New Classification Of Lung Adenocarcinoma Research Articles

Reproducibility of visual estimation of lung adenocarcinoma subtype proportions

In 2011, a new classification of lung adenocarcinoma was published. Since then there have been multiple studies regarding observer variability in predominant subtype determination, with levels of agreement generally in the weak to moderate range. In the 2011 and subsequent WHO 2015 classification, a recommendation was also made to visually assess and record the percentage of each subtype in 5% increments. The present study was initiated to determine the reproducibility of such gestalt assessments and to compare these data to a formal morphometric assessment. Five experienced pathologists reviewed multiple single images of 25 adenocarcinomas, taken at 2× and 10×, and estimated the percentage of lepidic, acinar, papillary, micropapillary, and solid components in 5% increments. After 2 months all the pathologists again reviewed the same images presented to them in a different order. We found that there was poor reproducibility within observers at 2× power using a 5% evaluation, but that this improved using 10% or 25% cutoffs. Use of 10× magnification allowed weak to moderate reproducibility at 5% increments, and this was again improved using 10% or 25% cutoffs. Correlation with morphometric assessment was poor except for the papillary and micropapillary subtypes. Differences among pathologists were generally low except for the acinar and, to a lesser degree, lepidic subtypes, which showed a wide spread of data. When estimating tumor subtype proportions, use of a 10× objective, and utilization of 10% or preferably 25% cutoffs provides a greater degree of consistency than a 5% cutoff.

Prognostic significance of histologic subtype in pStage I lung adenocarcinoma.

The International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society (IASLC/ATS/ERS) proposed a new histologic classification of lung adenocarcinoma in 2011. While several studies have already validated the prognostic value of this new classification of lung adenocarcinoma, we conducted own investigation in the present study. This study included 197 patients with invasive lung adenocarcinoma who underwent complete resection. Pathologic diagnoses were made in accordance with the new IASLC/ATS/ERS classification for lung adenocarcinoma. The lepidic/acinar/papillary group had a significantly better prognosis than the micropapillary/solid/invasive mucinous adenocarcinoma group (5-year recurrence-free survival [RFS] 73 vs. 21%: p<0.01, 5-year overall survival 85 vs. 52%: p<0.01). Age (hazard ratio [HR], 1.898; p=0.03), CEA (HR, 1.873; p=0.03), pStage (HR, 6.149; p<0.01), and histologic subtype (HR, 2.342; p=0.01) were independent prognostic factors for the RFS. Furthermore, age (HR, 3.242; p=0.04), CEA (HR, 3.405; p=0.03) and histologic subtype (HR, 11.108; p<0.01) were independent prognostic factors for the progression-free survival in pStage I. The histologic subtype correlated with the prognosis of pStage I of lung adenocarcinoma. Patients in the high-grade group of lung adenocarcinoma, which included solid, micropapillary and invasive mucinous adenocarcinoma with pStage I, should be considered candidates for postoperative adjuvant therapy.

Inaccuracy of lung adenocarcinoma subtyping using preoperative biopsy specimens

BackgroundThe prognostic significance of the new classification of lung adenocarcinoma proposed in the 2015 World Health Organization guideline has been validated. This study aimed to compare the preoperative classification of the adenocarcinoma subtype based on computed tomography–guided 18-gauge core needle biopsy (CTNB) or radial probe endobronchial ultrasound (R-EBUS) specimens, with the postoperative classification based on the resected specimens. MethodsWe retrospectively analyzed a consecutive series of 128 patients (60 CTNB and 68 R-EBUS) who underwent surgery for preoperatively confirmed lung adenocarcinoma between 2010 and 2014. Comprehensive histological subtyping was performed according to the 2015 World Health Organization classification system. Diagnostic concordance of subtypes between small biopsy and resection specimens was assessed. ResultsConcordant subtyping of adenocarcinomas between the predominant pattern on resections and biopsy sections was observed in 58.6% of cases (75 of 128; 95% confidence interval [CI], 49.9%-66.8%). Preoperative subtyping was accurate in only 30% of samples (3 of 10) with a predominance of solid patterns. None of the 5 micropapillary predominant cases was detected by CTNB or R-EBUS. For the concordance of the presence or absence of micropapillary/solid component, the sensitivity was as low as 16.5% (95% CI, 9.1%-26.5%). The detection rate by CTNB/R-EBUS increased with the increase in the percentage of micropapillary/solid component; however, even in the ≥40% micropapillary/solid group, only 24% of cases were detected by CTNB/R-EBUS. ConclusionsThe accuracy of the estimation of adenocarcinoma histological subtype based on preoperative biopsy sections was unsatisfactory.

