LGD-Net: Latent-Guided Dual-Stream Network for HER2 Scoring with Task-Specific Domain Knowledge

Virtual immunohistochemistry (IHC) staining from hematoxylin and eosin (H&E) images can accelerate diagnostics by providing preliminary molecular insight directly from routine sections, reducing the need for repeat sectioning when tissue is limited. Existing methods improve realism through contrastive objectives, prototype matching, or domain alignment, yet the generator itself receives no direct guidance from pathology foundation models. We present UNIStainNet, a SPADE-UNet conditioned on dense spatial tokens from a frozen pathology foundation model (UNI), providing tissue-level semantic guidance for stain translation. A misalignment-aware loss suite preserves stain quantification accuracy, and learned stain embeddings enable a single model to serve multiple IHC markers simultaneously. On MIST, UNIStainNet achieves state-of-the-art distributional metrics on all four stains (HER2, Ki67, ER, PR) from a single unified model, where prior methods typically train separate per-stain models. On BCI, it also achieves the best distributional metrics. A tissue-type stratified failure analysis reveals that remaining errors are systematic, concentrating in non-tumor tissue. Code is available at https://github.com/facevoid/UNIStainNet.

Immunohistochemistry (IHC) is essential for assessing specific immune biomarkers like Human Epidermal growth-factor Receptor 2 (HER2) in breast cancer. However, the traditional protocols of obtaining IHC stains are resource-intensive, time-consuming, and prone to structural damages. Virtual staining has emerged as a scalable alternative, but it faces significant challenges in preserving fine-grained cellular structures while accurately translating biochemical expressions. Current state-of-the-art methods still rely on Generative Adversarial Networks (GANs) or standard convolutional U-Net diffusion models that often struggle with "structure and staining trade-offs". The generated samples are either structurally relevant but blurry, or texturally realistic but have artifacts that compromise their diagnostic use. In this paper, we introduce HistDiT, a novel latent conditional Diffusion Transformer (DiT) architecture that establishes a new benchmark for visual fidelity in virtual histological staining. The novelty introduced in this work is, a) the Dual-Stream Conditioning strategy that explicitly maintains a balance between spatial constraints via VAE-encoded latents and semantic phenotype guidance via UNI embeddings; b) the multi-objective loss function that contributes to sharper images with clear morphological structure; and c) the use of the Structural Correlation Metric (SCM) to focus on the core morphological structure for precise assessment of sample quality. Consequently, our model outperforms existing baselines, as demonstrated through rigorous quantitative and qualitative evaluations.

As hematoxylin & eosin (H&E) staining constitutes the primary entry point in routine diagnostic workflows, computer-aided diagnosis from whole-slide H&E images is of particular clinical relevance. However, substantial variability in specimen preparation, staining protocols, and scanning conditions, together with inherent uncertainty in expert pixel-level annotations, makes automated analysis of H&E-stained images challenging. In this study, we propose a semantic segmentation-based framework for image-level diagnosis, grounded in the clinically motivated assumption that each histopathological image corresponds to a single cancer type. Image-level predictions are obtained by assigning the class of the dominant pixel-level label in the segmentation output. To ensure clinical relevance, we adopt the nnU-Net architecture and train it on a publicly available dataset collected in our study with pixel-level annotations for three liver cancer types: hepatocellular cacrcinoma (HCC; 55 images from 30 patients), cholangiocellular carcinoma (CCA; 55 images from 29 patients), and colorectal metastatic adenocarcinoma (CMA; 60 images from 30 patients). Annotations were independently provided by four pathologist. We hypothesize that the combination of stain normalization and semantic segmentation mitigates domain shift and reduces sensitivity to annotation noise. Five-fold cross-validation yielded balanced accuracy of 0.975 (HCC), 0.950 (CCA), and 1.000 (CMA), comparable to results obtained with immunohosthochemical staining and superior to several deep learning models trained on patch-level annotations. The proposed framework has the potential to support pathologists in prioritizing immunohistochemical marker selection, thereby reducing diagnostic costs and turnaround time. Integration with immunohistochemical findings improve overall diagnostic reliability.