Morphological and molecular genetic diagnosis of lung cancer: methods and problems
https://doi.org/10.17709/2409-2231-2020-7-3-5
Abstract
Lung cancer is one of the leading causes of death in the world. Despite improvements in diagnostic procedures, most cases of this disease are diagnosed at common and metastatic stages. In recent years, new approaches to systemic antitumor treatment have been registered, which are the main method of treatment in patients with stage IIIB-IV. The diagnosis and staging of patients with lung cancer in recent decades has increasingly relied on minimally invasive tissue sampling techniques, such as endobronchial ultrasound (EBUS) or endoscopic ultrasound (EUS) needle aspiration, transbronchial biopsy, and transthoracic image guided core needle biopsy. These modalities have been shown to have low complication rates, and provide adequate cellular material for pathologic diagnosis and necessary ancillary molecular testing. It is important to understand how a small amount of biopsy material obtained using minimally invasive techniques is processed and evaluated by pathologists. An important condition is obtaining a sufficient number of cell or tissue substrate, can reliably establish the malignant process, to determine the histologic tumor type (whether it’s adenocarcinoma or squamous cell carcinoma), carry out the immunohistochemical and molecular genetic study to determine indications for the purpose of targeted, immunotherapy and the selection of chemotherapy regimen. It is necessary to conduct a single procedure that is as gentle as possible and provides a sufficiently large amount of tissue. The method of obtaining the material should be selected individually depending on the location of the pathological formation, the patient's condition and the capabilities of the clinic.
About the Authors
V. S. Usachev
A.F.Tsyb Medical Radiological Research Center – Branch of the National Medical Research Radiological Center
Russian Federation
Russian Federation
Vladimir S. Usachev – researcher of the department of radiation and surgical treatment of thoracic region diseases
4 Korolev str., Obninsk 249036
SPIN: 1329-7915
AuthorID: 901529
Scopus Author ID: 57200716739
E. I. Smolenov
A.F.Tsyb Medical Radiological Research Center – Branch of the National Medical Research Radiological Center
Russian Federation
Russian Federation
Evgeny I. Smolenov – researcher of the department of radiation and surgical treatment of thoracic region diseases
4 Korolev str., Obninsk 249036
SPIN: 6376-2673
AuthorID: 808954
Yu. A. Ragulin
A.F.Tsyb Medical Radiological Research Center – Branch of the National Medical Research Radiological Center
Russian Federation
Russian Federation
Yury A. Ragulin – Cand. Sci. (Med.), researcher of the department of radiation and surgical treatment of thoracic region diseases
4 Korolev str., Obninsk 249036
SPIN: 6453-6594
AuthorID: 696041
ResearcherID: L-5417-2016
Scopus Author ID: 55463680700
References
1. Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92–98. https://doi.org/10.1056/nejmoa011954
2. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006 Dec 14;355(24):2542–2550. https://doi.org/10.1056/nejmoa061884
3. Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 2008; 26(21):3543–51. https://doi.org/10.1200/jco.2007.15.0375
4. Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger K, Yatabe Y, et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society: international multidisciplinary classification of lung adenocarcinoma: executive summary. Proc Am Thorac Soc. 2011 Sep;8(5):381–385. https://doi.org/10.1513/pats.201107-042st
5. Usachev VS, Ragulin YuA, Silantyeva NK. Comparative assessment of transthoracic biopsy procedures in the diagnosis of pulmonary and mediastinal tumors. Oncology. Journal named after P.A.Herzen. 2016;5(5):11–14. (In Russian). https://doi.org/10.17116/onkolog20165511-14
6. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011 Mar 4;144(5):646–674. https://doi.org/10.1016/j.cell.2011.02.013
7. Kris MG, Johnson BE, Berry LD, Kwiatkowski DJ, Iafrate AJ, Wistuba II, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014 May 21;311(19):1998–2006. https://doi.org/10.1001/jama.2014.3741
8. Mok TS, Wu Y-L, Thongprasert S, Yang C-H, Chu D-T, Saijo N, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep 3;361(10):947–957. https://doi.org/10.1056/nejmoa0810699
9. Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239–246. https://doi.org/10.1016/S1470-2045(11)70393-X
10. Sequist LV, Yang JC-H, Yamamoto N, O’Byrne K, Hirsh V, Mok T, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3327–3334. https://doi.org/10.1200/jco.2012.44.2806
11. Kwak EL, Bang Y-J, Camidge DR, Shaw AT, Solomon B, Maki RG, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010 Oct 28;363(18):1693–1703. https://doi.org/10.1056/nejmoa1006448
12. Costa DB, Shaw AT, Ou S-HI, Solomon BJ, Riely GJ, Ahn M-J, et al. Clinical Experience with Crizotinib in Patients with Advanced ALK-Rearranged Non-Small-Cell Lung Cancer and Brain Metastases. J Clin Oncol. 2015 Jun 10;33(17):1881–1888. https://doi.org/10.1200/jco.2014.59.0539
13. Shaw AT, Ou S-HI, Bang Y-J, Camidge DR, Solomon BJ, Salgia R, et al. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Nov 20;371(21):1963–1971. https://doi.org/10.1056/nejmoa1406766
14. Giroux Leprieur E, Dumenil C, Julie C, Giraud V, Dumoulin J, Labrune S, et al. Immunotherapy revolutionises non-small-cell lung cancer therapy: Results, perspectives and new challenges. Eur J Cancer. 2017;78:16–23. https://doi.org/10.1016/j.ejca.2016.12.041
15. Lindeman NI, Cagle PT, Beasley MB, Chitale DA, Dacic S, Giaccone G, et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. Arch Pathol Lab Med. 2013 Jun;137(6):828–860. https://doi.org/10.5858/arpa.2012-0720-OA
16. Frampton GM, Fichtenholtz A, Otto GA, Wang K, Downing SR, He J, et al. Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol. 2013 Nov;31(11):1023–1031. https://doi.org/10.1038/nbt.2696
17. Silvestri GA, Gonzalez AV, Jantz MA, Margolis ML, Gould MK, Tanoue LT, et al. Methods for staging non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013 May;143(5 Suppl):e211S–e250S. https://doi.org/10.1378/chest.12-2355
18. Kramer H, Groen HJM. Current concepts in the mediastinal lymph node staging of nonsmall cell lung cancer. Ann Surg. 2003 Aug;238(2):180–188. https://doi.org/10.1097/01.SLA.0000081086.37779.1a
19. Park BJ, Flores R, Downey RJ, Bains MS, Rusch VW. Management of major hemorrhage during mediastinoscopy. J Thorac Cardiovasc Surg. 2003 Sep;126(3):726–731. https://doi.org/10.1016/s0022-5223(03)00748-7
20. Kirschner PA. Cervical mediastinoscopy. Chest Surg Clin N Am. 1996 Feb;6(1):1–20.
21. Urschel JD. Conservative management (packing) of hemorrhage complicating mediastinoscopy. Ann Thorac Cardiovasc Surg. 2000 Feb;6(1):9–12.
