Pattern Analysis and Grading in Lung Adenocarcinomas

Öz

Adenocarcinoma is the most common histological type of lung cancer. The choice of treatment now holistically depends on the histological phenotype and molecular genotype. To address advances in the oncology, molecular biology, pathology, radiology, and surgery of lung adenocarcinoma, an international multidisciplinary classification was made in 2011 by the International Society for Lung Cancer Research, the American Thoracic Society, and the European Respiratory Society. In 2015, special emphasis was placed on the use of immunohistochemistry to make classification more accurate. Updated 2021 WHO classification of lung tumors. In the diagnosis of these tumors, which are clinically, pathologically and molecularly heterogeneous, based on a multidisciplinary approach, morphology supported first by immunohistochemistry and then by molecular techniques is essential. This review focuses on the heterogeneous morphology of Lung adenocarcinomas

Anahtar Kelimeler

• lung
• adenocarcinoma
• pattern analysis
• grading

Akciğer Adenokarsinomlarında Patern Analizi ve Derecelendirme

Öz

Adenokarsinom, akciğer kanserinin en sık görülen histolojik tipidir. tedavi seçimi artık bütünsel olarak histolojik fenotipe ve moleküler genotipe bağlıdır. Akciğer adenokarsinomunun onkolojisi, moleküler biyolojisi, patolojisi, radyolojisi ve cerrahisindeki ilerlemeleri ele almak için, 2011 yılında Uluslararası Akciğer Kanseri Araştırmaları Derneği, Amerikan Toraks Derneği ve Avrupa Solunum Derneği tarafından uluslararası bir multidisipliner sınıflandırma yapıldı. 2015 yılında, sınıflandırmayı daha doğru hale getirmek için immünohistokimyanın kullanılması özellikle vurgulandı. 2021 DSÖ akciğer tümörlerinin sınıflandırılması güncellendi. Klinik, patolojik ve moleküler olarak heterojen olan bu tümörlerin multidisipliner bir yaklaşıma dayanan teşhisinde önce immünohistokimya ve ardından moleküler tekniklerle desteklenen morfoloji esastır. Bu derlemede Akciğer adenokarsinomlarının heterojen morfolojisine odaklanmaktadır

Anahtar Kelimeler

• Akciğer
• Adenokarsinom
• Patern Analizi
• Derecelendirme

Kaynakça

1. 1. Sung, H., et al., Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 2021. 71(3): p. 209-249.
2. 2. Sağlık Bakanlığı, T.C., Türkiye Kanser İstatistikleri. 2017, T.H.S. Kurumu, Editor. 2021, Halk Sağlığı Genel Müdürlüğü Ankara
3. 3. Howlader, N., et al., SEER Cancer Statistics Review, 1975-2013 (p. based on November 2015 SEER data submission, posted to the SEER web site, April 2016). Bethesda, MD: National Cancer Institute. 2016.
4. 4. Howlader, N., et al., SEER Cancer Statistics Review, 1975-2017, National Cancer Institute. Bethesda, MD. 2020.
5. 5. Horn, L., Pulmonary adenocarcinoma: approaches to treatment. 2018: Elsevier Health Sciences.
6. 6. Travis, W.D., et al., The IASLC Lung Cancer Staging Project: Proposals for Coding T Categories for Subsolid Nodules and Assessment of Tumor Size in Part-Solid Tumors in the Forthcoming Eighth Edition of the TNM Classification of Lung Cancer. J Thorac Oncol, 2016. 11(8): p. 1204-1223.
7. 7. Ettinger, D.S., et al., NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 4.2016. J Natl Compr Canc Netw, 2016. 14(3): p. 255-64.
8. 8. Ge, C., et al., Phase I clinical trial of a novel autologous modified-DC vaccine in patients with resected NSCLC. BMC Cancer, 2017. 17(1): p. 884.

