Treatment-related changes in cytopathology and small biopsies: an increasing array of morphological findings with expanding therapeutic options

INTRODUCTION: Minimally invasive biopsies are ideal for procuring tumor tissue for cancer patients at various stages. With an expanding array of therapeutic agents and variable response of tumors to these agents, these small samples can also be valuable during or after treatment to determine response, residual disease, or new diagnosis. MATERIALS AND METHODS: In this narrative review, cytology and core biopsy cases mentioning therapy or treatment related changes were reviewed to look at different patterns that can arise with illustrative examples to provide morphologic clues to help when evaluating these specimens. RESULTS: The main patterns of morphological changes include epithelial atypia, epithelial and cellular degeneration, stromal changes, amorphous/foreign material, histiocytic and granulomatous inflammation, high-grade transformations, and immunophenotypic changes. Careful review of these cases with illustrative examples can help to maximize concordance between preliminary diagnoses at rapid on-site evaluation and final interpretations, in addition to providing guidance to the proceduralist during the procedure and helping to explain indeterminate imaging findings for cancer patients undergoing therapy. CONCLUSIONS: Given the increased use of novel therapies for cancer treatment and widespread use of imaging to follow-up cancer patients, cytopathology labs play an increasingly important role in evaluating specimens from these patients to exclude residual or recurrent tumor or to explain a mass lesion (eg, infection, new tumor, post-treatment changes). This review highlights the key patterns of changes that can be seen in tissue samples from patients who have had prior therapeutic intervention or are currently undergoing treatment, to demonstrate the impact of pathology review. Cytopathologists should be aware of these patterns and challenges when evaluating cytology and small biopsy specimens in the post-treatment setting to avoid overcalling malignancy and to understand clinical implications for the treating providers.