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

Abstract

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.

A predictive nomogram model for low anterior resection syndrome after rectal cancer resection

“…Consistent findings were demonstrated in a recent study which showed that a neoadjuvant modality is associated with more severe LARS and diminished quality of life 24 . Among the reasons for the more likely major LARS after preoperative radiotherapy are: neoadjuvant chemoradiotherapy may induce pathological features, including fibrosis, nerve injury, mucosal edema, ulcers, inflammatory cell infiltration and significant vascular lesions in the non‐neoplastic mucosa 25 . Furthermore, neoadjuvant chemo‐radiotherapy can cause excessive tissue edema, leading to a loss of surgical planes, thereby posing complications and an increased surgical challenge 3 …”

“…24 Among the reasons for the more likely major LARS after preoperative radiotherapy are: neoadjuvant chemoradiotherapy may induce pathological features, including fibrosis, nerve injury, mucosal edema, ulcers, inflammatory cell infiltration and significant vascular lesions in the non-neoplastic mucosa. 25 Furthermore, neoadjuvant chemo-radiotherapy can cause excessive tissue edema, leading to a loss of surgical planes, thereby posing complications and an increased surgical challenge. 3 This study also showed that the risk of major LARS was related to low tumour height.…”

Gastrointestinal Manifestations in Systemic Mastocytosis: The Need of a Multidisciplinary Approach

“…Moreover, MCs are components of the inflammatory microenvironment modulating carcinogenesis [53,54]. Depending on the milieu, MCs represent a source of either protumorigenic factors favoring angiogenesis and tumor growth or anti-tumorigenic molecules (TNFα and IL-9) with a protective function.…”

Recent Research on Gastrointestinal Carcinoma

“…Interestingly, preoperative short-course radiotherapy, among the standard treatments for rectal cancer, may induce morphological features simulating dysplasia in the adjacent normal mucosa, possibly resulting in overtreatment of a patient if misinterpreted. Zanelli and coauthors provide a comprehensive morphological description of radiation-induced abnormalities; through next-generation sequencing (NGS) analysis, they support the findings that radiation-induced “dysplastic-like” features are not genetically transformed [ 5 ]. It is well known that, in the era of precision medicine, molecular-biology-driven treatment has a pivotal role in improving patient selection and outcomes, thus avoiding unnecessary toxicities and providing better allocation of economic resources.…”