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Submucosal glands (SMGs) present throughout human esophagus with clusters at either the upper third or lower third of the organ. SMGs tend to atrophy with age, and neoplasms arising in these glands are rare. In order to bring convenience to diagnosis, we summarize the histopathologic characteristics of all esophageal submucosal gland tumors (SGTs). Due to the morphological similarity, the nomenclature of salivary tumors is adopted for SGTs. However, there is great confusion about the definition and histogenesis of these tumors, especially the malignant subtypes. In the literature, esophageal mucoepidermoid carcinoma and adenoid cystic carcinoma usually adjoin the surface squamous epithelium and coexist with intraepithelial neoplasia or invasive squamous cell carcinoma (SCC). In addition, the typical gene alterations of salivary tumors have not been reported in these SGTs. Therefore, we propose to apply stringent diagnostic criteria to esophageal SGTs so as to exclude mimickers that are SCCs with various degree of SMG differentiation.

Background and Aim: Piecemeal endoscopic resection for esophageal high grade intraepithelial neoplasia (HGIN) or early squamous cell carcinoma (ESCC) is usually performed by cap-assisted endoscopic resection. This requires submucosal lifting and multiple snares. Multiband mucosectomy (MBM) uses a modified variceal band ligator without submucosal lifting. In high-risk areas where ESCC is common and endoscopic expertise is limited, MBM may be a better technique. We aimed to compare MBM to the cap-assisted technique for piecemeal endoscopic resection of esophageal ESCCs., Methods: Patients with mucosal HGIN/ESCC (2 - 6 cm, maximum two-thirds of esophageal circumference) were included. Lesions, delineated by 1.25 % Lugol staining, were randomized to MBM or cap-assisted piecemeal resection. Endpoints were procedure time and costs, complete endoscopic resection, adverse events, and absence of HGIN/ESCC at 3-month and 12-month follow-up. , Results: Endoscopic resection was performed in 84 patients (59 men, mean age 60) using MBM (n = 42) or the endoscopic resection cap (n = 42). There were no differences in baseline characteristics. Endoscopic complete resection was achieved in all lesions. Procedure time was significantly shorter with MBM (11 vs. 22 minutes, P < 0.0001). One perforation, seen after using the endoscopic resection cap, was treated conservatively. Total costs of disposables were lower for MBM (€200 vs. €251, P = 0.04). At 3-month and 12-month follow-ups none of the patients had HGIN/ESCC at the resection site., Conclusion: Piecemeal endoscopic resection of esophageal ESCC with MBM is faster and cheaper than with the endoscopic resection cap. Both techniques are highly effective and safe. MBM may have significant advantages over the endoscopic resection cap technique, especially in countries where ESCC is extremely common but limited endoscopic expertise and resources exist. (Netherlands trial register: NTR 3246.)., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aims: To evaluate PIK3CA gene mutations and PIK3CA expression status in Chinese esophageal squamous cell carcinoma (ESCC) patients, and their correlation with clinicopathological characteristics and clinical outcomes., Methods: Direct sequencing was applied to investigate mutations in exons 9 and 20 of PIK3CA in 406 Chinese ESCC patients. PIK3CA expression was evaluated using immunohistochemistry analysis. The associations of PIK3CA gene mutations and PIK3CA expression with clinicopathological characteristics and clinical outcome were examined., Results: Thirty somatic point mutations (30/406, 7.4%) were identified in exon 9 whereas no mutations were detected in exon 20. PIK3CA mutations were not correlated with clinicopathological characteristics or clinical outcomes. However in the ESCC patients with family cancer history, PIK3CA mutations were independently correlated with worse overall survival (multivariate hazard ratio (HR) = 10.493, 95% CI: 2.432-45.267, P = 0.002). Compared to normal esophageal tissue, PIK3CA was significantly overexpressed in cancer tissue (P<0.001). PIK3CA overexpression was independently associated with higher risk of local recurrence (multivariate HR  = 1.435, 95% CI: 1.040-1.979, P = 0.028). In female ESCC patients, PIK3CA overexpression was independently correlated with worse overall survival (multivariate HR  = 2.341, 95% CI: 1.073-5.108, P = 0.033)., Conclusions: Our results suggest PIK3CA gene mutation and overexpression could act as biomarkers for individualized molecular targeted therapy for Chinese ESCC patients.

