Lepidic Adenocarcinoma Research Articles

Prognostic impact of cancer-associated active fibroblasts and invasive architectural patterns on early-stage lung adenocarcinoma

BackgroundInvasion is a crucial indicator of the prognosis in lung adenocarcinoma. The 2015 WHO classification of lung tumors defined invasion of adenocarcinoma mainly by the presence of non-lepidic histological subtypes including papillary, acinar, micropapillary and solid patterns, and the presence of cancer-associated active fibroblasts (CAF). In this study, we focused specifically on early-stage lepidic adenocarcinoma with CAF to evaluate its prognostic significance. MethodsWe included 1032 resected cases of lung adenocarcinoma, which consisted of pathological stage IA invasive cancer and adenocarcinoma in situ (AIS). Invasive adenocarcinoma was classified into two subgroups according to the type of invasion, INV-1 and INV-2. We defined INV-1 as adenocarcinoma of a non-lepidic histological subtype with or without CAF, and INV-2 as lepidic adenocarcinoma with CAF. The clinicopathological characteristics and prognosis were retrospectively analyzed. ResultsIncluded cases were classified into 696 (67.4 %) INV-1, 170 (16.5 %) INV-2, and 166 (16.1 %) AIS. The estimated 5-year recurrence-free probabilities of INV-1, INV-2, and AIS were 92.9 %, 100 %, and 100 %, respectively (p < 0.001). Although there were significant differences between INV-1 and INV-2 in terms of gender (more males in INV-1, p = 0.039), smoking habit (more smokers in INV-1, p = 0.046), and lymphovascular invasion (more invasion in INV-1, p < 0.001), there was no difference between AIS and INV-2. ConclusionThe presence of CAF is not always associated with a worse prognosis, and therefore it does not seem appropriate to include the presence of CAF alone in diagnostic criteria for invasion in early-stage lung adenocarcinoma.

Reciprocal expression of trefoil factor-1 and thyroid transcription factor-1 in lung adenocarcinomas.

Molecular targeted therapies against EGFR and ALK have improved the quality of life of lung adenocarcinoma patients. However, targetable driver mutations are mainly found in thyroid transcription factor‐1 (TTF‐1)/NK2 homeobox 1 (NKX2‐1)‐positive terminal respiratory unit (TRU) types and rarely in non‐TRU types. To elucidate the molecular characteristics of the major subtypes of non‐TRU‐type adenocarcinomas, we analyzed 19 lung adenocarcinoma cell lines (11 TRU types and 8 non‐TRU types). A characteristic of non‐TRU‐type cell lines was the strong expression of TFF‐1 (trefoil factor‐1), a gastric mucosal protective factor. An immunohistochemical analysis of 238 primary lung adenocarcinomas resected at Jichi Medical University Hospital revealed that TFF‐1 was positive in 31 cases (13%). Expression of TFF‐1 was frequently detected in invasive mucinous (14/15, 93%), enteric (2/2, 100%), and colloid (1/1, 100%) adenocarcinomas, less frequent in acinar (5/24, 21%), papillary (7/120, 6%), and solid (2/43, 5%) adenocarcinomas, and negative in micropapillary (0/1, 0%), lepidic (0/23, 0%), and microinvasive adenocarcinomas or adenocarcinoma in situ (0/9, 0%). Expression of TFF‐1 correlated with the expression of HNF4‐α and MUC5AC (P < .0001, P < .0001, respectively) and inversely correlated with that of TTF‐1/NKX2‐1 (P < .0001). These results indicate that TFF‐1 is characteristically expressed in non‐TRU‐type adenocarcinomas with gastrointestinal features. The TFF‐1‐positive cases harbored KRAS mutations at a high frequency, but no EGFR or ALK mutations. Expression of TFF‐1 correlated with tumor spread through air spaces, and a poor prognosis in advanced stages. Moreover, the knockdown of TFF‐1 inhibited cell proliferation and soft‐agar colony formation and induced apoptosis in a TFF‐1‐high and KRAS‐mutated lung adenocarcinoma cell line. These results indicate that TFF‐1 is not only a biomarker, but also a potential molecular target for non‐TRU‐type lung adenocarcinomas.

