Progress in the diagnosis and treatment of pulmonary invasive mucinous adenocarcinoma_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

GAO Shengguai ¹ , LI Bangsheng ² , MAO Jie ¹ , XUE Tiantian ¹ , WANG Xi ¹ ,  HUANG Yunchao ¹

1. Department of Thoracic SurgeryⅠ, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, P. R. China;
2. Department of Thoracic Tumor Center, Northeast Yunnan Central Hospital, Zhaotong, 657000, Yunnan, P. R. China;

Corresponding?author：

HUANG Yunchao, Email: huangych2001@aliyun.com

Keywords：

Lung adenocarcinoma; mucinous adenocarcinoma; pathogenesis; imaging features; pathological features; targeted therapy; immunotherapy; review

DOI：

10.7507/1007-4848.202601005

Video：

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Abstract Full text Figures/Tables Video References Cited by

Invasive mucinous adenocarcinoma (IMA) is a subtype of lung adenocarcinoma characterized by the presence of goblet or columnar tumor cells containing abundant mucin in the cytoplasm. IMA is relatively rare, accounting for 2% to 10% of all primary lung adenocarcinomas. Due to the lack of specificity in its clinical presentation and imaging features, IMA is highly prone to misdiagnosis or missed diagnosis in clinical practice. Previous studies have demonstrated that the prognosis of IMA is heterogeneous and closely related to tumor stage and radiological subtype. Patients with early-stage nodular-type IMA generally show a more favorable prognosis, whereas those with advanced pneumonic-type IMA tend to have poorer outcomes. Furthermore, due to the significant mucin secretion properties, IMA differs markedly from invasive non-mucinous lung adenocarcinoma in terms of pathological morphology, molecular characteristics, and prognosis. Although both subtypes are primarily treated with surgery, the application of emerging targeted and immunotherapies in IMA is still in the exploratory stage. This review aims to systematically summarize the etiology and pathogenesis, imaging features, pathological characteristics, treatment advances and prognosis of IMA, with the goal of providing valuable references for clinical decision-making.