Esophageal submucosal tumors are rare, but their pathological types are diverse. In addition to the relatively common leiomyomas, some rare submucosal lesions are occasionally reported. Waldeyer's ring is described as a unique subtype of mucosa-associated lymphoid tissue, located in the naso-oropharynx. Studies have reported that Waldeyer's ring is the most common site of primary extranodal lymphoma in the head and neck. Interestingly, we encountered an esophageal submucosal tumor-like lesion similar to the tonsillar structures of Waldeyer's ring. A 38-year-old man underwent esophagoscopy after experiencing swallowing discomfort for 3 months. A protruding submucosal mass with slightly rough mucosa was found at the cervical esophagus approximately 20 cm from the incisors. Considering the possibility of the coexistence of a submucosal tumor and a mucosal lesion, as well as the continuous symptoms of swallowing discomfort, the patient underwent endoscopic submucosal dissection. The lesion was removed en bloc. However, histology revealed a lesion similar to the tonsillar structure of Waldeyer's ring between the lamina propria and submucosa. The patient was followed up for 6 months without recurrence or complaints. We report a new submucosal lesion and discuss its origin and treatment. Diagnostic ESD might be an effective option until its malignant potential is clarified. [ABSTRACT FROM AUTHOR]

Primary small cell carcinoma of the esophagus (PSCCE) is a lethal neuroendocrine carcinoma. Previous studies proposed a genetic similarity between PSCCE and esophageal squamous cell carcinoma (ESCC) but provided little evidence for differences in clinical course and neuroendocrine differentiation. We perform whole-exome sequencing, RNA sequencing and immunohistochemistry profiling on 46 PSCCE cases. Integrated analyses enable the discovery of multiple mechanisms of RB1 disruption in 98% (45/46) of cases. The transcriptomic landscape of PSCCE closely resembles small cell lung cancer (SCLC) but differs from ESCC or esophageal adenocarcinoma (EAC). Distinct gene expression patterns regulated by ASCL1 and NEUROD1 define two molecular subtypes, PSCCE-A and PSCCE-N, which are highly similar to SCLC subtypes. A T cell excluded phenotype is widely observed in PSCCE. In conclusion, PSCCE has genomic alterations, transcriptome features and molecular subtyping highly similar to SCLC but distinct from ESCC or EAC. These observations are relevant to oncogenesis mechanisms and therapeutic vulnerability. Primary small cell carcinoma of the oesophagus has a poor prognosis, and has not been fully characterised molecularly. Here, the authors study the disease using multi-omics technology and find frequent RB1 disruptions and similarities to small cell lung cancer, opening potential therapeutic avenues. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is more prevalent than esophageal adenocarcinoma in Asia, especially in China, where more than half of ESCC cases occur worldwide. Many studies have reported that the automatic detection of lymph node metastasis using semantic segmentation shows good performance in breast cancer and other adenocarcinomas. However, the detection of squamous cell carcinoma metastasis in hematoxylin‐eosin (H&E)‐stained slides has never been reported. We collected a training set of 110 esophageal lymph node slides with metastasis and 132 lymph node slides without metastasis. An iPad‐based annotation system was used to draw the contours of the cancer metastasis region. A DeepLab v3 model was trained to achieve the best fit with the training data. The learned model could estimate the probability of metastasis. To evaluate the effectiveness of the detection model of learned metastasis, we used another large cohort of clinical H&E‐stained esophageal lymph node slides containing 795 esophageal lymph nodes from 154 esophageal cancer patients. The basic authenticity label for each slide was confirmed by experienced pathologists. After filtering isolated noise in the prediction, we obtained an accuracy of 94%. Furthermore, we applied the learned model to throat and lung lymph node squamous cell carcinoma metastases and achieved the following promising results: an accuracy of 96.7% in throat cancer and an accuracy of 90% in lung cancer. In this work, we organized an annotated dataset of H&E‐stained esophageal lymph node and trained a deep neural network to detect lymph node metastasis in H&E‐stained slides of squamous cell carcinoma automatically. Moreover, it is possible to use this model to detect lymph nodes metastasis in squamous cell carcinoma from other organs. This study directly demonstrates the potential for determining the localization of squamous cell carcinoma metastases in lymph node and assisting in pathological diagnosis. [ABSTRACT FROM AUTHOR]