Radiological Aspects of the New “International Multidisciplinary Classification of Lung Adenocarcinoma”: Methodological Bases and Own Experience

Purpose – to improve the efficiency of diagnosis and treatment of patients with pulmonary adenocarcinoma by introducing in Ukraine a new “International Multidisciplinary Classification ...” adopted by WHO in 2015. For radiologists, this classification recommends CT semiotics of pulmonary adenocarcinoma according to its histological subtypes. Distinguish: preinvasive (atypical adenomatous hyperplasia – AAG, adenocarcinoma in situ – AIS), minimally invasive (minimally invasive adenocarcinoma – MIA) and invasive (predominantly lepidic adenocarcinoma – LPA, invasive mucinous adenocarcinoma – IMA) lesions. In accordance with the recommendations of the International Association for the study of lung cancer, the American thoracic society and the European respiratory society: ground glass nodule (GGN) or partially solid formations with predominance of the GGN component in CT images should be interpreted using new Terms: AIS, MIA and LPA. On sufficiently thin (≤ 3 mm) CT sections, when evaluating partially solid composites, the size of the solid component and the total size, including GGN, should be separately measured. With limited resources of the country (region, institution) in conducting molecular and immunohistochemical studies, the authors of the "International Multidisciplinary Classification ..." recommend determining the stage of adenocarcinoma by all available methods and starting treatment of patients (surgical, chemotherapy) based on TNM factors. Conclusion. The implementation status of the new (WHO, 2015) “International Multidisciplinary Classification of Lung Adenocarcinoma” in Ukraine should be considered unsatisfactory. At the same time, on the basis of CT data, the radiologist has the opportunity to suggest the presence of one of its five histological subtypes and recommend to the clinician the next steps in making a diagnosis (specific additional examination, consultations of other specialists, the timing of the CT scan, etc.). Based on this information, the morphologist more accurately determines the histological type of the tumor, and the oncologist chooses the most effective way to treat the patient. Key words: multidisciplinary classification, pulmonary adenocarcinoma, computed tomography.

Canine Diffuse Lepidic Predominant Adenocarcinoma

Background: Due to their abundant vascular supply, the lungs are a usual metastatic site, with primary lung cancer presenting a low prevalence in dogs and cats. Among the primary pulmonary tumors afflicting dogs, lepidic carcinoma is the most common and can be classified by site of onset. Lepidic predominant adenocarcinoma is characterized by the proliferation of neoplastic cells along the pulmonary alveoli and pre-existing alveolar structures. Few reports of this specific tumor were found in the literature, so the objective of this study is to describe the clinical, pathological, and immunohistochemical findings of a dog with predominantly diffuse lepidic adenocarcinoma.Case: A 14-year-old, female, spayed, mixed-breed canine with a history of progressive weight loss, cough, respiratory distress, and pain while eating was brought in for a consultation. A presumptive diagnosis of pneumonia was suggested. However, in spite of treatment, the dog died, and a necropsy was performed. Upon gross examination, the lungs were diffusely enlarged, whitish, and stiffened with large and highly vascular nodules. Histopathological findings showed proliferation of neoplastic cells along the vascular walls and within the bronchioalveolar structures, with moderate fibrovascular stroma. The growth patterns resembled the pre-existing alveolar structures, with papillary protrusions into the alveolar lumen. After immunohistochemical evaluation, the definitive diagnosis was diffuse lepidic predominant adenocarcinoma. This tumor is uncommon and difficult to diagnose in the clinical veterinary routine, so it should be considered in the differential diagnosis of respiratory conditions in canines, especially in elderly animals with chronic clinical signs not responsive to antibiotic therapy. Complementary diagnostic examinations such as imaging, laboratory tests, and biopsy are indispensable to the early diagnosis of this lung neoplasm.Discussion: Due to its insidious character, primary lung cancer is underdiagnosed in veterinary medicine and is regularly an incidental x-ray finding. Affected dogs have no clinical signs, and this poses a diagnostic challenge. Primary lung cancer tends to be more prevalent in older and purebred animals. The most frequent clinical sign in dogs is a chronic non-responsive cough, which can be misdiagnosed as another respiratory disease. Hematological findings, such as anemia, neutrophilia, and lymphopenia, can be related to tumor progression. Most reported cases of lepidic adenocarcinoma in dogs have a single pulmonary nodule, and the diffuse form is less common. In this case report, besides the presence of a single pulmonary nodule, there was also widespread involvement of the parenchyma. Histopathology was compatible with lepidic predominant adenocarcinoma, and immunohistochemistry was positive for pan-cytokeratin, confirming the epithelial origin of the tumor, and negative for TFF-1. Despite being a highly specific marker for lung cancer in dogs, TFF-1 has variable sensitivity among the different types of lung cancer. Fixation time and the location of the tumor sections may have contributed to the seronegative result obtained. In conclusion, lepidic adenocarcinoma is a primary lung neoplasia that is uncommon and presents a diagnostic challenge to veterinary clinicians. Therefore, it should be included as a differential diagnosis in older, purebred animals presenting chronic respiratory clinical signs that are refractory to treatment.

Role of PET/CT in Management of Early Lung Adenocarcinoma.

OBJECTIVE. The purpose of this study was to explore the value of FDG PET combined with high-resolution CT (HRCT) in predicting the pathologic subtypes and growth patterns of early lung adenocarcinoma. MATERIALS AND METHODS. A retrospective analysis was conducted on the PET/CT data on ground-glass nodules (GGNs) resected from patients with stage IA lung adenocarcinoma. The efficacy of PET maximum standardized uptake value (SUVmax) combined with HRCT signs in prediction of histopathologic subtype and growth pattern of lung adeno-carcinoma was evaluated. RESULTS. SUVmax was significantly higher in GGNs with invasive HRCT signs. The diameter of GGN (odds ratio, 1.660; p = 0.000) and the difference in attenuation value (odds ratio, 1.012; p = 0.011) between ground-glass components and adjacent lung tissues were independent predictors of FDG uptake by GGNs. SUVmax was higher in invasive adenocarcinoma than in adenocarcinoma in situ (AIS)-minimally invasive adenocarcinoma (MIA) (median SUVmax, 2.0 vs 1.1; p = 0.008). An SUVmax of 2.0 was the optimal cutoff value for differentiating invasive adenocarcinoma from AIS-MIA. Acinar-papillary adenocarcinoma had a higher SUVmax than lepidic adenocarcinoma (median SUVmax, 2.1 vs 1.3; p = 0.037). An SUVmax of 1.4 was the optimal cutoff value for differentiating the growth pattern of adenocarcinoma. Use of PET/CT with HRCT significantly improved efficacy for differentiating invasive adeno-carcinoma from AIS-MIA. However, use of HRCT cannot significantly improve the diagnostic efficacy of FDG PET in the evaluation of tumors with different growth patterns. CONCLUSION. FDG PET can be used to predict the histopathologic subtypes and growth patterns of early lung adenocarcinoma. Combined with HRCT, it has value for predicting invasive histopathologic subtypes but no significance for predicting invasive growth patterns.

Qualitative and quantitative imaging features of pulmonary subsolid nodules: differentiating invasive adenocarcinoma from minimally invasive adenocarcinoma and preinvasive lesions

To explore the role of qualitative and quantitative imaging features of pulmonary subsolid nodules (SSNs) in differentiating invasive adenocarcinoma (IAC) from minimally invasive adenocarcinoma (MIA) and preinvasive lesions. We reviewed the clinical records of our institute from October 2010 to December 2015 and included 316 resected SSNs from 287 patients: 260 pure ground-glass nodules, 47 part-solid nodules with solid components ≤5 mm, and 9 ground-glass nodules (GGNs) with cystic airspaces. According to the pathologic review results, 307 SSNs in addition to nine GGNs with cystic airspaces were divided into two groups: A, including atypical adenomatous hyperplasia (AAH) (n=15), adenocarcinoma in situ (AIS) (n=56), and MIA (n=41); B, including 195 IACs. Univariate and binary logistic regression analyses were conducted to identify independent risk factors for IAC. Univariate analysis showed significant differences between groups regarding patient age, mean diameter, mean and relative computed tomography (CT) values, volume, mass (all P<0.001), and morphological features including lobulated sign (P<0.001), spiculated sign (P=0.028), vacuole sign/air bronchogram (P<0.001), and pleural retraction (P=0.017). Binary logistic regression and receiver operating characteristic analysis indicated the SSN mass as the only independent risk factor of IAC (odds ratio, 1.007; P<0.001), with an optimal cutoff value of 283.2 mg [area under curve (AUC): 0.859; sensitivity: 68.7%; specificity: 92.9%]. Among lepidic, acinar, and papillary adenocarcinomas, we found significant differences for the vacuole sign/air bronchogram (P=0.032) and mean and relative CT values (P<0.001). All nine GGNs with cystic airspaces were IACs. The SSN mass with an optimal cutoff value of 283.2 mg may be reliable for differentiating IAC from MIA and preinvasive lesions.

