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

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 multiscale 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 instancelevel detection, segmentation accuracy, and cell-type classification. This study provides valuable insights into the comparative strengths and limitations of general-purpose vs. histopathology foundation models, offering practical guidance for model selection in cell-focused histopathology and brain cytoarchitecture analysis workflows.