Giovanni Arpa1, Federica Grillo2, Paolo Giuffrida3, Gabriella Nesi4, Catherine Klersy5, Claudia Mescoli6, Marco Vincenzo Lenti3, Gessica Lobascio1, Michele Martino3, Giovanni Latella7, Deborah Malvi8, Maria Cristina Macciomei9, Paolo Fociani10, Vincenzo Villanacci11, Aroldo Rizzo12, Stefano Ferrero13, Fausto Sessa14, Augusto Orlandi15, Giovanni Monteleone16, Livia Biancone16, Laura Cantoro17, Francesco Tonelli18, Antonio Ciardi19, Gilberto Poggioli20, Fernando Rizzello21, Sandro Ardizzone22, Gianluca Sampietro23, Gaspare Solina24, Barbara Oreggia25, Claudio Papi26, Renata D'Incà27, Maurizio Vecchi28, Flavio Caprioli28, Roberto Caronna29, Antonietta D'Errico8, Roberto Fiocca2, Massimo Rugge6, Gino Roberto Corazza3, Ombretta Luinetti1, Marco Paulli1, Enrico Solcia1, Antonio Di Sabatino3, Alessandro Vanoli1. 1. Unit of Anatomic Pathology, Department of Molecular Medicine, University of Pavia, and Fondazione IRCCS San Matteo Hospital, Pavia, Italy. 2. Pathology Unit, Department of Surgical and Diagnostic Sciences, University Hospital and Ospedale Policlinico San Martino IRCCS, Genova, Italy. 3. Department of Internal Medicine, Fondazione IRCCS San Matteo Hospital, University of Pavia, Pavia, Italy. 4. Division of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy. 5. Service of Clinical Epidemiology & Biometry, Fondazione IRCCS San Matteo Hospital, Pavia, Italy. 6. Pathology Unit, Department of Medicine, University of Padua, Padua, Italy. 7. Gastroenterology Unit, Department of Life and Environmental Sciences, University of L'Aquila, L'Aquila, Italy. 8. Department of Experimental, Diagnostic and Specialty Medicine [DIMES], Institute of Oncology and Transplant Pathology, University of Bologna, Policlinico St Orsola-Malpighi Hospital, Bologna, Italy. 9. Pathology Unit, San Camillo-Forlanini Hospital, Rome, Italy. 10. Unit of Pathology, Luigi Sacco University Hospital, Milan, Italy. 11. Pathology Section, Spedali Civili Hospital, Brescia, Italy. 12. Pathology Unit, Cervello Hospital, Palermo, Italy. 13. Division of Pathology, Department of Biomedical, Surgical and Dental Sciences, University of Milan, and Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 14. Department of Medicine and Surgery, University of Insubria, Varese, Italy. 15. Department of Biopathology and Image Diagnostics, University of Tor Vergata, Rome, Italy. 16. Department of Systems Medicine, University of Tor Vergata, Rome, Italy. 17. Gastroenterologia Aziendale USL Umbria, Perugia, Italy. 18. Department of Surgery and Translational Medicine, University of Florence, Florence, Italy. 19. Department of Radiological, Oncological, Pathological Sciences, Umberto I Hospital, La Sapienza University, Rome, Italy. 20. Surgery of the Alimentary Tract, Department of Medical and Surgical Sciences, Sant'Orsola - Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy. 21. Intestinal Chronic Bowel Disease Unit, Department of Medical and Surgical Sciences, Sant'Orsola Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy. 22. Gastroenterology, Luigi Sacco University Hospital, Milan, Italy. 23. IBD Surgery, Luigi Sacco University Hospital, Milan, Italy. 24. General Surgery, Cervello Hospital, Palermo, Italy. 25. General Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Policlinico, Milan, Italy. 26. IBD, San Filippo Neri Hospital, Rome, Italy. 27. Gastroenterology Section, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy. 28. Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, and Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. 29. Surgical Sciences, Umberto I Hospital, La Sapienza University, Rome, Italy.
Abstract
BACKGROUND AND AIMS: Crohn's disease-associated small bowel carcinoma is a rare event, usually reported to have a severe prognosis. However, in previous investigations we have found a minority of cases displaying a relatively favourable behaviour, thus outlining the need to improve the histopathological prediction of Crohn's disease-associated small bowel carcinoma prognosis. METHODS: As in recent studies on colorectal cancer, a substantial improvement in prognostic evaluations has been provided by the histological analysis of the tumour invasive front; we therefore systematically analysed the tumour budding and poorly differentiated clusters in the invasive front of 47 Crohn's disease-associated small bowel carcinomas collected through the Small Bowel Cancer Italian Consortium. RESULTS: Both tumour budding and poorly differentiated cluster analyses proved highly effective in prognostic evaluation of Crohn's disease-associated small bowel carcinomas. In addition, they retained prognostic value when combined with two other parameters, i.e. glandular histology and stage I/II, both known to predict a relatively favourable small bowel carcinoma behaviour. In particular, association of tumour budding and poorly differentiated clusters in a combined invasive front score allowed identification of a minor subset of cancers [12/47, 25%] characterised by combined invasive front low grade coupled with a glandular histology and a low stage [I or II] and showing no cancer-related death during a median follow-up of 73.5 months. CONCLUSIONS: The improved distinction of lower- from higher-grade Crohn's disease-associated small bowel carcinomas provided by invasive front analysis should be of potential help in choosing appropriate therapy for these rare and frequently ominous neoplasms.
BACKGROUND AND AIMS: Crohn's disease-associated small bowel carcinoma is a rare event, usually reported to have a severe prognosis. However, in previous investigations we have found a minority of cases displaying a relatively favourable behaviour, thus outlining the need to improve the histopathological prediction of Crohn's disease-associated small bowel carcinoma prognosis. METHODS: As in recent studies on colorectal cancer, a substantial improvement in prognostic evaluations has been provided by the histological analysis of the tumour invasive front; we therefore systematically analysed the tumour budding and poorly differentiated clusters in the invasive front of 47 Crohn's disease-associated small bowel carcinomas collected through the Small Bowel Cancer Italian Consortium. RESULTS: Both tumour budding and poorly differentiated cluster analyses proved highly effective in prognostic evaluation of Crohn's disease-associated small bowel carcinomas. In addition, they retained prognostic value when combined with two other parameters, i.e. glandular histology and stage I/II, both known to predict a relatively favourable small bowel carcinoma behaviour. In particular, association of tumour budding and poorly differentiated clusters in a combined invasive front score allowed identification of a minor subset of cancers [12/47, 25%] characterised by combined invasive front low grade coupled with a glandular histology and a low stage [I or II] and showing no cancer-related death during a median follow-up of 73.5 months. CONCLUSIONS: The improved distinction of lower- from higher-grade Crohn's disease-associated small bowel carcinomas provided by invasive front analysis should be of potential help in choosing appropriate therapy for these rare and frequently ominous neoplasms.