Novel Insights Into the International Association for the Study of Lung Cancer Grading System for Lung Adenocarcinoma.

The new grading system for lung adenocarcinoma proposed by the International Association for the Study of Lung Cancer (IASLC) defines prognostic subgroups on the basis of histologic patterns observed on surgical specimens. This study sought to provide novel insights into the IASLC grading system, with particular focus on recurrence-specific survival (RSS) and lung cancer-specific survival among patients with stage I adenocarcinoma. Under the IASLC grading system, tumors were classified as grade 1 (lepidic predominant with <20% high-grade patterns [micropapillary, solid, and complex glandular]), grade 2 (acinar or papillary predominant with <20% high-grade patterns), or grade 3 (≥20% high-grade patterns). Kaplan-Meier survival estimates, pathologic features, and genomic profiles were investigated for patients whose disease was reclassified into a higher grade under the IASLC grading system on the basis of the hypothesis that they would strongly resemble patients with predominant high-grade tumors. Overall, 423 (29%) of 1443 patients with grade 1 or 2 tumors classified based on the predominant pattern-based grading system had their tumors upgraded to grade 3 based on the IASLC grading system. The RSS curves for patients with upgraded tumors were significantly different from those for patients with grade 1 or 2 tumors (log-rank P < .001) but not from those for patients with predominant high-grade patterns (P = .3). Patients with upgraded tumors had a similar incidence of visceral pleural invasion and spread of tumor through air spaces as patients with predominant high-grade patterns. In multivariable models, the IASLC grading system remained significantly associated with RSS and lung cancer-specific survival after adjustment for aggressive pathologic features such as visceral pleural invasion and spread of tumor through air spaces. The IASLC grading system outperforms the predominant pattern-based grading system and appropriately reclassifies tumors into higher grades with worse prognosis, even after other pathologic features of aggressiveness are considered.

Synthesis and activity of 3-oxo-α-ionone analogs as male attractants for the solanaceous fruit fly, Bactrocera latifrons (Diptera: Tephritidae).

A series of 3-oxygenated α-ionone analogs have been developed as highly specific male lures for the solanaceous fruit fly Bactrocera latifrons, a pest of solanaceous fruits. We compared the attractant and phagostimulant activities of analogs with or without (i) unsaturations at the 4,5- and/or 7,8-positions and (ii) oxygen moieties at the 3- and/or 9-positions of the ionone molecule. Since naturally occurring vomifoliol (V2) was found to induce a highly potent phagostimulant activity in B. latifrons males, related analogs including dehydrovomifoliol (V1), 6-hydroxy-α-ionone (U1), and 6-hydroxy-α-ionol (U2) were synthesized to evaluate their attractant and phagostimulant activities. Synthetic V1, V2, U1, and U2 exhibited low attractant activity, but their phagostimulant activity was relatively high. Optical isomers of 3-oxo-7,8-dihydro-α-ionone (P3) and V1 were prepared to examine the stereochemical specificity of attractants. (+)-(6R)-P3 and (+)-(6S)-V1 exhibited the corresponding activities, while their respective antipodal enantiomers were found entirely inactive.

V-domain Ig-containing suppressor of T-cell activation (VISTA), a potentially targetable immune checkpoint molecule, is highly expressed in epithelioid malignant pleural mesothelioma.

V-domain Ig-containing suppressor of T-cell activation (VISTA) is an immune checkpoint gene that inhibits anti-tumor immune responses. Since most malignant pleural mesotheliomas do not respond to anti-programmed cell death(-ligand)1 (PD-(L)1)/cytotoxic T-lymphocyte-associated protein 4 (CTLA4) therapy and given the recent finding of The Cancer Genome Atlas Study that pleural mesothelioma displays the highest expression of VISTA among all cancers studied, we examined VISTA expression in a large pleural mesothelioma cohort. VISTA and PD-L1 immunohistochemistry were performed on tissue microarray of immunotherapy-naive pleural mesotheliomas (254 epithelioid, 24 biphasic and 41 sarcomatoid) and ten whole-tissue sections of benign pleura (VISTA only). Percentages of tumor and inflammatory cells with positive staining were assessed. Optimal prognostic cutoff percentages were determined using maximally selected rank statistics. Overall survival was evaluated using Kaplan-Meier methods and Cox proportional hazard analysis. All benign mesothelium expressed VISTA. Eighty-five percent of 319 and 38% of 304 mesotheliomas expressed VISTA and PD-L1 (88% and 33% of epithelioid, 90% and 43% of biphasic, and 42% and 75% of sarcomatoid), respectively. Median VISTA score was significantly higher in epithelioid (50%) (vs. biphasic [20%] and sarcomatoid [0]) (p < 0.001), while median PD-L1 score was significantly higher in sarcomatoid tumors (20%) (vs. biphasic and epithelioid [both 0%]) (p < 0.001). VISTA and PD-L1 were expressed in inflammatory cells in 94% (n = 317) and 24% (n = 303) of mesothelioma, respectively. Optimal prognostic cutoffs for VISTA and PD-L1 were 40% and 30%, respectively. On multivariable analysis, VISTA and PD-L1 expression in mesothelioma were associated with better and worse overall survival (p = 0.001 and p = 0.002), respectively, independent of histology. In a large cohort of mesothelioma, we report frequent expression of VISTA and infrequent expression of PD-L1 with favorable and unfavorable survival correlations, respectively. These findings may explain poor responses to anti-PD-(L)1 immunotherapy and suggest VISTA as a potential novel target in pleural mesothelioma.

