Clinical and phenotypical characteristics of submucosal invasive carcinoma in non-ampullary duodenal cancer

Objective The rare incidence of submucosal invasive non-ampullary duodenal carcinoma has led to scant information in literature; therefore, we compared the clinicopathological features between submucosal invasive carcinoma (SM-Ca), mucosal carcinoma (M-Ca), and advanced carcinoma (Ad-Ca). Materials We retrospectively analyzed 165 patients with sporadic non-ampullary duodenal carcinomas (SNADCs) from four institutions between January 2003 and December 2018. The SNADCs were divided to three groups according to histological diagnosis: SM-Ca, M-Ca, and Ad-Ca. The clinicopathological characteristics and mucin phenotypes were compared between groups. Results Among the 165 SNADCs, 11 (7%) were classified as SM-Ca, 70 (42%) as M-Ca, and 84 (51%) as Ad-Ca. We found that all SM-Ca (P = 0.013) and most Ad-Ca (P = 0.020) lesions were located on the oral-Vater; however, an almost equal distribution of M-Ca lesions was found between the oral- and anal-Vater. No significant difference was observed between the tumor diameter of M-Ca and SM-Ca; however, 45% (5/11) of SM-Ca were ≤10 mm. A total of 73% (8/11) of SM-Ca were classified as gastric phenotype and no lesions were classified as intestinal phenotype; whereas most M-Ca were classified as intestinal phenotype (67%, 8/12). Conclusions SM-Ca lesions were all located on the oral-Vater and were highly associated with the gastric mucin phenotype, which were different from the features of most M-Ca.

Gastric mucin phenotype indicates aggressive biological behaviour in early differentiated gastric adenocarcinomas following endoscopic treatment

Background The distribution of mucin phenotypes and their relationship with clinicopathological features in early differentiated gastric adenocarcinomas in a Chinese cohort are unknown. We aimed to investigate mucin phenotypes and analyse the relationship between mucin phenotypes and clinicopathological features, especially biological behaviours, in early differentiated gastric adenocarcinomas from endoscopic specimens in a Chinese cohort. Methods Immunohistochemical staining of CD10, MUC2, MUC5AC, and MUC6 was performed in 257 tissue samples from patients with early differentiated gastric adenocarcinomas. The tumour location, gross type, tumour size, histological type, depth of invasion, lymphovascular invasion, mucosal background and other clinicopathological parameters were evaluated. The relationship between mucin phenotypes and clinicopathological features was analysed with the chi-square test. Results The incidences of gastric, gastrointestinal, intestinal and null phenotypes were 21 %, 56 %, 20 and 3 %, respectively. The mucin phenotypes were related to histology classification (P < 0.05). The proportion of the gastric phenotype became greater during the transition from differentiated to undifferentiated (P < 0.05). Complete intestinal metaplasia was higher in the gastric and intestinal phenotypes than in the gastrointestinal phenotype (P < 0.05). Tumours with poorly differentiated adenocarcinoma were mainly of the gastric phenotype, which was significantly higher than that of purely differentiated tubular adenocarcinoma (P < 0.05), and the depth of invasion in the mixed type was deeper (P < 0.05). Neither recurrence nor metastasis was detected. Conclusions The mucin phenotype of early-differentiated gastric adenocarcinoma has clinical implications, and the gastric phenotype has aggressive biological behaviour in early differentiated gastric cancers, especially in those with poorly differentiated adenocarcinoma or papillary adenocarcinoma components.

Clinical and Histopathological Features of Early Gastric Cancer With Unclear Lateral Demarcation

Background Magnifying-endoscopy with narrow band imaging (M-NBI) is useful to determine lateral demarcation of early gastric cancers, but determining the lateral demarcation is sometimes difficult. Features related to the unclear lateral demarcation remain unknown. We evaluated the clinical and histopathological features of early gastric cancers with unclear lateral demarcation by M-NBI. Methods This single-center retrospective cohort study analyzed early gastric cancer treated by endoscopic submucosal dissection (ESD) from January 2013 to August 2015. We evaluated clinicopathological and immunohistochemical features using anti-p53, -Ki-67, -MUC5AC, -MUC6, -MUC2, and -CD10 antibody staining. We compared the lateral demarcation between the demarcation clear (DC) and demarcation unclear (DU) lesions by using M-NBI. Results A total of 224 differentiated adenocarcinomas (DU group: 18 lesions; DC group: 206 lesions) were analyzed. The history of successful Helicobacter pylori eradication was significantly more frequent in the DU group (p = 0.001). We examined tissues of 72 lesions immunohistochemically, including 18 lesions in the DU group and 54 randomly selected lesions in the DC group. Non-neoplastic superficial epithelium is more frequently observed in the DU group (p = 0.0058). Additionally, the DU group showed a significantly higher expression of gastric phenotype marker (p = 0.023), lower p53 score (p = 0.0002), and lower Ki-67 labeling index (p = 0.0293). The non-neoplastic superficial epithelium and low p53 score were significant independent variables associated with unclear lateral demarcation by M-NBI in the multivariate analysis. Conclusions Non-neoplastic superficial epithelium and low p53 score were associated with the difficultly in determining lateral demarcation in early gastric cancers by M-NBI.

