International association for the study of lung cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma

William D. Travis, Elisabeth Brambilla, Masayuki Noguchi, Andrew G. Nicholson, Kim R. Geisinger, Yasushi Yatabe, David G. Beer, Charles A. Powell, Gregory J. Riely, Paul E. Van Schil, Kavita Garg, John H M Austin, Hisao Asamura, Valerie W. Rusch, Fred R. Hirsch, Giorgio Scagliotti, Tetsuya Mitsudomi, Rudolf M. Huber, Yuichi Ishikawa, James JettMontserrat Sanchez-Cespedes, Jean Paul Sculier, Takashi Takahashi, Masahiro Tsuboi, Johan Vansteenkiste, Ignacio Wistuba, Pan Chyr Yang, Denise Aberle, Christian Brambilla, Douglas Flieder, Wilbur Franklin, Adi Gazdar, Michael Gould, Philip Hasleton, Douglas Henderson, Bruce Johnson, David Johnson, Keith Kerr, Keiko Kuriyama, Jin Soo Lee, Vincent A. Miller, Iver Petersen, Victor Roggli, Rafael Rosell, Nagahiro Saijo, Erik Thunnissen, Ming Tsao, David Yankelewitz

Research output: Contribution to journalArticle

2632 Citations (Scopus)

Abstract

Adenocarcinoma is the most common histologic type of lung cancer. To address advances in oncology, molecular biology, pathology, radiology, and surgery of lung adenocarcinoma, an international multidisciplinary classification was sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification is needed to provide uniform terminology and diagnostic criteria, especially for bronchioloalveolar carcinoma (BAC), the overall approach to small nonresection cancer specimens, and for multidisciplinary strategic management of tissue for molecular and immunohistochemical studies. Methods: An international core panel of experts representing all three societies was formed with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons. A systematic review was performed under the guidance of the American Thoracic Society Documents Development and Implementation Committee. The search strategy identified 11,368 citations of which 312 articles met specified eligibility criteria and were retrieved for full text review. A series of meetings were held to discuss the development of the new classification, to develop the recommendations, and to write the current document. Recommendations for key questions were graded by strength and quality of the evidence according to the Grades of Recommendation, Assessment, Development, and Evaluation approach. Results: The classification addresses both resection specimens, and small biopsies and cytology. The terms BAC and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) for small solitary adenocarcinomas with either pure lepidic growth (AIS) or predominant lepidic growth with ≤5 mm invasion (MIA) to define patients who, if they undergo complete resection, will have 100% or near 100% disease-specific survival, respectively. AIS and MIA are usually nonmucinous but rarely may be mucinous. Invasive adenocarcinomas are classified by predominant pattern after using comprehensive histologic subtyping with lepidic (formerly most mixed subtype tumors with nonmucinous BAC), acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype. Variants include invasive mucinous adenocarcinoma (formerly mucinous BAC), colloid, fetal, and enteric adenocarcinoma. This classification provides guidance for small biopsies and cytology specimens, as approximately 70% of lung cancers are diagnosed in such samples. Non-small cell lung carcinomas (NSCLCs), in patients with advanced-stage disease, are to be classified into more specific types such as adenocarcinoma or squamous cell carcinoma, whenever possible for several reasons: (1) adenocarcinoma or NSCLC not otherwise specified should be tested for epidermal growth factor receptor (EGFR) mutations as the presence of these mutations is predictive of responsiveness to EGFR tyrosine kinase inhibitors, (2) adenocarcinoma histology is a strong predictor for improved outcome with pemetrexed therapy compared with squamous cell carcinoma, and (3) potential life-threatening hemorrhage may occur in patients with squamous cell carcinoma who receive bevacizumab. If the tumor cannot be classified based on light microscopy alone, special studies such as immunohistochemistry and/or mucin stains should be applied to classify the tumor further. Use of the term NSCLC not otherwise specified should be minimized. Conclusions: This new classification strategy is based on a multidisciplinary approach to diagnosis of lung adenocarcinoma that incorporates clinical, molecular, radiologic, and surgical issues, but it is primarily based on histology. This classification is intended to support clinical practice, and research investigation and clinical trials. As EGFR mutation is a validated predictive marker for response and progression-free survival with EGFR tyrosine kinase inhibitors in advanced lung adenocarcinoma, we recommend that patients with advanced adenocarcinomas be tested for EGFR mutation. This has implications for strategic management of tissue, particularly for small biopsies and cytology samples, to maximize high-quality tissue available for molecular studies. Potential impact for tumor, node, and metastasis staging include adjustment of the size T factor according to only the invasive component (1) pathologically in invasive tumors with lepidic areas or (2) radiologically by measuring the solid component of part-solid nodules.