Glucose and glutamine metabolism in relation to mutational status in NSCLC histological subtypes.

BackgroundBoth hypoxia and oncogenic mutations rewire tumor metabolism. In this study, glucose and glutamine metabolism‐related markers were examined in stage I ‐ resectable stage IIIA non‐small cell lung cancer (NSCLC). Furthermore, expression of metabolism‐related markers was correlated with mutational status to examine mutations associated with rewired tumor metabolism.MethodsMutation analysis was performed for 97 tumors. Glucose and glutamine metabolism‐related marker expression was measured by immunofluorescent staining (protein) and qPCR (mRNA) (n = 81).ResultsGlutamine metabolism‐related markers were significantly higher in adeno‐ than squamous cell NSCLCs. Glucose transporter 1 (GLUT1) protein expression was higher in solid compared to lepidic adenocarcinomas (P < 0.01). In adenocarcinomas, mRNA expression of glutamine transporter SLC1A5 correlated with tumor size (r(p) = 0.41, P = 0.005). Furthermore, SLC1A5 protein expression was significantly higher in adenocarcinomas with worse pTNM stage (r(s) = 0.39, P = 0.009). EGFR‐mutated tumors showed lower GLUT1 protein (P = 0.017), higher glutaminase 2 (GLS2) protein (P = 0.025) and higher GLS2 mRNA expression (P = 0.004), compared to EGFR wild‐type tumors. GLS mRNA expression was higher in KRAS‐mutated tumors (P = 0.019). TP53‐mutated tumors showed higher GLUT1 expression (P = 0.009).ConclusionsNSCLC is a heterogeneous disease, with differences in mutational status and metabolism‐related marker expression between adeno‐ and squamous cell NSCLCs, and also within adenocarcinoma subtypes. GLUT1 and SLC1A5 expression correlate with aggressive tumor behavior in adenocarcinomas but not in squamous cell NSCLCs. Therefore, these markers could steer treatment modification for subgroups of adenocarcinoma patients. TP53, EGFR and KRAS mutations are associated with expression of glucose and glutamine metabolism‐related markers in NSCLC.

EP1.17-25 Radio-Guided Localization of Small Lung Nodules

The widespread use of computed tomography and the obligation of early diagnosis and treatment of small lung nodules have increased in recent years. There are few localization techniques, ROLL seems one of the safest and most effective. The purpose of this study is to report our experience. We have retrospectively reviewed all patients with undetermined lung nodule that underwent radio-guided localization. The aim of the study was to evaluate the efficacy of the ROLL for the diagnosis and treatment of small lung nodules. The morning of the surgery, Tc99 macroaggregated albumin was injected guided by computer tomography. Afterwards a SPECT-CT was performed to check the correct localization of the tracer and the patient was brought into the operating room. During the surgery a gamma probe connected to a gamma ray was introduced and the lung surface scanned. After detecting the higher value area, a lung resection was performed and the lung is rescanned to check the residual activity (less than 10%). Between November 2011 and February 2019, 30 patients (22 male and 8 female) underwent radiotracer injection followed by lung resection surgery in our institute. Mean age was 66,3 years (range 52 to 76 years). The main complication was pneumothorax (9 patients, 30%), but no patient required chest drainage. There was one non-complicated aortic puncture. There were no other complications. The mean nodule size was 9,07mm +/- 4,35mm and the mean visceral pleural distance was 19,6mm +/-16,27mm. By radiology characteristics, 16 were ground glass opacities, 10 solid nodules and 4 partially solid nodules. The lesions were well detected in 100% cases. They were resected by wedge resection in all the cases. The final pathologic diagnosis confirmed 12 lung adenocarcinoma (6 lepidic growth adenocarcinoma, 3 adenocarcinoma in situ, 2 solid adenocarcinomas, 1 minimally invasive adenocarcinoma), 12 lung metastasis, 2 atypical adenomatous hyperplasia, 2 inflammatory nodules, 1 squamous carcinoma and 1 hamartoma. Clean margins were obtained in 28 patients (93,3%). There were not intraoperative and postoperative complications secondary to the procedure. The radio-guided localization is a simple, easy and safe procedure for the diagnosis and treatment of small lung nodules. There were not problems of radiotracer lung diffusion and misplacement.

