“…Attention is devoted to the color transformation process, which should overcome the problematic and undesirable color variation due to differences in color responses of slide scanners, raw materials and manufacturing techniques of stain vendors, as well as staining protocols across different pathology labs [ 17 ]. While some systems transform the RGB color space into more perceptual color spaces, such as CIE-Lab [ 18 – 22 ], Luv [ 23 – 25 ], Ycbcr [ 26 ], or 1D/2D color spaces [ 18 , 27 , 28 ], others perform illumination and color normalization through white shading correction methods [ 29 , 30 ], background subtraction techniques, (adaptive) histogram equalization [ 14 , 31 , 32 ], Gamma correction methods [ 33 ], Reinhard’s method [ 34 ], (improved) color deconvolution [ 35 , 36 ], Non-negative Matrix Factorization (NMF) and Independent Component Analysis (ICA) [ 17 , 37 – 40 ], decorrelation stretching techniques [ 14 , 32 , 41 ], anisotropic diffusion [ 22 ]. After these preprocessing steps, the labeled structures of interest are detected by morphological binary or gray level operators [ 28 , 42 – 45 ], automatic thresholding techniques [ 20 , 28 , 33 , 43 ], clustering techniques [ 46 , 47 ], the Fast Radial Symmetry Transform (FRST) [ 16 , 48 ], Gaussian Mixture Models [ 20 , 22 , 49 ], and edge detectors such as the Canny edge detector, Laplacian of Gaussian filters [ 50 ] or Difference of Gaussian filters [ 51 ].…”