Original languageEnglish
Pages (from-to)244-285
Number of pages42
JournalJournal of Thoracic Oncology
Volume6
Issue number2
DOIs
Publication statusPublished - 2011 Feb
Externally publishedYes

Fingerprint

Lung Neoplasms
Adenocarcinoma
Bronchiolo-Alveolar Adenocarcinoma
Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Cell Biology
Mucinous Adenocarcinoma
Squamous Cell Carcinoma
Neoplasms
Mutation
Biopsy
Pemetrexed
Adenocarcinoma of lung
Histology
TYK2 Kinase
Molecular Pathology
Colloids
Mucins
Growth
Terminology

Keywords

  • Acinar
  • Adenocarcinoma
  • Adenocarcinoma in situ
  • Bronchioloalveolar carcinoma
  • Classification
  • Clear cell
  • Colloid
  • Computed tomography
  • EGFR
  • EML4-ALK
  • Enteric
  • Fetal
  • Frozen section
  • Gene amplification
  • Gene profiling
  • Histologic
  • KRAS
  • Lepidic
  • Limited resection
  • Lung
  • Micropapillary
  • Minimally invasive adenocarcinoma
  • Molecular
  • Mucinous cystadenocarcinoma
  • Oncology
  • p63
  • Papillary
  • Pathology
  • Pulmonary
  • Radiology
  • Signet ring
  • Solid
  • Surgery
  • TTF-1

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

International association for the study of lung cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. / Travis, William D.; Brambilla, Elisabeth; Noguchi, Masayuki; Nicholson, Andrew G.; Geisinger, Kim R.; Yatabe, Yasushi; Beer, David G.; Powell, Charles A.; Riely, Gregory J.; Van Schil, Paul E.; Garg, Kavita; Austin, John H M; Asamura, Hisao; Rusch, Valerie W.; Hirsch, Fred R.; Scagliotti, Giorgio; Mitsudomi, Tetsuya; Huber, Rudolf M.; Ishikawa, Yuichi; Jett, James; Sanchez-Cespedes, Montserrat; Sculier, Jean Paul; Takahashi, Takashi; Tsuboi, Masahiro; Vansteenkiste, Johan; Wistuba, Ignacio; Yang, Pan Chyr; Aberle, Denise; Brambilla, Christian; Flieder, Douglas; Franklin, Wilbur; Gazdar, Adi; Gould, Michael; Hasleton, Philip; Henderson, Douglas; Johnson, Bruce; Johnson, David; Kerr, Keith; Kuriyama, Keiko; Lee, Jin Soo; Miller, Vincent A.; Petersen, Iver; Roggli, Victor; Rosell, Rafael; Saijo, Nagahiro; Thunnissen, Erik; Tsao, Ming; Yankelewitz, David.

In: Journal of Thoracic Oncology, Vol. 6, No. 2, 02.2011, p. 244-285.

