BreasTDLUSeg: A coarse-to-fine framework for segmentation of breast terminal duct lobular units on histopathological whole-slide images.

Automatic segmentation of breast terminal duct lobular units (TDLUs) on histopathological whole-slide images (WSIs) is crucial for the quantitative evaluation of TDLUs in the diagnostic and prognostic analysis of breast cancer. However, TDLU segmentation remains a great challenge due to its highly heterogeneous sizes, structures, and morphologies as well as the small areas on WSIs. In this study, we propose BreasTDLUSeg, an efficient coarse-to-fine two-stage framework based on multi-scale attention to achieve localization and precise segmentation of TDLUs on hematoxylin and eosin (H&E)-stained WSIs. BreasTDLUSeg consists of two networks: a superpatch-based patch-level classification network (SPPC-Net) and a patch-based pixel-level segmentation network (PPS-Net). SPPC-Net takes a superpatch as input and adopts a sub-region classification head to classify each patch within the superpatch as TDLU positive or negative. PPS-Net takes the TDLU positive patches derived from SPPC-Net as input. PPS-Net deploys a multi-scale CNN-Transformer as an encoder to learn enhanced multi-scale morphological representations and an upsampler to generate pixel-wise segmentation masks for the TDLU positive patches. We also constructed two breast cancer TDLU datasets containing a total of 530 superpatch images with patch-level annotations and 2322 patch images with pixel-level annotations to enable the development of TDLU segmentation methods. Experiments on the two datasets demonstrate that BreasTDLUSeg outperforms other state-of-the-art methods with the highest Dice similarity coefficients of 79.97% and 92.93%, respectively. The proposed method shows great potential to assist pathologists in the pathological analysis of breast cancer. An open-source implementation of our approach can be found at https://github.com/Dian-kai/BreasTDLUSeg.