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Differential Diagnosis of Peripheral Lung Lesions: Capabilities and Limitations of Current Methods

https://doi.org/10.24060/2076-3093-2025-15-2-64-74

Abstract

This article analyzes 63 scientific works dedicated to the diagnosis of peripheral lung lesions (PLL). The differential diagnosis of PLL poses challenges due to the diversity of underlying pathologies, which may include tuberculoma, cancer, and benign tumors. The absence of a unified diagnostic algorithm often necessitates surgical intervention. Non-invasive methods, including radiography, computed tomography (CT), positron emission tomography (PET), and sputum analysis, exhibit limited diagnostic yield, particularly for small lesions. The combination of fiberoptic bronchoscopy with endoscopic ultrasound (EUS) and transthoracic biopsy enhances diagnostic accuracy; however, they carry risks such as pneumothorax. Video-assisted thoracoscopic surgery (VATS) is an effective modality when biopsies are inconclusive, especially for lesions of less than 3 cm. It ensures high diagnostic accuracy and reduces hospitalization duration. Videoassisted thoracoscopic biopsy offers diagnostic accuracy comparable to that of open biopsy, while exhibiting reduced invasiveness. Conventional thoracotomy remains indicated for large or hard-to-reach lesions. It is recommended that a comprehensive approach combining CT, characterized by high informative value, and PET scan, characterized by high sensitivity and specificity for nodules >10 mm, with invasive methods be used. VATS proves effective for lesions below 3 cm, while thoracotomy is applied to large lesions. An individualized approach remains essential for optimal diagnosis. Despite the advancements, the challenge of differential diagnosis persists.

About the Authors

R. N. Islamov
Bashkir State Medical University ; Republican Clinical Phthisiopulmonology Center
Russian Federation

Rinat N. Islamov — Pulmonary Tuberculosis Surgery Unit, Department of Phthisiology

Ufa 



R. A. Sharipov
Bashkir State Medical University
Russian Federation

Raul A. Sharipov — Cand. Sci. (Med.), Assoc. Prof., Department of Phthisiology

Ufa 



M. A. Bagirov
Central Scientific Research Institute of Tuberculosis ; Russian Medical Academy of Postgraduate Education
Russian Federation

Mamad-Bagir A. Bagirov — Dr. Sci. (Med.), Prof., Chief Researcher, Department of Thoracic Surgery, Department of Surgery

Moscow 



R. K. Tukfatullin
Bashkir State Medical University
Russian Federation

Ravil K. Tukfatullin — Cand. Sci. (Med.), Assoc. Prof., Department of Phthisiology

Ufa 



G. V. Chitorelidze
Central Scientific Research Institute of Tuberculosis
Russian Federation

George V. Chitorelidze — Cand. Sci. (Med.), Researcher

Moscow 



E. V. Pavlova
Bashkir State Medical University
Russian Federation

Elena V. Pavlova — Cand. Sci. (Med.), Assoc. Prof., Department of Phthisiology

Ufa 



R. K. Yagafarova
Башкирский государственный медицинский университет
Russian Federation

Rosa K. Yagafarova — Dr. Sci. (Med.), Assoc. Prof., Department of Phthisiology

Ufa 



References

1. Gombolevskiy V.A., Chernina V.Yu., Blokhin I.A., Nikolaev A.E., Barchuk A.A., Morozov S.P. Main achievements of low-dose computed tomography in lung cancer screening. Tuberculosis and Lung Diseases. 2021;99(1):61–70 (In Russ.). DOI: 10.21292/2075-1230-2021-99-1-61-70

2. Pushkarev E.A., Vazhenin A.V., Kulaev K.I., Zujkov K.S., Yusupov I.M., Popova I.A. Diagnostic technique for peripheral lung growths with endosonographic control of endoscopic instrument position in pathological centre: Russian Federation patent 2719666 C1. 2019 June 17 (In Russ.).

3. Pilkevich D.N., Chekasina M.A., Anufrieva S.S. Atypical videothoracoscopic lung resection in focal tumors. RMJ. 2023;1:18–21 (In Russ.).