22. Hurtgen M, Friedel G, Toomes H, Fritz P. Radical video-assisted mediastinoscopic lymphadenectomy (VAMLA)--technique and first results. Eur J Cardiothorac Surg. 2002 Feb;21(2):348– 351. https://doi.org/10.1016/s1010-7940(01)01125-3
23. Kuzdzal J, Zieliński M, Papla B, Szlubowski A, Hauer Ł, Nabiałek T, et al. Transcervical extended mediastinal lymphadenectomy — the new operative technique and early results in lung cancer staging. Eur J Cardiothorac Surg. 2005 Mar;27(3):384–390; discussion 390. https://doi.org/10.1016/j.ejcts.2004.12.008
24. Zielinski M, Szlubowski A, Kołodziej M, Orzechowski S, Laczynska E, Pankowski J, et al. Comparison of endobronchial ultrasound and/or endoesophageal ultrasound with transcervical extended mediastinal lymphadenectomy for staging and restaging of nonsmall-cell lung cancer. J Thorac Oncol. 2013 May;8(5):630–636. https://doi.org/10.1097/jto.0b013e318287c0ce
25. Kuzdzal J, Zieliński M, Papla B, Urbanik A, Wojciechowski W, Narski M, et al. The transcervical extended mediastinal lymphadenectomy versus cervical mediastinoscopy in non-small cell lung cancer staging. Eur J Cardiothorac Surg. 2007 Jan;31(1):88– 94. https://doi.org/10.1016/j.ejcts.2006.10.026
26. Kużdżał J, Warmus J, Grochowski Z. Optimal mediastinal staging in non-small cell lung cancer: what is the role of TEMLA and VAMLA? Lung Cancer. 2014 Oct;86(1):1–4. https://doi.org/10.1016/j.lungcan.2014.07.015
27. De Leyn P, Dooms C, Kuzdzal J, Lardinois D, Passlick B, Rami-Porta R, et al. Revised ESTS guidelines for preoperative mediastinal lymph node staging for non-small-cell lung cancer. Eur J Cardiothorac Surg. 2014 May;45(5):787–798. https://doi.org/10.1093/ejcts/ezu028
28. Steinfort DP, Liew D, Conron M, Hutchinson AF, Irving LB. Cost-benefit of minimally invasive staging of non-small cell lung cancer: a decision tree sensitivity analysis. J Thorac Oncol. 2010 Oct;5(10):1564–1570. https://doi.org/10.1097/jto.0b013e3181e8b2e6
29. Varela-Lema L, Fernández-Villar A, Ruano-Ravina A. Effectiveness and safety of endobronchial ultrasound-transbronchial needle aspiration: a systematic review. Eur Respir J. 2009 May;33(5):1156–1164. https://doi.org/10.1183/09031936.00097908
30. Eapen GA, Shah AM, Lei X, Jimenez CA, Morice RC, Yarmus L, et al. Complications, consequences, and practice patterns of endobronchial ultrasound-guided transbronchial needle aspiration: Results of the AQuIRE registry. Chest. 2013 Apr;143(4):1044–1053. https://doi.org/10.1378/chest.12-0350
31. VanderLaan PA, Wang HH, Majid A, et al. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA): an overview and update for the cytopathologist. Cancer Cytopathol 2014;122(8):561–576. https://doi.org/10.1002/cncy.21431
32. Folch E, Santacruz J, Machuzak M, Gildea T, Majid A. Safety and Efficacy of EBUS-Guided TBNA Through the Pulmonary Artery: A Preliminary Report. CHEST. 2011 Oct 23;140(4):600A. https://doi.org/10.1378/chest.1119000
33. Micames CG, McCrory DC, Pavey DA, Jowell PS, Gress FG. Endoscopic ultrasound-guided fine-needle aspiration for non-small cell lung cancer staging: A systematic review and metaanalysis. Chest. 2007 Feb;131(2):539–548. https://doi.org/10.1378/chest.06-1437
34. Chang KJ, Erickson RA, Nguyen P. Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration of the left adrenal gland. Gastrointest Endosc. 1996 Nov;44(5):568–572.
35. Wallace MB, Pascual JMS, Raimondo M, Woodward TA, McComb BL, Crook JE, et al. Minimally invasive endoscopic staging of suspected lung cancer. JAMA. 2008 Feb 6;299(5):540–546. https://doi.org/10.1001/jama.299.5.540
36. Patel VK, Naik SK, Naidich DP, Travis WD, Weingarten JA, Lazzaro R, et al. A practical algorithmic approach to the diagnosis and management of solitary pulmonary nodules: part 1: radiologic characteristics and imaging modalities. Chest. 2013 Mar;143(3):825–839. https://doi.org/10.1378/chest.12-0960
37. Dwamena BA, Sonnad SS, Angobaldo JO, Wahl RL. Metastases from non-small cell lung cancer: mediastinal staging in the 1990s — meta-analytic comparison of PET and CT. Radiology. 1999 Nov;213(2):530–536.