Research output: Contribution to journalArticle

Travis, WD, Brambilla, E, Noguchi, M, Nicholson, AG, Geisinger, KR, Yatabe, Y, Beer, DG, Powell, CA, Riely, GJ, Van Schil, PE, Garg, K, Austin, JHM, 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 2011, 'International association for the study of lung cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma', Journal of Thoracic Oncology, vol. 6, no. 2, pp. 244-285. https://doi.org/10.1097/JTO.0b013e318206a221
Travis, William D. ; Brambilla, Elisabeth ; Noguchi, Masayuki ; Nicholson, Andrew G. ; Geisinger, Kim R. ; Yatabe, Yasushi ; Beer, David G. ; Powell, Charles A. ; Riely, Gregory J. ; Van Schil, Paul E. ; Garg, Kavita ; Austin, John H M ; Asamura, Hisao ; Rusch, Valerie W. ; Hirsch, Fred R. ; Scagliotti, Giorgio ; Mitsudomi, Tetsuya ; Huber, Rudolf M. ; Ishikawa, Yuichi ; Jett, James ; Sanchez-Cespedes, Montserrat ; Sculier, Jean Paul ; Takahashi, Takashi ; Tsuboi, Masahiro ; Vansteenkiste, Johan ; Wistuba, Ignacio ; Yang, Pan Chyr ; Aberle, Denise ; Brambilla, Christian ; Flieder, Douglas ; Franklin, Wilbur ; Gazdar, Adi ; Gould, Michael ; Hasleton, Philip ; Henderson, Douglas ; Johnson, Bruce ; Johnson, David ; Kerr, Keith ; Kuriyama, Keiko ; Lee, Jin Soo ; Miller, Vincent A. ; Petersen, Iver ; Roggli, Victor ; Rosell, Rafael ; Saijo, Nagahiro ; Thunnissen, Erik ; Tsao, Ming ; Yankelewitz, David. / International association for the study of lung cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. In: Journal of Thoracic Oncology. 2011 ; Vol. 6, No. 2. pp. 244-285.
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abstract = "Adenocarcinoma is the most common histologic type of lung cancer. To address advances in oncology, molecular biology, pathology, radiology, and surgery of lung adenocarcinoma, an international multidisciplinary classification was sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification is needed to provide uniform terminology and diagnostic criteria, especially for bronchioloalveolar carcinoma (BAC), the overall approach to small nonresection cancer specimens, and for multidisciplinary strategic management of tissue for molecular and immunohistochemical studies. Methods: An international core panel of experts representing all three societies was formed with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons. A systematic review was performed under the guidance of the American Thoracic Society Documents Development and Implementation Committee. The search strategy identified 11,368 citations of which 312 articles met specified eligibility criteria and were retrieved for full text review. A series of meetings were held to discuss the development of the new classification, to develop the recommendations, and to write the current document. Recommendations for key questions were graded by strength and quality of the evidence according to the Grades of Recommendation, Assessment, Development, and Evaluation approach. Results: The classification addresses both resection specimens, and small biopsies and cytology. The terms BAC and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) for small solitary adenocarcinomas with either pure lepidic growth (AIS) or predominant lepidic growth with ≤5 mm invasion (MIA) to define patients who, if they undergo complete resection, will have 100{\%} or near 100{\%} disease-specific survival, respectively. AIS and MIA are usually nonmucinous but rarely may be mucinous. Invasive adenocarcinomas are classified by predominant pattern after using comprehensive histologic subtyping with lepidic (formerly most mixed subtype tumors with nonmucinous BAC), acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype. Variants include invasive mucinous adenocarcinoma (formerly mucinous BAC), colloid, fetal, and enteric adenocarcinoma. This classification provides guidance for small biopsies and cytology specimens, as approximately 70{\%} of lung cancers are diagnosed in such samples. Non-small cell lung carcinomas (NSCLCs), in patients with advanced-stage disease, are to be classified into more specific types such as adenocarcinoma or squamous cell carcinoma, whenever possible for several reasons: (1) adenocarcinoma or NSCLC not otherwise specified should be tested for epidermal growth factor receptor (EGFR) mutations as the presence of these mutations is predictive of responsiveness to EGFR tyrosine kinase inhibitors, (2) adenocarcinoma histology is a strong predictor for improved outcome with pemetrexed therapy compared with squamous cell carcinoma, and (3) potential life-threatening hemorrhage may occur in patients with squamous cell carcinoma who receive bevacizumab. If the tumor cannot be classified based on light microscopy alone, special studies such as immunohistochemistry and/or mucin stains should be applied to classify the tumor further. Use of the term NSCLC not otherwise specified should be minimized. Conclusions: This new classification strategy is based on a multidisciplinary approach to diagnosis of lung adenocarcinoma that incorporates clinical, molecular, radiologic, and surgical issues, but it is primarily based on histology. This classification is intended to support clinical practice, and research investigation and clinical trials. As EGFR mutation is a validated predictive marker for response and progression-free survival with EGFR tyrosine kinase inhibitors in advanced lung adenocarcinoma, we recommend that patients with advanced adenocarcinomas be tested for EGFR mutation. This has implications for strategic management of tissue, particularly for small biopsies and cytology samples, to maximize high-quality tissue available for molecular studies. Potential impact for tumor, node, and metastasis staging include adjustment of the size T factor according to only the invasive component (1) pathologically in invasive tumors with lepidic areas or (2) radiologically by measuring the solid component of part-solid nodules.",
keywords = "Acinar, Adenocarcinoma, Adenocarcinoma in situ, Bronchioloalveolar carcinoma, Classification, Clear cell, Colloid, Computed tomography, EGFR, EML4-ALK, Enteric, Fetal, Frozen section, Gene amplification, Gene profiling, Histologic, KRAS, Lepidic, Limited resection, Lung, Micropapillary, Minimally invasive adenocarcinoma, Molecular, Mucinous cystadenocarcinoma, Oncology, p63, Papillary, Pathology, Pulmonary, Radiology, Signet ring, Solid, Surgery, TTF-1",
author = "Travis, {William D.} and Elisabeth Brambilla and Masayuki Noguchi and Nicholson, {Andrew G.} and Geisinger, {Kim R.} and Yasushi Yatabe and Beer, {David G.} and Powell, {Charles A.} and Riely, {Gregory J.} and {Van Schil}, {Paul E.} and Kavita Garg and Austin, {John H M} and Hisao Asamura and Rusch, {Valerie W.} and Hirsch, {Fred R.} and Giorgio Scagliotti and Tetsuya Mitsudomi and Huber, {Rudolf M.} and Yuichi Ishikawa and James Jett and Montserrat Sanchez-Cespedes and Sculier, {Jean Paul} and Takashi Takahashi and Masahiro Tsuboi and Johan Vansteenkiste and Ignacio Wistuba and Yang, {Pan Chyr} and Denise Aberle and Christian Brambilla and Douglas Flieder and Wilbur Franklin and Adi Gazdar and Michael Gould and Philip Hasleton and Douglas Henderson and Bruce Johnson and David Johnson and Keith Kerr and Keiko Kuriyama and Lee, {Jin Soo} and Miller, {Vincent A.} and Iver Petersen and Victor Roggli and Rafael Rosell and Nagahiro Saijo and Erik Thunnissen and Ming Tsao and David Yankelewitz",
year = "2011",
month = "2",
doi = "10.1097/JTO.0b013e318206a221",
language = "English",
volume = "6",
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TY - JOUR

