Diagnostic value of CD4, CD8 and CD68 immunohistochemical profiling in EBUS-TBNA samples for differentiating sarcoidosis and tuberculosis

Differentiating sarcoidosis from tuberculosis in patients with mediastinal and/or hilar granulomatous lymphadenopathy remains challenging due to overlapping clinical, radiological, and histopathological findings. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) allows minimally invasive sampling of lymph nodes; however, histopathological evaluation alone may be insufficient for accurate differentiation. This study aimed to investigate the diagnostic value of CD4 and CD8 T lymphocyte profiles and CD68 expression assessed by immunohistochemistry in EBUS-TBNA samples. This retrospective single-center study included patients who underwent EBUS-TBNA for mediastinal and/or hilar lymphadenopathy between January and December 2019 and were diagnosed with granulomatous lymphadenitis. CD4 + and CD8 + T lymphocyte counts, percentages, CD4/CD8 ratios, and CD68 staining intensity were evaluated immunohistochemically in cell block specimens. Patients were classified as sarcoidosis or tuberculosis based on clinical, radiological, microbiological, and follow-up data. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis. Eighty-five patients were included (sarcoidosis: n = 55; tuberculosis: n = 30). CD4 + T lymphocyte count and percentage were significantly higher in the sarcoidosis group ( p < 0.001 and p = 0.005, respectively). The CD4/CD8 ratio was also significantly elevated in sarcoidosis (median 1.44 vs. 0.35, p = 0.004). ROC analysis demonstrated moderate diagnostic performance for CD4 count (AUC 0.770), CD4% (AUC 0.686), and CD4/CD8 ratio (AUC 0.717). CD68 staining intensity did not differ significantly between groups. Granuloma necrosis was more frequent in tuberculosis (23.3% vs. 7.3%, p = 0.046). Immunohistochemical evaluation of CD4 + T lymphocyte profiles and CD4/CD8 ratio in EBUS-TBNA samples provides meaningful adjunctive information in differentiating sarcoidosis from tuberculosis. Integration of immunophenotypic analysis into routine pathological assessment may improve diagnostic accuracy in patients with granulomatous mediastinal lymphadenopathy.