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 (original) (raw)
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Modern Pathology, 2011
who had undergone a lobectomy with mediastinal lymph node dissection were retrospectively reviewed. Comprehensive histological subtyping was used to estimate the percentage of each histological subtype and to identify the predominant subtype. Tumors were classified according to the proposed new IASLC/ATS/ERS adenocarcinoma classification. Statistical analyses were made including Kaplan-Meier and Cox regression analyses. There were 323 females (63%) and 191 males (37%) with a median age of 69 years (33-89 years) and 298 stage IA and 216 stage IB patients. Three overall prognostic groups were identified: low grade: adenocarcinoma in situ (n ¼ 1) and minimally invasive adenocarcinoma (n ¼ 8) had 100% 5-year disease-free survival; intermediate grade: non-mucinous lepidic predominant (n ¼ 29), papillary predominant (n ¼ 143) and acinar predominant (n ¼ 232) with 90, 83 and 84% 5-year disease-free survival, respectively; and high grade: invasive mucinous adenocarcinoma (n ¼ 13), colloid predominant (n ¼ 9), solid predominant (n ¼ 67) and micropapillary predominant (n ¼ 12), with 75, 7170 and 67%, 5-year disease-free survival, respectively (Po0.001). Among the clinicopathological factors, stage 1B versus 1A (Po0.001), male sex (Po0.008), high histological grade (Po0.001), vascular invasion (P ¼ 0.002) and necrosis (Po0.001) were poorer prognostic factors on univariate analysis. Both gross tumor size (P ¼ 0.04) and invasive tumor size adjusted by the percentage of lepidic growth (Po0.001) were significantly associated with disease-free survival with a slightly stronger association for the latter. Multivariate analysis showed the prognostic groups of the IASLC/ATS/ERS histological classification (P ¼ 0.038), male gender (P ¼ 0.007), tumor invasive size (P ¼ 0.026) and necrosis (P ¼ 0.002) were significant poor prognostic factors. In summary, the proposed IASLC/ATS/ERS classification of lung adenocarcinoma identifies histological categories with prognostic differences that may be helpful in
Journal of Thoracic Oncology, 2011
Introduction: Adenocarcinoma is the most common histologic type of lung cancer. In order 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 (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS). This new adenocarcinoma classification is needed to provide uniform terminology and diagnostic criteria, especially for bronchioloalveolar carcinoma (BAC), the overall approach to small non-resection 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 ATS Documents Development and Implementation Committee. The search strategy identified 11368 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 (GRADE) approach. Results: The classification addresses both resection specimens, as well as, small biopsies and cytology. The terms bronchioloalveolar carcinoma (BAC) and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced such inserm-00561753, version 1-1 Feb 2011 Travis WD et al Lung Adenocarcinoma Classification 4 as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) for small solitary adenocarcinomas with either pure lepidic growth (AIS) and predominant lepidic growth with ≤5mm 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 percent of lung cancers are diagnosed in such samples. Non-small cell lung carcinomas (NSCLC), 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 (NOS) should be tested for EGFR mutations since 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 to squamous cell carcinoma, and 3) potential lifethreatening 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 NOS 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 inserm-00561753, version 1-1 Feb 2011 Travis WD et al Lung Adenocarcinoma Classification 5 issues, but it is primarily based on histology. This classification is intended to support clinical practice as well as research investigation and clinical trials. As EGFR mutation is a validated predictive marker for response and progression-free survival (PFS) with EGFR tyrosine kinase inhibitors (TKIs) 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 TNM 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.
