Mind the Gap: Evaluating Patch Embeddings from General-Purpose and Histopathology Foundation Models for Cell Segmentation and Classification

Abstract: Recent advancements in foundation models have transformed computer vision, driving significant performance improvements across diverse domains, including digital histopathology. However, the advantages of domain-specific histopathology foundation models over general-purpose models for specialized tasks such as cell analysis remain underexplored. This study investigates the representation learning gap between these two categories by analyzing multi-level patch embeddings applied to cell instance segmentation and classification. We implement an encoder-decoder architecture with a consistent decoder and various encoders. These include convolutional, vision transformer (ViT), and hybrid encoders pre-trained on ImageNet-22K or LVD-142M, representing general-purpose foundation models. These are compared against ViT encoders from the recently released UNI, Virchow2, and Prov-GigaPath foundation models, trained on patches extracted from hundreds of thousands of histopathology whole-slide images. The decoder integrates patch embeddings from different encoder depths via skip connections to generate semantic and distance maps. These maps are then post-processed to create instance segmentation masks where each label corresponds to an individual cell and to perform cell-type classification. All encoders remain frozen during training to assess their pre-trained feature extraction capabilities. Using the PanNuke and CoNIC histopathology datasets, and the newly introduced Nissl-stained CytoDArk0 dataset for brain cytoarchitecture studies, we evaluate instance-level detection, segmentation accuracy, and cell-type classification. This study provides insights into the comparative strengths and limitations of general-purpose vs. histopathology foundation models, offering guidance for model selection in cell-focused histopathology and brain cytoarchitecture analysis workflows.