Lesion architecture, assay-defined organism signal, and molecular-histologic correlates in ruminant Johne’s disease: A focused review

signal. This focused narrative review synthesizes primary ruminant tissue studies through 18 June 2026, by lesion architecture, anatomic compartment, cellular composition, organism-detection method, and the spatial relationship between histology and molecular measurement. Established lesion categories remain the most useful diagnostic vocabulary because they organize recurring relationships among architecture, dominant inflammatory cell pattern, and visible or assay-defined organism signal. Organism burden is most interpretable when defined by assay, because acid-fast staining, immunohistochemistry, in situ detection, polymerase chain reaction, culture, and shedding represent related but noninterchangeable evidence. Lesion-linked molecular findings are strongest when they remain anchored to histologic phenotype and tissue localization. Cattle provide the most developed lesion-classification framework, whereas ovine longitudinal and caprine compartmental studies clarify temporal and anatomic variations. Terms such as focal, multifocal, lymphocyte-rich, intermediate, paucibacillary, and macrophage-rich describe sampled morphologic phenotypes, not obligatory temporal stages. Because many molecular studies use cross-sectional tissues, bulk specimens, or related archives, claims about immune state, bacterial persistence, and mechanism should be bounded by localization, cell-composition control, assay target, and cohort independence. An evidence-to-claim framework can help integrate histology and molecular data without converting descriptive lesion categories into unsupported stages or mechanisms.