MS07.04 Stage I (Resectable) NSCLC: Surgery

MS07.04 Stage I (Resectable) NSCLC: Surgery

Prognostic Effects of Predominant Histologic Subtypes in Resected Pulmonary Adenocarcinomas

Background:Predominant histologic subtypes have been reported as predictors of survival of patients with pulmonary adenocarcinoma.Aims:To evaluate the predictive value of histologic classification in resected lung adenocarcinoma using the classification systems proposed by the International Association for the Study of Lung Cancer, American Thoracic Society, European Respiratory Society, and World Health Organization (2015).Study Design:Cross-sectional study.Methods:The histologic classification of a large cohort of 491 patients with resected lung adenocarcinoma (stages I-III) was retrospectively analyzed. The tumors were classified according to their predominant component (lepidic, acinar, papillary, solid, micropapillary, and mucinous), and their predictive values were assessed for clinicopathologic characteristics and overall survival.Results:The patient cohort comprised 158 (32.2%) patients with solid predominant, 150 (30.5%) with acinar predominant, 80 (16.3%) with papillary predominant, 75 (15.3%) with lepidic predominant, 22 (4.5%) with mucinous, and 5 (1.0%) with micropapillary subtype, and 1 (0.2%) with adenocarcinoma in situ. Overall 5-year survival of 491 patients was found to be 51.8%. Patients with lepidic, acinar, and mucinous adenocarcinoma had 70.9%, 59.0%, and 66.6% 5-year survival, respectively, and there was no statistically significant difference between them. Whereas patients with solid, papillary, and micropapillary predominant adenocarcinoma had 41.0%, 40.5%, and 0.0% 5-year survival, respectively. Compared to other histologic subtypes, patients with solid and papillary predominant adenocarcinoma had significantly lower survival than those with lepidic (p<0.001, p=0.002), acinar (p<0.001, p=0.008), and mucinous (p=0.048, p=0.048) subtypes, respectively. The survival difference between patients with solid subtype and those with papillary subtype was not statistically significant (p=0.67).Conclusion:Solid and papillary histologic subtypes are poor prognostic factors in resected invasive lung adenocarcinoma.

Is chemotherapy rechallenge feasible in advanced-stage non-small-cell lung cancer?

Despite recent progress, non-small cell lung cancer (NSCLC) first-line treatment remains a platinum-based doublet in most cases. No guidelines exist beyond third line. Chemotherapy rechallenge is an option, but little data is available in NSCLC. Our study aims to describe patients who underwent chemotherapy rechallenge while assessing its efficacy and safety. Consecutive patients with advanced-stage NSCLC receiving first-line treatment in Tenon hospital in 2011 were included, with a 5-year follow-up. Patients were analyzed according to chemotherapy rechallenge or not. Chemotherapy rechallenge was defined as re-initiation of a previously administered chemotherapy agent at any point in the treatment sequence, with at least one treatment regimen between first use and rechallenge. Of 149 patients, 18 underwent chemotherapy rechallenge (12%). They were younger (56 vs. 61 years, P=0.04), mostly women (61% vs. 30%, P=0.02), with lepidic adenocarcinoma (23% vs. 3.5%, P=0.03), a better general state of health (100% performance status 0-1 vs. 74%, P=0.04), and fewer cardiovascular comorbidities (16% vs. 42%, P=0.04). They were more likely to have received a receptor tyrosine kinase inhibitor treatment (89% vs. 43%, P=0.0003). Progression-free survival was longer at first use than at rechallenge (median 9.2 vs. 2.7 months, P=0.002). No increased toxicity was observed at rechallenge compared to first use. Finally, a subsequent line of treatment was given after rechallenge in 61% of the patients. Patients eligible for chemotherapy rechallenge were those with good prognostic factors. Chemotherapy rechallenge may provide a well-tolerated additional line of treatment, with decreased efficacy compared to its first application.

Selection of patients for stereotactic body radiation therapy (SBRT) or (bi)lobectomy (L) for the treatment of cT1-T2N0M0 NSCLC by the risk of node involvement using readily available preoperative factors.