Nouvelle classification OMS 2015 des adénocarcinomes pulmonaires et prénéoplasies

The 2015 WHO classification of tumors of the lung, pleura, thymus and heart has just been published with numerous important changes from the 2004 WHO classification. The most significant changes involve (1) use of immunohistochemistry throughout the classification, (2) integration of molecular testing for personalized strategies for advanced lung cancer patients, (3) a new classification for small biopsies and cytology, (4) a new classification of lung adenocarcinoma as proposed by the 2011 IASLC/ATS/ERS, (5) restriction of the diagnosis of large cell carcinoma only to resected tumors that lack any clear morphologic or immunohistochemical differentiation. Regarding adenocarcinoma, the terms bronchioloalveolar carcinoma (BAC) and mixed subtype adenocarcinoma have been suppressed and replaced for the former by the term adenocarcinoma in situ (AIS) as a preinvasive lesion to join atypical adenomatous hyperplasia (AAH). A new category has been defined, the minimally invasive adenocarcinoma (MIA), and invasive adenocarcinomas are now classified according to the predominant subtype after subtyping by semi-quantitatively percentage of various subtypes present in 5% increments. The term "lepidic" is restricted to a non-invasive component (previously classified as BAC) present as part of an invasive adenocarcinoma. "Invasive mucinous adenocarcinoma" is used for formerly adenocarcinomas classified as mucinous BAC, excluding tumors that meet criteria for AIS or MIA. The subtypes of clear cell and signet ring adenocarcinoma are discontinued, as well the term of mucinous cystadenocarcinoma, included in the category of colloid adenocarcinoma. Thus new classification of lung adenocarcinoma is sustained by genetics and has clinical impact for therapeutic strategies.

Prognosis and status of lymph node involvement in patients with adenocarcinoma in situ and minimally invasive adenocarcinoma-a systematic literature review and pooled-data analysis.

Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) have been brought up that substitute for bronchioloalveolar carcinoma (BAC), according to the new classification of lung adenocarcinoma. There has been increasing opinions that argues for the adjustment of lymph node disposition in patients with such early stage tumors. Therefore, we sought to overview the prognosis and status of lymph node involvement in AIS/MIA patients. PubMed, Springer and Ovid databases were searched for relevant studies. Data was extracted and results summarized to demonstrate the disposition of lymph nodes in AIS/MIA. Twenty-three studies consisting of 6,137 lung adenocarcinoma were included. AIS/MIA accounted for 821 of the total 6,137. All included patients received curative surgery. After a review of the summarized data we found that only one patient (with MIA) had N1 node metastasis, N2 disease was not found in any of the included patients. In concordance with this, studies that reported 5-year disease free survival (5-year DFS) have almost 100% rate. Our findings indicated that patients with AIS/MIA have good survival prognosis after surgical resection, and that recurrence and lymph node metastasis in these patients is rare. Therefore, we strongly encouraged further studies to determine the role of different lymph node disposition strategies.

