Immunohistochemical approaches to the diagnosis of undifferentiated malignant tumors

Undifferentiated malignant neoplasms are a daunting diagnostic problem for anatomical pathologists, calling for a tour de force in morphological skill, clinicopathologic correlation, and application of adjunctive laboratory studies. The most useful approach to these lesions begins with generic classification into 1 of 4 histologic categories: small round cell; spindle cell; large polygonal cell (epithelioid); and pleomorphic neoplasms. Once that step has been accomplished, one can systemically apply corresponding groups of antibody reagents in immunohistologic studies and interpret the results in an algorithmic fashion. This review presents the tumor markers that are the most useful in this contextual approach, as well as the specific algorithmic structures that can be applied to the 4 specified tumor groups. Other selected problems in the diagnosis of morphologically ambiguous tumors are considered as well.