Systems, devices and methods are provided for performing tissue removal and analysis based on the in-situ optical analysis of tissue and of liquid collected from the tissue region. In one example embodiment, a tissue removal and analysis probe includes an elongate tissue removal device, an optical fiber, and a fluid fillable conduit, where distal ends of the optical fiber and the conduit are in communication with an external region that is adjacent to a distal functional portion of the tissue removal device. The results of optical analysis one of both of external tissue and collected fluid may be employed to determine whether or not tissue removal is to be carried out. Various devices may be interfaced with the conduit for optical analysis of the collected fluid. In one example embodiment, the tissue removal device may be movable relative to the optical fiber and conduit.