World Health Organization Classification, Histopathological Grade and Pattern Analysis of Lung Adenocarcinoma

Yıl 2024, , 572 - 579, 19.09.2024

İ. Ebru Çakır

https://doi.org/10.53394/akd.1230983

Öz

"World Health Organization (WHO)-2021 Classification of Thoracic Tumors" is used to classify lung tumors histopathologically. In the last decade, as a result of the developments in the molecular basis and treatment of lung tumors, the previous WHO-2015 classification brought important innovations in adenocarcinomas. In the last classification, WHO-2021, the 2015 classification has preserved its main lines, except for a few newly defined entities and minor changes. In the WHO-2021 classification, as novelty, invasive adenocarcinoma was classified into two main categories as non-mucinous and mucinous types, additionally rare variants were specified. The WHO-2015 classification showed a good correlation with prognosis in non-mucinous adenocarcinomas, specifying the predominant pattern as a subtype, but a formal grading system has not been developed. In the latest WHO classification, subtype classification with the dominant pattern has remained and a new three-tiered grading system has been developed, which is related to prognosis. In this review article, the changes made in the latest WHO classification of adenocarcinomas, the new grading system and the basic patterns we used in the histopathological differentiation of these tumors from precursor lesions, subtype determination and grading are analyzed.

Anahtar Kelimeler

Akciğer adenokarsinomu, DSÖ sınıflaması, derecelendirme, patern analizi

Akciğer Adenokarsinomlarında Dünya Sağlık Örgütü Sınıflaması, Histopatolojik Derece ve Patern Analizi

Öz

Akciğer tümörlerinin histopatolojik olarak sınıflamak için “Dünya Sağlık Örgütü (DSÖ)-2021 Torasik Tümörler Sınıflaması” kullanılmaktadır. Son dekatda, akciğer tümörlerinin moleküler temelleri ve tedavisindeki gelişmeler sonucunda, bir önceki DSÖ-2015 sınıflaması, adenokarsinomlarda önemli yenilikler getirmiştir. Son sınıflama olan DSÖ- 2021’ de ise, az sayıda yeni tanımlanan antite ve minör değişiklikler dışında, 2015 sınıflaması ana hatlarını korumuştur. DSÖ-2021 sınıflamasında, yenilik olarak, invaziv adenokarsinom, non-müsinöz ve müsinöz tip olarak iki ana kategoride sınıflanmış, ek olarak nadir varyantlar belirtilmiştir. DSÖ-2015 sınıflamasında, non-müsinöz adenokarsinomlarda, baskın paterni alt tip olarak belirterek prognoz ile iyi bir korelasyon gösterilmiş ancak resmi bir derecelendirme sistemi geliştirilmemiştir. Son DSÖ sınıflamasında, adenokarsinomlarda baskın patern ile alt tip sınıflaması yerini korumuş ve prognoz ile ilişkili, üç kademeli yeni bir derecelendirme sistemi geliştirilmiştir. Bu derleme yazısında, adenokarsinomlarda son DSÖ sınıflamasında yapılan değişiklikler, yeni derecelendirme sistemi ve bu tümörlerin prekürsör lezyonlardan histopatolojik ayırımında, alt tip tayininde ve derecelendirmede kullandığımız paternler analiz edilmiştir.

