Lumen: Parameter-Efficient Alignment of Pretrained Vision and Language Encoders for Zero-Shot Computational Pathology

Pathology vision-language foundation models vary in performance across diseases and tasks, with no single model consistently performing best. The high cost of expert pathology annotation can also limit the labeled data available for task-specific adaptation. Combining complementary pretrained representations is a potential approach to these limitations, yet learning an effective fusion from few labeled examples remains challenging. We introduce Few-shot Fusion Foundation Models of Computational Pathology (FFM-CP), which is a framework that combines multiple pathology vision-language models in the few-shot learning setting. The framework first aligns heterogeneous representations using a closed-form Orthogonal Procrustes transformation estimated from corresponding support images. This alignment preserves within-model feature geometry without training an additional alignment network. Within the aligned space, a unified graph enables information exchange across backbones by jointly refining support-image features and visual and textual class prototypes. These refined representations support complementary text-prototype and case-retrieval branches that capture semantic class knowledge and within-class visual variation, respectively. Each branch learns to combine predictions from all ordered backbone pairs, allowing queries encoded by one model to draw on evidence represented by another. We evaluate three backbone combinations on six histopathology datasets at 4, 8, and 16 shots per class. FFM-CP achieves higher mean macro-F1 than the strongest individually adapted member of each fused set in 50 of 54 comparisons. These findings suggest that combining complementary pretrained representations can improve histopathological classification when annotations are limited.

Contrastive vision-language (VL) pretraining in computational pathology has generally relied on curated image-caption datasets sourced from social media, educational videos, and research publications. These corpora are sparse relative to the diversity of tissue morphology and difficult to scale further, as pathologists do not routinely produce descriptive captions in clinical practice. We propose to instead leverage slide-level pathology reports which can be generated during routine diagnostic workflows in a scalable manner. A key challenge in this weakly-supervised setting is that pathology reports describe macroscopic, diagnostic findings while patch-level visual features describe microscopic findings. We introduce Locked Image Multiple Instance PreTraining (LIMIT), which addresses this gap by freezing a pretrained vision encoder and fine-tuning only the text encoder: report embeddings serve as cross-attention queries over bags of patch features, producing report-conditioned slide representations optimized via InfoNCE. Using LIMIT, we establish CONCH-Z, which aligns the text encoder of CONCH v1.5 to 335k clinical reports. Evaluated across 22 tasks spanning patch-level classification, tumor detection, and slide-level subtyping, CONCH-Z establishes state-of-the-art zero-shot performance over VL encoders trained on curated caption datasets, while simultaneously closing the gap with slide-level foundation models trained with substantially more parameters and compute. The code and model is available at https://github.com/mahmoodlab/LIMIT.

Pathology vision-language models (VLMs) have shown strong visual perception ability, but their robustness in the language domain remains poorly characterized. Existing pathology VLM benchmarks largely rely on canonical closed-set prompts or perturb only generic templates, treating language as a fixed evaluation component rather than a variable axis of model behavior. In clinical practice, however, diagnostic language varies across reports, institutions, and candidate diagnoses. We introduce PathLang, a language-centered and clinically grounded zero-shot benchmark. PathLang holds the underlying slides, ground-truth labels, and image-text evaluation direction fixed while systematically varying only the diagnostic language, so that performance differences reflect how a diagnosis is phrased rather than what is imaged. The language variation follows how pathologists actually rephrase diagnoses (terminology, specificity, and reporting style), and all prompts and candidate pools are validated by six board-certified pathologists. PathLang covers four task families: (1) zero-shot classification with image-text alignment analysis, (2) cross-modal retrieval, (3) paraphrase robustness, including semantic-equivalence paraphrases, length and reporting-style variation, and prompt ensembling, and (4) open-vocabulary diagnosis retrieval over four candidate pools with distinct forms of semantic competition. Across nine VLMs and five public datasets spanning four organs, we find that performance is highly sensitive to clinically equivalent paraphrases, varies substantially across forms of semantic competition, and that image-text alignment quality does not necessarily translate into inter-class separability. We release the prompt corpus, candidate pools, pre-computed text embeddings, and evaluation code at https://anonymous.4open.science/r/PathLang.