Semi-supervised learning for automated perineural invasion detection in multi-organ H&E whole slide images.

MOTIVATION: Perineural invasion (PNI) is an important pathological phenotype associated with poor prognosis in multiple malignancies. The primary detection method is visual inspection of whole slide images (WSIs), which is labor-intensive, time-consuming, subjective, and prone to high inter-observer variability. Developing reliable, accurate deep learning models for PNI detection is constrained by the lack of pixel-level annotated WSIs. RESULTS: We evaluated four backbone architectures and two different approaches to improve PNI detection in a multi-organ dataset of colon, prostate, and pancreatic adenocarcinomas. We report three key findings. First, two pathology-pretrained foundation models, Virchow-2 and UNI, substantially outperformed ImageNet-pretrained CNNs (EfficientNet-B3, ConvNeXt-2), with distinct baseline error profiles reflecting differences in pretraining-data composition. Second, a data curation strategy driven by confidence-based pseudo-labelling (threshold P > .9) with human-in-the-loop review expanded the dataset from 262 to 352 WSIs, yielding a 12.4% relative F1 improvement (0.740 to 0.832) and a 55.5% reduction in false positives per slide; an ablation attributed 70% of the F1 gain to data volume and 41% of the FP reduction to benign-class curation. Third, per-organ analysis revealed that the primary driver of this improvement was not data volume alone but the targeted annotation enrichment of underrepresented morphologies in adjacent-normal and benign tissue, including desmoplastic stroma, crypts, and small blood vessels, that had been a systematic source of false positive predictions across tissue types. AVAILABILITY: Our implementation is available at https://github.com/AhmadAlkhan/PNI_SSL.