e20055 Background: Currently it is not known whether certain patients with early-stage non-small cell lung cancer(NSCLC) would be better served with stereotactic body radiation (SBRT) or surgery. The purpose of our investigation is to see if patients who are at higher risk of node involvement based upon pre-operative factors would be preferentially served with (bi)Lobectomy(L). Methods: The NCDB was queried for the years 2004-2014 to find patients with cT1-T2N0M0 NSCLC (excluding lepidic adenocarcinoma and their variants) &lt; 5cm treated via L or SBRT(N = 16,722). Recursive partition analysis was used in the L group to develop high, medium, and low risk node involvement groups in those patients having complete node assessment (10 or more nodes examined) by American College of Surgeons commission on cancer quality care measures(ACOS coc), N = 83,890. The L and SBRT groups were then propensity matched based upon factors associated with OS to assess whether there was an OS benefit for either the L or SBRT treatments by node risk category. OS was calculated by log-rank testing. Results: The high, medium, and low risk categories had an average risk for node involvement of 20.12, 11.3, and 4.57%, respectively. The low risk group was defined as tumors &lt; 21mm for all squamous cell carcinomas(SQ) and adenocarcinoma(AD) in the right upper lobe only. High risk categories were associated tumors &gt; 21 mm in the RUL in white Hispanics; and ages &lt; 60yr old for SQ, large cell ca, and NSCLC-NOS; and &gt; 21mm with non-RUL location and &lt; 55yr old. OS was significantly better in patients treated by L for the high, medium, and low risk groups with all p-values of &lt; 0.0001. Conclusions: When patients undergo a complete lymph node dissection by the ACOScoc quality measures and have (bi)lobectomy, their OS is superior to patients undergoing SBRT whether they are at high, low or medium risk of lymph node involvement.

Cytological differences between invasive and noninvasive or minimally invasive lung adenocarcinomas diagnosed in Japanese patients using needle biopsy specimens of pulmonary lesions ≤3 cm in diameter.

BackgroundAccording to the WHO classification for lung cancer, adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) have a better prognosis than invasive adenocarcinoma (IAD). However, detecting the foci of invasion in lung adenocarcinomas radiologically remains difficult. The present study examined whether or not differences in the cytological characteristics between IAD and AIS or MIA (noninvasive or minimally invasive adenocarcinomas [NMIAD]) plays a role in the differential diagnosis.MethodsSeventy surgical resection specimens of primary lung adenocarcinoma with preoperative cytology, in which several parameters were evaluated and assessed.ResultsThe histopathological diagnoses of surgical resection specimens were AIS in 8, MIA in 31, IAD in 31 including lepidic adenocarcinoma in 9, and papillary adenocarcinoma in 22. NMIAD had a 100% 5‐year recurrence‐free survival (RFS), while IAD had an 82.8% 5‐year RFS. The numbers of tumor cells (at ×10 magnification in 10 fields) were 60.3 ± 40.5 in IAD and 39.8 ± 28.7 in NMIAD (P = 0.0017). A univariate analysis of cytological parameters revealed significant differences in large tumor cell clusters, three‐dimensional (3D) tumor cell clusters, and irregular nuclear contours between the two groups. The frequency of irregular nuclear contours continued to be significantly different according to a multivariate analysis.ConclusionLarge or 3D tumor cell clusters and irregular nuclear contours may be important cytological factors for distinguishing IAD from NMIAD, with the latter being potentially more important for distinguishing between the two groups.

Ground-Glass Opacity Is a Strong Prognosticator for Pathologic Stage IA Lung Adenocarcinoma

A ground-glass opacity (GGO) component on chest computed tomography (CT) pathologically corresponds to lepidic adenocarcinoma. However, the precise correspondence relation and the prognostic significance remains unclear in patients with pathologic stage IA lung adenocarcinoma. We retrospectively reviewed the clinicopathologic features of 809 consecutive patients with pathologic stage IA lung adenocarcinoma who underwent complete resection between 2003 and 2014. We evaluated the prognostic impact of clinicopathologic variables including the radiologic appearance with a Cox proportional hazards model. Among the 809 patients, 465 (57%) were nodules with a GGO component, and 344 (43%) were solid nodules on chest CT. On final pathology, lepidic adenocarcinoma was identified in 445 (96%) of the GGO nodules and 239 (69%) of the solid nodules. The survival rate of the patients having a GGO nodule was significantly higher than that without GGO components (5-year overall survival, 97% versus 84%, p < 0.0001). In solid nodules, there was no significant prognostic difference between patients with and without a lepidic component (5-year overall survival, 87% versus 79%, p= 0.09). On multivariable analysis, solid appearance on chest CT was an independent prognostic factor (hazard ratio, 1.74; 95% confidence interval, 1.10 to 2.79; p= 0.019), but the pathologic invasive size and the pathologic lepidic growth component were not. In patients with pathologic stage IA lung adenocarcinoma, the radiologic appearance as a GGO nodule on chest CT is a better prognostic indicator than the presence of a lepidic component on pathology.