T1 - International association for the study of lung cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma

AU - Travis, William D.

AU - Brambilla, Elisabeth

AU - Noguchi, Masayuki

AU - Nicholson, Andrew G.

AU - Geisinger, Kim R.

AU - Yatabe, Yasushi

AU - Beer, David G.

AU - Powell, Charles A.

AU - Riely, Gregory J.

AU - Van Schil, Paul E.

AU - Garg, Kavita

AU - Austin, John H M

AU - Asamura, Hisao

AU - Rusch, Valerie W.

AU - Hirsch, Fred R.

AU - Scagliotti, Giorgio

AU - Mitsudomi, Tetsuya

AU - Huber, Rudolf M.

AU - Ishikawa, Yuichi

AU - Jett, James

AU - Sanchez-Cespedes, Montserrat

AU - Sculier, Jean Paul

AU - Takahashi, Takashi

AU - Tsuboi, Masahiro

AU - Vansteenkiste, Johan

AU - Wistuba, Ignacio

AU - Yang, Pan Chyr

AU - Aberle, Denise

AU - Brambilla, Christian

AU - Flieder, Douglas

AU - Franklin, Wilbur

AU - Gazdar, Adi

AU - Gould, Michael

AU - Hasleton, Philip

AU - Henderson, Douglas

AU - Johnson, Bruce

AU - Johnson, David

AU - Kerr, Keith

AU - Kuriyama, Keiko

AU - Lee, Jin Soo

AU - Miller, Vincent A.