Therapeutic approaches to lung adenocarcinomas differ because of their heterogeneous morphologies, prognoses, and clinical features. For this reason, new histopathologic classifications for lung adenocarcinomas were done by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society to form subtypes with homogeneous prognoses. There are limited clinical data in the literature on the prognosis of the subgroups formed according to the new classification. A total of 86 patients with adenocarcinoma who had undergone pathologic stages I and II curative resection and mediastinal lymph node dissection were retrospectively analyzed according to the seventh TNM staging system revised by the Union for International Cancer Control/American Joint Committee on Cancer. Histologic subtyping was reassessed according to the dominant histopathologic morphology. When survival rates of lung adenocarcinomas were compared according to their localizations, it was observed that adenocarcinomas localized to the right hemithorax had a longer survival than the ones with left hemithorax localization (P = 0.026). When necrosis was taken into account, it was seen that necrosis rate was higher in solid predominant type compared with other types, whereas it was lower in acinary type (P = 0.046). When peritumoral lymphovascular invasion data were assessed, it was observed that disease-free survival was influenced in a negative fashion (P = 0.018). New histopathologic classification of adenocarcinomas has been a step forward to attaining homogeneous groups, but when the biologic heterogeneity of the adenocarcinomas is taken into account, the authors believe that considering the peritumoral lymphatic vascular invasion, left hemithorax localization, and tumoral necrosis entities in the upcoming TNM classification will contribute to evaluating the prognosis.
Iaslc/Ats/Ers International Multidisciplinary Classification of Lung Adenocarcinoma‡
2014
Introduction: Adenocarcinoma is the most common histologic type of lung cancer. In order 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 (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS). This new adenocarcinoma classification is needed to provide uniform terminology and diagnostic criteria, especially for bronchioloalveolar carcinoma (BAC), the overall approach to small non-resection 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 ATS Documents Development and Implementation Committee. The search strategy identified 11368 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 (GRADE) approach. Results: The classification addresses both resection specimens, as well as, small biopsies and cytology. The terms bronchioloalveolar carcinoma (BAC) and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced such inserm-00561753, version 1-1 Feb 2011 Travis WD et al Lung Adenocarcinoma Classification 4 as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) for small solitary adenocarcinomas with either pure lepidic growth (AIS) and predominant lepidic growth with ≤5mm 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 percent of lung cancers are diagnosed in such samples. Non-small cell lung carcinomas (NSCLC), 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 (NOS) should be tested for EGFR mutations since 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 to squamous cell carcinoma, and 3) potential lifethreatening 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 NOS 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 inserm-00561753, version 1-1 Feb 2011 Travis WD et al Lung Adenocarcinoma Classification 5 issues, but it is primarily based on histology. This classification is intended to support clinical practice as well as research investigation and clinical trials. As EGFR mutation is a validated predictive marker for response and progression-free survival (PFS) with EGFR tyrosine kinase inhibitors (TKIs) 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 TNM 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.
Histologic features are important prognostic indicators in early stages lung adenocarcinomas
Modern Pathology, 2007
This study attempts to evaluate the clinicopathologic features of mixed subtype adenocarcinomas and the prognostic implications of histopathology classifications. Surgical specimens from 141 patients with clinical stage I or II lung adenocarcinoma during the period 1992-2004 were included. These cases were classified into four groups defined by the extent of the bronchioloalveolar carcinoma component: group I: pure bronchioloalveolar carcinoma; group II: mixed subtype with predominant bronchioloalveolar carcinoma component and r5 mm invasive component; group III: mixed subtype with bronchioloalveolar carcinoma component and 45 mm invasive component; group IV: invasive carcinoma with no bronchioloalveolar carcinoma component. Descriptive statistics were used to examine the groups with respect to age, tumor size, lymph node metastasis, and Ki-67 and p53 expression levels. Death rate for the groups was obtained by patient's charts and from the National Death Index database. The population was similar in age, tumor size and lymph node metastasis. Immunohistochemical results showed that the mean Ki-67 labeling and the amount of p53 overexpression had the same trend of increasing mean values or positive results