4. Pushkarev E.A., Vazhenin A.V., Kulaev K.I., Yusupov I.M., Zuikov K.S., Popova I.A. Effectiveness of a modified biopsy technique in endobronchial ultrasound (EBUS) in the diagnosis of peripheral lung neoplasms: results of a clinical study. Ural medical journal. 2022;21(6):19–25 (In Russ.). DOI: 10.52420/2071-5943-2022-21-6-19-25

5. Samorodov N.A., Sabanchieva Zh.Kh., Vasiliev I.V. Application of video-assisted thoracoscopic lung resections for differential diagnosis of lung diseases. Tuberculosis and Lung Diseases. 2021;99(2):16–20 (In Russ.). DOI: 10.21292/2075-1230-2021-99-2-16-20

6. Tyulkova T.E., Lugovkina T.K., Kutuzova D.M., Khabibullina N.F. Diagnosis of bacteriologically unconfirmed pulmonary tuberculosis (literature review). Russian Medical Inquiry. 2022;6(7):387–92 (In Russ.). DOI: 10.32364/2587-6821-2022-6-7-387-392

7. Tyurin I.E., Avdeev S.N., Gavrilov P.V., Esakov YU.S., Zyablova E.I., Ilina N.A., et al. Glossary of terms for thoracic imaging. Journal of Radiology and Nuclear Medicine. 2023;104(5):292–332 (In Russ.). DOI: 10.20862/0042-4676-2023-104-5-292-332

8. Chernichenko N.V., Lagkueva I.D., Susarev I.О., Dzhigkaeva M.M., Chkhikvadze V.D. CT navigation is the key to successful bronchоbiopsy for peripheral pulmonary nodules. Journal of Radiology and Nuclear Medicine. 2024;105(1):29–36 (In Russ.). DOI: 10.20862/0042-4676-2024-105-1-29-36

9. Chesalina Y.O., Karpina N.L., Berezovskij Y.S., Shishova S.V., Sivokozov I.V. First assessment of comparative efficacy of virtual bronchoscopy and radial endobronchial ultrasound for minimally invasive diagnosis of peripheral pulmonary lesions. Pul’monologiya. 2021;31(6):718–28 (In Russ.). DOI: 10.18093/0869-0189-2021-31-6-718-728

10. Shabalina I., Zaitseva A., Krasnikova E., Semenova L., Sivokozov I., Karpina N., et al. Evaluation of the radial endosonographic image of peripheral lung lesions for choosing the bronchobiopsies in the differential diagnosis of tuberculosis, mycobacteriosis and malignancy. Vrach (The Doctor). 2023;5:5–12 (In Russ.). DOI: 10.29296/25877305-2023-05-01

11. Clinical guidelines. Malignant neoplasm of the bronchi and lung. Moscow; 2021 (In Russ.).

12. Esakov Yu.S., Shrainer I.V., Kirpichnikova E.I., Kulikova E.A., Efteev L.A., Tukvadze Z.G., et al. Clinical efficiency of ct-guided transthoracic needle biopsy of peripheral lung lesions. Pirogov Russian Journal of Surgery = Khirurgiya. Zurnal im. N.I. Pirogova. 2022;5:34–42 (In Russ.). DOI: 10.17116/hirurgia202205134

13. Kireev A.A. Up-to-date cytomorphological classifications of benign and malignant lung lesions. Laboratory Service = Laboratornaya sluzhba. 2023;12(1):14–20 (In Russ.). DOI: 10.17116/labs20231201114

14. Archer J.M., Mendoza D.P., Hung Y.P., Lanuti M., Digumarthy S.R. Surgical resection of benign nodules in lung cancer screening: incidence and features. JTO Clin Res Rep. 2023;4(12):100605. DOI: 10.1016/j.jtocrr.2023.100605

15. Ho A.T.N., Gorthi R., Lee R., Chawla M., Patolia S. Solitary lung nodule: CT-guided transthoracic biopsy vs transbronchial biopsy with endobronchial ultrasound and flexible bronchoscope, a meta-analysis of randomized controlled trials. Lung. 2023;201(1):85–93 DOI: 10.1007/s00408-023-00596-9

16. Ho E., Cho R.J., Keenan J.C., Murgu S. The feasibility of using the “artery sign” for pre-procedural planning in navigational bronchoscopy for parenchymal pulmonary lesion sampling. Diagnostics. 2022;12(12):3059. DOI: 10.3390/diagnostics12123059

17. Jiang J., Lv Z.M., Lv F.J., Fu B.J., Liang Z.R., Chu Z.G. Clinical and computed tomography characteristics of solitary pulmonary nodules caused by fungi: a comparative study. Infect Drug Resist. 2022;15:6019–28. DOI: 10.2147/IDR.S382289

18. Kho S.S., Nyanti L.E., Chai C.S., Chan S.K., Tie S.T. Feasibility of manual bronchial branch reading technique in navigating conventional rEBUS bronchoscopy in the evaluation of peripheral pulmonary lesion. Clin Respir J. 2021;15(6):595–603. DOI: 10.1111/crj.13297

