Download PDF
Zentralbl Chir 2013; 138(S 01): S16-S24
DOI: 10.1055/s-0033-1350878
Übersicht
Georg Thieme Verlag KG Stuttgart · New York

Adenokarzinome der Lunge – die neue Klassifikation

The New Classification of Lung Adenocarcinoma
I. Petersen
Institut für Pathologie, Universitätsklinikum Jena Deutschland
› Author Affiliations
Further Information

Publication History

Publication Date:
22 October 2013 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Die neue, interdisziplinäre IASLC/ATS/ERS-Klassifikation des Adenokarzinoms der Lunge hat seit ihrer Publikation im Jahr 2011 eine große Beachtung gefunden. Sie teilt die Adenokarzinome in präinvasive, minimalinvasive und invasive Subtypen ein. Dabei haben die präinvasiven Läsionen atypische adenomatöse Hyperplasie (AAH) und Adenocarcinoma in situ (AIS) zusammen mit dem minimal invasivem Adenokarzinom (MIA) im Falle einer vollständigen Resektion eine exzellente Prognose (100 % Überleben). Zugleich wurde durch die Bestimmung des prädominanten histologischen Subtyps ein reproduzierbares Tumorgrading etabliert, das mittlerweile in mehreren Nachfolgearbeiten bestätigt werden konnte. Der sogenannte Mischtyp, der früher ca. 80 % aller Adenokarzinome ausmachte, wurde dadurch eliminiert. Gleichzeitig wurde die Bezeichnung des bronchioloalveolären Adenokarzinoms bzw. des bronchioloalveolären Wachstums aufgegeben. Hinter diesem Begriff verbargen sich verschiedene Entitäten, die nun eindeutig definiert und den In-situ-Läsionen AAH und AIS bzw. den Non-in-situ-/invasiven Subtypen MIA, lepidisch prädominantes Adenokarzinom (LPA) und invasiv-muzinöses Adenokarzinom (IMA) zugeordnet wurden. Die Klassifikation trägt der Tatsache Rechnung, dass ein Großteil der Adenokarzinome an Biopsien und Zytologien diagnostiziert werden. Sie enthält Empfehlungen für eine gewebesparende molekulare Analyse. Darüber hinaus ergeben sich aus der differenzierten morphologischen Analyse Hinweise auf molekulare Veränderungen einschließlich therapierelevanter Mutationen, die zielgerichtet analysiert werden können. In diesem Artikel werden wesentliche Daten der Klassifikation, die Bestandteil der nächsten WHO Klassifikation der Lungentumoren sein wird, und nachfolgender Publikationen dargestellt.

Abstract

The new, interdiciplinary IASLC/ATS/ERS classification of lung adenocarcinoma has achieved a considerable impact since its publication in the year 2011. It separates tumours into preinvasive, minimally invasive and invasive subtypes. The preinvasive lesions atypical, adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS) together with the minimally invasive adenocarcinoma (MIA), have an excellent prognosis after complete resection with 100 % survival. It enables a reproducible tumour grading by the determination of the predominant histological growth pattern which could be confirmed in several follow-up studies. Thereby the mixed subtype was eliminated which formerly represented about 80 % of all adenocarcinomas. Similarly, the terms bronchioloalveolar adenocarcinoma and bronchioloalveolar tumour growth were eliminated because they represented several distinct entities, specifically the in-situ lesions AAH and ACIS as well as the non-in-situ/invasive tumours like minimally invasive adenocarcinoma, lepidic predominant adenocarcinoma (LPA) and invasive mucinous adenocarcinoma (IMA). Although the classification is based on data from tumour resections it accommodates the fact that most tumours are diagnosed on biopsies and cytological specimens and includes recommendations for an efficient work-up to preserve tissue for molecular testing. Furthermore, the morphological analysis may provide hints for molecular changes including mutations with therapeutic relevance that may enable targeted molecular diagnostics. This review presents essentials facts of the new classification that will be part of the next WHO classification of lung tumors and its follow-up publications.