Abstract 4667: The impact of IASLC/ATS/ERS classification of lung adenocarcinoma on survival after recurrence in resected adenocarcinoma

Abstract Objective: Factors predicting post-recurrence survival (PRS) in lung adenocarcinoma have not been reported. This study aimed to investigate the prognostic factors of PRS, including the new classification of lung adenocarcinoma proposed by the International Association for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS), and the European Respiratory Society (ERS), in resected lung adenocarcinoma after recurrence. Methods: The clinicopathological characteristics of 140 patients with recurrence after complete resection of lung adenocarcinoma at Taipei Veterans General Hospital were retrospectively reviewed. The prognostic factors of PRS were analyzed. Results: The pattern of recurrence included local only in 22 (17.1%), distant only in 40 (31.0%), and both local and distant in 84 (51.9%) of patients. The 2- and 4-year PRS were 67.2% and 39.1%, respectively. The most common organ sites of metastasis were the contralateral lung (40.7%), followed by the brain (37.1%) and bone (30.7%). Univariate analysis showed that N2 status (vs. N0 and N1) (P = 0.007), stage III (vs. stage I and II) (P = 0.043), micropapillary/solid predominant pattern group (P = 0.012), liver metastasis (P = 0.033), and no treatment for recurrence (P &amp;lt; 0.001) were significant predictors of worse PRS. Multivariate analysis revealed that N2 status (P = 0.036), micropapillary/solid predominant pattern group (P = 0.018), and no treatment for recurrence (P &amp;lt; 0.001) were still significant predictors of worse PRS. Conclusions: N2 status, micropapillary/solid predominant pattern group, and no treatment for recurrence predict worse PRS in patients with resected lung adenocarcinoma. The new classification of lung adenocarcinoma had significant impact on PRS. Citation Format: Jung-Jyh Hung, Teh-Ying Chou, Wen-Hu Hsu, Yu-Chung Wu. The impact of IASLC/ATS/ERS classification of lung adenocarcinoma on survival after recurrence in resected adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4667. doi:10.1158/1538-7445.AM2014-4667

The revised lung adenocarcinoma classification-an imaging guide.

Advances in our understanding of the pathology, radiology and clinical behaviour of peripheral lung adenocarcinomas facilitated a more robust terminology and classification of these lesions. The International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification introduced new terminology to better reflect this heterogeneous group of adenocarcinomas formerly known as bronchoalveolar cell carcinoma (BAC). There is now a clear distinction between pre-invasive, minimally invasive and frankly invasive lesions. The radiographic appearance of these ranges from pure ground glass nodules to solid mass lesions. Radiologists must be aware of the new classification in order to work alongside multidisciplinary colleagues to allow accurate staging and treatment. This article reviews the new classification of lung adenocarcinomas. Management options of these lesions with particular focus on radiological implications of the new classification will be reviewed.

Histological subtypes of solitary pulmonary nodules of adenocarcinoma and their clinical relevance.

To explore the histological subtypes of solitary pulmonary nodules (SPNs) of invasive adenocarcinoma and their clinical relevance. A total of 188 patients with pathologically confirmed invasive adenocarcinoma in our hospital from January 2007 to December 2011 were enrolled in this study. In accordance with the new classification of lung adenocarcinoma, all the histological sections were reviewed and classified, and the clinical data were collected and analyzed. Of these 188 patients who had been initially diagnosed as SPNs of adenocarcinoma, there were 6 cases of lepidic predominant adenocarcinoma (LPA), 71 cases of acinar predominant adenocarcinoma (APA), 74 cases of papillary predominant adenocarcinoma (PPA), 15 cases of micorpapillary predominant adenocarcinoma (MPA), and 22 cases of solid predominant adenocarcinoma (SPA) with mucin production. The incidence of lymph node metastasis was 80.0% and 81.8% in MPA and SPA, respectively, which was significantly higher than those in LPA, APA, and PPA (all P<0.01). The incidence of LPA was 83.3% (5/6) in women, which was significantly higher than that in men (P=0.037). According to the new classification, MPA and SPA have high incidence of lymph node metastasis. LPA is more likely to occur in women. Sub-typing of the lung adenocarcinoma based on the newest international classification criteria is helpful to identify the clinical features of this disease.

