Invasive Mucinous Adenocarcinoma Research Articles

Combined CT-Based Radiomics and Clinic-Radiological Characteristics for Preoperative Differentiation of Solitary-Type Invasive Mucinous and Non-Mucinous Lung Adenocarcinoma.

The clinical, pathological, gene expression, and prognosis of invasive mucinous adenocarcinoma (IMA) differ from those of invasive non-mucinous adenocarcinoma (INMA), but it is not easy to distinguish these two. This study aims to explore the value of combining CT-based radiomics features with clinic-radiological characteristics for preoperative diagnosis of solitary-type IMA and to establish an optimal diagnostic model. In this retrospective study, a total of 220 patients were enrolled and randomly assigned to a training cohort (n = 154; 73 IMA and 81 INMA) and a testing cohort (n = 66; 31 IMA and 35 INMA). Radiomics features and clinic-radiological characteristics were extracted from plain CT images. The radiomics models for predicting solitary-type IMA were developed by three classifiers: linear discriminant analysis (LDA), logistic regression-least absolute shrinkage and selection operator (LR-LASSO), and support vector machine (SVM). The combined model was constructed by integrating radiomics and clinic-radiological features with the best performing classifier. Receiver operating characteristic (ROC) curves were used to evaluate models' performance, and the area under the curve (AUC) were compared by the DeLong test. Decision curve analysis (DCA) was conducted to assess the clinical utility. Regarding CT characteristics, tumor lung interface, and pleural retraction were the independent risk factors of solitary-type IMA. The radiomics model using the SVM classifier outperformed the other two classifiers in the testing cohort, with an AUC of 0.776 (95% CI: 0.664-0.888). The combined model incorporating radiomics features and clinic-radiological factors was the optimal model, with AUCs of 0.843 (95% CI: 0.781-0.906) and 0.836 (95% CI: 0.732-0.940) in the training and testing cohorts, respectively. The combined model showed good ability in predicting solitary-type IMA and can provide a non-invasive and efficient approach to clinical decision-making.

Radiomics and Clinical Characters Based Gaussian Naive Bayes (GNB) Model for Preoperative Differentiation of Pulmonary Pure Invasive Mucinous Adenocarcinoma From Mixed Mucinous Adenocarcinoma.

Objective: To develop and validate predictive models based on clinical parameters, and radiomic features to distinguish pulmonary pure invasive mucinous adenocarcinoma (pIMA) from mixed mucinous adenocarcinoma (mIMA) before surgery. Method: From January 2017 to December 2022, 193 pIMA and 111 mIMA were retrospectively analyzed at our hospital in this retrospective study. From contrast-enhanced computed tomography, 1037 radiomic features were extracted. The patients were randomly divided into a training group and a test group (n = 213 and 91, respectively) in a 7:3 ratio. The least absolute shrinkage and selection operator algorithm was used to select radiomic features. In this study, 9 machine learning radiomics prediction models were applied. The radiomics score was then calculated based on the best-performing machine learning model adopted. The clinical model was developed using the same machine learning model of radiomics. In the end, a combined model based on clinical factors and radiomics features was developed. The area under the receiver operating characteristic curve (AUC) value and decision curve analysis (DCA) were used to evaluate the clinical usefulness of the prediction model. Results: The combined model established by the Gaussian Naive Bayes machine learning method exhibited the best performance. The AUC of the combined model, clinical model, and radiomics model were 0.81, 0.80, and 0.68 in the training group and 0.91, 0.80, and 0.81 in the test group, respectively. The Brier scores of the combined model were 0.171 and 0.112. The DCA curve also showed that the combined model was beneficial to clinical settings. Conclusion: The combined model integration of radiomics features and clinical parameters may have potential value for the preoperative differentiation of pIMA from mIMA.