Schlüsselwörter

Thoraxchirurgie - Tumorwachstum - interdisziplinär

Key words

thoracic surgery - tumour growth - interdisciplinary
 

  • Referenzen

  • 1 Travis WD, Brambilla E, Noguchi M 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: 244-285
    CrossrefPubMedGoogle Scholar
  • 2 Petersen I. [Morphological and molecular pathology of lung cancer]. Pathologe 2010; 31 (Suppl. 02) S204-S210
    CrossrefPubMedGoogle Scholar
  • 3 Petersen I. The morphological and molecular diagnosis of lung cancer. Dtsch Arztebl Int 2011; 108: 525-531
    PubMedGoogle Scholar
  • 4 Warth A, Muley T, Meister M et al. The novel histologic International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification system of lung adenocarcinoma is a stage-independent predictor of survival. J Clin Oncol 2012; 30: 1438-1446
    CrossrefPubMedGoogle Scholar
  • 5 Warth A, Cortis J, Fink L et al. Training increases concordance in classifying pulmonary adenocarcinomas according to the novel IASLC/ATS/ERS classification. Virchows Arch 2012; 461: 185-193
    CrossrefPubMedGoogle Scholar
  • 6 Warth A, Stenzinger A, von Brünneck AC et al. Interobserver variability in the application of the novel IASLC/ATS/ERS classification for pulmonary adenocarcinomas. Eur Respir J 2012; 40: 1221-1227
    CrossrefPubMedGoogle Scholar
  • 7 Schnabel PA, Petersen I, Junker K. [Current issues in pulmonary pathology. Report of the working group on pulmonary pathology of the German Society of Pathology]. Pathologe 2012; 33 (Suppl. 02) S351-S354
    CrossrefPubMedGoogle Scholar
  • 8 Mireskandari M, Abdirad A, Zhang Q et al. Association of small foci of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) with adenocarcinoma of the lung. Pathol Res Pract 2013; DOI: 10.1016/j.prp.2013.06.019.
    PubMedGoogle Scholar
  • 9 Petersen I, Schnabel PA. [Whatʼs new in lung pathology: minutes from the Pulmonary Pathology Working Group of the German Society of Pathology]. Pathologe 2011; 32 (Suppl. 02) 351-357
    CrossrefPubMedGoogle Scholar
  • 10 Warth A, Herpel E, Schmähl A et al. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) in association with an adenocarcinoma: a case report. J Med Case Rep 2008; 2: 21
    CrossrefPubMedGoogle Scholar
  • 11 Jones KD. Whence Lepidic?. Arch Pathol Lab Med 2013; [Epub ahead of print]
    PubMedGoogle Scholar
  • 12 Thunnissen E, Beasley MB, Borczuk AC et al. Reproducibility of histopathological subtypes and invasion in pulmonary adenocarcinoma. An international interobserver study. Mod Pathol 2012; 25: 1574-1583
    CrossrefPubMedGoogle Scholar
  • 13 Miyoshi T, Satoh Y, Okumura S et al. Early-stage lung adenocarcinomas with a micropapillary pattern, a distinct pathologic marker for a significantly poor prognosis. Am J Surg Pathol 2003; 27: 101-109
    CrossrefPubMedGoogle Scholar
  • 14 Yoshida A, Tsuta K, Watanabe S et al. Frequent ALK rearrangement and TTF-1/p 63 co-expression in lung adenocarcinoma with signet-ring cell component. Lung Cancer 2011; 72: 309-315
    CrossrefPubMedGoogle Scholar
  • 15 Popat S, Gonzalez D, Min T et al. ALK translocation is associated with ALK immunoreactivity and extensive signet-ring morphology in primary lung adenocarcinoma. Lung Cancer 2012; 75: 300-305
    CrossrefPubMedGoogle Scholar
  • 16 Sica G, Yoshizawa A, Sima CS et al. A grading system of lung adenocarcinomas based on histologic pattern is predictive of disease recurrence in stage I tumors. Am J Surg Pathol 2010; 34: 1155-1162
    CrossrefPubMedGoogle Scholar
  • 17 Russell PA, Wainer Z, Wright GM 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: 1496-1504
    CrossrefPubMedGoogle Scholar
  • 18 Yoshizawa A, Motoi N, Riely GJ 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: 653-664
    CrossrefPubMedGoogle Scholar