19. Kirino Y., Tsuji T., Ohno S., Yoshimi R., Takeda Y., Misumi M., et al. [A solitary lung lesion in Wegener’s granulomatosis, which was difficult to differentiate from lung neoplasm]. Ryumachi. 2003;43(1):39–43. Japanese. PMID: 12692988

20. de Koning H.J., van der Aalst C.M., de Jong P.A., Scholten E.T., Nackaerts K., Heuvelmans M.A., et al. Reduced lung-cancer mortality with volume CT screening in a randomized trial. N Engl J Med. 2020;382(6):503–13. DOI: 10.1056/NEJMoa1911793

21. Korevaar D.A., Colella S., Fally M., Camuset J., Colby T.V., Hagmeyer L., et al. European Respiratory Society guidelines on transbronchial lung cryobiopsy in the diagnosis of interstitial lung diseases. Eur Respir J. 2022;60(5):2200425. DOI: 10.1183/13993003.00425-2022

22. Kurimoto N., Morita K. Bronchial branch tracing. Springer Nature; 2020. 173 p.

23. Lachkar S., Perrot L., Gervereau D., De Marchi M., Morisse Pradier H., Dantoing E., et al. Radial-EBUS and virtual bronchoscopy planner for peripheral lung cancer diagnosis: How it became the first-line endoscopic procedure. Thorac Cancer. 2022;13(20):2854–60. DOI: 10.1111/1759-7714.14629

24. Ren Q., Zhou Y., Yan M., Zheng C., Zhou G., Xia X. Imaging-guided percutaneous transthoracic needle biopsy of nodules in the lung base: fluoroscopy CT versus cone-beam CT. Clin Radiol. 2022;77(5):e394–9. DOI: 10.1016/j.crad.2022.02.005

25. Sainz Zuñiga P.V., Vakil E., Molina S., Bassett R.L. Jr, Ost D.E. Sensitivity of radial endobronchial ultrasound-guided bronchoscopy for lung cancer in patients with peripheral pulmonary lesions: an updated meta-analysis. Chest. 2020;157(4):994–1011. DOI: 10.1016/j.chest.2019.10.042

26. Sano A. Virtual bronchoscopy using Horos. Lung India. 2020;37(5):457–8. DOI: 10.4103/lungindia.lungindia_110_20

27. Takata S., Miyake K., Kumanogoh A. The superiority of manual over automated methods in identifying bronchial trees on identical CT images. Sci Rep. 2022;12(1):5416. DOI: 10.1038/s41598-022-09401-8

28. Taketa T., Nakamura T. Pulmonary sarcoidosis presenting as a solitary nodule mimicking lung cancer. Clin Case Rep. 2021;9(6):e04208. DOI: 10.1002/ccr3.4208

29. Udagawa H., Kirita K., Naito T., Nomura S., Ishibashi M., Matsuzawa R., et al. Feasibility and utility of transbronchial cryobiopsy in precision medicine for lung cancer: Prospective single-arm study. Cancer Sci. 2020;111(7):2488–98. DOI: 10.1111/cas.14489

30. Velez‐Perez A., Abuharb B., Bammert C.E. Detection of non‐haematolymphoid malignancies in bronchoalveolar lavages — A cancer centre’s 10-year experience. Cytopathology. 2022;33(4):449–53.

31. Zheng X., Xie F., Li Y., Chen J., Jiang Y., Sun J. Ultrathin bronchoscope combined with virtual bronchoscopic navigation and endobronchial ultrasound for the diagnosis of peripheral pulmonary lesions with or without fluoroscopy: A randomized trial. Thorac Cancer. 2021;12(12):1864–72. DOI: 10.1111/1759-7714.13995

32. Zheng X., Zhong C., Xie F., Li S., Wang G., Zhang L., et al. Virtual bronchoscopic navigation and endobronchial ultrasound with a guide sheath without fluoroscopy for diagnosing peripheral pulmonary lesions with a bronchus leading to or adjacent to the lesion: A randomized non-inferiority trial. Respirology. 2023;28(4):389–98. DOI: 10.1111/resp.14405

33. Zhong C.H., Su Z.Q., Luo W.Z., Rao W.-Y., Feng J.-X., Tang Ch.-L., et al. Hierarchical clock-scale hand-drawn mapping as a simple method for bronchoscopic navigation in peripheral pulmonary nodule. Respiratory Research. 2022;23(1):245. DOI: 10.1186/s12931-022-02160-0

34. Zhou Y., Yang W., Ao M., Höti N., Gabrielson E., Chan D.W., et al. Proteomic analysis of the air-way fluid in lung cancer. Detection of periostin in bronchoalveolar lavage (BAL). Front Oncol. 2020;10:1072. DOI: 10.3389/fonc.2020.01072

