Abstract
Aims
The association between lung cancer and idiopathic pulmonary fibrosis (IPF) is well-known, however the significance of this association is poorly understood. Bronchiolar honeycomb cysts have been proposed as possible precursors for development of carcinoma, but limited evidence of this hypothesis is available.
Methods and results
Thirty-three lung carcinomas arising in patients with IPF have been analyzed using a panel of immunohistochemical markers. The antibodies included pneumocyte markers (TTF1, Napsin-A, SPA1), the goblet cell marker MUC5AC, markers of basal/squamous cell differentiation (CK5/6, ΔN-p63) and markers related to enteric differentiation (CDX2, MUC2, CK20, villin). A series of 100 consecutive lung adenocarcinomas arising in smokers without IPF was investigated as control. All carcinomas arising in IPF were peripherally located at imaging analysis. The diagnosis were: 8 squamous cell carcinomas, 20 adenocarcinomas, 3 small-cell carcinomas (including one composite small-cell and adenocarcinoma) and 2 large cell carcinomas. Among adenocarcinomas, a "pneumocyte" profile (TTF1, Napsin-A, SPA1 triple-positive) was observed in 7/20 (35% versus 84% in non-IPF, p-value 0.0001). The remaining 13 adenocarcinomas (65%) exhibited rare histotypes: 4 invasive mucinous adenocarcinomas (20% in IPF versus 1% in non-IPF, p-value 0.002), 7 tumors (35%) were characterized by variable expression of markers of enteric differentiation and 2 tumors (10%) showed a peculiar "basaloid" component.
Conclusions
The immunohistochemical characterization of carcinomas arising in IPF shows striking divergence from those observed in non-IPF. The prevalence of rare entities exhibiting bronchiole-related markers is in line with the hypothesis that these tumors arise from transformed small airways in honeycomb lung areas where abnormal bronchiolar proliferation takes place.
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