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Open AccessArticle

Acute Radiation Colitis after Preoperative Short-Course Radiotherapy for Rectal Cancer: A Morphological, Immunohistochemical and Genetic Study

1
Pathology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy
2
Laboratory of Translational Research, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy
3
Dianon Pathology, Shelton, CT 06484, USA
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Surgical Oncology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy
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Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41121 Modena, Italy
6
Scientific Director, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy
7
Laboratory of Molecular Biology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy
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Radiotherapy Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy
9
Pathology Unit, Azienda Ospedaliero-Universitaria-Ospedali Riuniti di Foggia, 71122 Foggia, Italy
10
Pathology Unit, Azienda Ospedaliera S. Maria di Terni, University of Perugia, 05100 Terni, Italy
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(9), 2571; https://doi.org/10.3390/cancers12092571
Received: 19 July 2020 / Revised: 4 September 2020 / Accepted: 8 September 2020 / Published: 9 September 2020
(This article belongs to the Special Issue Recent Research on Gastrointestinal Carcinoma)
Radiotherapy is the standard treatment for locally advanced rectal cancer with a high risk of local recurrence, if treated with surgery alone. The two regimens accepted are preoperative long-course radiotherapy with concomitant chemotherapy and preoperative short-course radiotherapy. The aim of our retrospective study is to provide a comprehensive morphological description of radiation-induced changes in rectal cancer specimens. We compared 2 groups of 95 rectal cancer patients treated preoperatively with either short-course (45 patients) or long-course radiotherapy (50 patients). Interestingly, in the non-neoplastic mucosa we identified features closely mimicking dysplasia/pre-neoplasia only in the group treated with short-course radiotherapy. Pathologists awareness of radiation-induced abnormalities is essential, as the misinterpretation may lead to patient’s overtreatment. In our study, next generation sequencing analysis supported the morphological concept that short-course radiotherapy-induced abnormalities do not represent true dysplasia, as somatic mutations were not identified in “dysplastic-like” tissues.
Preoperative radiotherapy is a widely accepted treatment procedure in rectal cancer. Radiation-induced changes in the tumor are well described, whereas less attention has been given to the non-neoplastic mucosa. Our aim is to provide a detailed analysis of the morphological features present in non-neoplastic mucosa that pathologists need to be familiar with, in order to avoid misdiagnosis, when evaluating rectal cancer specimens of patients preoperatively treated with radiotherapy, especially with short-course regimen. We compared 2 groups of 95 rectal cancer patients treated preoperatively with either short-course (45 patients) or long-course radiotherapy (50 patients). Depending on the type of protocol, different histopathological features, in terms of inflammation, glandular abnormalities and endocrine differentiation were seen in the non-neoplastic mucosa within the irradiated volume. Of note, features mimicking dysplasia, such as crypt distortion, nuclear and cytoplasmic atypia of glandular epithelium, were identified only in the short-course group. DNA mutation analysis, using a panel of 56 genes frequently mutated in cancer, and p53 immunostaining were performed on both tumor and radiation-damaged mucosa in a subset of short course cases. Somatic mutations were identified only in tumors, supporting the concept that tissues with radiation-induced “dysplastic-like” features are not genetically transformed. Pathologists should be aware of the characteristic morphological changes induced by radiation. The presence of features simulating dysplasia in the group treated with short-course radiotherapy may lead to serious diagnostic mistakes, if erroneously interpreted. Next generation sequencing (NGS) analysis further validated the morphological concept that radiation-induced abnormalities do not represent pre-neoplastic lesions. View Full-Text
Keywords: neoadjuvant; radiation; radiotherapy; short-course; long-course; rectal cancer; colitis neoadjuvant; radiation; radiotherapy; short-course; long-course; rectal cancer; colitis
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Zanelli, M.; Ciarrocchi, A.; De Petris, G.; Zizzo, M.; Costantini, M.; Bisagni, A.; Torricelli, F.; Nicoli, D.; Ramundo, D.; Ricci, S.; Palicelli, A.; Sanguedolce, F.; Ascani, S.; Castro Ruiz, C.; Annessi, V.; Zamponi, R.; Bortesi, M.; Martino, V.; Marchetti, M.; De Marco, L. Acute Radiation Colitis after Preoperative Short-Course Radiotherapy for Rectal Cancer: A Morphological, Immunohistochemical and Genetic Study. Cancers 2020, 12, 2571.

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