  • 19 Shim HS, Lee da H, Park EJ et al. Histopathologic characteristics of lung adenocarcinomas with epidermal growth factor receptor mutations in the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society lung adenocarcinoma classification. Arch Pathol Lab Med 2011; 135: 1329-1334
    CrossrefPubMedGoogle Scholar
  • 20 Solis LM, Behrens C, Raso MG et al. Histologic patterns and molecular characteristics of lung adenocarcinoma associated with clinical outcome. Cancer 2012; 118: 2889-2899
    CrossrefPubMedGoogle Scholar
  • 21 Sterlacci W, Savic S, Schmid T et al. Tissue-sparing application of the newly proposed IASLC/ATS/ERS classification of adenocarcinoma of the lung shows practical diagnostic and prognostic impact. Am J Clin Pathol 2012; 137: 946-956
    CrossrefPubMedGoogle Scholar
  • 22 Yeh YC, Wu YC, Chen CY 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: 910-918
    CrossrefPubMedGoogle Scholar
  • 23 Russell PA, Barnett SA, Walkiewicz M 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: 461-468
    CrossrefPubMedGoogle Scholar
  • 24 Gu J, Lu C, Guo J et al. Prognostic significance of the IASLC/ATS/ERS classification in Chinese patients-A single institution retrospective study of 292 lung adenocarcinoma. J Surg Oncol 2013; 107: 474-480
    CrossrefPubMedGoogle Scholar
  • 25 Yoshizawa A, Sumiyoshi S, Sonobe M 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: 52-61
    CrossrefPubMedGoogle Scholar
  • 26 Petersen I, Kotb WF, Friedrich KH et al. Core classification of lung cancer: correlating nuclear size and mitoses with ploidy and clinicopathological parameters. Lung Cancer 2009; 65: 312-318
    CrossrefPubMedGoogle Scholar
  • 27 Kotb WF, Petersen I. Morphology, DNA ploidy and HPV in lung cancer and head and neck cancer. Pathol Res Pract 2012; 208: 1-8
    CrossrefPubMedGoogle Scholar
  • 28 Schulze S, Petersen I. Gender and ploidy in cancer survival. Cell Oncol (Dordr) 2011; 34: 199-208
    CrossrefPubMedGoogle Scholar
  • 29 Nakazato Y, Minami Y, Kobayashi H et al. Nuclear grading of primary pulmonary adenocarcinomas: correlation between nuclear size and prognosis. Cancer 2010; 116: 2011-2019
    CrossrefPubMedGoogle Scholar
  • 30 Nakazato Y, Maeshima AM, Ishikawa Y et al. Interobserver agreement in the nuclear grading of primary pulmonary adenocarcinoma. J Thorac Oncol 2013; 8: 736-743
    CrossrefPubMedGoogle Scholar
  • 31 Kadota K, Suzuki K, Kachala SS et al. A grading system combining architectural features and mitotic count predicts recurrence in stage I lung adenocarcinoma. Mod Pathol 2012; 25: 1117-1127
    CrossrefPubMedGoogle Scholar
  • 32 Weihmann J, Weichert C, Petersen I et al. [Evaluation of a cell block method in cytological diagnostics]. Pathologe 2012; 33: 553-559
    CrossrefPubMedGoogle Scholar
  • 33 Warth A, Bubendorf L, Gütz S et al. [Molecular pathological diagnosis in cytopathology of non-small-cell lung cancer : Standardization of specimen processing]. Pathologe 2013; 34: 310-317
    CrossrefPubMedGoogle Scholar
  • 34 Herth FJ, Bubendorf L, Gütz S et al. [Diagnostic and predictive analyses of cytological specimens of non-small cell lung cancer: strategies and challenges]. Pneumologie 2013; 67: 198-204
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 Kayser G, Csanadi A, Otto C et al. Simultaneous multi-antibody staining in non-small cell lung cancer strengthens diagnostic accuracy especially in small tissue samples. PLoS One 2013; 8: e56333
    CrossrefPubMedGoogle Scholar
  • 36 Lindeman NI, Cagle PT, Beasley MB 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; 137: 828-860
    CrossrefPubMedGoogle Scholar
  • 37 Thunnissen E, Bubendorf L, Dietel M et al. EML4-ALK testing in non-small cell carcinomas of the lung: a review with recommendations. Virchows Arch 2012; 461: 245-257
