one of 16 directions in Multimodal LLMs / vision-language models.
- Builds on 21 of its 29 references that are in the map.
- First posted on arXiv 30 Apr 2025.

## Placed in

- Multimodal LLMs / vision-language models / [Medical vision-language models](https://mlsanity.com/mllm/medical-vision-language-models/)

## Builds on (most cited first, 21 of 21)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [Learning Transferable Visual Models From Natural Language Supervision](https://mlsanity.com/paper/2103.00020/) (2021)
- [An Image is Worth 16x16 Words: Transformers for Image Recognition at Scale](https://mlsanity.com/paper/2010.11929/) (2020)
- [Training language models to follow instructions with human feedback](https://mlsanity.com/paper/2203.02155/) (2022)
- [DINOv2: Learning Robust Visual Features without Supervision](https://mlsanity.com/paper/2304.07193/) (2023)
- [Visual Instruction Tuning](https://mlsanity.com/paper/2304.08485/) (2023)
- [Emerging Properties in Self-Supervised Vision Transformers](https://mlsanity.com/paper/2104.14294/) (2021)
- [LLaVA-Med: Training a Large Language-and-Vision Assistant for Biomedicine in One Day](https://mlsanity.com/paper/2306.00890/) (2023)
- [CoCa: Contrastive Captioners are Image-Text Foundation Models](https://mlsanity.com/paper/2205.01917/) (2022)
- [Scaling Vision Transformers to Gigapixel Images via Hierarchical Self-Supervised Learning](https://mlsanity.com/paper/2206.02647/) (2022)
- [Quilt-1M: One Million Image-Text Pairs for Histopathology](https://mlsanity.com/paper/2306.11207/) (2023)
- [Visual Language Pretrained Multiple Instance Zero-Shot Transfer for Histopathology Images](https://mlsanity.com/paper/2306.07831/) (2023)
- [Virchow: A Million-Slide Digital Pathology Foundation Model](https://mlsanity.com/paper/2309.07778/) (2023)
- [Quilt-LLaVA: Visual Instruction Tuning by Extracting Localized Narratives from Open-Source Histopathology Videos](https://mlsanity.com/paper/2312.04746/) (2023)
- [A General-Purpose Self-Supervised Model for Computational Pathology](https://mlsanity.com/paper/2308.15474/) (2023)
- [Computational Pathology: A Survey Review and The Way Forward](https://mlsanity.com/paper/2304.05482/) (2023)
- [Task Supportive and Personalized Human-Large Language Model Interaction: A User Study](https://mlsanity.com/paper/2402.06170/) (2024)
- [IPO: Interpretable Prompt Optimization for Vision-Language Models](https://mlsanity.com/paper/2410.15397/) (2024)
- [Dr-LLaVA: Visual Instruction Tuning with Symbolic Clinical Grounding](https://mlsanity.com/paper/2405.19567/) (2024)
- [A New Era in Computational Pathology: A Survey on Foundation and Vision-Language Models](https://mlsanity.com/paper/2408.14496/) (2024)
- [Towards Robust Prompts on Vision-Language Models](https://mlsanity.com/paper/2304.08479/) (2023)

## Built on by (most cited first, 3 of 3)

- [Zero-shot segmentation of skin tumors in whole-slide images with vision-language foundation models](https://mlsanity.com/paper/2511.18978/) (2025)
- [Simple Token-Efficient Vision-Language Model for Case-level Pathology Synoptic Report Generation](https://mlsanity.com/paper/2605.30716/) (2026)
- [Beyond Sparse Captions: Aligning Slide-Level Text and Patch-Level Vision in Pathology](https://mlsanity.com/paper/2610.17233/) (2026)

## Abstract (arXiv)

Vision-language models (VLMs) have gained significant attention in computational pathology due to their multimodal learning capabilities that enhance big-data analytics of giga-pixel whole slide image (WSI). However, their sensitivity to large-scale clinical data, task formulations, and prompt design remains an open question, particularly in terms of diagnostic accuracy. In this paper, we present a systematic investigation and analysis of three state of the art VLMs for histopathology, namely Quilt-Net, Quilt-LLAVA, and CONCH, on an in-house digestive pathology dataset comprising 3,507 WSIs, each in giga-pixel form, across distinct tissue types. Through a structured ablative study on cancer invasiveness and dysplasia status, we develop a comprehensive prompt engineering framework that systematically varies domain specificity, anatomical precision, instructional framing, and output constraints. Our findings demonstrate that prompt engineering significantly impacts model performance, with the CONCH model achieving the highest accuracy when provided with precise anatomical references. Additionally, we identify the critical importance of anatomical context in histopathological image analysis, as performance consistently degraded when reducing anatomical precision. We also show that model complexity alone does not guarantee superior performance, as effective domain alignment and domain-specific training are critical. These results establish foundational guidelines for prompt engineering in computational pathology and highlight the potential of VLMs to enhance diagnostic accuracy when properly instructed with domain-appropriate prompts.