Systemic immune-inflammation index predicts survival in patients with resected lung invasive mucinous adenocarcinoma

BackgroundThe prognostic-related factors of lung invasive mucinous adenocarcinoma(IMA) are unclear because of its rarity. Various inflammation-based biomarkers were reported to predict the survival of malignant diseases. This study aims to explore the prognostic significance of the systemic immune-inflammation index(SII), which is calculated using absolute platelet, neutrophil, and lymphocyte counts, among patients with invasive mucinous adenocarcinoma. MethodsFrom January 2015 to December 2019, 106 patients were identified as having IMA accepted radical resection and enrolled in the retrospective study. We analyzed the overall survival and disease-free survival using the Kaplan-Meier method and log-rank test. Receiver operating characteristic curve was used to find the optimal SII cut-off values for survival. A Cox regression model was carried out for multivariable analyses. ResultsThe study cohort included 53 men and 53 women, with a mean age of 60 years (range 29 to 78 years, median 61 years). The median SII measured before surgery was 378.47 (range: 79.87–1701.97). ROC analyses revealed that the optimal cut-off values of SII was 379.43 for predicting both OS and DFS. An elevated SII (≥379.43) was observed in 52 patients (49.1 %), and was associated with younger age (P = 0.02), advanced T staging (P = 0.042), lymph node metastasis (P = 0.018) and pneumonic-type IMA (P = 0.018). Multivariable analysis showed that SII and pneumonic-type IMA were independent prognostic predictors of OS and DFS in radically resected IMA patients (P < 0.05). ConclusionHigh SII is correlated with worse outcome and can be a novel prognostic biomarker for IMA patients accepted radical surgery.

Retracted: Diagnostic Efficacy of CT Radiomic Features in Pulmonary Invasive Mucinous Adenocarcinoma.

[This retracts the article DOI: 10.1155/2022/5314225.].

ASO Visual Abstract: Distinct Recurrence Pattern and Survival Outcomes of Invasive Mucinous Adenocarcinoma of the Lung: The Potential Role of Local Therapy in Intrapulmonary Spread.

ASO Visual Abstract: Distinct Recurrence Pattern and Survival Outcomes of Invasive Mucinous Adenocarcinoma of the Lung: The Potential Role of Local Therapy in Intrapulmonary Spread.

Micropapillary Pattern in Invasive Mucinous Adenocarcinoma of the Lung: Comparison With Invasive Non-Mucinous Adenocarcinoma.

Background. The presence of a micropapillary pattern is associated with poor outcomes in lung adenocarcinoma. This study aimed to assess the clinicopathological features of micropapillary pattern in mucinous adenocarcinoma of the lung. Methods. The patients were stratified into three groups: the invasive mucinous adenocarcinoma group (60 patients), the mixed invasive mucinous adenocarcinoma group (33 patients), and the invasive non-mucinous adenocarcinoma group (237 patients). The presence of micropapillary pattern and its clinicopathological features were analyzed and compared between the three groups. Results. Compared to mixed invasive mucinous adenocarcinoma, invasive mucinous adenocarcinoma had lower frequencies of micropapillary pattern (28.3% vs 87.9%, respectively; P < .001) and lymph node metastasis (00.0% vs 15.1%, respectively; P = .005). The frequency of tumor spread through air space (STAS) in invasive mucinous adenocarcinoma (23.3%) was higher than that in invasive non-mucinous adenocarcinoma (6.3%; P < .001), while lower than that in mixed invasive mucinous adenocarcinoma (60.6%; P < .001). When the three groups were all accompanied by micropapillary pattern, there was no obvious difference in STAS between invasive mucinous adenocarcinoma with micropapillary pattern and mixed mucinous adenocarcinoma with micropapillary pattern (P > .05). No filigree pattern occurred in invasive mucinous adenocarcinoma with micropapillary pattern. Conclusions. The micropapillary pattern is frequently observed in invasive mucinous adenocarcinoma and has a better prognosis compared to mixed invasive mucinous adenocarcinoma and invasive non-mucinous adenocarcinoma. However, the malignancy of the micropapillary pattern in mixed mucinous adenocarcinoma was similar to that in invasive non-mucinous adenocarcinoma, even with the presence of mucus. These findings suggest that the development mechanisms of the micropapillary pattern in invasive mucinous adenocarcinoma and mixed mucinous adenocarcinoma may differ.

EP07.01-01 Nomogram for Predicting Prognosis and Adjuvant Chemotherapy Benefits in Early-stage Invasive Mucinous Lung Adenocarcinoma

EP07.01-01 Nomogram for Predicting Prognosis and Adjuvant Chemotherapy Benefits in Early-stage Invasive Mucinous Lung Adenocarcinoma

EP05.01-06 Stepwise Progression of Invasive Mucinous Adenocarcinoma Based on the Radiological and Biological Characteristics

EP05.01-06 Stepwise Progression of Invasive Mucinous Adenocarcinoma Based on the Radiological and Biological Characteristics

EP06.03-03 Oncogenic Drivers of Pulmonary Invasive Mucinous Adenocarcinoma, Detected by Trusight Oncology 500

EP06.03-03 Oncogenic Drivers of Pulmonary Invasive Mucinous Adenocarcinoma, Detected by Trusight Oncology 500

Pulmonary invasive mucinous adenocarcinoma.

