Pulmonary fibrosis and lung carcinoma: A comparative study of metaplastic epithelia in honeycombed areas of usual interstitial pneumonia with or without lung carcinoma

Abstract

Usual interstitial pneumonia (UIP), or idiopathic pulmonary fibrosis, has been considered to be associated with a high risk for lung carcinoma. To investigate this well-known but still equivocal relationship, we reviewed the clinical features of UIP autopsy cases with or without lung carcinoma (n = 32 and 38, respectively), and compared the morphology and cell kinetics of metaplastic epithelia in the honeycombed areas (n = 11, each group). Thirty-two of 70 UIP autopsy cases showed lung carcinomas. Clinically, UIP with lung carcinoma showed a male predominance (P = 0.001), a higher rate of smoking history (P = 0.001) and a later onset of UIP (P = 0.02), compared with UIP without lung carcinoma. Most of the carcinomas were peripheral in origin (90%), and 65% were topographically associated with honeycombed areas or the border between honeycombing and non-fibrotic areas. Quantitative assessment of the metaplastic epithelia in the honeycombed areas revealed that squamous metaplasia, but not cuboidal cell metaplasia or bronchial cell metaplasia, occurred more frequently in UIP with lung carcinoma than in UIP without lung carcinoma (P = 0.02). There were no significant differences between the two groups with regard to the labeling indexes of Ki-67 and p53 in the metaplastic epithelia, including squamous metaplasia. The degree of atypical squamous metaplasia was not different between the two groups. The quantitative predominance of squamous metaplasia in the honeycombed areas may not be a precursor for lung carcinoma, but might reflect a constitutional susceptibility of UIP patients to develop a lung carcinoma.

Abnormal Re-epithelialization and Lung Remodeling in Idiopathic Pulmonary Fibrosis: The Role of ΔN-p63

“…In normal bronchial and bronchiolar basal cells, the hidden basal position could represent a means to avoid contact with potentially noxious agents, including tobacco smoke, transported by respiratory gases. Accordingly, the incidence of peripheral carcinoma is significantly increased in IPF/UIP (Hironaka and Fukayama, 1999), including squamous carcinoma (Kawasaki et al, 2001), a cancer type that can be considered as typically derived from the basal cell transformation and characterized by p63 gene amplification (Hibi et al, 2000). …”

When Malignancies Mimic Interstitial Lung Disease: A Case Series and Review of the Literature

“…Chronic inflammation leads to impaired epithelial cell reparation, with proliferation and metaplasia [14] and cytologically atypical epithelial proliferations can be demonstrated in areas of honeycombing. On the other hand, a recent review [15,16] recorded an explicitly higher prevalence of lung cancer in the IPF population of 4.8%-48% versus 2%-6.4% in the non-IPF affected cohort. The prognosis of IPF is worse in those patients, making lung cancer an consolidations with air bronchogram and cystic changes (Figure 2a).…”

Dickkopf proteins influence lung epithelial cell proliferation in idiopathic pulmonary fibrosis

“…Squamous cell carcinoma accounts for 20% of all human lung cancers and basal cell metaplasia is a premalignant finding in the bronchial epithelium [35]. Importantly, bronchial epithelial cell metaplasia is also a common feature in IPF lung tissue specimens [36]. In addition, CHILOSI et al [37] reported abnormal proliferation of bronchial epithelial cells in IPF, but not other interstitial pneumonias, such as acute or nonspecific pneumonias.…”