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Peer-reviewedCC BY-NC-NDBMC pulmonary medicine

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

6 affiliations
  1. 1Department of Chest Diseases, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital,, University of Health Sciences Turkey, Istanbul, Turkey. [email protected].
  2. 2Department of Chest Diseases, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital,, University of Health Sciences Turkey, Istanbul, Turkey.
  3. 3Department of Pathology, Haseki Training and Research Hospital, University of Health Sciences Turkey, Istanbul, Turkey.
  4. 4Department of Chest Diseases, Faculty of Medicine, İstanbul Nişantaşı University, Istanbul, Turkey.
  5. 5Department of Chest Diseases, Göztepe Prof. Dr. Süleyman Yalçın City Hospital, University of Health Sciences Turkey, Istanbul Medeniyet University, Istanbul, Turkey.
  6. 6Department of Medical Oncology, Ankara Bilkent City Hospital, University of Health Sciences Turkey, Ankara, Turkey.

Abstract

Background

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.Methods

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.Results

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).Conclusions

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.

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BibTeX
@article{ozbolat2026diagnostic,
  title = {{Diagnostic value of CD4, CD8 and CD68 immunohistochemical profiling in EBUS-TBNA samples for differentiating sarcoidosis and tuberculosis.}},
  author = {Zehra Büşra Özbolat and Mediha Gönenç Ortaköylü and Halide Nur Ürer and Mehmet Atilla Uysal and Belma Akbaba Bağcı and Esma Seda Akalın and Mehmet Akif Parlar and Umut İlhan},
  journal = {BMC pulmonary medicine},
  year = {2026},
  month = aug,
  doi = {10.1186/s12890-026-04535-1},
  url = {https://europepmc.org/article/MED/42972329},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Diagnostic value of CD4, CD8 and CD68 immunohistochemical profiling in EBUS-TBNA samples for differentiating sarcoidosis and tuberculosis.
AU  - Zehra Büşra Özbolat
AU  - Mediha Gönenç Ortaköylü
AU  - Halide Nur Ürer
AU  - Mehmet Atilla Uysal
AU  - Belma Akbaba Bağcı
AU  - Esma Seda Akalın
AU  - Mehmet Akif Parlar
AU  - Umut İlhan
PY  - 2026
DA  - 2026/08/06
JO  - BMC pulmonary medicine
DO  - 10.1186/s12890-026-04535-1
UR  - https://europepmc.org/article/MED/42972329
AB  - Background  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.Methods  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.Results  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).Conclusions  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.
SN  - 1471-2466
ER  -