Invasive mucinous adenocarcinoma (IMA) is a relatively rare subtype of lung adenocarcinoma, composed of goblet and/or columnar tumour cells containing abundant intracytoplasmic mucin vacuoles. While a majority of IMAs are driven by KRAS mutations, recent studies have identified distinct genomic alterations, such as NRG1 and ERBB2 fusions. IMAs also more frequently present as a pneumonic-like pattern with multifocal and multilobar involvement, and comparative genomic profiling predominantly shows a clonal relationship, suggesting intrapulmonary metastases rather than synchronous primary tumours. Accordingly, these unique features require different therapeutic approaches when compared to nonmucinous adenocarcinomas in general. In this article, we review recent updates on the histopathological, clinical, and molecular features of IMAs, and also highlight some unresolved issues for future studies.

Distinct Recurrence Pattern and Survival Outcomes of Invasive Mucinous Adenocarcinoma of the Lung: The Potential Role of Local Therapy in Intrapulmonary Spread.

Invasive mucinous adenocarcinoma (IMA) is distinct from non-mucinous adenocarcinoma, but studies on recurrent IMA are scarce. Thus, this study aimed to evaluate the recurrence patterns of IMA and the role of pulmonary local therapy (LT) in resectable pulmonary recurrence of IMA. The study reviewed 403 patients with surgically resected IMA between 1998 and 2018. The recurrence patterns were categorized as solitary pulmonary recurrence (SPR), multiple pulmonary recurrence (MPR), and extra-pulmonary recurrence (EPR). The clinicopathologic characteristics, overall survival (OS), and post-recurrence survival (PRS) were analyzed according to the recurrence pattern and LT administration. Recurrences were found in 91 (22.6%) patients, including 18 patients with SPR, 37 patients with MPR, and 36 patients with EPR. Compared with the MPR and EPR groups, the SPR group had a longer disease-free interval (32.5 vs. 9.6 vs. 10.1 months, respectively; p < 0.01) and a better OS (5-year OS: 88.5%, 41.5%, and 22.9%, respectively; p < 0.01). In case of resectable pulmonary recurrence, pulmonary LT was administered to 15 patients with SPR and 3 patients with MPR. These patients showed a better 5-year PRS than the other patients with pulmonary recurrence (86.3% vs. 30.4%; p < 0.01). Notably, long-term survival was observed for one patient with MPR undergoing LT and two patients with SPR undergoing a second LT for a second pulmonary recurrence. In this series, the patients with recurrent IMA showed different prognoses according to the recurrence pattern. The patients with pulmonary recurrence of IMA undergoing LT showed a favorable prognosis, suggesting the potential role of LT for resectable pulmonary recurrence of IMA.

International Association for the Study of Lung Cancer Study of Reproducibility in Assessment of Pathologic Response in Resected Lung Cancers After Neoadjuvant Therapy

IntroductionPathologic response has been proposed as an early clinical trial end point of survival after neoadjuvant treatment in clinical trials of NSCLC. The International Association for the Study of Lung Cancer (IASLC) published recommendations for pathologic evaluation of resected lung cancers after neoadjuvant therapy. The aim of this study was to assess pathologic response interobserver reproducibility using IASLC criteria. MethodsAn international panel of 11 pulmonary pathologists reviewed hematoxylin and eosin–stained slides from the lung tumors of resected NSCLC from 84 patients who received neoadjuvant immune checkpoint inhibitors in six clinical trials. Pathologic response was assessed for percent viable tumor, necrosis, and stroma. For each slide, tumor bed area was measured microscopically, and pre-embedded formulas calculated unweighted and weighted major pathologic response (MPR) averages to reflect variable tumor bed proportion. ResultsUnanimous agreement among pathologists for MPR was observed in 68 patients (81%), and inter-rater agreement (IRA) was 0.84 (95% confidence interval [CI]: 0.76–0.92) and 0.86 (95% CI: 0.79–0.93) for unweighted and weighted averages, respectively. Overall, unweighted and weighted methods did not reveal significant differences in the classification of MPR. The highest concordance by both methods was observed for cases with more than 95% viable tumor (IRA = 0.98, 95% CI: 0.96–1) and 0% viable tumor (IRA = 0.94, 95% CI: 0.89–0.98). The most common reasons for discrepancies included interpretations of tumor bed, presence of prominent stromal inflammation, distinction between reactive and neoplastic pneumocytes, and assessment of invasive mucinous adenocarcinoma. ConclusionsOur study revealed excellent reliability in cases with no residual viable tumor and good reliability for MPR with the IASLC recommended less than or equal to 10% cutoff for viable tumor after neoadjuvant therapy.

