Ciliated adenocarcinomas of the lung: a tumor of non-terminal respiratory unit origin

Mod Pathol. 2012 Sep;25(9):1265-74. doi: 10.1038/modpathol.2012.76. Epub 2012 May 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Bronchiolo-Alveolar / genetics
  • Adenocarcinoma, Bronchiolo-Alveolar / metabolism
  • Adenocarcinoma, Bronchiolo-Alveolar / mortality
  • Adenocarcinoma, Bronchiolo-Alveolar / pathology*
  • Alveolar Epithelial Cells / metabolism
  • Alveolar Epithelial Cells / pathology
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Bronchioles / metabolism
  • Bronchioles / pathology*
  • Cilia
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Male
  • Metaplasia
  • Middle Aged
  • Mutation
  • Neoplasm Staging
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins p21(ras)
  • Survival Rate
  • ras Proteins / genetics
  • ras Proteins / metabolism

Substances

  • Biomarkers, Tumor
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins