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M. Noguchi
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E04 - Lung Cancer Pathology Classification (ID 4)
- Event: WCLC 2013
- Type: Educational Session
- Track: Pathology
- Presentations: 1
- Moderators:E. Duhig, M.S. Tsao
- Coordinates: 10/28/2013, 14:00 - 15:30, Parkside 110 A+B, Level 1
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E04.1 - Adenocarcinoma (ID 387)
14:05 - 14:25 | Author(s): M. Noguchi
- Abstract
- Presentation
Abstract
In 2011, an international multidisciplinary classification of adenocarcinoma was published (2011 IASLC classification) (1) (Table). Pathologists, oncologists, radiologists, and basic scientists in the field of lung cancer are involved in this project. The new concepts of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) in this classification are based on the multistep carcinogenesis of adenocarcinoma (2). Pulmonary adenocarcinoma develops to invasive adenocarcinoma through atypical adenomatous hyperplasia (AAH), AIS, and MIA. The diagnostic criteria for AIS and MIA were first defined in this new classification. AAH is a localized proliferation of mildly to moderately atypical cells lining involved alveoli and, sometimes, respiratory bronchioles. AAH is usually less than 5 mm in diameter and lacks any underlying interstitial inflammation or fibrosis. Before, AAH was detected as incidental findings in the adjacent lung parenchyma in resected lung adenocarcinoma, but recently it is found by thin-slice CT scan examination and shows characteristic ground glass opacity (GGO), similar to AIS. AAH shows positivity for TTF-1 antigen and is a preinvasive lesion of peripheral-type adenocarcinoma, especially the terminal respiratory unit (TRU) type (3). Adenocarcinoma with pure lepidic growth is a special subtype, because it mimics AAH, which is a preinvasive form of adenocarcinoma and has an extremely favorable prognosis. Among the pure lepidic adenocarcinomas, “adenocarcinoma in situ” is defined as localized small (< 3 cm) adenocarcinoma with growth restricted to neoplastic cells along preexisting alveolar structures (lepidic growth), lacking stromal, vascular, or pleural invasion. Differential diagnosis between AAH and AIS is sometimes very difficult. AIS corresponds to type A and B adenocarcinoma according to the 1995 Noguchi classification (4). AIS is usually nonmucinous but rarely may be mucinous. MIA is a small, solitary adenocarcinoma (< 3 cm), with a predominantly lepidic pattern and < 5 mm invasion in greatest dimension in any one focus. By definition, the invasive component is composed of histological subtypes other than the lepidic pattern (i.e. acinar, papillary, micropapillary, and/or solid) or tumor cells infiltrating myofibroblastic stroma (malignant stroma). MIA is excluded if the tumor invades lymphatics, blood vessels, or pleura, or contains tumor necrosis. If the tumor is larger than 2 cm, diagnosis should be done with caution, and the tumor needs to be extensively sampled, especially the solid component. On thin-slice CT examination, MIA reveals pure GGO or a partly solid appearance. MIA corresponds to type C’ adenocarcinoma according to the modified Noguchi classification (5). We believe that the 5-year survival of patients with localized resected MIA is more than 95%, but there are no actual data on the clinical outcome of MIA. In Japan, leading radiologists and pathologists have just started a joint project to clarify the natural history of MIA, supported by the Ministry of Health, Labor and Welfare. First, they are defining the radiological diagnostic criteria for MIA. Then, based on the criteria, they will follow up cases for more than 5 years. In the course of follow-up, the growing cases will be surgically resected and examined histologically. Finally we will understand the radiological and biological characteristics of MIA in more detail. Invasive adenocarcinomas are classified by predominant pattern after using comprehensive histologic subtyping with lepidic, acinar, papillary, micropapillary, and solid patterns. Among the subtypes, lepidic growth represents in situ growth or spreading of invasive adenocarcinoma and the region showing lepidic growth does not influence the patient’s outcome. Therefore, it is very important to report the percentage of the lepidic subtype in the invasive adenocarcinoma. In order to verify the utility of invasive adenocarcinoma classification, interobserver agreement (kappa value) of the diagnostic criteria was assessed (6). Eight Japanese pathologists used the 2011 IASLC classification to independently evaluate the histologic grade of 122 adenocarcinoma cases resected in the National Cancer Center Hospital (Tokyo). The mean (±SD) value of the kappa statistic for the 2011 IASLC classification was 0.46±0.09 (range: 0.24 to 0.61) and the value was not enough for practical use. But, if we modified the classification into low grade (lepidic, acinar, and papillary) and high grade (solid and micropapillary), the mean (±SD) value rose to 0.66±0.09 (range: 0.47 to 0.85) reaching the level of practical use (Figure). Therefore, the modified 2011 IASLC classification shows the clinical outcome of the invasive adenocarcinoma. References (1) Travis WD, Elisabeth B, 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 Thoracic Oncol 6:244-285, 2011. (2) Noguchi M. Stepwise progression of pulmonary adenocarcinoma. Clinical and molecular implications. Cancer Metastasis Rev 29:15-21, 2010. (3) Yatabe Y, Kosaka T, Takaashi T, et al. EGFR mutation is specific for terminal respiratory unit type adenocarcinoma. Am J Surg Pathol 29:633-9, 2005. (4) Noguchi M, Morikawa A, Kawasaki M, et al. Small adenocarcinoma of the lung. Histologic characteristics and prognosis. Cancer 75:2844-2852, 1995. (5) Minami Y, Matsuno Y, Iijima T, et al. Prognistication of small-sized primary pulmonary adenocarcinomas by hitopathlogical and karyometric analyasis. Lung Cancer 48:339-348, 2005. (6) Nakazato Y, Maeshima AM, Ishikawa Y, et al. Interobserver agreement in the nuclear grading of primary pulmonary adenocarcinoma. J Thoracic Oncol 8:736-743, 2013
Figure 1Figure 2IASLC/ATS/ERS Classification of Lung Adenocarcinoma Preinvasive lesions Atypical adenomatous hyperplasia (AAH) Adenocarcinoma in situ (<3cm formerly BAC) Minimally invasive adenocarcinoma (MIA) (<3cm lepidic predominant tumor with <5mm invasion) Invasive adenocarcinoma Lepidic predominant Acinar predominant Papillary predominant Micropapillary predominant Solid predominant with mucin production Variants (Invasive mucinous ad., Collid, Fetal, Enteric Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
