Next-Generation Immunohistochemistry in the Workup of Neoplasm of Uncertain Lineage and CUP

Abstract

Immunohistochemistry is an indispensable complement to a morphology and epidemiology-based approach to tumor diagnosis. This chapter presents a comprehensive review of my approach to assigning tumor lineage and site of origin. It is based on, but expands upon, a review I published in Advances in Anatomic Pathology in 2020 with additional consideration of basic immunohistochemical concepts, discussion of clinical aspects of cancer of unknown primary, an algorithmic approach to the immunohistochemical workup of small round blue cell tumors, an immunohistochemical approach to undifferentiated/dedifferentiated carcinoma, and immunohistochemistry in the evaluation of hereditary cancer predisposition syndromes. Next-generation immunohistochemistry mines discoveries in the developmental biology and molecular genetic literature as a source of novel, highly accurate diagnostic markers. Many of these are lineage-restricted transcription factors. These new tools supplement a scaffold of “tried and true” markers, including those traditionally utilized in the initial immunohistochemical assessment of the high-grade tumor of uncertain lineage (i.e., keratin, S-100, CD45).