A Stepwise Approach for Postlobectomy Bronchopleural Fistula.

Although rare, bronchopleural fistula (BPF) following anatomic lung resection is a serious complication associated with high rates of mortality (25%-71%). Risk factors for BPF include surgical approach, neoadjuvant therapy, diabetes mellitus, and chronic obstructive pulmonary disease. As neoadjuvant treatment is increasingly being administered to patients with locally advanced lung cancer, and as more patients are being diagnosed with lung cancer at an older age-elderly patients present with a higher index of multiple comorbidities-the incidence of BPF among patients undergoing anatomic resection for lung cancer is expected to increase. In this manuscript, we detail risk factors and considerations for BPF and describe a stepwise approach to treat BPF following lobectomy for lung cancer.

Minimally Invasive Lobectomy Is Associated With Lower Noncancer-specific Mortality in Elderly Patients: A Propensity Score Matched Competing Risks Analysis.

OBJECTIVE: To investigate cancer- and noncancer-specific mortality following lobectomy by minimally invasive surgery (MIS) versus open thoracotomy in elderly patients with nonsmall cell lung cancer (NSCLC). BACKGROUND: Two-thirds of patients with NSCLC are ≥65 years of age. As age increases, the risk of competing events, such as noncancer death, also increases. METHODS: Elderly patients (≥65 yrs of age) who have undergone curative-intent lobectomy for stage I-III NSCLC without induction therapy (2002-2013) were included (n=1,303). Of those, 607 patients had undergone MIS and 696 had undergone thoracotomy. Propensity-score matching was performed to identify pairs of thoracotomy and MIS patients with comparable clinical characteristics (eg, year of surgery, comorbidities, and pulmonary function). Association between surgical approach (MIS vs thoracotomy) and lung cancer-specific and noncancer-specific cumulative incidence of death (CID) was analyzed using competing risks approach. RESULTS: Following propensity score matching of patients who had undergone thoracotomy (n=338) versus MIS (n=338), MIS was associated with shorter length of stay (P <0.001), lower noncancer-specific 1-year mortality (P=0.027), and lower noncancer-specific CID (P=0.014) compared with thoracotomy; there was no difference in lung cancer-specific CID between surgical approaches. On multivariable analysis, thoracotomy was a significant risk factor for noncancer-specific death (subhazard ratio 2.45, 95% CI 1.18-5.06, P=0.016) independent of age, sex, and diffusion capacity of the lungs for carbon monoxide. CONCLUSION: In a propensity score-matched cohort, multivariable analysis has indicated that lobectomy performed by MIS is associated with lower incidence of noncancer-specific mortality compared with lobectomy performed by open thoracotomy in elderly patients with NSCLC.

Successful lung lobectomy for a lung cancer following thoracic endovascular aortic repair for a thoracic aortic aneurysm: report of a case.

Lung cancer and a thoracic aortic aneurysm were detected simultaneously in a 79-year-old male patient with diabetes. The aneurysm was first treated by thoracic endovascular aortic repair. A right lower lobectomy was subsequently performed after the blood flow of the bronchial and intercostal arteries was confirmed by computed tomographic angiography. The bronchial stump was covered with an intercostal muscle flap. The patient's postoperative course was uneventful. Thoracic endovascular aortic repair is a useful and less invasive treatment for such cases, but a blood flow evaluation of the aortic branches should be done following this procedure before a lung resection is considered.