Management strategy of pulmonary nodule in 2013

Lung nodules are commonly found on computed tomography (CT) and need a standardized approach in order to avoid misdiagnosing lung cancer and delaying surgical excision whilst simultaneously avoiding unnecessary invasive procedures if the lesions prove to be benign. Great advances have been made in the last decade in various areas affecting the management of lung nodules: the understanding of the molecular mechanisms behind carcinogenesis, a new classification of lung adenocarcinoma, new data on lung cancer screening, widespread use of multi-detector row CT and development of volumetric analysis software for nodules. Recent decision-making algorithms are based on the size, density and follow-up of the nodule. The distinction between solid nodules, sub-solid nodules and pure ground glass nodules is fundamental, and has a strong correlation with the histologic spectrum of adenocarcinoma. In the absence of criteria suggesting benign disease, the radiologist's report should offer one of the following two options: follow-up based on the recommendations if the nodule is equivocal, or multidisciplinary discussion to consider invasive management if the nodule is highly suspicious of malignancy. Recent data from this statement are reviewed and practical guidelines are offered based on international expert consensus opinion.

The pivotal role of pathology in the management of lung cancer.

The last decade has seen significant advances in our understanding of lung cancer biology and management. Identification of key driver events in lung carcinogenesis has contributed to the development of targeted lung cancer therapies, heralding the era of personalised medicine for lung cancer. As a result, histological subtyping and molecular testing has become of paramount importance, placing increasing demands on often small diagnostic specimens. This has triggered the review and development of the first structured classification of lung cancer in small biopsy/cytology specimens and a new classification of lung adenocarcinoma from the IASLC/ATS/ERS. These have enhanced the clinical relevance of pathological diagnosis, and emphasise the role of the modern surgical pathologist as an integral member of the multidisciplinary team, playing a crucial role in clinical trials and determining appropriate and timely management for patients with lung cancer.

The new classification of lung adenocarcinomas: implications for pathologists and radiologists

The present manuscript is a summary of two lectures which were given respectively by B. Weynand and G.R. Ferretti. The new classification of lung adenocarcinomas has changed the view of the radiologists and the pathologists especially regarding the former bronchiolo-alveolar carcinoma (BAC). The aim of this paper is to correlate radiological and histopathological images according to the 2011 classification for lung adenocarcinoma proposed by the International Association for the Study of Lung cancer, the American Thoracic Society and the European Respiratory Society and to draw attention to the way these lesions can be approached preoperatively.

Year in review 2012: Lung cancer, respiratory infections, tuberculosis, pleural diseases, bronchoscopic intervention and imaging

This Year in Review series addresses the most relevant articles published in Respirology and other respiratory medicine journals during 2012 concerning five specific areas that we consider to be of importance to practicing pulmonologists, namely lung cancer, respiratory infections, tuberculosis (TB), pleural diseases, and interventional pulmonology and imaging. Some important findings that will be commented on more in depth are that: 1) screening for lung cancer using low-dose computed tomography (CT) in high risk populations is promising, although not firmly established, 2) an enhanced CURB (which stands for confusion, urea, respiratory rate, blood pressure) score as well as the Japanese A-DROP (age, dehydration, respiratory failure, orientation disturbance, and pressure) prognostic scale are as accurate as the pneumonia severity index (PSI) scoring system to predict mortality in patients with community-acquired pneumonia (CAP), 3) randomized trials are urgently needed to optimize multidrug-resistant (MDR)-TB treatment, 4) the use of video-assisted thoracoscopic surgery (VATS) to quantify pleural tumor burden and, if feasible, perform an intrathoracic cytoreduction in patients with malignant effusions secondary to ovarian cancer (OC) may have a significant impact on further patient management plans, and 5) respiratory endoscopy and its different diagnostic and therapeutic modalities, is a safe procedure with overall complication rates less than 1%.

