Current Approach to Undifferentiated Neoplasms, With Focus on New Developments and Novel Immunohistochemical Stains

center dot Context.-Workup of the poorly differentiated or undif-ferentiated tumor remains a significant and challenging entity in the practice of anatomic pathology. Particularly in the setting of small biopsies and limited material, these cases demand a balanced approach that considers the patient's clinical and radiologic presentation, a basic assessment of tumor morphology, a reasonably broad immunohistochemical panel, and diligent preservation of tissue for prognostic and therapeutic studies. Objective.-To illustrate some of the new and emerging immunohistochemical markers in the evaluation of tumors with undifferentiated or poorly differentiated morphology, with a focus on the workup in limited tissue samples to raise awareness of the issues involved with the pathologic workup in these challenging tumors. Data Sources.-A literature review of new ancillary studies that can be applied to cytologic specimens was performed. Conclusions.-Knowledge of the patient's history and communication with the patient's clinical team is essential in formulating a differential diagnosis that can appropri-ately limit the differential diagnosis based on morphology, especially in small specimens. This information, in con-junction with classifying the tumor morphology (eg, epithelioid, spindled, neuroendocrine, basaloid/biphasic, mixed) gives a logical approach to choosing an initial immunohistochemical panel. Fortunately, immunohisto-chemistry is evolving quickly in the wake of groundbreak-ing molecular studies to develop new and better markers to further classify these difficult tumors beyond where we traditionally have been able to go.