Background: Endoscopic resection cap technique (ER-Cap), multiband mucosectomy (MBM), and endoscopic submucosal dissection (ESD) have been widely applied in the treatment of esophageal squamous neoplasia and cancer. However, little is known with regards to the comparison of these methods. This study aimed to compare the feasibility, safety, effectiveness, and costs of these three techniques. Methods: A retrospective analysis of patients with squamous premalignant or early malignant lesions of the esophagus undergoing ER-Cap, MBM, or ESD from January 2009 to December 2015 in one of the centers in China was performed. The procedural data and follow-up data for all patients were recorded. Results: A total of 672 patients with 733 lesions were included; 148 lesions (133 patients) were treated with ER-Cap, 427 lesions (388 patients) with MBM, and 158 lesions (151 patients) with ESD. The mean age was 61.59 years and the male-to-female ratio was 2.78:1. The operation time was significantly shorter for ER-Cap (29.26 ± 16.73 mins, p < 0.001) group, and the hospitalization costs were significantly lower in the MBM group (20,942.03 ± 8435.56￥, p = 0.003). The resection sample size of ESD was significantly larger (4.40 ± 1.20 cm, p < 0.001) and the en bloc resection rate of ESD was significantly higher (p < 0.001) than that of the other two groups. The frequencies of perforation, bleeding, and cicatricial stenosis were significantly lower in the MBM group (p < 0.001, p = 0.011, p = 0.009). Three local recurrences were observed in the ER-Cap group, while no recurrence was observed in MBM and ESD groups. There were three and two metastatic patients observed in the MBM and ESD groups, respectively. Conclusions: ER-Cap, MBM, and ESD are all minimally invasive, safe, and effective methods for treating early esophageal squamous cell carcinoma. MBM could be considered as a good alternative when performed by a less-experienced endoscopist in high-incidence areas with limited resources. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemotherapy has been increasingly practiced on gastric cancer (GC), and histological evaluation to predict outcome is urgent in clinical practice. There are five classic tumor regression grading (TRG) systems, including Mandard-TRG system, the Japanese Gastric Cancer Association (JGCA)-TRG system, College of American Pathologists (CAP)-TRG system, China-TRG system and Becker-TRG system.Methods: Totally, 192 patients of gastric adenocarcinoma (including adenocarcinoma of the esophagogastric junction) treated by neoadjuvant chemotherapy and surgery were evaluated using the above five TRG systems. The clinicopathological characteristics were also assessed. The correlation among TRG systems, clinicopathological characteristics and prognosis were analyzed.Results: All the five TRG systems were significantly correlated with differentiation, postsurgical T category, postsurgical N category, American Joint Committee on Cancer (AJCC) stage, lymph-vascular invasion, perineural invasion, as well as tumor size. All the five TRG systems were statistically significant in univariate Cox survival analysis. However, only postsurgical T category, postsurgical N category and R0 resection were independent in multivariate Cox survival analysis. The tight correlation between the TRG systems and other characteristics such as postsurgical stage might affect the independent prognostic role of the TRG systems. As compared with other TRG systems, the hazard ratio of no/slightly response in both Mandard TRG system and JGCA TRG system revealed higher hazard of death and disease progression than that of severe response when using univariate Cox survival analysis. The median survival time of complete response and nearly complete response were much longer than that of partial response, all classified by Mandard-TRG system. This could help clinicians predict prognosis more reasonably than JGCA-TRG which does not have the category of nearly complete response.Conclusion: We recommend Mandard-TRG system for GC after neoadjuvant chemotherapy due to its better prediction of prognosis. [ABSTRACT FROM AUTHOR]

Background and Aim: Piecemeal endoscopic resection for esophageal high grade intraepithelial neoplasia (HGIN) or early squamous cell carcinoma (ESCC) is usually performed by cap-assisted endoscopic resection. This requires submucosal lifting and multiple snares. Multiband mucosectomy (MBM) uses a modified variceal band ligator without submucosal lifting. In high-risk areas where ESCC is common and endoscopic expertise is limited, MBM may be a better technique. We aimed to compare MBM to the cap-assisted technique for piecemeal endoscopic resection of esophageal ESCCs.Methods: Patients with mucosal HGIN/ESCC (2 - 6 cm, maximum two-thirds of esophageal circumference) were included. Lesions, delineated by 1.25 % Lugol staining, were randomized to MBM or cap-assisted piecemeal resection. Endpoints were procedure time and costs, complete endoscopic resection, adverse events, and absence of HGIN/ESCC at 3-month and 12-month follow-up. Results: Endoscopic resection was performed in 84 patients (59 men, mean age 60) using MBM (n = 42) or the endoscopic resection cap (n = 42). There were no differences in baseline characteristics. Endoscopic complete resection was achieved in all lesions. Procedure time was significantly shorter with MBM (11 vs. 22 minutes, P < 0.0001). One perforation, seen after using the endoscopic resection cap, was treated conservatively. Total costs of disposables were lower for MBM (€200 vs. €251, P = 0.04). At 3-month and 12-month follow-ups none of the patients had HGIN/ESCC at the resection site.Conclusion: Piecemeal endoscopic resection of esophageal ESCC with MBM is faster and cheaper than with the endoscopic resection cap. Both techniques are highly effective and safe. MBM may have significant advantages over the endoscopic resection cap technique, especially in countries where ESCC is extremely common but limited endoscopic expertise and resources exist. (Netherlands trial register: NTR 3246.). [ABSTRACT FROM AUTHOR]

Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy but rarely occurs in the esophagus. It is easily confused with adenosquamous carcinoma and squamous cell carcinoma (SCC) with mucus-secreting components. MAML2 gene rearrangement detected by fluorescence in situ hybridization (FISH), RT-PCR or next-generation sequencing (NGS) can aid in the diagnosis. We present a case of esophageal MEC with MAML2 gene rearrangement detected by FISH. To the best of our knowledge, this is the first report of an esophageal MEC with MAML2 gene rearrangement. We also reveal that esophageal MEC patients were reported to have a higher risk of recurrence and death than SCC patients in previous literature. However, all the cases were diagnosed using previous diagnostic criteria and not confirmed by MAML2 gene rearrangement detection, and most of them might not be true MECs. [ABSTRACT FROM AUTHOR]