Association between the novel classification of lung adenocarcinoma subtypes and EGFR/KRAS mutation status: A systematic literature review and pooled-data analysis

ObjectivesThis study aims to determine the association of EGFR/KRAS mutation status with histological subtypes of lung adenocarcinoma (LAC) based on the IASLC/ATS/ERS classification. MethodsPubmed and Cochrane databases were searched from January 2011 to June 2018 for studies that included patients with LAC who underwent surgical resection were classified according to the new IASLC/ATS/ERS classification. EGFR/KRAS status assessment was requireded. The primary outcome was determined by the odds ratio (OR) of the incidence of mutation status of certain of each histological subtype. The reference group consisted of EGFR/KRAS mutation negative patients. ResultsTwenty-seven eligible studies involving 9022 patients with mutation gene detection were included for analysis. Among them, 6717 (74.5%) patients were from the Asian region and, 2305 (25.5%) patients were from Non-Asian regions. The most prevalent subtype was acinar (34.7%), followed by papillary (22.9%), lepidic (18.9%), solid (13.6%), micropapillary (6.3%), and invasive mucinous adenocarcinoma (3.5%). EGFR mutations were more common in patients with resected lepidic predominant adenocarcinoma (OR,1.76; 95%CI, 1.38–2.24;p < 0.01) and were rarely found in solid predominant adenocarcinoma (OR,0.28; 95%CI, 0.23–0.34;p < 0.01) or IMA (OR,0.10; 95%CI, 0.06–0.14;p < 0.01). Conversely, KRAS mutations were characterized by IMA (OR,7.01; 95%CI, 5.11–9.62;p < 0.01), and were less frequently identified in lepidic (OR,0.58; 95%CI, 0.45–0.75;p < 0.01) and acinar (OR,0.65; 95%CI, 0.55–0.78;p < 0.01) predominant subtypes. Further analyses were performed in Asian and Non-Asian groups and the results were consistent. ConclusionsThe current study confirms that the IASLC/ATS/ERS classification is associated with driver gene alterations in resected LAC.

Consensus on early stage non-mucinous lepidic lung adenocarcinoma frozen section diagnosis

尽管2015版WHO分类对早期肺腺癌的各类亚型（原位腺癌、微浸润腺癌等）的经典的组织学特征及诊断标准作了比较详细的描述，但由于早期肺腺癌的组织学异质性及冷冻切片本身的技术缺陷等诸多因素，致使早期肺腺癌的冷冻切片诊断与术后石蜡切片诊断存在一定的误差率并使各级医院病理科医师在诊断中产生一定的困难或压力。为此中华医学会病理学分会胸部疾病学组制订出中国早期肺腺癌冷冻切片病理诊断术语的专家共识。其内容为：符合原位腺癌；倾向原位腺癌；符合微浸润性腺癌；微浸润性腺癌可能性大；至少为微浸润性腺癌，浸润性腺癌不能除外；符合浸润性腺癌等六部分，并从CT影像、大体特征、冷冻切片组织学特征等逐条作出解读，以期能提高早期肺腺癌冷冻切片病理诊断水平。.

Radiological Aspects of the New “International Multidisciplinary Classification of Lung Adenocarcinoma”: Methodological Bases and Own Experience

Purpose – to improve the efficiency of diagnosis and treatment of patients with pulmonary adenocarcinoma by introducing in Ukraine a new “International Multidisciplinary Classification ...” adopted by WHO in 2015. For radiologists, this classification recommends CT semiotics of pulmonary adenocarcinoma according to its histological subtypes. Distinguish: preinvasive (atypical adenomatous hyperplasia – AAG, adenocarcinoma in situ – AIS), minimally invasive (minimally invasive adenocarcinoma – MIA) and invasive (predominantly lepidic adenocarcinoma – LPA, invasive mucinous adenocarcinoma – IMA) lesions. In accordance with the recommendations of the International Association for the study of lung cancer, the American thoracic society and the European respiratory society: ground glass nodule (GGN) or partially solid formations with predominance of the GGN component in CT images should be interpreted using new Terms: AIS, MIA and LPA. On sufficiently thin (≤ 3 mm) CT sections, when evaluating partially solid composites, the size of the solid component and the total size, including GGN, should be separately measured. With limited resources of the country (region, institution) in conducting molecular and immunohistochemical studies, the authors of the "International Multidisciplinary Classification ..." recommend determining the stage of adenocarcinoma by all available methods and starting treatment of patients (surgical, chemotherapy) based on TNM factors. Conclusion. The implementation status of the new (WHO, 2015) “International Multidisciplinary Classification of Lung Adenocarcinoma” in Ukraine should be considered unsatisfactory. At the same time, on the basis of CT data, the radiologist has the opportunity to suggest the presence of one of its five histological subtypes and recommend to the clinician the next steps in making a diagnosis (specific additional examination, consultations of other specialists, the timing of the CT scan, etc.). Based on this information, the morphologist more accurately determines the histological type of the tumor, and the oncologist chooses the most effective way to treat the patient. Key words: multidisciplinary classification, pulmonary adenocarcinoma, computed tomography.

