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

Context.—: Workup of the poorly differentiated or undifferentiated 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 appropriately limit the differential diagnosis based on morphology, especially in small specimens. This information, in conjunction with classifying the tumor morphology (eg, epithelioid, spindled, neuroendocrine, basaloid/biphasic, mixed) gives a logical approach to choosing an initial immunohistochemical panel. Fortunately, immunohistochemistry is evolving quickly in the wake of groundbreaking molecular studies to develop new and better markers to further classify these difficult tumors beyond where we traditionally have been able to go.