Application of immunohistochemistry in undifferentiated neoplasms: A practical approach

Context.-Advances in interventional technology have enhanced the ability to safely sample deep-seated suspicious lesions by fine-needle aspiration procedures. These procedures often yield scant amounts of diagnostic material, yet there is an increasing demand for the performance of more ancillary tests, especially immunohistochemistry and, not infrequently, molecular assays, to increase diagnostic sensitivity and specificity. A systematic approach to conserving diagnostic material is the key, and our previously proposed algorithm can be applied aptly in this context. Objective.-To elaborate a simple stepwise approach to the evaluation of cytology fine-needle aspiration specimens and small biopsy tissue specimens, illustrating the algorithmic application of small panels of immunohistochemical stains in providing an accurate diagnosis with scant amounts of tissue, including the potential pitfalls that may arise while using immunohistochemical staining on small quantities of tissue. Data Sources.-The sources include literature (PubMed), the first Chinese American Pathologists Association Diagnostic Pathology Course material, and the review authors' research data as well as practice experience. Seven examples selected from the CoPath database at Geisinger Medical Center (Danville, Pennsylvania) are illustrated. Conclusions.-A stepwise approach to the evaluation of fine-needle aspiration and small biopsy tissue specimens in conjunction with a small panel of select immunohistochemical stains has been successful in accurately assessing the lineage/origin of the metastatic tumors of unknown primaries. The awareness of the common pitfalls of these biomarkers is essential in many instances.