A severe combined immunodeficiency disease mouse model of human adenocarcinoma with lepidic-predominant growth

Severe combined immunodeficiency disease (SCID) mice with human lepidic adenocarcinoma were established by the intrabronchial implantation of fresh surgically resected specimens. Human pulmonary adenocarcinoma tissue from 16 different cases was transplanted into SCID mice, and SCID mouse tumors were established from four of these cases (25%). Among the four tumors, the tumor cells of two SCID mice showed replacement lepidic growth of mouse alveolar structures accompanied by multiple intrapulmonary lesions. Human lung carcinoma cell lines showing lepidic growth are rare and the xenograft models using the SCID mouse model developed in the current study will be useful for analyzing the growth and/or progression patterns and clinical behavior of lepidic adenocarcinoma, the major histological subtype of human carcinoma of the lung.

Predictive accuracy of lepidic growth subtypes in early-stage adenocarcinoma of the lung by quantitative CT histogram and FDG-PET

ObjectivesThe aim of this study was to analyze the accuracy of computed tomography (CT) and F-18 fluorodeoxyglucose-positron emission tomography/CT (FDG-PET/CT) to distinguish lepidic growth adenocarcinoma (LGA), including adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and lepidic-predominant adenocarcinoma, all of which have favorable survival outcomes, from the more aggressive and invasive non-LGA subtypes. Materials and MethodsWe identified 225 patients with c-0/I adenocarcinoma of the lung who underwent PET/CT and 3DCT followed by complete resection. Maximum standardized uptake values (SUVmax) of FDG and several histogram parameters were analyzed. Histological grades were classified according to the predominant subtype (G1: lepidic; G3: micropapillary or solid; and G2: subtypes other than G1/G3). ResultsThe proportion of pathological invasive factors (lymphatic vessel involvement/blood vessel invasion/pleural invasion/lymph node metastasis) of patients with preinvasive adenocarcinoma, G1, G2, and G3 tumors were 0%, 3.6%, 48.0%, and 100%, respectively; p < 0.001). Multivariate analysis with CT-related parameters demonstrated that 75th percentile CT attenuation value (75th%, p < 0.001) and maximum CT attenuation value (maxCT, p = 0.009) were associated with incidence of non-LGA, whereas the value of SUVmax demonstrated a significant correlation (p < 0.001). When all patients were dichotomized according to ground-glass opacities (GGO)/solid-dominancy for CT maximum diameter, a significant correlation with non-LGA was shown in patients with solid-dominant tumor on SUVmax (p < 0.001) and with GGO-dominant tumor on 75th% (p = 0.006) and maxCT (p = 0.007). The combination of one of the two significant histogram parameters and SUVmax revealed higher predictive performance for pathological high malignant features (positive pathological invasive factors, non-LGA, and the highly malignant subtype covering G2 with moderately or poorly-differentiated carcinoma and G3) than the individual use of either factor. ConclusionThe 75th%, maxCT, and SUVmax were highly useful in distinguishing LGA from non-LGA in c-0/I adenocarcinoma.

Port access thoracoscopic anatomical lung multiplex subsegmentectomy—S6b-S8a-S9a trisubsegmentectomy

A 77-year-old man with chronic obstructive lung disease was referred to our hospital for further management of his lung nodule. Chest computed tomography (CT) showed a lung nodule that increased in size up to 1.9 cm in the S8a of his left lung. Primary lung cancer was suspected. Thoracoscopic anatomical left S6b-S8a-S9a multiplex subsegmentectomy was performed according to the CT simulation. The operative time was 142 min, and the blood loss was 13 mL. Air leakage was not observed and the chest tube was removed on postoperative day (POD) 1. The final diagnosis was a lepidic adenocarcinoma, and he lives well without recurrence in this 4-year period after the surgery.