Takehide Fukuchi1, Kingo Hirasawa2, Chiko Sato1, Makomo Makazu1, Hiroaki Kaneko3, Ryosuke Kobayashi1, Masafumi Nishio1, Ryosuke Ikeda1, Atsushi Sawada1, Yuichiro Ozeki1, Makoto Sugimori1, Yoshiaki Inayama4, Yoko Tateishi5, Shin Maeda3. 1. Division of Endoscopy, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan. 2. Division of Endoscopy, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan. kingo_h@yokohama-cu.ac.jp. 3. Department of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan. 4. Department of Diagnostic Pathology, Yokohama City University Medical Center, 4-57 Urafune-cho Minami-ku, Yokohama, 232-0024, Japan. 5. Department of Pathology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Abstract
BACKGROUND: Cigarette smoking, alcohol consumption, and Lugol-voiding lesions (LVLs) are the major causative risk factors of esophageal squamous cell carcinoma (ESCC); however, reports on ESCC cases unrelated to these risk factors are very limited. Here, we investigated the clinicopathological features and etiology of such cases. METHODS: We retrospectively analyzed 704 consecutive superficial ESCC tumors of 512 patients who were treated with endoscopic submucosal dissection. The enrolled patients were divided into two groups-the very low-risk (VLR)-group and risk (R)-group-based on the presence of the abovementioned risks. Clinical, endoscopic, and pathological characteristics and genetic findings were assessed in both groups. RESULTS: The VLR-group consisted of 21 (4.1%) patients, who were characteristically female. Patients in the VLR-group presented gastroesophageal reflux disease (GERD), hiatal hernia, and non-open-type atrophic gastritis, and were negative for Helicobacter pylori. We found unique endoscopic features-frequently observed in the posterior wall of the middle thoracic esophagus-with a linear shape that closely resembled the erosion-like form of GERD. Additionally, histopathological examination showed that these tumors presented atypical nuclei limited to the basal and parabasal layer, sequential to the surrounding changes that presented pathological chronic inflammation of esophagitis. Evaluation of somatic mutations in cancer-related genes using next-generation sequencing revealed that the positive carcinogenic potential (TP53 mutation) of the tumors was relatively frequent in the VLR-group. CONCLUSIONS: Our study suggests that ESCC without major causative factors is related to GERD, with no remarkable oncogenic difference.
BACKGROUND: Cigarette smoking, alcohol consumption, and Lugol-voiding lesions (LVLs) are the major causative risk factors of esophageal squamous cell carcinoma (ESCC); however, reports on ESCC cases unrelated to these risk factors are very limited. Here, we investigated the clinicopathological features and etiology of such cases. METHODS: We retrospectively analyzed 704 consecutive superficial ESCC tumors of 512 patients who were treated with endoscopic submucosal dissection. The enrolled patients were divided into two groups-the very low-risk (VLR)-group and risk (R)-group-based on the presence of the abovementioned risks. Clinical, endoscopic, and pathological characteristics and genetic findings were assessed in both groups. RESULTS: The VLR-group consisted of 21 (4.1%) patients, who were characteristically female. Patients in the VLR-group presented gastroesophageal reflux disease (GERD), hiatal hernia, and non-open-type atrophic gastritis, and were negative for Helicobacter pylori. We found unique endoscopic features-frequently observed in the posterior wall of the middle thoracic esophagus-with a linear shape that closely resembled the erosion-like form of GERD. Additionally, histopathological examination showed that these tumors presented atypical nuclei limited to the basal and parabasal layer, sequential to the surrounding changes that presented pathological chronic inflammation of esophagitis. Evaluation of somatic mutations in cancer-related genes using next-generation sequencing revealed that the positive carcinogenic potential (TP53 mutation) of the tumors was relatively frequent in the VLR-group. CONCLUSIONS: Our study suggests that ESCC without major causative factors is related to GERD, with no remarkable oncogenic difference.