Zanelli Magda, Ciarrocchi Alessia, De Petris Giovanni, Zizzo Maurizio, Costantini Massimo, Bisagni Alessandra, Torricelli Federica, Nicoli Davide, Ramundo Dafne, Ricci Stefano, Palicelli Andrea, Sanguedolce Francesca, Ascani Stefano, Castro Ruiz Carolina, Annessi Valerio, Zamponi Raffaella, Bortesi Mara, Martino Veronica, Marchetti Marialisa, De Marco Loredana
Pathology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy.
Laboratory of Translational Research, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy.
Cancers (Basel). 2020 Sep 9;12(9):2571. doi: 10.3390/cancers12092571.
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.
术前放疗是直肠癌中一种广泛接受的治疗方法。辐射引起的肿瘤变化已有详细描述，而对非肿瘤性黏膜的关注较少。我们的目的是详细分析非肿瘤性黏膜中存在的形态学特征，病理学家在评估接受术前放疗（尤其是短程放疗方案）患者的直肠癌标本时需要熟悉这些特征，以避免误诊。我们比较了两组95例术前接受短程放疗（45例）或长程放疗（50例）的直肠癌患者。根据方案类型，在照射体积内的非肿瘤性黏膜中观察到不同的组织病理学特征，包括炎症、腺体异常和内分泌分化。值得注意的是，仅在短程放疗组中发现了类似发育异常的特征，如隐窝扭曲、腺上皮细胞核和细胞质异型性。在一部分短程放疗病例中，对肿瘤和受辐射损伤的黏膜进行了56个癌症中常见突变基因的DNA突变分析和p53免疫染色。体细胞突变仅在肿瘤中被鉴定出来，支持了具有辐射诱导的“发育异常样”特征的组织未发生基因转化的概念。病理学家应意识到辐射引起的特征性形态学变化。如果错误解读，短程放疗组中出现的类似发育异常的特征可能会导致严重的诊断错误。下一代测序（NGS）分析进一步验证了辐射诱导的异常不代表肿瘤前病变的形态学概念。
