Hyperplastic epithelial foci in honeycomb lesions in idiopathic pulmonary fibrosis

Abstract

Seventy-two cases of idiopathic pulmonary fibrosis (IPF) were examined from 2856 consecutive autopsy cases at the Japanese Red Cross Medical Center in Tokyo from 1973-1996. Primary lung cancer had arisen in 31 of 72 cases of IPF (43%), significantly higher than the incidence in cases without IPF (8.1%) and in the cases with non-IPF chronic lung diseases (11.9%). Hyperplastic epithelial foci in the honeycomb lesions of IPF cases were significantly more prominent in the lower than in the upper lobe, in cases with or without lung cancer, and they were more prominent in the lower lobe of IPF with than in those without cancer. The length of hyperplastic epithelial foci in the lower lobe of IPF cases was longer than that in interstitial pneumonia-associated with collagen vascular diseases. There was a higher PCNA labeling index of hyperplastic epithelial foci in IPF cases than in cases of interstitial pneumonia-associated with collagen vascular diseases. The PCNA labeling index was almost the same between smokers and nonsmokers with IPF. Overexpression of p53 was observed in hyperplastic epithelial foci in honeycomb lesion of IPF. DNA ploidy analysis of hyperplastic epithelial foci in the paraffin sections of 12 IPF cases revealed aneuploidy patterns in eight cases. These results strongly suggest that accelerated cell proliferation occurs in the honeycomb lesion of IPF, and that regenerative epithelia becomes susceptible to carcinogenic agents in addition to the smoking effect.

Type 2 alveolar cells are stem cells in adult lung

“…One potential reason for this deficiency is that MRC5 cells do not adequately recapitulate the human alveolar stem cell niche in this model. Interestingly, hyperplastic AEC2s and accelerated cell proliferation are common features of IPF (45), suggesting that dysregulation of the alveolar niche may be an important mechanism in pathological remodeling of the lung parenchyma. Future experiments will test the hypothesis that stromal cells are critical regulators of alveolar homeostasis and are dysregulated in tissue remodeling.…”

Comorbidities in idiopathic pulmonary fibrosis patients: a systematic literature review

“…The prevalence of lung cancer among IPF patients was reported in 15 studies [26,28,34,48,[82][83][84][85][86][87][88][89][90][91][92] (online supplementary table S4 and figure 5) and was typically lower than the prevalence of other respiratory comorbidities of interest. Analyses of insurance claims and electronic medical records databases from the USA and the UK estimated the prevalence of lung cancer to be 3-4% [26,82,83].…”

Lung Cancer in Pulmonary Fibrosis: Tales of Epithelial Cell Plasticity

“…This leads to aberrant growth factor activation and perpetuation of the fibrotic transformation and aggregation of activated myofibroblasts (fibroblast foci), which promote excessive extracellular matrix deposition [6,7]. Hyperplastic proliferating alveolar epithelial cells are frequently found in IPF, and alveolar epithelial cell proliferation may be involved in impaired repair mechanisms [8,9,10]. …”