Various image diagnostic systems, and methods of operating thereof, are disclosed herein. Example embodiments relate to operating the image diagnostic system to identify one or more tissue types within an image patch according to a hierarchical histological taxonomy, identifying an image patch associated with normal tissue, generating a pixel-level segmented image patch for an image patch, generating an encoded image patch for an image patch of at least one tissue, searching for one or more histopathological images, and assigning an image patch to one or more pathological cases.