Anahtar Kelimeler

Akciğer adenokarsinomu, DSÖ sınıflaması, derecelendirme, patern analizi

Kaynakça

• 1. Travis WD, Brambilla E, Müller-Hermelink HK, Harris CC. Pathology and Genetics: Tumours of the Lung, Pleura, Thymus and Hearth. Lyon: IARC, 2004.
• 2-Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG. WHO Classification of Tumours of The Lung, Pleura, Thymus and Heart. 4th ed. Lyon: IARC, 2015.
• 3-WHO Classification of Tumours Editorial Board. Thoracic Tumours. 5th ed. Lyon (France): International Agency for Research on Cancer, 2021.
• 4-Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, Beer DG, Powell CA, Riely GJ, Van Schil PE, Garg K, Austin J, Asamura H, Rusch VW, Hirsch FR, Scagliotti G, Mitsudomi T, Huber RM, Ishikawa Y, Jett J, Sanchez-Cespedes M, Sculier JP, Takahashi T, Tsuboi M, Vansteenkiste J, Wistuba I, Yang PC, Aberle D, Brambilla C, Flieder D, Franklin W, Gazdar A, Gould M, Hasleton P, Henderson D, Johnson B, Johnson D, Kerr K, Kuriyama K, Lee JS, Miller VA, Petersen I, Roggli V, Rosell R, Saijo N, Thunnissen E, Tsao M, Yankelewitz D. 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(22):244-85.
• 5-Takahashi Y, Eguchi T, Kameda K, Lu S, Vaghjiani R, Tan KS, Travis WD, Jones DR, Adusumilli PS.Histologic subtyping in pathologic stage I-IIA lung adenocarcinoma provides risk-based stratification for surveillance. Oncotarget, 2018; (9): 35742-51.
• 6-Yoshizawa A, Sumiyoshi S, Sonobe M, Kobayashi M, Fujimoto M, Kawakami F, Tsuruyama T, Travis WD, Date H, Haga H. 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: 52–61.
• 7-Boland JM, Wampfler JA, Yang P, Yi ES. Growth pattern-based grading of pulmonary adenocarcinoma-Analysis of 534 cases with comparison between observers and survival analysis, Lung Cancer 2017; 109:14–2.
• 8-Yoshizawa A, Motoi N, Riely G, Sima CS, Gerald WL, Kris MG, Park BJ, Rusch VW, Travis WD. 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, Modern Pathology 2011;24:653–64.
• 9-Strand TE, Rostad H, Strøm EH, Hasleton P. The percentage of lepidic growth is an independent prognostic factor in invasive adenocarcinoma of the lung. Diagnostic Pathology 2015;10:94.
• 10-Hou Y, Song W, Chen M, Zhang J, Luo Q, Um SW, Facchinetti F, Bongiolatti S, Zhou Q. The presence of lepidic and micropapillary/solid pathological patterns as minor components has prognostic value in patients with intermediate-grade invasive lung adenocarcinoma. Transl Lung Cancer Res 2022;11(1):64-74.
• 11- Moreira AL, Ocampo PSS, Xiab Y, Zhongb H, Russell PA, Minami Y, Cooper WA , Yoshida A, Bubendorf L, Papotti M, Pelosi G, Lopez-Rios F, Kunitoki K, Ferrari-Light D, Sholl LM, Beasley LM, Borczuk A, Botling J, Brambilla E, Chen G, Chou T, Chung JH, Dacic S, Jain D, Hirsch FR, Hwang D, Lantuejoul S, Lin D, Longshore JW, Motoi N, Noguchi M, Poleri C, Rekhtman N, Tsao MS, Thunnissen E, Travis WD, Yatabe Y, Roden AC, Daigneault JB, Wistuba II, Kerr K, Pass H, Nicholson AG, Mino-Kenudson M. A Grading System for Invasive Pulmonary Adenocarcinoma: A Proposal From the International Association for the Study of Lung Cancer Pathology Committee. Thorac Oncol 2020;15(10):1599–1610.
• 12-Sivakumar S, San Lucas FA, McDowell TL, Lang W, Xu L, Fujimoto J, Zhang J, Futreal PA, Fukuoka J, Yatabe Y, Dubinett SM, Spira AE, Fowler J, Hawk ET, Wistuba II, Scheet P, Kadara H. Genomic Landscape of Atypical Adenomatous Hyperplasia Reveals Divergent Modes to Lung Adenocarcinoma. Cancer Res 2017; 77(22):6119-30.