35. Zhu H., Liu H., Wen J., Yuan T., Ren G., Jiang Y., et al. Overexpression of human aspartyl (asparaginyl) β-hydroxylase in NSCLC: its diagnostic value by means of exosomes of bronchoalveolar lavage. Appl Immunohistochem Mol Morphol. 2021;29(10):720–7. DOI: 10.1097/PAI.0000000000000963

36. Zou X., Zhu Y., Hu Q., Qi Q., Hua H., Fei F., et al. Diagnostic value of ultrasound-guided transbronchial lung biopsy in peripheral tuberculous pulmonary lesions. Diagn Cytopathol. 2022;50(12):572–8. DOI: 10.1002/dc.25041

37. Zou X., Cui N., Ma Q., Lin Z., Zhang J., Li X. Conventional versus cone-beam computed tomography in lung biopsy: diagnostic performance, risks, and the advantages of tract embolization with gelfoam particle suspension. Quant Imaging Med Surg. 2024;14(9):6479–92. DOI: 10.21037/qims-24-342

38. Tanahashi M. Thoracotomy approach to large tumors. Kyobu Geka. 2024;77(10):828–34. Japanese. PMID: 39617380

39. Abid A., Ahmad T., Shaikh K.A., Nasreen S., Sikander N., Mazcuri M. Video Assisted Thoracoscopy as a therapeutic modality in evacuating retained or clotted haemothoraces. J Pak Med Assoc. 2021;71(5):1428– 31. DOI: 10.47391/JPMA.288

40. Kruglova I.A., Paranina T.V., Zinoviev S.V., Utkin O.V., Denisenko A.N. Urgent intraoperative cytological diagnosis of spherical lung mass lesions. Pul’monologiya. 2023;33(3):357–65 (In Russ.). DOI: 10.18093/0869-0189-2023-33-3-357-365

41. Afonin G.V., Glukhareva A.E., Smolenov E.I., Kolobaev I.V., Beketov E.E., Petrov L.O., et al. The application of PET/CT with 18F-FDG in the differential diagnosis of lung solitary lesions. Research and Practical Medicine Journal. 2022;9(3):80–90 (In Russ.). DOI: 10.17709/2410-1893-2022-9-3-6

42. Gavrilov P.V., Suvorova S.S., Smolnikova U.A., Ushkov A.D. Pulmonary hamartoma: a singlecenter analysis of 142 cases. Journal of Radiology and Nuclear Medicine. 2024;105(1):13–9 (In Russ.). DOI: 10.20862/0042-4676-2024-105-1-13-19

43. Bagirov M.A., Lepeha L.N., Sadovnikova S.S., Erokhina M.V., Karpina N.L., Krasnikova E.V. Nowaday indicacions to surgery for lung tuberculemas. Tuberculosis and socially significant diseases. 2018;2:43–8 (In Russ.).

44. Vasil’eva I.A., Balasanyants G.S., Borisov S.E., Burmistrova I.A., Valiev R.Sh., Vaniev E.V et al. Tuberculosis in adults. Clinical guidelines. Moscow; 2021 (In Russ.).

45. Diez-Ferrer M., Morales A., Tebé C., Cubero N., López-Lisbona R., Padrones S., et al. Ultrathin bronchoscopy with and without virtual bronchoscopic navigation: influence of segmentation on diagnostic yield. Respiration. 2019;97(3):252–58. DOI: 10.1159/000493270

46. Goel M.K., Kumar A., Maitra G., Singh B., Ahlawat S., Jain P., et al. Safety and diagnostic yield of transbronchial lung cryobiopsy by flexible bronchoscopy using laryngeal mask airway in diffuse and localized peripheral lung diseases: A single-center retrospective analysis of 326 cases. Lung India. 2021;38(2):109–16. DOI: 10.4103/lungindia.lungindia_220_20

47. Gorospe L., Ajuria-Illarramendi O., de la Puente-Bujidos C., MuñozMolina G.M., Cabañero-Sánchez A., Moreno-Mata N., et al. PET/CT findings of granulomatosis with polyangiitis presenting as a solitary pulmonary nodule and mimicking lung cancer. J Clin Rheumatol. 2020;26(5):e122–3. DOI: 10.1097/RHU.0000000000000994

48. Gutiérrez J., Yumay P., Schiappacasse G., Fernándeza P.F., Truebab A.A., Santosa J.S., et al. Nódulo pulmonar solitario como presentación inhabitual de infección por Mycobacterium abscessus. Reporte de un caso clínico. Revista médica de Chile. 2023;151(12):1636–9.