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1. Siegel RL, Kratzer TB, Giaquinto AN, et al. Cancer statistics, 2025. CA Cancer J Clin, 2025, 75(1): 10-45.
2. Kish JK, Ro JY, Ayala AG, et al. Primary mucinous adenocarcinoma of the lung with signet-ring cells: a histochemical comparison with signet-ring cell carcinomas of other sites. Hum Pathol, 1989, 20(11): 1097-1102.
3. Travis WD, Brambilla E, Noguchi M, et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol, 2011, 6(2): 244-285.
4. Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol, 2015, 10(9): 1243-1260.
5. Li X, Chen Y, Lan R, et al. Transmembrane mucins in lung adenocarcinoma: understanding of current molecular mechanisms and clinical applications. Cell Death Discov, 2025, 11(1): 163.
6. Masago K, Kuroda H, Seto K, et al. Genomic landscape of resected invasive mucinous adenocarcinoma of the lung. Clin Lung Cancer, 2025, 26(7): 583-594. e4.
7. Di Federico A, Hong L, Elkrief A, et al. Lung adenocarcinomas with mucinous histology: clinical, genomic, and immune microenvironment characterization and outcomes to immunotherapy-based treatments and KRASG12C inhibitors. Ann Oncol, 2025, 36(3): 297-308.
8. Zhao T, Yi J, Luo D, et al. Prognostic factors for invasive mucinous adenocarcinoma of the lung: systematic review and meta-analysis. World J Surg Oncol, 2024, 22(1): 41.
9. Upadhyay M, Shanker P, Joshi S, et al. The great mimicker: pulmonary adenocarcinoma with interstitial lung disease-like presentation. Eur J Case Rep Intern Med, 2025, 12(10): 005790.
10. Kabashi-Mu?aj S, Dedushi-Hoti K, Shatri J, et al. Pulmonary mucinous adenocarcinoma in the presence of reactivated tuberculosis: a case report. Radiol Case Rep, 2021, 16(12): 3647-3651.
11. Cheng X, Nie L, Meng C, et al. Trends of congenital pulmonary airway malformation (CPAMs) in Haidian district, Beijing, 2013-2023. Am J Respir Crit Care Med, 2025, 211: A4411.
12. Stocker JT, Madewell JE, Drake RM. Congenital cystic adenomatoid malformation of the lung. Classification and morphologic spectrum. Hum Pathol, 1977, 8(2): 155-171.
13. Windrich J, Braubach P, L?nger F, et al. RAS-MAPK pathway mutations in congenital pulmonary airway malformations. Am J Respir Crit Care Med, 2024, 209(10): 1266-1268.
14. Stuart WD, Ito M, Baldauf IF, et al. Patho-transcriptomic analysis of invasive mucinous adenocarcinoma of the lung (IMA): comparison with lung adenocarcinoma with signet ring cell features (SRCC). bioRxiv [Preprint], 2024. PMID: 38948839.
15. Zhou P, Zhaxi C, Jiang L. A unique case of pulmonary minimally invasive mucinous adenocarcinoma arising from atypical goblet cell hyperplasia in the bronchial epithelium of a 9-year-old girl. BMC Pediatr, 2025, 25(1): 333.
16. Shin DH, Kim SH, Choi M, et al. Oncogenic KRAS promotes growth of lung cancer cells expressing SLC3A2-NRG1 fusion via ADAM17-mediated shedding of NRG1. Oncogene, 2022, 41(2): 280-292.
17. Deng Y, Wang M, Tian T, et al. The effect of hexavalent chromium on the incidence and mortality of human cancers: a meta-analysis based on published epidemiological cohort studies. Front Oncol, 2019, 9: 24.
18. Poinen-Rughooputh S, Rughooputh MS, Guo Y, et al. Occupational exposure to silica dust and risk of lung cancer: an updated meta-analysis of epidemiological studies. BMC Public Health, 2016, 16(1): 1137.
19. Ang L, Chan CPY, Yau WP, et al. Association between family history of lung cancer and lung cancer risk: a systematic review and meta-analysis. Lung Cancer, 2020, 148: 129-137.
20. Bauer AK, Umer M, Richardson VL, et al. Requirement for MUC5AC in KRAS-dependent lung carcinogenesis. JCI Insight, 2018, 3(15): e120941.
21. Li BT, Michelini F, Misale S, et al. HER2-mediated internalization of cytotoxic agents in ERBB2 amplified or mutant lung cancers. Cancer Discov, 2020, 10(5): 674-687.
22. Chu Q, Yao C, Qi X, et al. STK11 is required for the normal program of ciliated cell differentiation in airways. Cell Discov, 2019, 5: 36.
23. Kim M, Hwang J, Kim KA, et al. Genomic characteristics of invasive mucinous adenocarcinoma of the lung with multiple pulmonary sites of involvement. Mod Pathol, 2022, 35(2): 202-209.
24. Tomoshige K, Stuart WD, Fink-Baldauf IM, et al. FOXA2 cooperates with mutant KRAS to drive invasive mucinous adenocarcinoma of the lung. Cancer Res, 2023, 83(9): 1443-1458.
25. Odarenko KV, Zenkova MA, Markov AV. The nexus of inflammation-induced epithelial-mesenchymal transition and lung cancer progression: a roadmap to pentacyclic triterpenoid-based therapies. Int J Mol Sci, 2023, 24(24): 17325.
26. Zhou Y, Qian M, Li J, et al. The role of tumor-associated macrophages in lung cancer: from mechanism to small molecule therapy. Biomed Pharmacother, 2024, 170: 116014.
27. Araya R, Lam K, Huang A, et al. Neutrophil dynamics in the tumor microenvironment determines therapy efficacy and is regulated by microbiota. J Immunol, 2022, 208(1_Supple): 120.03.
28. Zheng J, Deng Y, Huang B, et al. Prognostic implications of STK11 with different mutation status and its relationship with tumor-infiltrating immune cells in non-small cell lung cancer. Front Immunol, 2024, 15: 1387896.
29. Sun X, Zeng B, Tan X, et al. Invasive mucinous adenocarcinoma of the lung: clinicopathological features, 18F-FDG PET/CT findings, and survival outcomes. Ann Nucl Med, 2023, 37(3): 198-207.
30. Zhang J, Hao L, Qi M, et al. Radiomics nomogram for preoperative differentiation of pulmonary mucinous adenocarcinoma from tuberculoma in solitary pulmonary solid nodules. BMC Cancer, 2023, 23(1): 261.
31. Xiao Z, Chen J, Feng X, et al. Use of CT-derived radiomic features to preoperatively identify invasive mucinous adenocarcinoma in solitary pulmonary nodules ≤3 cm. Heliyon, 2024, 10(9): e30209.
32. 張俊杰, 郝李剛, 許茜, 等. 基于臨床及CT特征構建預測肺浸潤性黏液腺癌的機器學習模型. 中華全科醫學, 2023, 21(1): 6-9.Zhang JJ, Hao LG, Xu Q, et al. Machine learning model for predicting pulmonary invasive mucinous adenocarcinoma based on clinical and CT features. Chin J Gen Pract, 2023, 21(1): 6-9.
33. Hong R, Ping X, Liu Y, et al. Combined CT-based radiomics and clinic-radiological characteristics for preoperative differentiation of solitary-type invasive mucinous and non-mucinous lung adenocarcinoma. Int J Gen Med, 2024, 17: 4267-4279.
34. Zhong F, Wu L, Liu Z, et al. Nomogram model for the diagnosis of solitary nodular pulmonary mucinous adenocarcinoma. Sci Rep, 2024, 14(1): 18085.
35. Xue H, Ma Y, Wang Q, et al. Application of imaging techniques to distinguish between lung mucinous and non-mucinous adenocarcinoma. Asian J Surg, 2024, 47(1): 600-601.
36. Yu X, Zhang S, Xu J, et al. Nomogram using CT radiomics features for differentiation of pneumonia-type invasive mucinous adenocarcinoma and pneumonia: multicenter development and external validation study. AJR Am J Roentgenol, 2023, 220(2): 224-234.
37. Zhao W, Xiong Z, Jiang Y, et al. Radiomics based on enhanced CT for differentiating between pulmonary tuberculosis and pulmonary adenocarcinoma presenting as solid nodules or masses. J Cancer Res Clin Oncol, 2023, 149(7): 3395-3408.
38. 陳馳華, 周婷, 廖凱兵. CT影像特征及影像組學在肺部淋巴瘤與肺浸潤性黏液腺癌診斷中的應用. 中國CT和MRI雜志, 2023, 21(9): 82-85.Chen CH, Zhou T, Liao KB. Application of CT imaging features and radiomics in the diagnosis of pulmonary lymphoma and pulmonary invasive mucinous adenocarcinoma. Chin J CT MRI, 2023, 21(9): 82-85.
39. Tian S, Li X, Liu J, et al. Radial endobronchial ultrasound - guided bronchoscopy for the diagnosis of peripheral pulmonary lesions: a systematic review and meta-analysis of prospective trials. Heliyon, 2024, 10(8): e29446.
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