9. 9. Pal, P., M. Cabanero, and M.S. Tsao, Chapter 2 - Pulmonary Adenocarcinoma - Pathology and Molecular Testing, in Pulmonary Adenocarcinoma: Approaches to Treatment, L. Horn, Editor. 2019, Elsevier. p. 13-33.
10. 10. Travis, W.D., et al., The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification. J Thorac Oncol, 2015. 10(9): p. 1243-1260.
11. 11. Nicholson, A.G., et al., The 2021 WHO Classification of Lung Tumors: Impact of Advances Since 2015. J Thorac Oncol, 2022. 17(3): p. 362-387.
12. 12. Thway, K., et al., Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion: a new tumor entity. The American journal of surgical pathology, 2011. 35(11): p. 1722-1732.
13. 13. Saito, R., et al., Novel Histologic Classification of Small Tumor Cell Nests for Lung Adenocarcinoma With Prognostic and Etiological Significance: Small Solid Nests and Pure Micropapillary Nests. The American Journal of Surgical Pathology, 2021. 45(5): p. 604-615.
14. 14. Xing, Y., et al., Analysis of pre‐invasive lung adenocarcinoma lesions on thin‐section computerized tomography. The clinical respiratory journal, 2015. 9(3): p. 289-296.
15. 15. Travis, W.D., et al., International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol, 2011. 6(2): p. 244-85.
16. 16. Sacks, D., et al., Multisociety Consensus Quality Improvement Revised Consensus Statement for Endovascular Therapy of Acute Ischemic Stroke. Int J Stroke, 2018. 13(6): p. 612-632.
17. 17. Sakurai, H., et al., Bronchioloalveolar carcinoma of the lung 3 centimeters or less in diameter: a prognostic assessment. Ann Thorac Surg, 2004. 78(5): p. 1728-33.
18. 18. Cohen, J.G., et al., Lung adenocarcinomas: correlation of computed tomography and pathology findings. Diagn Interv Imaging, 2016. 97(10): p. 955-963.
19. 19. Nicholson, A.G., et al., Eighth Edition Staging of Thoracic Malignancies: Implications for the Reporting Pathologist. Arch Pathol Lab Med, 2018. 142(5): p. 645-661.
20. 20. Yeh, Y.C., et al., Stromal invasion and micropapillary pattern in 212 consecutive surgically resected stage I lung adenocarcinomas: histopathological categories for prognosis prediction. J Clin Pathol, 2012. 65(10): p. 910-8.
21. 21. Thunnissen, E., et al., Elastin in pulmonary pathology: relevance in tumours with a lepidic or papillary appearance. A comprehensive understanding from a morphological viewpoint. Histopathology, 2022. 80(3): p. 457-467.
22. 22. Zugazagoitia, J., et al., The new IASLC/ATS/ERS lung adenocarcinoma classification from a clinical perspective: current concepts and future prospects. J Thorac Dis, 2014. 6(Suppl 5): p. S526-36.
23. 23. Moreira, A.L., et al., Cribriform and fused glands are patterns of high-grade pulmonary adenocarcinoma. Hum Pathol, 2014. 45(2): p. 213-20.
24. 24. Butnor, K.J., Controversies and challenges in the histologic subtyping of lung adenocarcinoma. Transl Lung Cancer Res, 2020. 9(3): p. 839-846.
25. 25. Borczuk, A.C., Prognostic considerations of the new World Health Organization classification of lung adenocarcinoma. Eur Respir Rev, 2016. 25(142): p. 364-371.
26. 26. Warth, A., et al., Clinical Relevance of Different Papillary Growth Patterns of Pulmonary Adenocarcinoma. Am J Surg Pathol, 2016. 40(6): p. 818-26.
27. 27. Ninomiya, H., et al., Correlation between morphology and EGFR mutations in lung adenocarcinomas Significance of the micropapillary pattern and the hobnail cell type. Lung Cancer, 2009. 63(2): p. 235-40.
28. 28. Emoto, K., et al., Expansion of the Concept of Micropapillary Adenocarcinoma to Include a Newly Recognized Filigree Pattern as Well as the Classical Pattern Based on 1468 Stage I Lung Adenocarcinomas. J Thorac Oncol, 2019. 14(11): p. 1948-1961.
29. 29. Ohe, M., et al., Stromal micropapillary component as a novel unfavorable prognostic factor of lung adenocarcinoma. Diagn Pathol, 2012. 7: p. 3.
30. 30. Yoshizawa, A., et al., Validation of the IASLC/ATS/ERS lung adenocarcinoma classification for prognosis and association with EGFR and KRAS gene mutations: analysis of 440 Japanese patients. J Thorac Oncol, 2013. 8(1): p. 52-61.
31. 31. Lee, G., et al., Clinical impact of minimal micropapillary pattern in invasive lung adenocarcinoma: prognostic significance and survival outcomes. Am J Surg Pathol, 2015. 39(5): p. 660-6.
32. 32. Russell, P.A., et al., Does lung adenocarcinoma subtype predict patient survival?: A clinicopathologic study based on the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary lung adenocarcinoma classification. J Thorac Oncol, 2011. 6(9): p. 1496-504.
33. 33. Murakami, S., et al., Prognostic value of the new IASLC/ATS/ERS classification of clinical stage IA lung adenocarcinoma. Lung Cancer, 2015. 90(2): p. 199-204.
34. 34. Matsubara, D., et al., Inactivating mutations and hypermethylation of the NKX2-1/TTF-1 gene in non-terminal respiratory unit-type lung adenocarcinomas. Cancer Sci, 2017. 108(9): p. 1888-1896.
35. 35. Hwang, D.H., et al., KRAS and NKX2-1 Mutations in Invasive Mucinous Adenocarcinoma of the Lung. J Thorac Oncol, 2016. 11(4): p. 496-503.
36. 36. Snyder, E.L., et al., Nkx2-1 represses a latent gastric differentiation program in lung adenocarcinoma. Mol Cell, 2013. 50(2): p. 185-99.
37. 37. Sugano, M., et al., HNF4α as a marker for invasive mucinous adenocarcinoma of the lung. Am J Surg Pathol, 2013. 37(2): p. 211-8.
38. 38. Chang, J.C., et al., Comprehensive Molecular and Clinicopathologic Analysis of 200 Pulmonary Invasive Mucinous Adenocarcinomas Identifies Distinct Characteristics of Molecular Subtypes. Clin Cancer Res, 2021. 27(14): p. 4066-4076.
39. 39. Nakaoku, T., et al., Druggable oncogene fusions in invasive mucinous lung adenocarcinoma. Clin Cancer Res, 2014. 20(12): p. 3087-93.
40. 40. Kuhn, E., et al., Adenocarcinoma classification: patterns and prognosis. Pathologica, 2018. 110(1): p. 5-11. 41. Cha, M.J., et al., Micropapillary and solid subtypes of invasive lung adenocarcinoma: clinical predictors of histopathology and outcome. J Thorac Cardiovasc Surg, 2014. 147(3): p. 921-928.e2.
41. 42. Kadota, K., et al., KRAS Mutation Is a Significant Prognostic Factor in Early-stage Lung Adenocarcinoma. Am J Surg Pathol, 2016. 40(12): p. 1579-1590.
42. 43. Rossi, G., et al., Primary mucinous (so-called colloid) carcinomas of the lung: a clinicopathologic and immunohistochemical study with special reference to CDX-2 homeobox gene and MUC2 expression. Am J Surg Pathol, 2004. 28(4): p. 442-52.
43. 44. Chen, M., et al., Distinctive features of immunostaining and mutational load in primary pulmonary enteric adenocarcinoma: implications for differential diagnosis and immunotherapy. J Transl Med, 2018. 16(1): p. 81.
44. 45. Travis, W.D., Pathology and Genetics Tumours of The Lung, Pleura, Thymus and Heart. World Health Organization Classification of Tumours, 2004.
45. 46. Nakatani, Y., et al., Pulmonary adenocarcinomas of the fetal lung type: a clinicopathologic study indicating differences in histology, epidemiology, and natural history of low-grade and high-grade forms. Am J Surg Pathol, 1998. 22(4): p. 399-411.
46. 47. Nakatani, Y., et al., Aberrant nuclear localization and gene mutation of beta-catenin in low-grade adenocarcinoma of fetal lung type: up-regulation of the Wnt signaling pathway may be a common denominator for the development of tumors that form morules. Mod Pathol, 2002. 15(6): p. 617-24.
47. 48. Palmirotta, R., et al., Pulmonary enteric adenocarcinoma: an overview. Expert Rev Mol Med, 2020. 22: p. e1. 49. Truini, A., et al., Classification of different patterns of pulmonary adenocarcinomas. Expert Rev Respir Med, 2015. 9(5): p. 571-86.
48. 50. Kadota, K., et al., Tumor Spread through Air Spaces is an Important Pattern of Invasion and Impacts the Frequency and Location of Recurrences after Limited Resection for Small Stage I Lung Adenocarcinomas. J Thorac Oncol, 2015. 10(5): p. 806-814.
49. 51. Warth, A., et al., Prognostic Impact of Intra-alveolar Tumor Spread in Pulmonary Adenocarcinoma. Am J Surg Pathol, 2015. 39(6): p. 793-801.
50. 52. Bains, S., et al., Procedure-Specific Risk Prediction for Recurrence in Patients Undergoing Lobectomy or Sublobar Resection for Small (≤2 cm) Lung Adenocarcinoma: An International Cohort Analysis. J Thorac Oncol, 2019. 14(1): p. 72-86.
51. 53. Aly, R.G., et al., Spread Through Air Spaces (STAS) Is Prognostic in Atypical Carcinoid, Large Cell Neuroendocrine Carcinoma, and Small Cell Carcinoma of the Lung. J Thorac Oncol, 2019. 14(9): p. 1583-1593.
52. 54. Liu, H., et al., Prognostic Impact of Tumor Spread Through Air Spaces in Non-small Cell Lung Cancers: a Meta-Analysis Including 3564 Patients. Pathol Oncol Res, 2019. 25(4): p. 1303-1310.
53. 55. Lu, S., et al., Spread through Air Spaces (STAS) Is an Independent Predictor of Recurrence and Lung Cancer-Specific Death in Squamous Cell Carcinoma. J Thorac Oncol, 2017. 12(2): p. 223-234.
54. 56. Yokoyama, S., et al., Tumor Spread Through Air Spaces Identifies a Distinct Subgroup With Poor Prognosis in Surgically Resected Lung Pleomorphic Carcinoma. Chest, 2018. 154(4): p. 838-847.
55. 57. Kadota, K., et al., Limited Resection Is Associated With a Higher Risk of Locoregional Recurrence than Lobectomy in Stage I Lung Adenocarcinoma With Tumor Spread Through Air Spaces. Am J Surg Pathol, 2019. 43(8): p. 1033-1041.
56. 58. Eguchi, T., et al., Lobectomy Is Associated with Better Outcomes than Sublobar Resection in Spread through Air Spaces (STAS)-Positive T1 Lung Adenocarcinoma: A Propensity Score-Matched Analysis. J Thorac Oncol, 2019. 14(1): p. 87-98.
57. 59. Yoshizawa, A., et al., Impact of proposed IASLC/ATS/ERS classification of lung adenocarcinoma: prognostic subgroups and implications for further revision of staging based on analysis of 514 stage I cases. Mod Pathol, 2011. 24(5): p. 653-64.
58. 60. Tsuta, K., et al., The utility of the proposed IASLC/ATS/ERS lung adenocarcinoma subtypes for disease prognosis and correlation of driver gene alterations. Lung Cancer, 2013. 81(3): p. 371-376.
59. 61. Song, Z., et al., Prognostic value of the IASLC/ATS/ERS classification in stage I lung adenocarcinoma patients--based on a hospital study in China. Eur J Surg Oncol, 2013. 39(11): p. 1262-8. 62. Russell, P.A., et al., Correlation of mutation status and survival with predominant histologic subtype according to the new IASLC/ATS/ERS lung adenocarcinoma classification in stage III (N2) patients. J Thorac Oncol, 2013. 8(4): p. 461-8.
60. 63. von der Thüsen, J.H., et al., Prognostic significance of predominant histologic pattern and nuclear grade in resected adenocarcinoma of the lung: potential parameters for a grading system. J Thorac Oncol, 2013. 8(1): p. 37-44. 64. Wang, W., et al., Both the presence of a micropapillary component and the micropapillary predominant subtype predict poor prognosis after lung adenocarcinoma resection: a meta-analysis. J Cardiothorac Surg, 2020. 15(1): p. 154.
61. 65. Yuan, Y., et al., Presence of micropapillary and solid patterns are associated with nodal upstaging and unfavorable prognosis among patient with cT1N0M0 lung adenocarcinoma: a large-scale analysis. J Cancer Res Clin Oncol, 2018. 144(4): p. 743-749.
62. 66. Zhao, Y., et al., Minor Components of Micropapillary and Solid Subtypes in Lung Adenocarcinoma are Predictors of Lymph Node Metastasis and Poor Prognosis. Ann Surg Oncol, 2016. 23(6): p. 2099-105.
63. 67. Moreira, A.L., et al., A Grading System for Invasive Pulmonary Adenocarcinoma: A Proposal From the International Association for the Study of Lung Cancer Pathology Committee. J Thorac Oncol, 2020. 15(10): p. 1599-1610.