Saving Lives in Thoracic Surgery: Balancing Oncological Radicality and Functional Preservation, Transitioning from Standard Pneumonectomy to Targeted Sublobar Resection.

This review chronicles the evolution of thoracic surgical interventions, from the standardized pneumonectomy to the precise approach of sublobar resections. It discusses the emergence and acceptance of minimally invasive and robot-assisted surgical techniques, highlighting their impact on improving outcomes beyond cancer and their influence on the surgical management of early-stage lung cancer. Evaluating historical developments alongside present methodologies, this review underscores the critical need for meticulous surgical planning and execution to optimize both oncological radicality and functional preservation. This evolution portrayed not only technical advancements but also a shift in the clinical approach towards tailored, organ-preserving methodologies, culminating in a contemporary framework promoting sublobar resections as the standard for specific patient profiles, signifying a new era of precision in thoracic surgery.

Sublobar resection or lobectomy and postoperative respiratory complications in emphysematous lungs.

OBJECTIVES: Pulmonary resection in patients with severe emphysema may impact postoperative respiratory complications. Low-attenuation areas evaluated using three-dimensional computed tomography to assess emphysematous changes are strongly associated with postoperative respiratory complications. Herein, we investigated the relationship between low-attenuation area, the surgical procedure and resected lung volume, which has not been explored in previous studies. METHODS: We retrospectively evaluated patients with primary or metastatic lung cancer who underwent surgical resection. The low-attenuation area percentage (low-attenuation area/total lung area × 100) and resected lung volume were calculated using three-dimensional computed tomography software, and the relationship with postoperative respiratory complications was analysed. RESULTS: Postoperative respiratory complications occurred in 66 patients (17%) in the total cohort (n = 383). We set the median value of 1.1% as the cut-off value for low-attenuation area percentage to predict postoperative respiratory complications, which occurred in 24% and 10% of patients with low-attenuation area >1.1% and <1.1%, respectively (P < 0.001). Postoperative respiratory complications occurred in approximately one-third of the patients with low-attenuation area >1.1%, whose resected lung volume was ≥15.8% or ≥5 resected subsegments. Multivariable analysis revealed that sublobar resection was associated with a significantly lower risk of postoperative respiratory complications in patients with low-attenuation area >1.1% (odds ratio 0.4, 95% confidence interval 0.183-0.875). CONCLUSIONS: Emphysema is a risk factor for postoperative respiratory complications, and lobectomy is an independent predictive risk factor. Preserving more lung parenchyma may yield better short-term prognoses in patients with emphysematous lungs.

Segmentectomy-oriented anatomical model for enhanced precision surgery of the left upper lobe.

Objective: To optimize surgical outcomes and minimize complications in complex segmentectomy of the left upper lobe, we investigated the topographical anatomy of the left upper lobe and developed a segmentectomy-oriented anatomical model. Methods: A state-of-the-art 3-dimensional computed tomography workstation was used to visualize the intersegmental planes and associated veins to categorize the anatomical patterns influencing surgical procedures during left upper lobe segmentectomy. This included the central vein affecting S1+2 (apicoposterior segment) segmentectomy, the transverse S3 (anterior segment) affecting S3 segmentectomy, and other venous branching patterns in 395 patients who underwent thoracic surgery at our institution. Results: The central vein was observed in 32% of the patients, necessitating access from the interlobar area after segmental artery and bronchus division. Transverse S3 incidence was 27%, revealing that only one-third of the patients required complete left upper lobe transection between S4 and S3 during S3 segmentectomy. A significant negative correlation was observed between the presence of transverse S3 and the central vein (<10% of patients with the central vein had transverse S3 and vice versa). In 6% of patients, the lingular segmental veins partially or entirely drained into the inferior pulmonary vein, potentially causing excessive or insufficient resection during surgery. Conclusions: This study offers valuable insights into the topographic anatomy of the left upper lobe and presents a segmentectomy-oriented anatomical model for complex segmentectomies. Our approach enables a more precise and individualized surgical planning for patients undergoing segmentectomy based on their unique anatomy, which could thereby lead to improved patient outcomes.

Improving intraoperative diagnosis of spread through air spaces: A cryo-embedding-medium inflation method for frozen section analysis.