Stepwise progression of invasive mucinous adenocarcinoma based on radiological and biological characteristics

IntroductionInvasive mucinous lung adenocarcinoma (IMA) has unique radiological findings and pathological characteristics. IMA is classified into solitary and pneumonic types; however, it is unclear whether these are biologically identical. MethodsA single-center retrospective analysis was performed for 70 IMA patients (solitary type [n = 38] and pneumonic type [n = 32]) who underwent pulmonary resection between January 2010 and December 2018. We compared clinical and biological characteristics between the two types. ResultsThe frequencies of genetic alternations such as EGFR, KRAS, BRAF, GNAS, ERBB2, TP53, NRG1, and MET were not different. Immunohistochemically, expression of MUC1 was significantly more common in the pneumonic type (5.0% versus 20.0%, p = 0.01) and diffuse MUC6 positive in the solitary type (39.0% versus 13.0%, p = 0.02). We further classified solitary types into those with or without ground-glass opacity (GGO) and pneumonic types into those with or without crazy-paving appearance (CPA), and evaluated their surgical outcomes. Five-year overall survival and relapse free survival rates were 95.8%/86.6%, 64.3%/70.7%, 74.6%/68.9%, and 50.0%/28.6% in patients with solitary type with GGO, solitary type without GGO, pneumonic type without CPA, and pneumonic type with CPA, respectively. ConclusionsThere were no differences in genetic alternations; however, mucin expression pattern was different. Surgical outcomes were different according to the presence of GGO in the solitary type and the presence of CPA in the pneumonic type. These findings suggested a stepwise progression from solitary to pneumonic IMA.

Claudin18.2 expression in pulmonary mucinous adenocarcinoma.

Pulmonary invasive mucinous adenocarcinoma (IMA) is a unique type of lung adenocarcinoma with a high recurrence rate and limited treatment strategies. The tight-junction-associated protein claudin18.2 is a new therapeutic target for several solid tumors. This study aimed to detect the expression of claudin18.2 in IMA and its clinicopathological association with the disease. The expression of claudin18.2 was immunohistochemically evaluated in an IMA cohort of 84 patients, who underwent partial pneumonectomy between January 2017 and December 2021. Positive staining for claudin18.2 was defined as ≥ 10% of tumor cells showing ≥ 1 + membrane staining or any ≥ 2 + membrane staining. Claudin18.2 was detected in 76.2% (64/84) of IMA patients, significantly higher than that in non-mucinous adenocarcinoma (NMA). 46.4% (39/84) of the IMA patients met the enrollment criteria of the clinical trials of monoclonal antibodies (≥ 75% of tumor cells demonstrating ≥ 2 + staining intensity). Positive staining for claudin18.2 was significantly associated with smaller tumor size (p = 0.010), less pleural invasion (p = 0.019), and earlier pN stage (p < 0.001). Expression of claudin18.2 was not related to prognosis in multivariate analysis. To summarize, in this study we found that claudin18.2 was remarkably highly expressed in IMA and the overexpression was associated with low invasive capacity. Thus, this protein appears to be a promising therapeutic target and deserves further investigation in IMA patients.

Confluent cavitated nodules in invasive mucinous adenocarcinoma: A case report

Invasive mucinous adenocarcinoma is a rare variant of lung adenocarcinoma. Here, we present the case of a patient with invasive mucinous adenocarcinoma with cavitary lung lesions. A 61-year-old painter-and-bricklayer. She was admitted due to mMRC2 dyspnea, a dry cough that during hospitalization mobilizes dense, abundant secretions, and becomes demanding. Differential diagnoses were made based on clinical symptoms and images, performing multiple laboratory tests ruling out immunosuppression, and two video-bronchofibroscopies finding the diagnosis in the transbronchial lung biopsy: Invasive mucinous adenocarcinoma that would explain the abundant bronchorrhea, advanced stage and poor prognosis led to ventilatory failure and death of the patient.

Demographics of the tumor formerly known as bronchiolo-alveolar carcinoma.

e20604 Background: Bronchiolo-alveolar carcinoma (BAC) is a rare subtype of non-small cell lung cancer of the lung periphery, often characterized by lepidic growth. Although BAC has undergone various reclassifications in recent years, International Classification of Disease codes still classifies these subtypes using the same codes that previously belonged to BAC. Changing diagnostic criteria and other factors cause BAC to be among the most overdiagnosed forms of lung cancer and thus a demographic study could provide insight into trends. Methods: A retrospective cohort analysis utilizing the National Cancer Database (NCDB) from 2004 – 2020 included patients with malignant forms of BAC (Invasive mucinous adenocarcinoma, mixed invasive mucinous, and nonmucinous adenocarcinoma) confirmed through histology. Demographic factors such as sex, age, race, Hispanic status, median household income, insurance status, facility type, county population, distance from facility, and Charlson Deyo score were analyzed by descriptive statistics and incidence trends. Results: In total, 12,607 patients were identified in the database with a confirmed diagnosis of BAC between 2004 – 2020. The number of cases per year remained steady (mean = 565.4) until 2018. From 2018 to 2020, the average number of diagnoses per year was 1575.0. The average age of diagnosis was 69.3 years (SD = 10.7, range = 10 to &gt; 90 years). 58.1% of the cases were female patients. The top primary sites were the lower and upper lobes (46.2% and 39.9% respectively). The majority (59.2%) had Charlson-Deyo comorbidity scores of 0. Most cases occurred in Non-Hispanic White persons (86.8%). More patients were in the top quartile of income earners (34.0%) compared to those in lower quartiles. Medicare was the insurance provider for most patients (65.0%). More patients were diagnosed in counties with a population over 1 million (52.4%). More patients were treated in comprehensive community cancer programs (38.1%) followed closely by academic cancer programs (35.2%). Patients lived an average of 31.6 miles (SD = 113.0, range = 0.1 – 2390.7) from the treatment facility. Conclusions: This is the first NCDB analysis on the demographics of BAC. The sudden rise in cases per year in 2018 aligns with the changing pathologic and histologic definitions for BAC. A 2006 review of BAC found that 50-70% of cases occur in female patients, similar to our results. The majority of BAC patients tend to be non-Hispanic and White with a primary site diagnosis in the lower lobe, followed by the upper lobe. BAC patients are more likely to be in the top income quartile, live in densely-populated metropolitan areas, and receive treatment in a non-academic program. Further research is needed to better understand the impact of demographic, socioeconomic, and environmental factors on the diagnosis and prognosis of BAC, especially because its diagnostic criteria have changed recently.

Prognostic value of KRAS G12C mutation in lung adenocarcinoma stratified by stages and radiological features

ObjectivesThe role of KRAS G12C is of particular interest given the promising clinical activity of KRAS G12C-specific inhibitors. This study comprehensively investigated the clinicopathological characteristics and prognostic value of KRAS G12C mutation in patients with surgically resected lung adenocarcinoma. MethodsData were collected on 3828 patients with completely resected primary lung adenocarcinomas who underwent KRAS mutation analysis between 2008 and 2020. The association between KRAS G12C and clinicopathologic characteristics, molecular profiles, recurrence patterns, and postoperative outcome were explored. ResultsTwo hundred seventy-five patients (7.2%) were confirmed to harbor a KRAS mutation, of whom 83 (30.2%) had the G12C subtype. KRAS G12C was more frequent in men, former/current smokers, radiologic solid nodules, invasive mucinous adenocarcinoma, and solid predominant tumors. KRAS G12C tumors had more lymphovascular invasion and higher programmed death-ligand 1 expression than KRAS wild-type tumors. TP53 (36.8%), STK11 (26.3%), and RET (18.4%) mutations were the 3 most frequent in the KRAS G12C group. Logistic regression analysis showed patients with KRAS G12C mutation were prone to experience early recurrence and locoregional recurrence. KRAS G12C mutation was found to be significantly associated with poor survival after propensity score matching. Stratified analysis showed that the KRAS G12C was an independent prognostic factor in stage I tumors and part-solid lesions, respectively. ConclusionsThe KRAS G12C mutation had a significant prognostic value in stage I lung adenocarcinomas as well as in part-solid tumors. Furthermore, it exhibited a potentially aggressive phenotype associated with early and locoregional recurrence. These findings might be relevant as better KRAS treatments are developed for clinical application.