• 13-Hu X, Fujimoto J, Ying L, Fukuoka J, Ashizawa K, Sun W, Reuben A, Chow C, McGranahan N, Chen R, Hu J, Godoy MC, Tabata K, Kuroda K, Shi L, Li J, Behrens C, Parra ER, Little LD, Gumbs C, Mao X, Song X, Tippen S, Thornton RL, Kadara H, Scheet P, Roarty E, Ostrin EJ, Wang X, Carter BW, Antonoff MB, Zhang J, Vaporciyan AA, Pass H, Swisher SG, Heymach JV, Lee JJ, Wistuba II, Hong WK, Futreal PA, Su D, Zhang J. Multi-region exome sequencing reveals genomic evolution from preneoplasia to lung adenocarcinoma. Nature Communications 2019;10:2978.
• 14-Borczuk AC. Updates in grading and invasion assessment in lung Adenocarcinoma. Modern Pathology 2022:35;28-35.
• 15-K Inamura. Clinicopathological Characteristics and Mutations Driving Development of Early Lung Adenocarcinoma: Tumor Initiation and Progression. Int J Mol Sci 2018;19:1259.
• 16-Boland JM, Froemming AT, Wampfler JA, Maldonado F, Peikert T, Hyland C, Andrade M, Aubry MC, Yang P, Yi ES. Adenocarcinoma in situ, minimally invasive adenocarcinoma, and invasive pulmonary adenocarcinoma-analysis of interobserver agreement, survival, radiographic characteristics and gross pathology in 296 nodules. Human Pathology 2016;51:41-50.
• 17-Jones KD. Whence Lepidic? The History of a Canadian Neologism. Arch Pathol Lab Med 2013;137:1822–4.
• 18-Amin MB, Edge SB, Greene FL, Byrd DR, Brookland RK, Washington MK, Gershenwald JE, Compton CC, Hess KR, Sullivan DC, Jessup JM, Brierley JD, Gaspar LE, Schilsky RL, Balch CM, Winchester DP, Asare EA, Madera M, Gress DM, Meyer LR eds. AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer; 2017.
• 19- Moore DA, Sereno M, Das M, Acevedo JDB, Sinnadurai S, Smith C, McSweeney A, Su X, Officer L, Jones C, Dudek K, Guttery D, Taniere P, Spriggs RV, Quesne JL. In situ growth in early lung adenocarcinoma may represent precursor growth or invasive clone outgrowth-a clinically relevant distinction. Modern Pathology 2019;32:1095-1105.
• 20-Borczuk AC. Assessment of invasion in lung adenocarcinoma classification, including adenocarcinoma in situ and minimally invasive adenocarcinoma. Modern Pathology 2012;25:1–10.
• 21-Yotsukura M, Asamurac H, Suzukid S, Asakurac K, Yoshidab Y, Nakagawab K. Prognostic impact of cancer-associated active fibroblasts and invasive architectural patterns on early-stage lung adenocarcinoma. Lung Cancer 2020;145:158-66.
• 22-Thunnissen E, Belien JAM, Kerr KM, Chung J, Flieder DB, Noguchi M, Yatabe Y, Hwang DM, Lely RJ, Hartemink KJ, Meijer-Jorna LB, Tsao MS. In Compressed Lung Tissue Microscopic Sections of Adenocarcinoma In Situ May Mimic Papillary Adenocarcinoma. Arch Pathol Lab Med 2013;137:1792–97.
• 23- Thunnissen E, Motoi N, Minami Y, Matsubara D, Timens W, Nakatani Y, Ishikawa Y, Baez‐Navarro X, Radonic T, Blaauwgeers H, Borczuk AC, Noguchi M. Elastin in pulmonary pathology: relevance in tumours with a lepidic or papillary appearance. A comprehensive understanding from a morphological viewpoint, Histopathology 2022;80: 457–67.
• 24-Kerr KM. Pulmonary adenocarcinomas: classification and reporting, Histopathology 2009; 54:12–27.
• 25- Yanga F, Dongb Z, Shena Y, Shia J, Wuc Y, Zhao Z, Jiang G, Song X. Cribriform growth pattern in lung adenocarcinoma: More aggressive and poorer prognosis than acinar growth pattern. Lung Cancer 2020;147: 187–92.
• 26- Kadota K, Kushida Y, Kagawa S, Ishikawa R, Ibuki E, Inoue K, Go T, Yokomise H, Ishii T, Kadowaki N, Haba R. Cribriform Subtype is an Independent Predictor of Recurrence and Survival After Adjustment for the Eighth Edition of TNM Staging System in Patients With Resected Lung Adenocarcinoma. Journal of Thoracic Oncology 2019;14(2):245-54.
