Tissue-marking pigments in modern surgical pathology workflows and their methodological implications

Tissue-marking pigments are routinely used in surgical pathology to indicate specimen orientation and delineate resection margins during gross examination, embedding, sectioning, and microscopic evaluation. Accurate margin assessment is essential for clinical decision-making, yet these pigments have traditionally been regarded as simple technical aids whose material properties are rarely examined systematically. However, the increasing use of immunohistochemistry, multiplex staining, and digital pathology has made their behavior during histological processing more relevant than ever, while comprehensive evaluations of their performance remain limited. To address this research gap, this review synthesizes current evidence on the materials, microscopic recognizability, processing tolerance, and analytical compatibility of commonly used tissue-marking pigments. By integrating comparative studies of surgical margin inks and experimental research on dye–tissue interactions, the manuscript examines how pigment composition, tissue background, and histological processing steps influence the microscopic presentation of marking signals. The available evidence indicates that pigment performance varies across materials and conditions. Color fidelity, boundary continuity, and chromogenic behavior may change during dehydration, sectioning, or immunohistochemical staining, and tissue background and observer-dependent color discrimination further affect recognizability. These findings suggest that pigment stability and visibility are context-dependent rather than intrinsic properties. Overall, tissue-marking pigments function as methodological variables within the pathology workflow and their evaluation should thus be incorporated into laboratory quality control and standardization strategies in order to improve reproducibility in margin assessment.