FOXA2 Cooperates with Mutant KRAS to Drive Invasive Mucinous Adenocarcinoma of the Lung.

FOXA2 expression combined with mutant KRAS drives invasive mucinous adenocarcinoma of the lung by synergistically promoting a mucous transcriptional program, suggesting strategies for targeting this lung cancer type that lacks effective therapies.

Portrayal of video-assisted mediastinoscopic lymphadenectomy’s range subsequent to its simultaneous use with uniportal VAT-lobectomy for left-sided NSCLC: a case-based perspective

BackgroundVideo-assisted mediastinoscopic lymphadenectomy (VAMLA) is the most precise approach combining staging and therapeutic interventions in non-small cell lung cancer (NSCLC). In the case of left-sided NSCLC, the likelihood of mediastinal lymph node metastases depends on the involvement of the left lung regional lymphatic network. As such, it appears obvious – at least for selected patients with mediastinal staging by either PET-CT or EBUS-TBNA ± EUS-FNA and with cN ≤ 2 – to merge VAMLA and left-sided video-assisted thoracoscopic (VAT) lobectomy for a single-stage therapeutical procedure.Case presentationWe present the clinical course of an 83-year-old patient following simultaneous VAMLA and VAT-lobectomy for invasive mucinous adenocarcinoma of the left upper lobe with a provisional cT3cN0cM0 stage. The patient developed a clinically relevant postoperative pneumothorax due to a persistent parenchymal air leak. CT scan revealed a substantial pneumomediastinum and showed the capability of VAMLAs range for mediastinal lymph node dissection in a unique way. Following the prompt insertion of a second chest tube, the situation was stabilized with an unremarkable further in-hospital stay. The patient remains free of tumor recurrence or distant metastases at a one-year follow-up.ConclusionPresenting this aperçu, we encourage reviving the debate on (1) precise mediastinal staging in general and (2) VAMLA’s important role as a diagnostic and therapeutic tool.

Mucous Gland Adenoma of the Lung: A Neoplastic Counterpart of Mucinous Bronchial Glands

Mucous gland adenoma (MGA) is a rare benign tumor that usually arises in the proximal airway and consists of mucus-secreting cells resembling bronchial glands. Here, we report 2 cases of MGAs and describe their morphologic, immunohistochemical, and molecular profiles in comparison with 19 pulmonary tumors of 5 other histologic types with mucinous cells (invasive mucinous adenocarcinoma, mucoepidermoid carcinoma, mixed squamous cell and glandular papilloma, bronchiolar adenoma/ciliated muconodular papillary tumor, and sialadenoma papilliferum). Two MGAs were found in 1 male patient and 1 female patient, located in the bronchus and trachea, respectively. One MGA was examined by RNA sequencing, and no putative driver mutations (including BRAF, KRAS, and AKT1 mutations) or gene fusions were identified. In another case of MGA, V600E mutations of BRAF and E17K mutations of AKT1 were not detected by allele-specific real-time PCR or digital PCR, respectively. However, a gene expression analysis revealed that the MGA presented a specific RNA expression profile with multiple genes enriched in the salivary gland. The gene expression of NKX3.1 was significantly higher in the MGA case in comparison to normal control lungs (P < .001). We then examined NKX3.1 immunohistochemistry for 2 MGAs and 19 tumors of 5 other histologic types. NKX3.1 was positive in MGA (2/2, 100%), whereas all constituent cells, including mucinous cells, were negative for NKX3.1 in other histologic types (0%, 0/19). In normal lung tissue, NKX3.1 was positive for mucinous acinar cells of the bronchial glands. In conclusion, the gene expression profile, taken together with the histologic similarity between MGA and bronchial glands, and the preferred location of the tumors (proximal airways with submucosal glands) suggest that MGA is a neoplastic counterpart of mucinous bronchial glands. NKX3.1 immunohistochemistry can be a sensitive and specific ancillary marker that distinguishes MGA from other histologic mimics.