• 27-Warth A, Muley T, Harms A, Hoffmann H, Dienemann H, Schirmacher P, Weichert W. Clinical Relevance of Different Papillary Growth Patterns of Pulmonary Adenocarcinoma. Am J Surg Pathol 2016;40:818–2.
• 28-Rekhtman N, Ang DC, Riely GC, Ladanyi M, Moreira AL. KRAS mutations are associated with solid growth pattern and tumor-infiltrating leukocytes in lung adenocarcinoma. Modern Pathology 2013;26:1307–19.
• 29-Ohe M, Yokose T, Sakuma Y, Osanai S, Hasegawa C, Washimi K. Stromal micropapillary pattern predominant lung adenocarcinoma - a report of two cases. Diagnostic Pathology 2011; 6:92.
• 30- Emoto K, Eguchi T, Tan KS, Takahashi Y, Aly RG, Rekhtman N, Travis WD, PS Adusumilli. 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): 1948–61.
• 31-Saito R, Ninomiya H, Okumura S, Mun M, Sasano H, Ishikawa Y. Novel Histologic Classification of Small Tumor Cell Nests for Lung Adenocarcinoma With Prognostic and Etiological Significance Small Solid Nests and Pure Micropapillary Nests. Am J Surg Pathol 2021;45:604–15.
• 32-Kondo K, Yoshizawa A, Nakajima N, Sumiyoshi S, Teramoto Y, Rokutan-Kurata M, Sonobe M, Menju T, Date H, Haga H. Large nest micropapillary pattern of lung adenocarcinoma has poorer prognosis than typical floret pattern: analysis of 1,062 resected tumors. Transl Lung Cancer Res 2020;9(3):587-602.
• 33-Moreira AL, Joubert P, Downey RJ, Rekhtman N. Cribriform and fused glands are patterns of high-grade pulmonary adenocarcinoma. Human Pathology 2014;45:213–20.
• 34- Yu X, Dong Z, Wang W, Mao S, Pan Y, Liu Y, Yang S, Chen B, Wang C, Li X, Zhao C, Jia K, Shao C, Wu C, Ren S, Zhou C. Adenocarcinoma of High-Grade Patterns Associated with Distinct Outcome of First-Line Chemotherapy or EGFR-TKIs in Patients of Relapsed Lung Cancer. Cancer Manag Res 2021;13:3981–90.
• 35-Deng C, Zheng Q, Zhang Y, Jin Y, Shen X, Nie X, Fu F, Ma X, Ma Z, Wen Z, Wang S, Li Y, Chen H. Validation of the Novel International Association for the Study of Lung Cancer Grading System for Invasive Pulmonary Adenocarcinoma and Association With Common Driver Mutations, J Thorac Oncol 2021;16(10):1684-93.
• 36- Bai J, Deng C, Zheng Q, Li D, Fu F, Li Y, Zhang Y, Chen H. Comprehensive analysis of mutational profile and prognostic significance of complex glandular pattern in lung adenocarcinoma. Transl Lung Cancer Res 2022;11(7):1337-47.
• 37-Bossé Y, Gagné A, Althakfi W, Orain M, Fiset PO, Desmeules , Joupert P. Prognostic value of complex glandular patterns in invasive pulmonary adenocarcinomas. Human Pathology 2022: 128;56-68.
• 38-Thunnissen E, Beasley MB, Borczuk AC, Brambilla E, Chirieac LR, Dacic S, Flieder D, Gazdar A, Geisinger K, Hasleton P, Ishikawa Y, Kerr KM, Lantejoul S, Matsuno Y, Minami Y, Moreira AL, Motoi N, Nicholson AG, Noguchi M, Nonaka D, Pelosi G, Petersen I, Rekhtman N, Roggli V, Travis WD, Tsao MS, Wistuba I, Xu H, Yatabe Y, Zakowski M, Witte B, Kuik DJ. Reproducibility of histopathological subtypes and invasion in pulmonary adenocarcinoma: An international interobserver study. Mod Pathol 2012;25(12):1574-83.
• 39-Wei JW, Tafe LJ, Linnik YA, Vaickus LJ, Tomita N, Hassanpour S. Pathologist-level classification of histologic patterns on resected lung adenocarcinoma slides with deep neural networks. Scientific Reports 2019;9:3358.
• 40- Gertych A, Swiderska-Chadaj Z, Ma Z, Ing N, Markiewicz T, Cierniak S. Convolutional neural networks can accurately distinguish four histologic growth patterns of lung adenocarcinoma in digital slides. Scientific Reports 2019;9:1483.