Mixed adenocarcinomas of the lung: place in new proposals in classification, mandatory for target therapy (original) (raw)
Related papers
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.
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.
Rare subtypes of adenocarcinoma of the lung
Expert Review of Anticancer Therapy, 2011
The 1999 WHO classification of adenocarcinoma of the lung and pleural tumors listed five rare variants of adenocarcinoma of the lung: well-differentiated fetal adenocarcinoma, colloid 'mucinous' adenocarcinoma, mucinous cystadenocarcinoma, signet ring adenocarcinoma and clear-cell adenocarcinoma. The International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society developed a multidisciplinary, international classification of lung adenocarcinoma that was published in the February 2011 issue of the Journal of Thoracic Oncology. This most current classification lists four rare variants of invasive adenocarcinoma of the lung: invasive mucinous adenocarcinoma (formerly mucinous bronchioloalveolar carcinoma), colloid adenocarcinoma (retained and expanded), fetal adenocarcinoma (retained) and enteric adenocarcinoma (new). Signet ring adenocarcinoma and clear-cell adenocarcinoma were removed from the list of variants of adenocarcinoma of the lung. Mucinous cystadenocarcinoma was merged into colloid adenocarcinoma. The new 2011 classification also takes into consideration of the amount of tissue sample available according to the two major methods how the tumor is procured: resection specimens versus small biopsy/cytology. Rare variants of invasive adenocarcinoma of the lung will only now be classified from resection specimens where adequate architecture of tumor can be identified.
Journal of thoracic imaging, 2012
In 2011, the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society proposed a new classification for lung adenocarcinoma that included a number of changes to previous classifications. This classification now considers resection specimens, small biopsies, and cytology specimens. Two former histopathologic terms, bronchioloalveolar carcinoma and mixed subtype adenocarcinoma, are no longer to be used. For resection specimens, the new terms of adenocarcinoma in situ and minimally invasive adenocarcinoma are introduced for small adenocarcinomas showing pure lepidic growth and predominantly lepidic growth, with invasion ≤5 mm, respectively. Invasive adenocarcinomas are now classified by their predominant pattern as lepidic, acinar, papillary, and solid; a micropapillary pattern is newly added. This classification also provides guidance for small biopsies and cytology specimens. For adenocarcinomas that include both an invasive ...
Journal of thoracic disease, 2014
A decade ago, lung cancer could conveniently be classified into two broad categories-either the small cell lung carcinoma (SCLC), or the non-small cell lung carcinoma (NSCLC), mainly to assist in further treatment related decision making. However, the understanding regarding the eligibility of adenocarcinoma histology for treatments with agents such as pemetrexed and bevacizumab made it a necessity for NSCLC to be classified into more specific sub-groups. Then, the availability of molecular targeted therapy with oral tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib not only further emphasized the need for accurate sub-classification of lung cancer, but also heralded the important role of molecular profiling of lung adenocarcinomas. Given the remarkable advances in molecular biology, oncology and radiology, a need for felt for a revised classification for lung adenocarcinoma, since the existing World Health Organization (WHO) classification of lung cancer, published ...
Journal of Thoracic Oncology, 2011
Introduction: Lung adenocarcinoma is a heterogeneous group of tumors with a highly variable prognosis, not well predicted by the current pathologic classification system. The 2004 World Health Organization classification results in virtually all tumors encountered in clinical practice being allocated to the adenocarcinoma of mixed subtype category. A new classification developed by an international multidisciplinary expert panel sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society, is based on histomorphologic subtype and has recently been validated in a North American series of 514 stage I lung adenocarcinomas. We investigated the relationship between the new classification and patient survival in a series of Australian patients with stages I, II, and III lung adenocarcinoma. Methods: We identified 210 patients from a surgical database who underwent resection of lung adenocarcinoma from 1996 to 2009. Two pathologists, blinded to patient outcome, independently performed histopathologic subtyping according to the new classification. Kaplan-Meier curves were used to calculate 5-year survival for each separate histopathologic subtype/variant. Univariate and multivariate analyses were undertaken to control for validated prognostic factors. Results: We confirmed that the new subtypes of adenocarcinoma in situ, minimally invasive adenocarcinoma and lepidic-predominant adenocarcinoma had a 5-year survival approaching 100%, whereas micropapillary-predominant and solid with mucin-predominant adenocarcinomas were associated with particularly poor survival. Papillarypredominant and acinar-predominant adenocarcinomas had an intermediate prognosis. This effect persisted after controlling for stage. Conclusions: Classification of lung adenocarcinoma according to the new International Association for the Study of Lung Cancer/ American Thoracic Society/European Respiratory Society classification correlated with 5-year survival. These relationships persisted after controlling for known prognostic patient and tumor characteristics. The new classification has advantages not only for individual patient care but also for better selection and stratification for clinical trials and molecular studies.