AU - Petersen, Iver

AU - Roggli, Victor

AU - Rosell, Rafael

AU - Saijo, Nagahiro

AU - Thunnissen, Erik

AU - Tsao, Ming

AU - Yankelewitz, David

PY - 2011/2

Y1 - 2011/2

N2 - Adenocarcinoma is the most common histologic type of lung cancer. To address advances in oncology, molecular biology, pathology, radiology, and surgery of lung adenocarcinoma, an international multidisciplinary classification was sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification is needed to provide uniform terminology and diagnostic criteria, especially for bronchioloalveolar carcinoma (BAC), the overall approach to small nonresection cancer specimens, and for multidisciplinary strategic management of tissue for molecular and immunohistochemical studies. Methods: An international core panel of experts representing all three societies was formed with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons. A systematic review was performed under the guidance of the American Thoracic Society Documents Development and Implementation Committee. The search strategy identified 11,368 citations of which 312 articles met specified eligibility criteria and were retrieved for full text review. A series of meetings were held to discuss the development of the new classification, to develop the recommendations, and to write the current document. Recommendations for key questions were graded by strength and quality of the evidence according to the Grades of Recommendation, Assessment, Development, and Evaluation approach. Results: The classification addresses both resection specimens, and small biopsies and cytology. The terms BAC and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) for small solitary adenocarcinomas with either pure lepidic growth (AIS) or predominant lepidic growth with ≤5 mm invasion (MIA) to define patients who, if they undergo complete resection, will have 100% or near 100% disease-specific survival, respectively. AIS and MIA are usually nonmucinous but rarely may be mucinous. Invasive adenocarcinomas are classified by predominant pattern after using comprehensive histologic subtyping with lepidic (formerly most mixed subtype tumors with nonmucinous BAC), acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype. Variants include invasive mucinous adenocarcinoma (formerly mucinous BAC), colloid, fetal, and enteric adenocarcinoma. This classification provides guidance for small biopsies and cytology specimens, as approximately 70% of lung cancers are diagnosed in such samples. Non-small cell lung carcinomas (NSCLCs), in patients with advanced-stage disease, are to be classified into more specific types such as adenocarcinoma or squamous cell carcinoma, whenever possible for several reasons: (1) adenocarcinoma or NSCLC not otherwise specified should be tested for epidermal growth factor receptor (EGFR) mutations as the presence of these mutations is predictive of responsiveness to EGFR tyrosine kinase inhibitors, (2) adenocarcinoma histology is a strong predictor for improved outcome with pemetrexed therapy compared with squamous cell carcinoma, and (3) potential life-threatening hemorrhage may occur in patients with squamous cell carcinoma who receive bevacizumab. If the tumor cannot be classified based on light microscopy alone, special studies such as immunohistochemistry and/or mucin stains should be applied to classify the tumor further. Use of the term NSCLC not otherwise specified should be minimized. Conclusions: This new classification strategy is based on a multidisciplinary approach to diagnosis of lung adenocarcinoma that incorporates clinical, molecular, radiologic, and surgical issues, but it is primarily based on histology. This classification is intended to support clinical practice, and research investigation and clinical trials. As EGFR mutation is a validated predictive marker for response and progression-free survival with EGFR tyrosine kinase inhibitors in advanced lung adenocarcinoma, we recommend that patients with advanced adenocarcinomas be tested for EGFR mutation. This has implications for strategic management of tissue, particularly for small biopsies and cytology samples, to maximize high-quality tissue available for molecular studies. Potential impact for tumor, node, and metastasis staging include adjustment of the size T factor according to only the invasive component (1) pathologically in invasive tumors with lepidic areas or (2) radiologically by measuring the solid component of part-solid nodules.