Gastric Mucin Phenotype Indicated Aggressive Biological Behavior in Early Differentiated Gastric Adenocarcinomas by Endoscopic Treatment

Background:The distribution of mucin phenotypes and its relationship with clinicopathological features in early differentiated gastric adenocarcinomas among the Chinese cohort is unknow. We aim to investigate the mucin phenotypes and analyze the relationship between mucin phenotypes and clinicopathological features, especially the biological behavior, in early differentiated gastric adenocarcinomas from endoscopic specimens in a Chinese cohort.Methods:Immunohistochemical staining of CD10, MUC2, MUC5AC, MUC6 was performed in 257 patients with early differentiated gastric adenocarcinomas. Tumor location, gross type, tumor size, histological type, depth of invasion, lymphovascular invasion, mucosal background and other clinicopathological parameters were evaluated. Analyzed the relationship between mucin phenotypes and clinicopathological features through chi-square test.ResultsThe incidence of ໿ gastric-, gastrointestinal-, intestinal- and null-phenotype was 21%, 56%, 20% and 3% respectively. The mucin phenotypes were related with histology classification (P༜0.05). The proportion of gastric-phenotype became greater during the transition from differentiated to undifferentiated (P༜0.05). Complete intestinal metaplasia in gastric- and intestinal-phenotype was higher than gastrointestinal-phenotype (P༜0.05). Those mixed with poorly differentiated adenocarcinoma were mainly of gastric-phenotype, which was significantly higher than that of purely differentiated tubular adenocarcinoma (P < 0.05), and the depth of infiltration of mixed type was deeper (P < 0.05). Neither recurrence nor metastasis were detected.ConclusionsThe mucin phenotype of early differentiated gastric adenocarcinoma is of clinical implication, and gastric-phenotype has aggressive biological behavior in early differentiated gastric cancers, especially in those mixed with poorly differentiated adenocarcinoma or papillary adenocarcinoma component.

Relationship between Immunophenotype and Clinicopathological Findings for Superficial Nonampullary Duodenal Epithelial Tumor

<b><i>Introduction:</i></b> The natural history and prognosis of superficial nonampullary duodenal epithelial tumors (SNADETs) remain uncertain. We elucidated the relationship between immunophenotype and clinicopathological features. <b><i>Materials and Methods:</i></b> A total of 98 SNADETs were divided into 3 groups according to immunohistochemical findings: gastric phenotype (G type), gastrointestinal phenotype (GI type), and intestinal phenotype (I type). Cellular dysplasia was divided into low-grade dysplasia and high-grade dysplasia/adenocarcinoma (≥HGD). White opaque substance (WOS) deposition was categorized into diffuse WOS, partial WOS, and no WOS, based on endoscopic findings. <b><i>Results:</i></b> Of the 98 SNADETs, 4 lesions (4.1%) were G type, 32 lesions (32.7%) were GI type, and 62 lesions (63.2%) were I type. All G-type SNADETs were located in the oral side of the papilla including the bulb, and the rate of bulbar lesions was significantly higher in the G type than in the GI and I types (<i>p</i> = 0.004). The most frequent type of WOS was no WOS (4/4, 100%) for G type, partial WOS (19/32, 59.4%) for GI type, and diffuse WOS (34/62, 54.8%) for I type (<i>p</i> &#x3c; 0.001), and loss of intestinal character was significantly correlated with WOS deficiency. GI/I-type SNADETs with partial or no WOS and G-type SNADETs were associated with ≥HGD. Additionally, the frequency of ≥HGD lesion was significantly higher in the CD10-negative group than in the CD10-positive group (57.1 vs. 19.8%, <i>p</i> = 0.043). <b><i>Conclusion:</i></b> Pathological intestinal character was correlated with the presence of WOS, and CD10 loss was associated with malignant potential of SNADETs.

