Exploring Prompt Alignment with Clinical Factors in Zero-Shot Segmentation VLMs for NSCLC Tumor Segmentation

Foreground segmentation is the critical first step of every computational pathology pipeline, yet existing methods rely on hand-tuned heuristics or supervised models that overfit to narrow stain and scanner distributions, failing silently on specialised stains such as Jones silver or Elastica van Gieson. We propose a coarse-to-fine approach that recasts foreground segmentation as a visual perception task and leverages general-purpose vision-language models (VLMs) as zero-annotation oracles. Our key insight is that tissue-versus-background discrimination is a natural-image recognition problem, not a histopathological one, so VLMs trained on internet-scale corpora generalise where domain-specific models cannot. We introduce Leica-75, a benchmark of 75 renal transplant whole-slide images spanning three stain families. On Leica-75, our method achieves the highest segmentation quality on out-of-distribution stains (Dice 0.858 +/- 0.027 on Jones, 0.853 +/- 0.041 on EVG) with 7x lower cross-stain variance than the best supervised baseline, while remaining competitive on in-distribution H&E. Few-shot prompting with automatically curated exemplars (Auto-context) rescues hard cases on Stress-32 (n=32), a curated stress-test subset (Dice 0.470 to 0.819 for the 2B model). VLM-based annotation review matches human expert consensus (kappa=0.989 for blur detection; mean precision/recall grading accuracy 0.708 vs. human 0.646 for segmentation mask review). The resulting pseudo-labels are used to distil lightweight student models that are as performant as the teacher model while running for a fraction of the cost. Our framework provides a principled, scalable solution to a persistent infrastructure bottleneck in digital pathology.

Accurate delineation of tumors and surrounding organs-at-risk is essential for radiotherapy, surgery and treatment response assessment, yet remains time-consuming and expertise-intensive. Existing artificial intelligence systems often require manual spatial prompts or task-specific retraining, while generic class labels provide limited semantic grounding for heterogeneous disease targets. Here we present SyRe, a promptable segmentation foundation model based on Synergistic vision-language Reinforcement. SyRe strengthens bidirectional interaction between visual and linguistic representations to improve semantically grounded spatial understanding. To support large-scale training, we introduce the Color Region Description strategy and construct SyReData, comprising 20 million image-mask-description triplets across 9 modalities and 229 segmentation tasks. Training with diversified prompt forms further enables open-ended prompting, invalid-prompt rejection and flexible switching between single- and multi-target analysis. SyRe achieves accurate text-prompted segmentation across diverse clinical scenarios, with particularly strong performance on disease-related targets. Across 28 unseen external datasets, including 20 cancer types and multinational in-house cohorts, SyRe generalizes robustly under real-world distribution shifts. SyRe-generated masks also preserve clinically relevant quantitative information in pathology and yield radiomics features that stratify survival and improve prognostic modeling across five retrospective CT and MRI tumor cohorts. Finally, clinician-in-the-loop refinement enables efficient case-level correction when greater precision is required. These results establish SyRe as a generalizable foundation for scalable quantitative oncology and clinician-guided segmentation refinement.

Vision-language models (VLMs) for radiology have emerged as a scalable paradigm by leveraging image-report pairs naturally produced in clinical workflows. However, this pairing reveals a mismatch in scale: each finding occupies only a small region of the image, yet supervision is provided only at the global image-report level. This poses a central challenge: prior approaches spread weight densely across all patches rather than concentrating on the sparse subset relevant to a given query. To address this, we present GLINT (Gated Language-Image alignmeNT), a framework that explicitly models this sparse correspondence. On the alignment side, we introduce Sparsely Gated Alignment, a novel architecture in which a sigmoid gate over a separate gate embedding space activates only the patches relevant to each textual query, enforcing explicit sparsity. On the representation side, we add Dense Feature Regularization, which anchors the trainable encoder's intermediate features to a frozen self-supervised learning (SSL) teacher, preserving the fine-grained patch features that the gate relies on. The same recipe applies to both 2D chest X-ray (CXR) and 3D chest computed tomography (CT), built with DINOv3 and V-JEPA 2.1, respectively. GLINT enables zero-shot classification, grounding, and segmentation from free-text queries, and to our knowledge is the first to demonstrate zero-shot segmentation on 3D CT volumes without mask supervision. Notably, the most pronounced gains arise on zero-shot grounding and segmentation, where sparse, query-specific localization is required, consistent with our design intent. In downstream evaluation, GLINT outperforms both SSL encoders and medical VLMs on classification, report generation, and segmentation.