Immunohistochemistry in Undifferentiated Neoplasm/Tumor of Uncertain Origin

Context.-Immunohistochemistry has become an indispensable ancillary study in the identification and classification of undifferentiated neoplasms/tumors of uncertain origin. The diagnostic accuracy has significantly improved because of the continuous discoveries of tissue-specific biomarkers and the development of effective immunohistochemical panels. Objectives.-To identify and classify undifferentiated neoplasms/tumors of uncertain origin by immunohistochemistry. Data Sources.-Literature review and authors' research data and personal practice experience were used. Conclusions.-To better guide therapeutic decisions and predict prognostic outcomes, it is crucial to differentiate the specific lineage of an undifferentiated neoplasm. Application of appropriate immunohistochemical panels enables the accurate classification of most undifferentiated neoplasms. Knowing the utilities and pitfalls of each tissue-specific biomarker is essential for avoiding potential diagnostic errors because an absolutely tissue-specific biomarker is exceptionally rare. We review frequently used tissue-specific biomarkers, provide effective panels, and recommend diagnostic algorithms as a standard approach to undifferentiated neoplasms.