Anna Caliò1, Veronica Lever1, Andrea Rossi2, Eliana Gilioli1, Matteo Brunelli1, Alessandra Dubini3, Sara Tomassetti4, Sara Piciucchi5, Alessia Nottegar1, Giulio Rossi6, Marianne Kambouchner7, Alessandra Cancellieri8, Mattia Barbareschi9, Giuseppe Pelosi10, Claudio Doglioni11, Alberto Cavazza12, Rodolfo Carella13, Paolo Graziano14, Bruno Murer15, Venerino Poletti4, Marco Chilosi1,16. 1. Department of Pathology AOUI, University of Verona, Verona, Italy. 2. Department of Pneumology AOUI, University of Verona, Verona, Italy. 3. Department of Pathology, Forlì Hospital, Forlì, Italy. 4. Department of Pneumology, Forlì Hospital, Forlì, Italy. 5. Department of Radiology, Forlì Hospital, Forlì, Italy. 6. Operative Unit of Pathology, Azienda USL Valle d'Aosta, Aosta, Italy. 7. Department of Pathology, Avicenne Hospital, Paris, France. 8. Department of Pathology, Maggiore Hospital, Bologna, Italy. 9. Department of Pathology, Santa Chiara Hospital, Trento, Italy. 10. Department of Pathology, University of Milan, Milan, Italy. 11. Department of Pathology, San Raffaele Hospital, Milan, Italy. 12. Department of Pathology, Arcispedale S. Maria Nuova/I.R.C.C.S., Reggio Emilia, Italy. 13. Department of Pathology, Central Hospital, Bolzano, Italy. 14. Department of Pathology, San Giovanni Rotondo Hospital, San Giovanni Rotondo, Italy. 15. Department of Pathology, Mestre Hospital, Mestre, Italy. 16. Department of Pathology, Pederzoli Hospital, Peschiera del Garda, Verona, Italy.
Abstract
AIMS: The association between lung cancer and idiopathic pulmonary fibrosis (IPF) is well known, but the significance of this association is poorly understood. Bronchiolar honeycomb cysts have been proposed as possible precursors for the development of carcinoma, but limited evidence in support of this hypothesis is available. The aim of this study was to investigate this hypothesis analysing a series of carcinomas arising in IPF by immunohistochemistry. METHODS AND RESULTS: Thirty-three lung carcinomas arising in patients with IPF were analysed with a panel of immunohistochemical markers. The antibodies included those against pneumocyte markers [thyroid transcription factor 1 (TTF1), napsin-A, and surfactant protein A], the goblet cell marker mucin 5AC, markers of basal/squamous cell differentiation [cytokeratin (CK) 5/6 and ΔN-p63], and markers related to enteric differentiation (CDX2, mucin 2, CK20, and villin). A series of 100 consecutive lung adenocarcinomas arising in smokers without IPF were investigated as controls. All carcinomas arising in IPF patients were peripherally located on imaging analysis. The diagnoses were: eight squamous cell carcinomas, 20 adenocarcinomas, three small-cell carcinomas (including one composite small-cell carcinoma and adenocarcinoma), and two large-cell carcinomas. Among adenocarcinomas, a 'pneumocyte' profile (TTF1/napsin-A/SPA1-triple-positive) was observed in seven of 20 (35% versus 84% in non-IPF controls, P = 0.0001). The remaining 13 adenocarcinomas (65%) showed rare histotypes: four invasive mucinous adenocarcinomas (20% in IPF patients versus 1% in non-IPF controls, P = 0.002), seven tumours (35%) that were characterized by variable expression of markers of enteric differentiation, and two tumours (10%) that showed a peculiar basaloid component. CONCLUSIONS: The immunohistochemical characterization of carcinomas arising in IPF patients shows striking divergence from that in non-IPF smokers. The prevalence of rare entities showing bronchiole-related markers is in line with the hypothesis that these tumours arise from transformed small airways in honeycomb lung areas where abnormal bronchiolar proliferation takes place.
AIMS: The association between lung cancer and idiopathic pulmonary fibrosis (IPF) is well known, but the significance of this association is poorly understood. Bronchiolar honeycomb cysts have been proposed as possible precursors for the development of carcinoma, but limited evidence in support of this hypothesis is available. The aim of this study was to investigate this hypothesis analysing a series of carcinomas arising in IPF by immunohistochemistry. METHODS AND RESULTS: Thirty-three lung carcinomas arising in patients with IPF were analysed with a panel of immunohistochemical markers. The antibodies included those against pneumocyte markers [thyroid transcription factor 1 (TTF1), napsin-A, and surfactant protein A], the goblet cell marker mucin 5AC, markers of basal/squamous cell differentiation [cytokeratin (CK) 5/6 and ΔN-p63], and markers related to enteric differentiation (CDX2, mucin 2, CK20, and villin). A series of 100 consecutive lung adenocarcinomas arising in smokers without IPF were investigated as controls. All carcinomas arising in IPF patients were peripherally located on imaging analysis. The diagnoses were: eight squamous cell carcinomas, 20 adenocarcinomas, three small-cell carcinomas (including one composite small-cell carcinoma and adenocarcinoma), and two large-cell carcinomas. Among adenocarcinomas, a 'pneumocyte' profile (TTF1/napsin-A/SPA1-triple-positive) was observed in seven of 20 (35% versus 84% in non-IPF controls, P = 0.0001). The remaining 13 adenocarcinomas (65%) showed rare histotypes: four invasive mucinous adenocarcinomas (20% in IPF patients versus 1% in non-IPF controls, P = 0.002), seven tumours (35%) that were characterized by variable expression of markers of enteric differentiation, and two tumours (10%) that showed a peculiar basaloid component. CONCLUSIONS: The immunohistochemical characterization of carcinomas arising in IPF patients shows striking divergence from that in non-IPF smokers. The prevalence of rare entities showing bronchiole-related markers is in line with the hypothesis that these tumours arise from transformed small airways in honeycomb lung areas where abnormal bronchiolar proliferation takes place.
Authors: Namrata Kewalramani; Carlos Machahua; Venerino Poletti; Jacques Cadranel; Athol U Wells; Manuela Funke-Chambour Journal: ERJ Open Res Date: 2022-06-20