Overview and Strategic Management of Subsolid Pulmonary Nodules

A new classification of lung adenocarcinoma has been proposed recently-the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. Abundant information from recent lung cancer computed tomography (CT) screening programs has increased our understanding of the strong, although imperfect, correlation between histologic findings of lung adenocarcinoma and subsolid pulmonary nodules on CT, including both "pure" ground-glass nodules (GGNs) and "part-solid" GGNs. Moreover, serial CT imaging has demonstrated stepwise progression of these nodules in a subset of patients, characterized by increase in size and density of GGNs and development of a solid component. Given the higher incidence of malignancy and the considerably lower growth rate of subsolid nodules, dedicated standardized guidelines for management of these nodules have been proposed, including long-term (≥3 y) CT follow-up using a low-dose technique. Radiologists should be familiar with the new terminology of lung adenocarcinomas and strategic management of subsolid pulmonary nodules.

Adenocarcinomas With Prominent Lepidic Spread

Recently, a new classification of lung adenocarcinomas has been proposed for tumors with lepidic spread. The greatest diameter of the invasive component determines minimally invasive cancers, and the term bronchioloalveolar carcinoma is no longer used. We retrospectively reviewed 87 resected adenocarcinomas of the lung; 30 tumors with lepidic growth and without high-grade invasive areas were identified, and the invasive component was measured morphometrically and categorized. A dimension of 5 mm was the cutoff for invasion. Regional lymph node involvement and short-term follow-up were compared among subtypes of these well-differentiated and moderately differentiated adenocarcinomas. There were 11 well-differentiated adenocarcinomas with lepidic growth: 3 adenocarcinomas in situ (nonmucinous) and 8 minimally invasive adenocarcinomas (MIAs) (4 mucinous and 4 nonmucinous). There were 19 invasive moderately differentiated adenocarcinomas with a prominent lepidic growth pattern (LPAs). The mean size of the 3 adenocarcinomas in situ cases was 0.9±0.7 mm; the total size of the 8 MIA cases was 1.4±1.8 cm and that of the 19 LPA cases was 3.2±2.1 cm. The invasive size of the MIA was 0.3±0.6 and that of the LPA was 2.2±0.3. The invasive pattern of the LPAs was papillary and acinar without desmoplasia (n=3) and acinar with desmoplasia (n=16). Seven of the invasive desmoplastic tumors showed complex single-cell invasion or lymphatic invasion. Identification of the transition from lepidic to invasive acinar was straightforward because of the presence of elastotic desmoplasia. The transition between complex acinar papillary invasion and lepidic growth was often difficult to discern. Lymph node metastases were present in 5 cases (26%), all in tumors with an acinar, desmoplastic invasive component of >1 cm, with areas of single-cell invasion. With follow-up, progressive nodal involvement or distant metastases occurred in 4 patients, all with complex invasive patterns; 3 with invasion >1 cm and 1 with lymphatic invasion in smaller invasive tumors. Recurrent lung nodules occurred in 5 patients, including 1 patient with MIA, 1 with nondesmoplastic invasion, 2 with desmoplastic invasion, and 1 with complex desmoplastic invasion. Approximately one third of lung adenocarcinomas have significant lepidic spread, and of these nearly one third are minimally invasive. Measurement of the invasive component may be difficult without elastotic desmoplasia. In this small series, lymph node and distant metastases occurred only in those with complex invasive patterns, but lung recurrence occurred in all subtypes, including MIAs.

New classification of adenocarcinoma: what radiologists need to know

The International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society recently introduced a new classification of lung adenocarcinoma addressing the latest advances in oncology, molecular biology, pathology, radiology, and surgery of lung adenocarcinoma. In this classification, new uniform terminology and diagnostic criteria are described, including the introduction of adenocarcinoma in situ as a second preinvasive lesion, as well as the concept of minimally-invasive adenocarcinoma and new subtyping of invasive adenocarcinomas stratified according to predominant patterns. In addition, the previously widely-used term bronchioloalveolar carcinoma is no longer considered valid and has been recategorized. This classification also provides, for the first time, guidance for small biopsies and cytology specimens. This new classification has profound implications for radiology, as much investigation will be needed to correlate these newly introduced concepts (such as histologic subtypes) with radiologic features. Understanding the newly described concept of minimally-invasive adenocarcinoma will be essential in determining sublobar resection for adenocarcinomas. In this manuscript, we briefly review the new classification of lung adenocarcinoma and discuss its radiologic relevance to the reporting, biopsy, and future studies of adenocarcinoma.