Objective: Accurate intraoperative diagnosis of spread through air spaces (STAS), a known poor prognostic factor in lung cancer, is crucial for guiding surgical decision-making during sublobar resections. This study aimed to evaluate the diagnostic sensitivity of STAS using frozen section (FS) slides prepared with the cryo-embedding medium inflation technique. Methods: In this prospective study at Shinshu University Hospital, 99 patients undergoing lung resection for tumors <3 cm in size were included, a total of 114 lesions. FS slides were prepared with injecting diluted cryo-embedding medium into the lung parenchyma of resected specimens. The diagnostic performance of these FS slides for STAS detection was evaluated by comparing FS-STAS results with the gold-standard STAS status. Results: The incidence of STAS, determined by the gold standard, was 43 (38%) of 114 lesions, including 31 (37%) of 84 primary lung cancers and 12 (40%) of 30 metastatic lung tumors. The sensitivity, specificity, positive and negative predictive values, and accuracy of FS slides for STAS detection were 81%, 89%, 81%, 89%, and 86%, respectively. Specifically, in primary lung cancers, these values were 90%, 89%, 82%, 94%, and 89%, respectively. Regarding metastatic lung tumors, the corresponding values were 58%, 89%, 78%, 76%, and 77%, respectively. Conclusions: Our adapted cryo-embedding medium inflation method has demonstrated enhanced sensitivity in detecting STAS on FS slides, providing results similar to the gold-standard STAS detection. Compared with historical benchmarks, this technique could show excellent performance and be readily incorporated into clinical practice without requiring additional resources beyond those used for standard FS analysis.

Personalized Medicine in Thoracic Surgery: The Role and Future of Robotic-Assisted Techniques.

The advent of robotic-assisted thoracic surgery (RATS) has revolutionized the field of thoracic surgery, offering a new paradigm for personalized, precision, and individualized medicine [...].

Port Placement Variations for Robotic Lung Resection: Focusing on Their History, Conventional Look-Up-View and Horizontal Open-Thoracotomy-View Techniques, and More.

This is a narrative review that summarizes the variations in approaches and port placements used for performing robotic lung resections on the da Vinci Surgical Platforms. Currently, the four-arm, look-up-view method, in which the intrathoracic cranial side is viewed from the caudal side, is considered the mainstream approach worldwide. Several variations were devised from this conventional technique, including the so-called horizontal open-thoracotomy-view techniques in which the intrathoracic craniocaudal axis is aligned with the horizontal direction of the console monitor, and fewer port and incision techniques. In September 2022, 166 reports were surveyed using a PubMed English literature search, and this review finally included 30 reports describing the approaches. We categorized the variations into four-phase groups considering advent histories: (I) early era, three-arm technique with utility incisions; (II) four-arm, total port technique without robotic staplers; (III) four-arm technique using robotic staplers; (IV) maximizing the functional features of the Xi, significant alterations in viewing directions, and reducing ports, including the ultimate uniport technique. To comprehensibly visualize these variations for practical use, we created elaborate illustrations based on the literature. The familiarity of thoracic surgeons with the variations and characteristics allows them to choose the optimal procedure that best suits each patient and their preferences.

Harnessing 3D-CT Simulation and Planning for Enhanced Precision Surgery: A Review of Applications and Advancements in Lung Cancer Treatment.

The clinical application of three-dimensional computed tomography (3D-CT) technology has rapidly expanded in the last decade and has been applied to lung cancer surgery. Two consecutive reports of large-scale prospective clinical trials from Japan and the United States have brought a paradigm shift in lung cancer surgery and may have led to a rapid increase in sublobar lung resections. Sublobar resection, especially segmentectomy, requires a more precise understanding of the anatomy than lobectomy, and preoperative 3D simulation and intraoperative navigation support it. The latest 3D simulation software packages are user-friendly. Therefore, in this narrative review, we focus on recent attempts to apply 3D imaging technologies, particularly in the sublobar resection of the lung, and review respective research and outcomes. Improvements in CT accuracy and the use of 3D technology have advanced lung segmental anatomy. Clinical applications have enabled the safe execution of complex sublobar resection through a minimally invasive approach, such as video-assisted thoracoscopic surgery and robotic surgery. However, currently, many facilities still render 3D images on two-dimensional monitors for usage. In the future, it will be challenging to further spread and advance intraoperative navigation through the application of 3D output technologies such as extended reality.

Anatomical resection for right B3 downwards-shifting malformation.