49. Herth F.J., Mayer M., Thiboutot J., Kapp C.M., Sun J., Zhang X., et al. Safety and performance of transbronchial cryobiopsy for parenchymal lung lesions. Chest. 2021;160(4):1512–9. DOI: 10.1016/j.chest.2021.04.063

50. Andolfi M., Potenza R., Capozzi R., Liparulo V., Puma F., Yasufuku K. The role of bronchoscopy in the diagnosis of early lung cancer: a review. J Thorac Dis. 2016;8(11):3329–37. DOI: 10.21037/jtd.2016.11.81

51. Ernst A., Eberhardt R., Krasnik M., Herth F.J. Efficacy of endobronchial ultrasound-guided transbronchial needle aspiration of hilar lymph nodes for diagnosing and staging cancer. J Thorac Oncol. 2009;4(8):947–50. DOI: 10.1097/JTO.0b013e3181add88d

52. Megyesfalvi Z., Tallosy B., Pipek O., Fillinger J., Lang C., Klikovits T., et al. The landscape of small cell lung cancer metastases: organ specificity and timing. Thorac Cancer. 2021;12(6):914–23. DOI: 10.1111/1759-7714.13854

53. Sanz-Santos J., Andreo F., Serra P., Monsó E., Ruiz-Manzano J. The role of endobronchial ultrasound in central early lung cancer. Thorac Cancer. 2012;3(2):139–44. DOI: 10.1111/j.1759-7714.2011.00102.x

54. Lee J., Song J.U. Diagnostic yield of radial probe endobronchial ultrasonography-guided transbronchial biopsy without fluoroscopy in peripheral pulmonary lesions: A systematic review and meta-analysis. Thorac Cancer. 2023;14(2):195–205. DOI: 10.1111/1759-7714.14733

55. Kuijvenhoven J.C., Leoncini F., Crombag L.C., Spijker R., Bonta P.I., Korevaar D.A., et al. Endobronchial ultrasound for the diagnosis of centrally located lung tumors: a systematic review and meta-analysis. Respiration. 2020;99(5):441–50. DOI: 10.1159/000500363

56. Albert R.H., Russell J.J. Evaluation of the solitary pulmonary nodule. Am Fam Physician. 2009;80(8):827–31. PMID: 19835344

57. Kattih Z., Bade B., Hatabu H., Brown K., Parambil J., Hata A., et al. Interstitial lung abnormality: narrative review of the approach to diagnosis and management. Chest. 2025;167(3):781–99. DOI: 10.1016/j.chest.2024.09.033

58. Moffatt S.D., Mitchell J.D., Whyte R.I. Role of video-assisted thoracoscopic surgery and classic thoracotomy in lung cancer management. Curr Opin Pulm Med. 2002;8(4):281–6. DOI: 10.1097/00063198-200207000-00007

59. Kokkonouzis I., Strimpakos A.S., Lampaditis I., Tsimpoukis S., Syrigos K.N. The role of endobronchial ultrasound in lung cancer diagnosis and staging: a comprehensive review. Clin Lung Cancer. 2012;13(6):408–15. DOI: 10.1016/j.cllc.2012.05.001

60. Rusch V.W., Asamura H., Watanabe H., Giroux D.J., Rami-Porta R., Goldstraw P., et al. The IASLC lung cancer staging project: a proposal for a new international lymph node map in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol. 2009;4(5):568–77. DOI: 10.1097/JTO.0b013e3181a0d82e

61. Gupta A., Youness H., Dhillon S.S., Harris K. The value of using radial endobronchial ultrasound to guide transbronchial lung cryobiopsy. J Thorac Dis. 2019;11(1):329–34. DOI: 10.21037/jtd.2018.10.116

62. Kops S.E.P., Heus P., Korevaar D.A., Damen J.A.A., Idema D.L., Verhoeven R.L.J., et al. Diagnostic yield and safety of navigation bronchoscopy: A systematic review and meta-analysis. Lung Cancer. 2023;180:107196. DOI: 10.1016/j.lungcan.2023.107196

63. Ahn J.H. An update on the role of bronchoscopy in the diagnosis of pulmonary disease. Yeungnam Univ J Med. 2020;37(4):253–61. DOI: 10.12701/yujm.2020.00584


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Islamov R.N., Sharipov R.A., Bagirov M., Tukfatullin R.K., Chitorelidze G.V., Pavlova E.V., Yagafarova R.K. Differential Diagnosis of Peripheral Lung Lesions: Capabilities and Limitations of Current Methods. Creative surgery and oncology. 2025;15(2):64-74. (In Russ.) https://doi.org/10.24060/2076-3093-2025-15-2-64-74

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