38. Gould MK, Kuschner WG, Rydzak CE, Maclean CC, Demas AN, Shigemitsu H, et al. Test performance of positron emission tomography and computed tomography for mediastinal staging in patients with non-small-cell lung cancer: a meta-analysis. Ann Intern Med. 2003 Dec 2;139(11):879–892. https://doi.org/10.7326/0003-4819-139-11-200311180-00013
39. Rivera MP, Mehta AC, Wahidi MM. Establishing the diagnosis of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013 May;143(5 Suppl):e142S–e165S. https://doi.org/10.1378/chest.12-2353
40. Silanteva NK, Petrosian AP, Shavladze ZN, Usacheva AYu, Ragulin YuA, Usache VS. Solitary pulmonary nodules: effectiveness of dynamic CT in the differential diagnosis. Siberian Journal of Oncology. 2017;16(5):18–26. https://doi.org/10.21294/1814-4861-2017-16-5-18-26
41. Wiener RS, Schwartz LM, Woloshin S, Welch HG. Population-based risk for complications after transthoracic needle lung biopsy of a pulmonary nodule: an analysis of discharge records. Ann Intern Med. 2011 Aug 2;155(3):137–144. https://doi.org/10.7326/0003-4819-155-3-201108020-00003
42. Annema JT, van Meerbeeck JP, Rintoul RC, Dooms C, Deschepper E, Dekkers OM, et al. Mediastinoscopy vs endosonography for mediastinal nodal staging of lung cancer: a randomized trial. JAMA. 2010 Nov 24;304(20):2245–2252. https://doi.org/10.1001/jama.2010.1705
43. Farjah F, Flum DR, Ramsey SD, Heagerty PJ, Symons RG, Wood DE. Multi-modality mediastinal staging for lung cancer among medicare beneficiaries. J Thorac Oncol. 2009 Mar;4(3):355– 363. https://doi.org/10.1097/jto.0b013e318197f4d9
44. Silvestri GA, Gould MK, Margolis ML, Tanoue LT, McCrory D, Toloza E, et al. Noninvasive staging of non-small cell lung cancer: ACCP evidenced-based clinical practice guidelines (2nd edition). Chest. 2007 Sep;132(3 Suppl):178S–201S. https://doi.org/10.1378/chest.07-1360
45. Little AG, Rusch VW, Bonner JA, Gaspar LE, Green MR, Webb WR, et al. Patterns of surgical care of lung cancer patients. Ann Thorac Surg. 2005 Dec;80(6):2051–2056. https://doi.org/10.1016/j.athoracsur.2005.06.071
46. Osarogiagbon RU, Yu X. Mediastinal lymph node examination and survival in resected early-stage non-small-cell lung cancer in the surveillance, epidemiology, and end results database. J Thorac Oncol. 2012 Dec;7(12):1798–806. https://doi.org/10.1097/jto.0b013e31827457db
47. Osarogiagbon RU, Allen JW, Farooq A, Wu JT. Objective review of mediastinal lymph node examination in a lung cancer resection cohort. J Thorac Oncol. 2012 Feb;7(2):390–396. https://doi.org/10.1097/jto.0b013e31823e5e2d
48. Darling GE, Dickie AJ, Malthaner RA, Kennedy EB, Tey R. Invasive mediastinal staging of non-small-cell lung cancer: a clinical practice guideline. Curr Oncol. 2011 Dec;18(6):e304–e310. https://doi.org/10.3747/co.v18i6.820
49. Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG. Introduction to The 2015 World Health Organization Classification of Tumors of the Lung, Pleura, Thymus, and Heart. J Thorac Oncol. 2015 Sep;10(9):1240–1242. https://doi.org/10.1097/jto.0000000000000663
50. Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger K, Yatabe Y, et al. Diagnosis of lung cancer in small biopsies and cytology: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. Arch Pathol Lab Med. 2013 May;137(5):668–684. https://doi.org/10.5858/arpa.2012-0263-RA
51. Bishop JA, Teruya-Feldstein J, Westra WH, Pelosi G, Travis WD, Rekhtman N. p40 (ΔNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma. Mod Pathol. 2012 Mar;25(3):405–415. https://doi.org/10.1038/modpathol.2011.173
52. Schneider F, Smith MA, Lane MC, Pantanowitz L, Dacic S, Ohori NP. Adequacy of core needle biopsy specimens and fine-needle aspirates for molecular testing of lung adenocarcinomas. Am J Clin Pathol. 2015 Feb;143(2):193–200. https://doi.org/10.1309/AJCPMY8UI7WSFSYY
53. Coley SM, Crapanzano JP, Saqi A. FNA, core biopsy, or both for the diagnosis of lung carcinoma: Obtaining sufficient tissue for a specific diagnosis and molecular testing. Cancer Cytopathol. 2015 May;123(5):318–326. https://doi.org/10.1002/cncy.21527
54. Wang S, Yu B, Ng CC, Mercorella B, Selinger CI, O’Toole SA, et al. The suitability of small biopsy and cytology specimens for EGFR and other mutation testing in non-small cell lung cancer. Transl Lung Cancer Res. 2015 Apr;4(2):119–125. https://doi.org/10.3978/j.issn.2218-6751.2015.01.05
55. Vanderlaan PA, Yamaguchi N, Folch E, Boucher DH, Kent MS, Gangadharan SP, et al. Success and failure rates of tumor genotyping techniques in routine pathological samples with non-small-cell lung cancer. Lung Cancer. 2014 Apr;84(1):39–44. https://doi.org/10.1016/j.lungcan.2014.01.013
56. Sholl LM, Aisner DL, Varella-Garcia M, Berry LD, Dias-SantagataD, Wistuba II, et al. Multi-institutional Oncogenic Driver Mutation Analysis in Lung Adenocarcinoma: The Lung Cancer Mutation Consortium Experience. J Thorac Oncol. 2015 May;10(5):768–777. https://doi.org/10.1097/jto.0000000000000516
57. Van der Heijden EHFM, Casal RF, Trisolini R, Steinfort DP, Hwangbo B, Nakajima T, et al. Guideline for the acquisition and preparation of conventional and endobronchial ultrasound-guided transbronchial needle aspiration specimens for the diagnosis and molecular testing of patients with known or suspected lung cancer. Respiration. 2014;88(6):500–517. https://doi.org/10.1159/000368857
58. Reynolds JP, Tubbs RR, Minca EC, MacNamara S, Almeida FA, Ma PC, et al. EGFR mutational genotyping of liquid based cytology samples obtained via fine needle aspiration (FNA) at endobronchial ultrasound of non-small cell lung cancer (NSCLC). Lung Cancer. 2014 Nov;86(2):158–163. https://doi.org/10.1016/j.lungcan.2014.09.003
59. Kaprin AD, Galkin VN, Zhavoronkov LP, Ivanov VK, Ivanov SA, Romanko YuS. Synthesis of basic and applied research is the basis of obtaining high-quality findings and translating them into clinical practice. Radiation and Risk. 2017;26(2):26–40. https://doi.org/10.21870/0131-3878-2017-26-2-26-40
Review
For citations:
Usachev V.S., Smolenov E.I., Ragulin Yu.A. Morphological and molecular genetic diagnosis of lung cancer: methods and problems. Research and Practical Medicine Journal. 2020;7(3):51-62. (In Russ.) https://doi.org/10.17709/2409-2231-2020-7-3-5
Views:
1894
Email this article 