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
Prognostic significance of percentage of bronchioloalveolar pattern in adenocarcinomas of the lung
Annals of Diagnostic Pathology, 2001
of the lung is considered to have a better prognosis than that of common adenocarcinomas of the lung. However, a minor component of the BA pattern is common in many lung adenocarcinomas and the criteria for designating an adenocarcinoma as BA are not well defined. We assessed the clinicopathologic features of 238 cases of lung adenocarcinoma with a partial or predominant BA pattern. Tumors were classified as BA if more than 75% of the tumor had a BA growth pattern. In other words, the tumor grew along pre-existing lung structures without invasion or destruction of parenchyma. Tumors with 50% to 75% BA pattern were considered mixed and tumors with less than 50% BA pattern were designated as solid/acinar (S/A). Fixed, paraffin-embedded tissue sections of each neoplasm were also assessed using immunohistochemical methods with a panel of antibodies specific for p53, retinoblastoma protein, p16, cyclin D1, and cyclin E, and the results were correlated with clinical and pathologic parameters. Our results show that the 5-year survival rate of patients with BA and mixed tumors, 63% and 60%, respectively, was significantly better than that of patients with S/A tumors (P ؍ .026). Patients with BA tumors were more frequently women (55.9%) compared with patients with mixed (48.3%) and S/A (43.8%) tumors. Bronchioloalveolar and mixed tumors were similarly associated with tobacco use, 88.2% and 85%, respectively; slightly less than S/A tumors (93.8%). Clinical and pathologic parameters did not correlate with immunohistochemical results. In conclusion, patients with BA or mixed tumors have similar 5-year survival, better than that of patients with S/A tumors, suggesting that adenocarcinomas can be designated as BA when at least 50% of the tumor has a BA pattern.
Adenocarcinoma of the lung: from BAC to the future
Insights into Imaging, 2020
Adenocarcinoma in situ, minimally invasive adenocarcinoma, lepidic predominant adenocarcinoma and invasive mucinous adenocarcinoma are relatively new classification entities which replace the now retired term, bronchoalveolar carcinoma (BAC). The radiographic appearance of these lesions ranges from pure, ground glass nodules to large, solid masses. A thorough understanding of the new classification is essential to radiologists who work with MDT colleagues to provide accurate staging and treatment. A 2-year review was performed of all surgically resected cases of adenocarcinoma in situ, minimally invasive adenocarcinoma and lepidic predominant adenocarcinoma in our institution. Cases are broken down by age, gender, tumour type and tumour location. A pictorial review is presented to illustrate the radiologic and pathologic features of each entity.
Lung Cancer, 2014
Objectives: The characteristics of non-terminal respiratory unit (TRU) type lung adenocarcinoma are still unclear. The aim of the present study was to characterize non-TRU type lung adenocarcinoma. Materials and methods: We analyzed the expression of mucins MUC5B and MUC5AC, as well as thyroid transcription factor-1 (TTF-1), using a tissue microarray comprising lung adenocarcinoma specimens from 244 consecutive patients. The presence of mutations in EGFR and KRAS were also determined. Results: TTF-1, MUC5B, and MUC5AC were detected in 219 (89.8%), 75 (30.7%), and 33 cases (13.5%), respectively. Cluster analysis of protein expression profiles and EGFR and KRAS mutations yielded five groups of tumors as follows: TRU1-type [TTF-1(+), MUC5B(−), MUC5AC(−), EGFR mutations(−)]; TRU2-type [TTF-1(+), MUC5B(−), MUC5AC(−), EGFR mutations(+)]; Combined-type [TTF-1(+), MUC5B(+), and/or MUC5AC(+)]; Bronchiolar-type [TTF-1(−), MUC5B(+) and/or MUC5AC(+)]; and Null-type [TTF-1(−), MUC5B(−), MUC5AC(−), EGFR mutations(−), KRAS mutations(−)]