<p>Due to its low incidence and non-specific clinical manifestations, early diagnosis of splenic tuberculosis (STB) is extremely challenging. Pathology is the gold standard for disease diagnosis. The spleen’s unique structural and functional characteristics may confer distinct pathological features and immune microenvironment in STB. However, no relevant study has been reported to date. Here, we collected seven cases of STB and compared their clinical and pathological characteristics with those of pulmonary tuberculosis (PTB). CT scans revealed that STB primarily manifests as significant enlargement of the spleen, with multiple round-shaped low-density shadows visible within. Compared to the PTB group, the positive rates for molecular detection and acid-fast staining were significantly lower in the STB group, while the proportion of coagulative necrosis was substantially higher. Granulomas, caseous necrosis, abscesses, fibrous proliferation, collagen degeneration, and granulation tissue formation did not show significant differences between the two groups. We further compared infiltrating immune cells and found that the numbers of T cells, CD8⁺ T cells, and macrophages were significantly higher in the STB group than those in the PTB group, but there was no statistical difference compared to normal spleen tissue, suggesting that tuberculosis infection may not have a significant impact on the immune response in STB cases. The number of PD-L1⁺ immune cells in the STB group was significantly higher than that in the PTB group and normal spleen tissue, while the number of PD-1⁺ immune cells did not differ significantly among the three groups. In summary, STB has unique pathological features and immune microenvironment, with a higher incidence of coagulative necrosis and an extreme immune suppression state.</p>