Quantification of structural heterogeneity in H&E stained clear cell renal cell carcinoma using refractive index tomography.

Clear cell renal cell carcinoma (ccRCC) is a common histopathological subtype of renal cancer and is notorious for its poor prognosis. Its accurate diagnosis by histopathology, which relies on manual microscopic inspection of stained slides, is challenging. Here, we present a correlative approach to utilize stained images and refractive index (RI) tomography and demonstrate quantitative assessments of the structural heterogeneities of ccRCC slides obtained from human patients. Machine-learning-assisted segmentation of nuclei and cytoplasm enabled the quantification at the subcellular level. Compared to benign regions, malignant regions exhibited a considerable increase in structural heterogeneities. The results demonstrate that RI tomography provides quantitative information in synergy with stained images on the structural heterogeneities in ccRCC.