from groups I to IV. The reported proportion of deaths ranged from 0% for groups I and II, 20% in patients with predominant invasive component with bronchioloalveolar carcinoma (group III), and 18% in patients with invasive carcinomas and no bronchioloalveolar carcinoma component (group IV). The difference between the proportion of patients with reported deaths in the time period of this study in the combined greater than 5 mm þ pure invasive groups (groups III, IV), and the o5 mm þ noninvasive groups (groups I, II) is statistically significant. These results suggest that histological features may be useful in defining categories of lung adenocarcinomas with differing survival and prognostic features. These results are helpful in defining a subcategory of 'minimally invasive adenocarcinoma', which has features similar to bronchioloalveolar carcinoma. Prognosis of small pulmonary adenocarcinoma J Yim et al Prognosis of small pulmonary adenocarcinoma J Yim et al Prognosis of small pulmonary adenocarcinoma J Yim et al
Can non-small cell lung cancer histologic subtypes predict survival? A single institution experience
Journal of Mind and Medical Sciences, 2018
Introduction. The latest histological classification of lung adenocarcinoma includes lepidic, acinar, papillary, micropapillary, and solid as subtypes. Testing these subtypes for their prognostic and predictive value is an ongoing scientific challenge. The present research article aims to describe the influence this classification has on patient survival. Materials and Methods. Thirty-three patients were included in the trial. The most important enrollment criterion was the clear specification of the adenocarcinoma subtype in the pathology report. Patients were stratified into three groups which included the adenocarcinoma pathological subtypes as follows: lepidic (LEP), acinar and papillary (ACN/PAP), and micropapillary/solid (MIP/SOL). The primary endpoint was progression-free survival. Other endpoints included overall survival. Results. The lepidic subtype of ADC had superior PFS and OS, regardless of stage. Papillary and acinar subtype showed an intermediate prognosis, whereas micropapillary and solid subtypes were the most aggressive. Conclusions. The experience of this single center confirmed data in the literature. Further studies are needed to demonstrate all the possible implications of this pathology classification.
Prognostic Role of Subtype Classification in Small-Sized Pathologic N0 Invasive Lung Adenocarcinoma
The Annals of thoracic surgery, 2016
The prognosis of patients with small, node-negative lung cancers, which the current indication for adjuvant chemotherapy never includes, is sometimes poor despite complete tumor resection. The present study aimed to identify independent prognostic factors and to clarify possible candidates for adjuvant chemotherapy among patients with small, node-negative invasive adenocarcinoma. This study involved 153 patients with completely resected small (≤20 mm) pathologic N0 invasive adenocarcinomas. Invasive adenocarcinoma was classified as lepidic predominant (LPA), papillary or acinar predominant (PA), or solid or micropapillary predominant (SM), according to the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society classification. Overall survival and recurrence-free survival were estimated from Kaplan-Meier curves. Prognostic factors for recurrence-free survival were determined using univariate and multivariate Cox proportiona...
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2015
To examine the significance of the proposed International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) histologic subtypes of lung adenocarcinoma for patterns of recurrence and, among patients who recur following resection of stage I lung adenocarcinoma, for postrecurrence survival (PRS). We reviewed patients with stage I lung adenocarcinoma who had undergone complete surgical resection from 1999 to 2009 (N = 1,120). Tumors were subtyped by using the IASLC/ATS/ERS classification. The effects of the dominant subtype on recurrence and, among patients who recurred, on PRS were investigated. Of 1,120 patients identified, 188 had recurrent disease, 103 of whom died as a result of lung cancer. Among patients who recurred, 2-year PRS was 45%, and median PRS was 26.1 months. Compared with patients with nonsolid tumors, patients with solid predominant tumors had earlier (P = .007), more extrathoracic (P < .001), and ...
Journal of thoracic disease, 2014
A new histologic classification of lung adenocarcinoma was proposed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) in 2011 to provide uniform terminology and diagnostic criteria for multidisciplinary strategic management. This classification proposed a comprehensive histologic subtyping (lepidic, acinar, papillary, micropapillary, and solid pattern) and a semi-quantitative assessment of histologic patterns (in 5% increments) in an effort to choose a single, predominant pattern in invasive adenocarcinomas. The prognostic value of this classification has been validated in large, independent cohorts from multiple countries. In patients who underwent curative-intent surgery, those with either an adenocarcinoma in situ (AIS) or a minimal invasive adenocarcinoma have nearly 100% disease-free survival and are designated "low grade…