MOTIVATION: The presence of tumor cell clusters in pleural effusion may be a signal of cancer metastasis. The instance segmentation of single cell from cell clusters plays a pivotal role in cluster cell analysis. However, current cell segmentation methods perform poorly for cluster cells due to the overlapping/touching characters of clusters, multiple instance properties of cells, and the poor generalization ability of the models. RESULTS: In this article, we propose a contour constraint instance segmentation framework (CC framework) for cluster cells based on a cluster cell combination enhancement module. The framework can accurately locate each instance from cluster cells and realize high-precision contour segmentation under a few samples. Specifically, we propose the contour attention constraint module to alleviate over- and under-segmentation among individual cell-instance boundaries. In addition, to evaluate the framework, we construct a pleural effusion cluster cell dataset including 197 high-quality samples. The quantitative results show that the numeric result of APmask is > 90%, a more than 10% increase compared with state-of-the-art semantic segmentation algorithms. From the qualitative results, we can observe that our method rarely has segmentation errors.

The appearance of tumor cell clusters in pleural effusion is usually a vital sign of cancer metastasis. Segmentation, as an indispensable basis, is of crucial importance for diagnosing, chemical treatment, and prognosis in patients. However, accurate segmentation of unstained cell clusters containing more detailed features than the fluorescent staining images remains to be a challenging problem due to the complex background and the unclear boundary. Therefore, in this paper, we propose a fused 3-stage image segmentation algorithm, namely Coarse segmentation-Mapping-Fine segmentation (CMF) to achieve unstained cell clusters from whole slide images. Firstly, we establish a tumor cell cluster dataset consisting of 107 sets of images, with each set containing one unstained image, one stained image, and one ground-truth image. Then, according to the features of the unstained and stained cell clusters, we propose a three-stage segmentation method: 1) Coarse segmentation on stained images to extract suspicious cell regions-Region of Interest (ROI); 2) Mapping this ROI to the corresponding unstained image to get the ROI of the unstained image (UI-ROI); 3) Fine Segmentation using improved automatic fuzzy clustering framework (AFCF) on the UI-ROI to get precise cell cluster boundaries. Experimental results on 107 sets of images demonstrate that the proposed algorithm can achieve better performance on unstained cell clusters with an F1 score of 90.40%.