TTF-1 and Napsin a Double Staining in Diagnosing Lung Adenocarcinoma

Pulmonary cancer is the most commonly diagnosed cancer worldwide, and is the leading cause of cancer mortality in men [1]. Lung cancer is divided into small cell cancer and Non-Small Cell Cancer (NSCLC). NSCLC accounts for 80% of all lung cancers and is comprised of Adenocarcinoma (ADC), Squamous Cell Carcinoma (SqCCA) and large cell carcinoma [2]. In addition, 60% of NSCLCs present with locally advanced disease at the time of initial diagnosis [3]. Traditionally, the pathologic lung cancer differential diagnosis was between small cell carcinoma and NSCLC, as sub-typing NSCLC had not been shown to predict differences in patient outcomes. Recent advances in molecular biology have led to an increase in target-specific chemotherapeutic therapies that require the sub-categorization of NSCLCs. The International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society has outlined a new classification of lung ADCs based on a multidisciplinary approach. They have outlined the importance of further classifying NSCLCs as either ADCs or SqCCAs, since ADCs should be tested for Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) fusion gene mutations, as targeted chemotherapeutic agents can be used with greater efficacy [4]. Lung ADCs are often associated with EGFR mutations, and can be effectively treated with tyrosine kinase inhibitors such as gefitinib [5,6]. In addition, ADC have been shown to have improved outcomes when compared to SqCCAs when treated with pemetrexed therapy, which inhibits specific enzymes in purine and pyrimidine synthesis. Finally, the distinction between ADC and SqCCA can avoid potentially hazardous outcomes, as life-threatening hemorrhages have been rarely reported when patients with SqCCAs are treated with bevacizumab, a vascular endothelial growth factor inhibitor [7]. If the classification of NSCLCs cannot be achieved with cytologic/histologic criteria alone, Immunohistochemistry (IHC) staining should be employed. Thyroid Transcription Factor 1 (TTF-1) and Napsin A are both stains that have been proven to stain a majority of lung ADCs. TTF-1 is a nuclear stain that has been reported in 87% lung ADCs and 2% of SqCCAs [8]. Napsin A is a cytoplasmic stain that is relatively specific for ADC of the lung and reportedly stains 80% of cases [9]. A combined TTF-1 and Napsin A double stain has also been shown to be useful in the diagnosis of ADC in cell blocks from fine needle aspirates (FNAs) [10].

Histopathologic Characteristics of Lung Adenocarcinomas With Epidermal Growth Factor Receptor Mutations in the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Lung Adenocarcinoma Classification

The proposed International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification of lung adenocarcinomas has been published. To evaluate the correlation between epidermal growth factor receptor mutations and histologic subtypes of lung adenocarcinomas according to the upcoming new classification of lung adenocarcinomas. Medical records and pathologic slides were reviewed for a total of 107 surgically resected lung adenocarcinomas. All tumors were reclassified according to the predominant histologic subtype, and comprehensive histologic subtyping with semiquantitative assessment of each of the histologic subtypes in increments of 5% was performed. Correlations with epidermal growth factor receptor status were then evaluated. Epidermal growth factor receptor mutations were found in 54 cases (50.5%). Epidermal growth factor receptor mutations were significantly associated with the micropapillary-predominant subtype (P = .02) and with the presence (any amount) of the lepidic component (P = .02). The upcoming International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification of lung adenocarcinoma is relevant in that it shows a phenotype-genotype correlation. Comprehensive histologic subtyping should be recommended because of the association of particular subtypes with epidermal growth factor receptor mutations.