    CrossrefPubMedGoogle Scholar
  • 38 Thunnissen E, Kerr KM, Herth FJ et al. The challenge of NSCLC diagnosis and predictive analysis on small samples. Practical approach of a working group. Lung Cancer 2012; 76: 1-18
    CrossrefPubMedGoogle Scholar
  • 39 Warth A, Stenzinger A, Weichert W. [Novel morphological and molecular aspects of lung cancer]. Pathologe 2013; 34: 419-428
    CrossrefPubMedGoogle Scholar
  • 40 Travis WD, Brambilla E, Noguchi M et al. Diagnosis of lung adenocarcinoma in resected specimens: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. Arch Pathol Lab Med 2013; 137: 685-705
    CrossrefPubMedGoogle Scholar
  • 41 Lederlin M, Puderbach M, Muley T et al. Correlation of radio- and histomorphological pattern of pulmonary adenocarcinoma. Eur Respir J 2013; 41: 943-951
    CrossrefPubMedGoogle Scholar
  • 42 Goeckenjan G, Sitter H, Thomas M et al. [Prevention, diagnosis, therapy, and follow-up of lung cancer]. Pneumologie 2010; 64 (Suppl. 02) e1-e164
    Article in Thieme ConnectPubMedGoogle Scholar
  • 43 Petersen I. Morphologische Analyse und molekulare Diagnostik. Schwerpunkt: Lungenkarzinom. ONKOLOGIE heute 2012; 3: 11-13
    PubMedGoogle Scholar
  • 44 Takeuchi K, Soda M, Togashi Y et al. RET, ROS1 and ALK fusions in lung cancer. Nat Med 2012; 18: 378-381
    CrossrefPubMedGoogle Scholar
  • 45 Cardarella S, Johnson BE. The impact of genomic changes on treatment of lung cancer. Am J Respir Crit Care Med 2013; Jul 10 [Epub ahead of print]
    PubMedGoogle Scholar
  • 46 Nitsche K, Günther B, Katenkamp D et al. Thoracic neoplasms at the Jena reference center for soft tissue tumors. J Cancer Res Clin Oncol 2012; 138: 415-424
    CrossrefPubMedGoogle Scholar
  • 47 Jakobsen JN, Sørensen JB. Clinical impact of ki-67 labeling index in non-small cell lung cancer. Lung Cancer 2013; 79: 1-7
    CrossrefPubMedGoogle Scholar
  • 48 Kadota K, Nitadori J, Sarkaria IS et al. Thyroid transcription factor-1 expression is an independent predictor of recurrence and correlates with the IASLC/ATS/ERS histologic classification in patients with stage I lung adenocarcinoma. Cancer 2013; 119: 931-938
    CrossrefPubMedGoogle Scholar
  • 49 Ordóñez NG. Napsin A expression in lung and kidney neoplasia: a review and update. Adv Anat Pathol 2012; 19: 66-73
    CrossrefPubMedGoogle Scholar
  • 50 Penzel R, Sers C, Chen Y et al. EGFR mutation detection in NSCLC–assessment of diagnostic application and recommendations of the German Panel for Mutation Testing in NSCLC. Virchows Arch 2011; 458: 95-98
    CrossrefPubMedGoogle Scholar
  • 51 von Laffert M, Warth A, Penzel R et al. Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC): Results of a multi-centre ALK-testing. Lung Cancer 2013; 81: 200-206
    CrossrefPubMedGoogle Scholar
  • 52 Imielinski M, Berger AH, Hammerman PS et al. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 2012; 150: 1107-1120
    CrossrefPubMedGoogle Scholar
  • 53 Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144: 646-674
    CrossrefPubMedGoogle Scholar
  • 54 Yang L, Chen Y, Cui T et al. Desmoplakin acts as a tumor suppressor by inhibition of the Wnt/β-catenin signaling pathway in human lung cancer. Carcinogenesis 2012; 33: 1863-1870
    CrossrefPubMedGoogle Scholar
  • 55 Cui T, Chen Y, Yang L et al. The p 53 target gene desmocollin 3 acts as a novel tumor suppressor through inhibiting EGFR/ERK pathway in human lung cancer. Carcinogenesis 2012; 33: 2326-2333
    CrossrefPubMedGoogle Scholar
  • 56 Soda M, Takada S, Takeuchi K et al. A mouse model for EML4-ALK-positive lung cancer. Proc Natl Acad Sci U S A 2008; 105: 19893-19897
    CrossrefPubMedGoogle Scholar
  • 57 Arai Y, Totoki Y, Takahashi H et al. Mouse model for ROS1-rearranged lung cancer. PLoS One 2013; 8: e56010
    CrossrefPubMedGoogle Scholar