The right B3 downwards-shifting malformation is rare. This malformation often leads to the following complications: abnormal pulmonary arteries that accompany the downward-displaced B3, and complete fusion of the upper and middle lobes into one lobe, with no horizonal fissure. When performing pulmonary anatomical resection in the right upper or middle lobes in patients with this malformation, careful preoperative planning and surgical technique are required, with which the surgeon should be familiar. Herein, we present the anatomical features necessary for anatomical resection of the right B3 downwards-shifting malformation based on our technical experiences with anatomic segmentectomy and lobectomy techniques.

Clinical features of recurrent spontaneous pneumomediastinum.

Background: Spontaneous pneumomediastinum recurrence is rare, and its clinical presentation is unclear. We investigated the clinical features of and predisposing factors for spontaneous pneumomediastinum recurrence. Methods: We retrospectively investigated 30 consecutive patients treated for new-onset spontaneous pneumomediastinum at Shinshu Ueda Medical Center between 2012 and 2021. We evaluated the patient background characteristics, trigger activity, radiological findings, and clinical course of spontaneous pneumomediastinum, including those of recurrent cases. Predisposing factors for spontaneous pneumomediastinum recurrence were evaluated by comparing patients with and without recurrence. Results: Most patients were male (87%). The median age of the patients was 16 years (range, 12-26 years). Among the 30 patients, five experienced at least one recurrence of spontaneous pneumomediastinum. All recurrences occurred within 1 year after new-onset spontaneous pneumomediastinum. Clinical presentations associated with spontaneous pneumomediastinum recurrence, including vital signs, laboratory data, length of hospital stay, and radiological extent of spontaneous pneumomediastinum, were similar to or less aggressive than those associated with new-onset spontaneous pneumomediastinum. Patients with recurrence were more likely to have a medical history of preexisting lung diseases, such as asthma, than those without recurrence (60% vs. 8%; P=0.022). Only one of five patients with recurrence had trigger activity at spontaneous pneumomediastinum onset (20%); however, 60% of patients without recurrence had trigger activity (P=0.15). Conclusions: Spontaneous pneumomediastinum recurrence may have a similar or less aggressive clinical presentation than new-onset spontaneous pneumomediastinum. The presence of preexisting lung diseases may increase the risk of spontaneous pneumomediastinum recurrence.

Bronchial branching patterns and volumetry in the right upper lobe: impact on segmentectomy planning.

OBJECTIVES: The use of segmentectomy is expected to increase. However, understanding of the segmental bronchial branching is limited. Herein, we aimed to investigate bronchial branching pattern complexity and segmental volumetry of the right upper lung lobe to develop an accurate understanding of segmental anatomy and contribute to the advancement of safe and efficient lung segmentectomy. METHODS: We evaluated chest computed tomography scans of 303 patients and categorized the branching of segmental bronchi (segment 1, apical; segment 2, posterior; and segment 3, anterior) into 4 major types (typical trifurcated, bifurcated non-defective, bifurcated defective and atypical trifurcated) and 11 subtypes. Segmental volumetry was performed to determine the predominant segment in each case (volume difference <5% was considered equal). Branching complexity was evaluated separately for volumetry-predominant and volumetry-non-predominant segments. RESULTS: Trifurcated non-defective was the most frequent branching type (64.4%), followed by bifurcated non-defective (22.1%), bifurcated defective (8.6%) and trifurcated half-defective (4.0%). In terms of segmental volumetry, most cases had a one-segment-predominant distribution (71%) and only 5% of cases had equal distribution (segment 1 = segment 2 = segment 3). More than half of the cases had a segment 3-predominant distribution (52%). Branching complexity analysis revealed that the volumetry-non-predominant segment was associated with a higher risk of complex branching patterns compared with the volumetry-predominant segment (37% vs 19%, respectively; P < 0.005). CONCLUSIONS: Volumetric assessment of the right upper lobe showed a heterogeneous segmental volume distribution. Care should be taken during lung segmentectomy of the volumetry-non-predominant segments because of the high risk associated with complex bronchial branching patterns. CLINICAL TRIAL REGISTRATION: No. 4840.

Predicting 1-year non-cancer-related adverse events after lung resection.