Large Fundic Gland Polyp Associated with Long-Term Proton Pump Inhibitor Administration Mimicking Gastric-Type Neoplasm

A 57-year-old man with a 10-year history of proton pump inhibitor (PPI) use presented with multiple fundic gland polyps (FGPs) including one &#x3e;20 mm, whitish, semi-pedunculated polyp. Black spots and cobblestone-like mucosa were also observed in the stomach upon endoscopy; therefore, the lesion was considered to result from long-term PPI administration. Endoscopically, we diagnosed this polyp as a neoplastic lesion with gastric phenotype rather than a non-neoplastic lesion. Biopsy revealed an atypical glandular lesion that was indeterminate for neoplasia; therefore, we performed en bloc resection via endoscopic submucosal dissection (ESD) of the 22 × 22 × 10 mm-sized polyp. Histologically, the polyp was composed of hyperplastic foveolar epithelia in the upper half of the mucosa and hyperplastic fundic glands in the lower half of the mucosa, with luminal dilatation and parietal cell protrusion. The pathological diagnosis for this ESD specimen was FGP associated with PPI administration. We herein describe this rare case of a large FGP in <i>Helicobacter pylori</i>-uninfected gastric mucosa associated with long-term PPI administration, which was mimicking gastric-type neoplasm and resected by endoscopy.

Conventional Direct Smear Yields Diagnostic Indicators of Gastric-Type Mucinous Carcinoma Compared with Cytomorphological Features Identified by Liquid-Based Cervical Cytology

<b><i>Introduction:</i></b> Gastric-type mucinous carcinoma (GAS) of the uterine cervix is an adenocarcinoma subtype with a gastric phenotype that poses diagnostic pitfalls in cervical screening cytology because of its blunt morphologic atypia and the limited utility of human papillomavirus testing and ancillary immunochemical staining. Despite the recent widespread uptake of liquid-based cytology (LBC) systems, the cytomorphological features of GAS in LBC samples and the differential features between GAS and usual-type endocervical adenocarcinoma (UEA) remain unclear. <b><i>Methods:</i></b> Eight GAS cases, all of which were surgically treated following histological confirmation, were examined. Direct Papanicolaou-stained smears and LBC samples were reviewed and compared with 10 UEA cases as controls. Featured cytomorphological findings were as follows: background (mucinous, inflammatory, or necrotic), cell crowding (size of neoplastic cell clusters), cytoplasm (golden mucin and cell border), and nuclei (nuclear chromatin and nucleoli). <b><i>Results:</i></b> Of 18 adenocarcinomas, 16 were detected against a non-mucinous background in LBC samples, most of which were accompanied by mild to moderate inflammation. Clusters comprising &#x3e;300 neoplastic cells were identified in both GAS and UEA in conventional smears (CSs), while no LBC samples harboured clusters as large as these. Cell borders of GAS were more distinct than those of UEA in CSs (<i>p</i> &#x3c; 0.001), although fewer populations of neoplastic clusters revealed distinct cell borders in both GAS and UEA in LBC samples. Three of 8 and 2 of 8 GAS cases had golden mucin in CSs and in LBC samples, respectively, which was not detected in UEA at all. Nucleoli against fine nuclear chromatin were more pronounced in GAS than in UEA on CS (<i>p</i> = 0.03), although the difference between GAS and UEA was not apparent in LBC samples. <b><i>Discussion/Conclusion:</i></b> This study demonstrated that the diagnostic clues to detect GAS using the conventional approach, namely distinct cell borders and prominent nucleoli, are not useful for excluding UEA in LBC samples. Conventional cervical smears may indicate a diagnosis of GAS; however, specific high-risk HPV detection approaches, such as HPV test or immunocytochemical p16/Ki-67 dual staining, are desirable to differentiate GAS from UEA in the setting of LBC with ambiguous cytomorphological features.

The clinicopathological features of submucosal invasive non-ampullary duodenal carcinoma

Background Little is known about submucosal invasive non-ampullary duodenal carcinoma because of its extreme rarity, so we investigated the clinicopathological features, comparing submucosal invasive carcinoma (SM-Ca) with mucosal carcinoma (M-Ca) and advanced carcinoma (Ad-Ca). Methods We retrospectively analyzed 165 sporadic non-ampullary duodenal carcinomas (SNADCs) at 4 institutions between January 2003 and December 2018. In addition, we compared the mucin phenotype between SM-Ca and M-Ca. Results There were only 11 cases (7%) of SM-Ca, while there were 70 cases of M-Ca (42%) and 84 cases of Ad-Ca (51%). Although the distribution of M-Ca was almost equal between the oral and anal sides of the papilla of Vater, all SM-Ca was located on the oral-Vater (P = 0.013) and Ad-Ca tended to be located on the oral-Vater (P = 0.020). Mixed macroscopic type was more frequent in SM-Ca than in M-Ca (64% vs. 10%, P < 0.001). There was no significant difference in tumor diameter between M-Ca and SM-Ca, but 45% of SM-Ca were ≤ 10 mm. 73% (8/11) of SM-Ca were classified as gastric phenotype and no lesions were intestinal phenotype, whereas most M-Ca were intestinal phenotype (67%, 8/12). Conclusions SM-Ca was highly associated with tumor location (oral-Vater) and gastric mucin phenotype, different from M-Ca. The possibility of SM-Ca should be considered when superficial SNADCs are located on oral-Vater and have mixed macroscopic type even if tumor diameters are ≤ 10 mm.