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Although mucinous metaplasia has been suspected as a precursor lesion, direct molecular evidence supporting this progression is limited. In this study, we applied morphology\u2010guided spatial transcriptomics to investigate epithelial lineage relationships across the mucinous spectrum of lung lesions. Formalin\u2010fixed, paraffin\u2010embedded lung tissues from 26 patients were analyzed using the GeoMx digital spatial profiling platform. A total of 118 cytokeratin\u2010positive regions of interest representing normal bronchioles, bronchiolar metaplasia, mucinous metaplasia, mucinous dysplasia, IMA, nonmucinous terminal respiratory unit\u2013type adenocarcinoma, squamous metaplasia\/dysplasia, and squamous cell carcinoma were profiled. Spatial transcriptomic data were integrated with two independent public cohorts and mapped to the Human Lung Cell Atlas for epithelial cell\u2010type assignment. Unsupervised clustering identified a distinct mucinous cluster comprising IMA and most mucinous dysplasia regions, characterized by enrichment of gastric\u2010type differentiation markers, including\n                    <jats:italic>MUC5AC<\/jats:italic>\n                    ,\n                    <jats:italic>MUC6<\/jats:italic>\n                    ,\n                    <jats:italic>TFF1<\/jats:italic>\n                    ,\n                    <jats:italic>TFF2<\/jats:italic>\n                    , and\n                    <jats:italic>CLDN18<\/jats:italic>\n                    . Label\u2010transfer analysis demonstrated that mucinous metaplasia and dysplasia were predominantly associated with club and goblet cell identities, whereas IMAs showed enrichment of club and goblet signatures. In contrast, nonmucinous adenocarcinomas consistently aligned with alveolar type 2 cell identity across all datasets. Immunohistochemistry confirmed uniform CLDN18 expression in IMAs and its absence in nonmucinous adenocarcinomas. These findings provide spatial transcriptomic evidence supporting a club cell\u2013associated mucinous pathway in lung tumorigenesis and identify CLDN18 as a defining molecular feature of IMA. \u00a9 2026 The Author(s).\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.70120","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T03:53:03Z","timestamp":1788925983000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatial transcriptomics reveals club cell features and strong\n                    <scp>CLDN18<\/scp>\n                    expression along the mucinous pathway to invasive mucinous adenocarcinoma"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4193-2520","authenticated-orcid":false,"given":"Joon Young","family":"Park","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Medicine Pusan National University  Yangsan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8562-5884","authenticated-orcid":false,"given":"Do Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology Dental and Life Science Institute, School of Dentistry, Pusan National University  Yangsan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2995-6060","authenticated-orcid":false,"given":"Hyun Jung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine Pusan National University  Yangsan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3003-2217","authenticated-orcid":false,"given":"Jung Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine Pusan National University  Yangsan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1908-0824","authenticated-orcid":false,"given":"Hae Ryoun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology Dental and Life Science Institute, School of Dentistry, Pusan National University  Yangsan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4980-9295","authenticated-orcid":false,"given":"Dong Hoon","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine Pusan National University  Yangsan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/s41568-025-00791-1","article-title":"Translating premalignant biology to accelerate non\u2010small\u2010cell lung cancer interception","volume":"25","author":"Mazzilli SA","year":"2025","journal-title":"Nat Rev Cancer"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/j.1440-1827.2007.02098.x","article-title":"Epidermal growth factor receptor mutations in lung cancers","volume":"57","author":"Yatabe Y","year":"2007","journal-title":"Pathol Int"},{"key":"e_1_2_8_4_1","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1097\/01.pas.0000157935.28066.35","article-title":"EGFR mutation is specific for terminal respiratory unit type adenocarcinoma","volume":"29","author":"Yatabe Y","year":"2005","journal-title":"Am J Surg 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