Cytopathology of the microbiome-immune interface: Emerging applications of cytology in infectious, inflammatory, and neoplastic conditions

Objectives: The objective of the study is to synthesize current evidence on the microbiome–immune interface as reflected in cytopathologic specimens and to explore the emerging diagnostic, prognostic, and translational applications of cytology in infectious, inflammatory, and neoplastic diseases. Material and Methods: This narrative review integrates published literature on cytopathology, microbiome research, and immune profiling. Relevant studies examining cytologic specimens, including fine-needle aspiration, effusion cytology, liquid-based cytology, and lavage samples, were evaluated for their contributions to understanding host-microbe interactions. Emphasis was placed on studies incorporating molecular microbiome analysis (16S ribosomal ribonucleic acid sequencing, metagenomics), immunocytochemistry, cytokine profiling, and digital image analysis. Results: Cytologic specimens provide a minimally invasive platform that captures dynamic interactions between epithelial cells, immune infiltrates, and microbial communities. In infectious diseases, cytology enables direct pathogen visualization while reflecting immune activation patterns such as granuloma formation and neutrophilic inflammation. In chronic inflammatory disorders, cytologic features including lymphoid infiltrates and macrophage activation may correspond with microbiome-driven immune dysregulation. In oncology, tumor-associated microbiota detectable in cytology samples influence immune checkpoint expression, macrophage polarization, and tumor microenvironment remodeling. Integration of molecular assays, single-cell technologies, and artificial intelligence further enhances the ability of cytology to characterize microbiome–immune signatures within limited specimens. Conclusion: Cytopathology is evolving from a purely morphologic discipline into an integrative platform that bridges microbial ecology and immune dynamics. Incorporating microbiome profiling and immune phenotyping into routine cytologic evaluation holds promise for improved disease stratification, early detection, and personalized therapeutic decision-making. Recognizing cytology as a window into the microbiome-immune interface may redefine its role in precision medicine across infectious, inflammatory, and neoplastic conditions.