International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma

Abstract

Introduction 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 o...

Lung adenocarcinoma: Sustained subtyping with immunohistochemistry and EGFR, HER2 and KRAS mutational status

“…25---32 All morphological registered patterns comprising this series of lung adenocarcinomas expressed CK7 positivity, without differences (p > 0.05), and predominant negativity for CK20, like other series published in the literature. 8,27,33,34 CK20 was expressed in 3 cases of primary lung adenocarcinoma, with expression of CK7 and TTF1.…”

“…8 IHC was made to validate the pure condition of bronchialpulmonary adenocarcinomas mainly to validate solid pattern and establish differential diagnosis, as well as characterize proliferation index (Ki67-MIB1 antibody). We tried also to identify differences of expression between the patterns studied in order to understand and validate the importance of differentiating patterns.…”

“…At this point it is relevant to make a comment about the recently proposed classification for lung adenocarcinomas. 8 This classification proposes the replacement of BA ---bronchiolo-alveolar pattern carcinoma designation for lepidic. When dealing with classical non-mucinous BAC, this histological type concerns TRU (terminal respiratory unit) cells, pool of adult stem cells in the lung where pneumocytes type II and Clara cells malignant counterparts are recognized; the proposed lepidic pattern seems to mean going for a morphologic description undervaluing carcinogenesis.…”

Molecular pathology of lung cancer: key to personalized medicine

“…[1][2][3] These tumors can be further classified into several major histological subtypes, including adenocarcinoma, squamous cell carcinoma, large cell carcinoma, adenosquamous cell carcinoma, and sarcomatoid carcinoma. 4 In recent years, attention has been paid to the role that 'driver mutations,' such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), have in the tumorigenesis of adenocarcinomas, and their potential use as targets for therapy. [5][6][7][8][9] Recent data suggest EGFR may also serve as a prognostic factor, in addition to its role as a predictive factor, as patients-bearing EGFR mutations have shown favorable clinical outcomes even with conventional chemotherapy.…”

Early-stage pulmonary adenocarcinoma (T1N0M0): a clinical, radiological, surgical, and pathological correlation of 104 cases. The MD Anderson Cancer Center Experience

“…In addition, more recently, in a study conducting a review of the current literature, the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society 2 proposed that tumors up to 3.0 cm in greatest dimension with a pure lepidic growth pattern and lacking stromal, vascular, or pleural invasion should be categorized as in situ adenocarcinoma. Also, the same group designated a separate category of minimally invasive adenocarcinoma for tumors with a predominantly lepidic growth pattern and o5 mm invasion in greatest dimension in any one focus.…”