AB - Adenocarcinoma is the most common histologic type of lung cancer. To address advances in oncology, molecular biology, pathology, radiology, and surgery of lung adenocarcinoma, an international multidisciplinary classification was sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification is needed to provide uniform terminology and diagnostic criteria, especially for bronchioloalveolar carcinoma (BAC), the overall approach to small nonresection cancer specimens, and for multidisciplinary strategic management of tissue for molecular and immunohistochemical studies. Methods: An international core panel of experts representing all three societies was formed with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons. A systematic review was performed under the guidance of the American Thoracic Society Documents Development and Implementation Committee. The search strategy identified 11,368 citations of which 312 articles met specified eligibility criteria and were retrieved for full text review. A series of meetings were held to discuss the development of the new classification, to develop the recommendations, and to write the current document. Recommendations for key questions were graded by strength and quality of the evidence according to the Grades of Recommendation, Assessment, Development, and Evaluation approach. Results: The classification addresses both resection specimens, and small biopsies and cytology. The terms BAC and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) for small solitary adenocarcinomas with either pure lepidic growth (AIS) or predominant lepidic growth with ≤5 mm invasion (MIA) to define patients who, if they undergo complete resection, will have 100% or near 100% disease-specific survival, respectively. AIS and MIA are usually nonmucinous but rarely may be mucinous. Invasive adenocarcinomas are classified by predominant pattern after using comprehensive histologic subtyping with lepidic (formerly most mixed subtype tumors with nonmucinous BAC), acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype. Variants include invasive mucinous adenocarcinoma (formerly mucinous BAC), colloid, fetal, and enteric adenocarcinoma. This classification provides guidance for small biopsies and cytology specimens, as approximately 70% of lung cancers are diagnosed in such samples. Non-small cell lung carcinomas (NSCLCs), in patients with advanced-stage disease, are to be classified into more specific types such as adenocarcinoma or squamous cell carcinoma, whenever possible for several reasons: (1) adenocarcinoma or NSCLC not otherwise specified should be tested for epidermal growth factor receptor (EGFR) mutations as the presence of these mutations is predictive of responsiveness to EGFR tyrosine kinase inhibitors, (2) adenocarcinoma histology is a strong predictor for improved outcome with pemetrexed therapy compared with squamous cell carcinoma, and (3) potential life-threatening hemorrhage may occur in patients with squamous cell carcinoma who receive bevacizumab. If the tumor cannot be classified based on light microscopy alone, special studies such as immunohistochemistry and/or mucin stains should be applied to classify the tumor further. Use of the term NSCLC not otherwise specified should be minimized. Conclusions: This new classification strategy is based on a multidisciplinary approach to diagnosis of lung adenocarcinoma that incorporates clinical, molecular, radiologic, and surgical issues, but it is primarily based on histology. This classification is intended to support clinical practice, and research investigation and clinical trials. As EGFR mutation is a validated predictive marker for response and progression-free survival with EGFR tyrosine kinase inhibitors in advanced lung adenocarcinoma, we recommend that patients with advanced adenocarcinomas be tested for EGFR mutation. This has implications for strategic management of tissue, particularly for small biopsies and cytology samples, to maximize high-quality tissue available for molecular studies. Potential impact for tumor, node, and metastasis staging include adjustment of the size T factor according to only the invasive component (1) pathologically in invasive tumors with lepidic areas or (2) radiologically by measuring the solid component of part-solid nodules.

KW - Acinar

KW - Adenocarcinoma

KW - Adenocarcinoma in situ

KW - Bronchioloalveolar carcinoma

KW - Classification

KW - Clear cell

KW - Colloid

KW - Computed tomography

KW - EGFR

KW - EML4-ALK

KW - Enteric

KW - Fetal

KW - Frozen section

KW - Gene amplification

KW - Gene profiling

KW - Histologic

KW - KRAS

KW - Lepidic

KW - Limited resection

KW - Lung

KW - Micropapillary

KW - Minimally invasive adenocarcinoma

KW - Molecular

KW - Mucinous cystadenocarcinoma

KW - Oncology

KW - p63

KW - Papillary

KW - Pathology

KW - Pulmonary

KW - Radiology

KW - Signet ring

KW - Solid

KW - Surgery

KW - TTF-1

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M3 - Article

C2 - 21252716

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