OBJECTIVES: Assessing the risk for non-cancer-related outcomes following lung cancer surgery is crucial for high-risk patients. This study examined non-cancer-related adverse events within 1 year after lung resection, emphasizing the role of resected lung volume and postoperative atrial fibrillation (POAF). METHODS: We conducted a retrospective analysis of 460 patients who underwent anatomical lung resection for malignant lung tumours. We assessed perioperative factors, such as the number of resected subsegments and POAF, as potential predictors of 1-year non-cancer-related adverse events. Additionally, we validated a previously published nomogram for predicting POAF. RESULTS: One-year non-cancer-related adverse events occurred in 20% of patients. Multivariable analysis identified higher age, lower percentage-predicted forced expiratory volume in 1 second, greater number of resected subsegments and POAF as independent predictors of these adverse events. The incidence of POAF was 8.5%, with higher age, history of atrial fibrillation, and open thoracotomy as independent predictors. A temporal link between POAF and other severe postoperative complications was observed, as 71% of POAF cases preceded other complications. The nomogram's predicted risk for POAF was associated well with the actual incidence. CONCLUSIONS: Resected lung volume and POAF are statistically significant factors associated with non-cancer-related outcomes after lung resection. Minimizing resected lung volume when oncologically and technically feasible, along with identifying patients at risk for POAF, may contribute to improved postoperative outcomes. Our results have implications for risk stratification and preoperative decision-making in lung cancer surgery.

Successful resection after first-line lenvatinib therapy in an advanced thymic carcinoma.

Thymic carcinoma is a highly malignant tumor and treatment options are limited. Lenvatinib, a novel multitargeted kinase inhibitor, has recently been approved for the treatment of unresectable thymic carcinoma. There are no reports of complete surgical resection after the administration of first-line lenvatinib in advanced thymic carcinoma. A 50-year-old man visited our hospital because a computed tomography (CT) scan of the chest showed a large thymic squamous cell carcinoma. We suspected malignant pericardial effusion, invasion of the left upper lobe of the lung, and left mediastinal lymph node metastases. The patient was diagnosed with WHO classification stage IVb disease. Lenvatinib therapy was started at 24 mg/day as first-line therapy. Gradual dose reduction to 16 mg/day was required because of hypertension, diarrhea, and palmar-plantar erythrodysesthesia syndrome as side effects. Chest CT findings after 6 months of lenvatinib therapy showed reduction of the main tumor, disappearance of the mediastinal lymph node metastases, and pericardial effusion. Complete salvage resection was successfully performed a month after discontinuation of lenvatinib. The patient has been disease-free for 1 year without adjuvant therapy. Lenvatinib therapy is one of the promising therapeutic options for thymic carcinoma and may make salvage surgery increasingly useful for advanced thymic carcinoma.

Micropapillary and Solid Histologic Patterns in N1 and N2 Lymph Node Metastases Are Independent Factors of Poor Prognosis in Patients With Stages II to III Lung Adenocarcinoma.

INTRODUCTION: High-grade histologic patterns are associated with poor prognosis in patients with primary nonmucinous lung adenocarcinoma (ADC). We investigated whether the presence of micropapillary (MIP), solid (SOL), or both patterns in lymph node (LN) metastases has prognostic value. METHODS: Patients who underwent lobectomy for pathologic stages II to III lung ADC with N1 or N2 LN metastases (N = 360; 2000-2012) were analyzed. We assessed overall survival (OS), lung cancer-specific cumulative incidence of death (LC-CID), and cumulative incidence of recurrence (CIR) between patients with and without MIP/SOL patterns in LN metastases. Multivariable Cox regression analysis was used to quantify the association between MIP/SOL patterns and outcomes. RESULTS: MIP and SOL in LN metastases were associated with a higher incidence of smoking history (p = 0.004), tumor necrosis (p = 0.013), and spread of tumor through air spaces (p < 0.0001), a higher prevalence of MIP or SOL in the primary tumor (p < 0.0001), shorter OS (5-y OS, 40% [95% confidence interval or CI: 29%-56%] versus 63% [48%-83%] for no MIP/SOL in LNs, p = 0.03), higher LC-CID (5-y, 43% [29%-56%] versus 14% [4%-29%], p = 0.013), and higher CIR (5-y, 65% [50%-77%] versus 43% [25%-60%], p = 0.057). MIP and SOL in LN metastases were independently associated with poor outcomes: OS (hazard ratio [HR] = 1.81 [95% CI: 1.00-3.29], p = 0.05), LC-CID (HR = 3.10 [1.30-7.37], p = 0.01), and CIR (HR = 2.06 [1.09-3.90], p = 0.026). CONCLUSIONS: MIP/SOL histologic patterns in N1 or N2 LN metastases are associated with worse outcomes in patients with stages II to III lung ADC. MIP/SOL histologic patterns in LN metastases can stratify patients with high-risk stages II to III lung ADC.