title: Ciliated adenocarcinomas of the lung: a tumor of non-terminal respiratory unit origin.
abstract: Whereas most carcinomas occur through a sequential step, atypical adenomatous hyperplasia and bronchioloalveolar carcinoma pathway is known for pulmonary adenocarcinoma. This type is known as terminal respiratory unit adenocarcinoma. Based on our observation of transitions from normal ciliated columnar cells to adenocarcinoma via dysplastic mucous columnar cells, we reviewed our archive of pulmonary adenocarcinoma. Terminal respiratory unit type adenocarcinoma was defined as adenocarcinoma with type II pneumocyte, Clara cell, or bronchiolar cell morphology according to previous reports. Among 157 cases, 121 cases have been identified as terminal respiratory unit type adenocarcinoma and 36 cases as non-terminal respiratory unit type adenocarcinoma. Among non-terminal respiratory unit type adenocarcinoma, 24 cases revealed mucous columnar cell changes that were continuous with bronchial ciliated columnar cells. The mucous columnar cells became dysplastic showing loss of cilia, disorientation, and enlarged nuclei. Adenocarcinoma arose from these dysplastic mucous columnar cells and, characteristically, this type of adenocarcinoma showed acute inflammation, and honeycombing changes in the background. TTF1 immunostaining was consistently negative. In a case study with 14 males and 10 females, including 12 smokers or ex-smokers, EGFR and KRAS mutations were detected in 3 and 6 patients, respectively. We think that this kind of adenocarcinoma arising through mucous columnar cell change belongs to non-terminal respiratory unit type adenocarcinoma, and mucous columnar cell change is a precursor lesion of pulmonary adenocarcinoma.
authors.affiliation: Department of Pathology, School of Medicine, Pusan National University, Yangsan, Korea.
authors.forename: Won Young
authors.initials: WY
authors.lastname: Park
authors.forename: Mi Hyun
authors.initials: MH
authors.lastname: Kim
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Shin
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Kyung Un
authors.initials: KU
authors.lastname: Choi
authors.forename: Jee Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Do Youn
authors.initials: DY
authors.lastname: Park
authors.forename: Chang Hun
authors.initials: CH
authors.lastname: Lee
authors.forename: Mee Young
authors.initials: MY
authors.lastname: Sol
mesh_terms: D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D056809:Alveolar Epithelial Cells / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D055745:Bronchioles / Q000378:metabolism / Q000473:pathology*; D002923:Cilia; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D015996:Survival Rate; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins