Gastric adenocarcinoma of the fundic gland(chief cell-predominant type): A review of endoscopic and clinicopathological features

Gastric adenocarcinoma of the fundic gland(chief cellpredominant type, GA-FG-CCP) is a rare variant of welldifferentiated adenocarcinoma, and has been proposed to be a novel disease entity. GA-FG-CCP originates from the gastric mucosa of the fundic gland region without chronic gastritis or intestinal metaplasia. The majority of GA-FG-CCPs exhibit either a submucosal tumor-like superficial elevated shape or a flat shape on macroscopic examination. Narrow-band imaging with endoscopic magnification may reveal a regular or an irregular microvascular pattern, depending on the degree of tumor exposure to the mucosal surface. Pathological analysis of GA-FG-CCPs is characterized by a high frequency of submucosal invasion, rare occurrences of lymphatic and venous invasion, and low-grade malignancy. Detection of diffuse positivity for pepsinogen-I by immunohistochemistry is specific for GA-FG-CCP. Careful endoscopic examination and detailed pathological evaluation are essential for early and accurate diagnosis of GA-FG-CCP. Nearly all GA-FG-CCPs are treated by endoscopic resection due to their small tumor size and low risk of recurrence or metastasis.     

胃底腺型肿瘤内镜黏膜下剥离术治疗的临床效果评价及病理学特点分析

为研究胃底腺型肿瘤内镜黏膜下剥离术（endoscopic submucosal dissection,ESD）治疗的临床效果并分析其病理学特点,收集2018年8月—2022年6月于首都医科大附属北京朝阳医院消化内镜中心行ESD,并且术后病理提示为胃底腺型胃癌或胃泌酸腺腺瘤的7例患者临床病理资料,评估患者临床特征、手术并发症情况、术前及术后病理资料和随访相关数据。7例患者病变均位于胃底部,均完成ESD治疗,术中及术后均未出现出血、穿孔等并发症。术后病理提示肿瘤细胞均起源于黏膜深层,具有浸润性生长模式,大部分肿瘤表面覆盖有正常的小凹上皮,4例患者肿瘤细胞浸润至黏膜下层,其中1例患者黏膜下浸润深度>500 μm（550 μm）。免疫组化提示MUC‑6均呈弥漫性阳性,提示肿瘤为主细胞来源,所有病例MUC‑2、MUC‑5AC、CDX‑2、CD10、CgA表达均为阴性。患者平均随访时间为22个月,术后溃疡愈合良好,未见病变复发。说明胃底腺型肿瘤有相对独特的生物学特性,ESD是治疗胃底腺型肿瘤首选的治疗方式。另外胃底腺型肿瘤组织学特点明确,可依靠免疫组化指标与其他胃部肿瘤进行鉴别。     

Gastric adenocarcinoma of fundic gland type with signet-ring cell carcinoma component: A case report and review of the literature

A depressed lesion was found at a gastric angle of 76-yearold Japanese woman by esophagogastroduodenoscopy. Four years prior, she was diagnosed with a Helicobacter pylori infection but no eradication was performed. The pathological diagnosis of biopsy specimens was signet-ring cell carcinoma. Endoscopic submucosal dissection(ESD) was performed. Histopathological examination of the ESD specimen revealed proliferation of well-differentiated tubular adenocarcinoma mimicking fundic gland cells at the deep layer of the lamina propria mucosae. These tumor cells expressed focally pepsinogen-Ⅰ, diffusely MUC6, and scattered H~+/K~+ ATPase according to immunohistochemistry. Therefore, we diagnosed this tumor as gastric adenocarcinoma of fundic gland type(GA-FG). Adjacent to the GA-FG, proliferation of signet-ring cell carcinoma which diffusely expressed MUC 2 and MUC 5AC was observed. Intestinal metaplasia was focally observed in the surrounding mucosa of the signet-ring cell carcinoma. To the best of our knowledge, this is the first case report of GA-FG with a signet-ring cell carcinoma component. The origin of signet-ring cell carcinoma, i.e., whether it accidentally arose from a non-neoplastic mucosa and coexisted with the GA-FG or dedifferentiated from the GA-FG is unclear at present. We expect the accumulation of similar cases and further analysis to clarify this issue.     

Gastric adenocarcinoma of fundic gland type: Endoscopic and clinicopathological features

Gastric adenocarcinoma of fundic gland type(GA-FG) with chief cell differentiation was recently proposed as an extremely rare type of gastric adenocarcinoma. Here, we report 4 cases of GA-FG with chief cell differentiation. Endoscopic features included a submucosal tumor shape or a flat shape, whitish discoloration and dilated vessels on the surface. The tumors were located in the upper or middle third of the stomach. All cases were preoperatively diagnosed as GA-FG by biopsy, and endoscopic submucosal dissection was performed. Resected specimens revealed well-differentiated adenocarcinomas resembling chief cells. Tumor cells were diffusely positive for pepsinogen-Ⅰ, but partially positive for H+/K+-ATPase in scattered locations around the tumor margin. Despite the presence of minimal invasion of the carcinoma into the submucosal layer, which was observed in two cases, neither lymphatic nor venous invasion was detected in any of the cases. Finally, all cases showed less aggressive clinical behavior with low grade malignancy.     

主细胞为主型胃底腺型胃癌的内镜及临床病理特征分析

目的　探讨主细胞为主型胃底腺型胃癌（gastric adenocarcinoma of fundic gland type of chief cell predominant type,GA‑FG‑CCP）的临床、内镜与病理学特征、治疗及预后。方法　收集2018年1月—2023年5月在宁波市医疗中心李惠利医院和上海市东方医院经病理组织学诊断为GA‑FG‑CCP的40例患者（41个病变）资料,分析其临床及内镜特征、病理学特征、免疫组化结果、内镜治疗、预后情况。结果　40例GA‑FG‑CCP患者中,男15例、女25例,平均年龄60.03岁,临床上多无明显不适症状,均无肿瘤家族史。除1例外,其余均无幽门螺杆菌感染。白光观察的内镜特征：①主要位于胃体上部（63.41%,26/41）;②褪色/白色调（56.10%,23/41）;③扩张的树枝状血管（78.05%,32/41）;④背景黏膜无萎缩改变（100.00%,41/41）。窄带光成像放大观察：①无明显边界（85.37%,35/41）;②腺窝开口部扩大（87.80%,36/41）;③窝间部增宽（92.68%,38/41）;④缺乏不规则的微血管结构（95.12%,39/41）。患者活检标本病理均证实为胃底腺型肿瘤。肿瘤主要由异型程度低、类似主细胞分化的细胞组成,但也有散在壁细胞,多呈不规则、融合性生长的腺管。40例患者中20例未接受内镜治疗。接受内镜切除治疗的20例21个病变中,12个浸润至黏膜下层（20~520 µm）,9个为黏膜内癌。无淋巴管及血管浸润,水平及垂直切缘阴性。免疫组化染色结果：胃蛋白酶原Ⅰ和MUC6阳性,H+‑K+‑ATPase散在少数阳性,Ki‑67肿瘤细胞增殖指数低,MUC5AC、MUC2和CD10均阴性。患者平均随访15.85个月,期间均无复发或转移。结论　GA‑FG‑CCP是一种分化非常好的罕见肿瘤类型,临床症状不明显,但内镜下有特征性表现,应用白光和窄带光成像放大观察可提高检出率,病理和免疫组化染色可明确诊断。     

胃底腺黏膜型腺癌一例报道并文献复习

目的探讨胃底腺黏膜型腺癌的临床病理学特征及免疫组化表型。 方法总结山东省立医院西院病理科确诊的1例胃底腺黏膜型腺癌的临床及病理学资料,分析其组织形态学特点及免疫组织化学染色表达,并复习相关文献。 结果老年女性,胃底大弯侧见直径2.0 cm的不规则表浅隆起,中央浅糜烂,行内镜下黏膜剥脱术,肿瘤组织镜下为中-高分化管状腺癌,伴有乳头状腺癌,免疫组化染色小凹上皮分化区域MUC5AC(＋);胃底腺分化区域MUC6(＋)、pepsinogen-I(＋);Ki-67指数约5%。 结论胃底腺黏膜型腺癌是一种新的肿瘤类型,发病率极低,既有胃底腺型腺癌的内镜和病理特征,又有小凹上皮来源腺癌的内镜和病理特征;加强该肿瘤的认识有助于对其正确诊断与治疗。     

Gastric adenocarcinoma of fundic gland (chief cell predominant type) coexisting with well differentiated intestinal adenocarcinoma: A case report

Rationale:Gastric adenocarcinoma of fundic gland (chief cell predominant type) (GA-FG-CCP) is a new, rare variant of gastric adenocarcinoma, which is characterized by mild nuclear atypia and specific immunohistochemical markers.Patient concerns:An 84-year-old Chinese man was referred to our hospital for endoscopic resection of a gastric lesion.Interventions:We performed endoscopic submucosal dissection, and successfully removed the lesion.Diagnosis:Esophago gastroduodenoscopy showed a slightly elevated lesion with a diameter of 22 mm in the posterior wall of cardia. Magnifying endoscopy with narrow band imaging revealed an abnormal microsurface and microvessels on the tumor surface. Endoscopic ultrasonography revealed a hypoechoic mass located in the first layer. The pathological diagnosis of the biopsy specimens indicated that the tumor was high grade intraepithelial neoplasia. The pathological diagnosis differed between the superficial and deeper part of the lesion. The superficial part was composed of a tubular structure with prominent atypia and was diagnosed as well differentiated intestinal adenocarcinoma. The deeper part was composed of a well-differentiated tubular adenocarcinoma mimicking the fundic gland cells, mainly the chief cells. The tumor cells showed mild nuclear atypia and was positive for pepsinogen-I (PG-I) and mucin-6 (MUC6). This deeper part was diagnosed as GA-FG-CCP.Outcomes:The tumor was successfully removed. This patient had no discomfort during the follow-up period (10 months).Lessons:We present a rare case of GA-FG-CCP coexisted with well-differentiated tubular adenocarcinoma. GA-FG-CCP exists in the deep mucosal layer and the muscularis mucosa, which could not be found under endoscopy, but could be discerned in pathology with mild nuclear atypia and special biomarkers.     

Update on diagnosis and treatment of early signet-ring cell gastric carcinoma: A literature review

Gastric signet-ring cell gastric carcinoma(GSRC) is an unfavorable subtype of gastric cancer(GC) that presents with greater invasiveness and poorer prognosis in advanced stage than other types of GC. However, GSRC in early stage is often considered an indicator of less lymph node metastasis and more satisfying clinical outcome compared to poorly differentiated GC. Therefore, the detection and diagnosis of GSRC at early stage undoubtedly play a crucial role in the management of GSRC patients. In ...     

Curative ESD for intraepithelial esophageal carcinoma with leiomyoma mimicking submucosal invasive carcinoma

This case report presents a 65-year-old man who developed early esophageal cancer with leiomyoma treated by endoscopic submucosal dissection (ESD). There have been several reports of co-existing superficial esophageal cancer and leiomyoma treated by endoscopic mucosal resection. However, there is no previous report describing the co-existing lesion treated by ESD. In order to determine treatment strategies for esophageal cancer, accurate endoscopic evaluation of the cancerous depth is essential. In the present case, the combination of endoscopic ultrasonography and narrow-band imaging system with magnifying endoscopy was extremely useful to evaluate the superficial esophageal cancer with leiomyoma, which lead to the appropriate treatment, ESD.     

Two cases of adenocarcinoma occurring in sporadic fundic gland polyps observed by magnifying endoscopy with narrow band imaging

Gastric fundic gland polyps(FGPs) are common nonadenomatous gastric polyps arising from normal fundic mucosa without Helicobacter pylori(H. pylori) infection. Although systemic FGPs associated with familial adenomatous polyposis(FAP) often have dysplasia, there are few reports of dysplasia occurring in sporadic F G P s, e s p e c i a l l y w h e n d e t e c t e d b y m a g n i f y i n g endoscopy with narrow band imaging(ME-NBI). We experienced two cases of adenocarcinoma occurring in sporadic FGPs, and their ME-NBI findings were very useful for differentiating FGP with cancer from nondysplastic FGP. A 68-year-old man and a 63-year-old woman were referred to our institution for medical checkup. H. pylori was negative in both patients. Endoscopic examination revealed a small reddishpolypoid lesion on the anterior wall of the upper gastric body and several FGPs. ME-NBI showed an irregular microvascular architecture composed of closed loop- or open loop-type vascular components, plus an irregular microsurface structure composed of oval-type surface components which was different from that of FGPs. FAP was denied because of the absence of colon polyps and no familial history of FAP. Pathological diagnosis was adenocarcinoma occurring in sporadic FGP.     

Endoscopic diagnosis and management of type I neuroendocrine tumors

Type I gastric neuroendocrine tumors (TI-GNETs) are related to chronic atrophic gastritis with hypergastrinemia and enterochromaffin-like cell hyperplasia. The incidence of TI-GNETs has significantly increased, with the great majority being TI-GNETs. TI-GNETs present as small (< 10 mm) and multiple lesions endoscopically and are generally limited to the mucosa or submucosa. Narrow band imaging and high resolution magnification endoscopy may be helpful for the endoscopic diagnosis of TI-GNETs. TI-GNETs are usually histologically classified by World Health Organization criteria as G1 tumors. Therefore, TI-GNETs tend to display nearly benign behavior with a low risk of progression or metastasis. Several treatment options are currently available for these tumors, including surgical resection, endoscopic resection, and endoscopic surveillance. However, debate persists about the best management technique for TI-GNETs.     

Diagnosis of small intramucosal signet ring cell carcinoma of the stomach by non-magnifying narrow-band imaging: A pilot study

AIM: To examine the efficacy of non-magnifying narrow-band imaging(NM-NBI) imaging for small signet ring cell carcinoma(SRC).METHODS: We retrospectively analyzed 14 consecutive small intramucosal SRCs that had been treated with endoscopic submucosal dissection(ESD) and 14 randomly selected whitish gastric ulcer scars(control). The strength and shape of the SRCs and whitish scars by NM-NBI and white-light imaging(WLI) were assessed with Image J(NIH, Bethesda).RESULTS: NM-NBI findings of SRC showed a clearly isolated whitish area amid the brown color of the surrounding normal mucosa. The NBI index, which indicates the potency of NBI for visualizing SRC, was significantly higher than the WLI index(P = 0.001), indicating SRC was more clearly identified by NM-NBI. Although the NBI index was not significantly different between SRCs and controls, the circle(C)-index, as an index of circularity of tumor shape, was significantly higher in SRCs(P = 0.001). According to the receiveroperating characteristic analysis, the resulting cut-off value of the circularity index(C-index) for SRC was 0.60(85.7% sensitivity, 85.7% specificity). Thus a lesion with a C-index ≥ 0.6 was significantly more likely to be an SRC than a gastric ulcer scar(OR = 36.0; 95%CI: 4.33-299.09; P = 0.0009).CONCLUSION: Small isolated whitish round area by NM-NBI endoscopy is a useful finding of SRCs which is the indication for ESD.     

Usefulness of the DL in ME with NBI for determining the expanded area of early-stage differentiated gastric carcinoma

AIM: To investigate whether magnifying endoscopy with narrow band imaging (ME-NBI) is useful for evaluating the area of superficial, depressed- or flat-type differentiated adenocarcinoma of the stomach. METHODS: This procedure was performed in Saitama Medical University International Medical Center, Japanese Red Cross Kumamoto Hospital and Kitakyushu Municipal Medical Center. The subjects were 31 patients in whom biopsy findings, from superficial, depressed- or flat-type gastric lesion, suggested differentiated adenocarcinoma in the above 3 hospitals between January and December 2009. Biopsy was performed on the lesion and non-lesion sides of a boundary (imaginary boundary) visualized on ME-NBI. The results were pathologically investigated. We evaluated the accuracy of estimating a demarcation line (DL) on ME-NBI in comparison with biopsy findings as a gold standard. RESULTS: The DL that could be recognized at 2 points on the orifice and anal sides of each lesion during ME-NBI was consistent with the pathological findings in 22 patients with 0-Ⅱc lesions, 7 with 0-Ⅱb lesions, and 2 with 0-Ⅱb + Ⅱc lesions, showing an accuracy of 100%. CONCLUSION: The results suggest the usefulness of ME-NBI for evaluating the area of superficial, depressed- and flat-type differentiated adenocarcinoma of the stomach.     

Grasper type scissors for endoscopic submucosal dissection of gastric epithelial neoplasia

AIM:To evaluate the efficacy and safety of grasper type scissors(GTS)for endoscopic submucosal dissection(ESD)of gastric epithelial neoplasia.METHODS:The study was performed by 4 endoscopists in 4 institutions affiliated to The Catholic University of Korea.ESD was performed in 76 consecutive patients with gastric epithelial neoplasia by using the GTS(37 patients)or the hook knife plus coagrasper(HKC)(39 patients).The complete resection rate,complication rate,total time elapsed and elapsed time per square centimeter of the dissected specimen were analyzed between the GTS and HKC group.RESULTS:The mean age of the GTS group was 62.3±11.4 years and mean age of the HKC group was 65.6±10.1 years.Differentiated adenocarcinoma was found in32.4%in the GTS group and 33.3%in the HKC group.The procedures were performed without interruption in every case in both groups.The en bloc resection rates of both groups were 100%.The total time elapsed during the procedure was 44.54±21.72 min in the GTS group and 43.77±21.84 min in the HKC group(P=0.88)and the time elapsed per square centimeter of the resected lesion was 7.53±6.35 min/cm2in the GTS group and 6.92±5.93 min/cm2in the HKC group(P=0.66).The overall complication rate was not significantly different between the two groups.CONCLUSION:GTS is a safe and effective device for ESD compared with HKC.ESD can be performed with GTS alone,which can reduce the costs for ESD.     

Advantage of endoscopic mucosal resection with a cap for rectal neuroendocrine tumors

AIM: To compare the outcomes of endoscopic mucosal resection with a cap(EMR-C) with those of endoscopic submucosal dissection(ESD) for the resection of rectal neuroendocrine tumors.METHODS: One hundred and sixteen lesions in 114 patients with rectal neuroendocrine tumor(NET) resected with EMR-C or ESD were included in the study. This study was performed at Pusan National University Yangsan Hospital between July 2009 and August 2014. We analyzed endoscopic complete resection rate,pathologic complete resection rate,procedure time,and adverse events in the EMR-C(n = 65) and ESD(n = 51) groups. We also performed a subgroup analysis by tumor size.RESULTS: Mean tumor size was 4.62 ± 1.66 mm in the EMR-C group and 7.73 ± 3.14 mm in the ESD group(P 0.001). Endoscopic complete resection rate was 100% in both groups. Histologic complete resection rate was significantly greater in the EMR-C group(92.3%) than in the ESD group(78.4%)(P = 0.042). Mean procedure time was significantly longer in the ESD group(14.43 ± 7.26 min) than in the EMR-C group(3.83 ± 1.17 min)(P 0.001). Rates of histologic complete resection without complication were similar for tumor diameter ≤ 5 mm(EMR-C,96%; ESD,100%,P = 0.472) as well as in cases of 5 mm tumor diameter ≤ 10 mm(EMR-C,80%; ESD,71.0%,P = 0.524).CONCLUSION: EMR-C may be simple,faster,and more effective than ESD in removing rectal NETs and may be preferable for resection of small rectal NETs.     

2020年日本食管癌内镜黏膜下剥离术和内镜黏膜切除术指南的解读：食管鳞癌部分

2020年日本胃肠内镜学会制定并发布了食管癌内镜黏膜下剥离术/内镜黏膜切除术指南。该指南基于已发表的大量临床研究证据,针对18个临床问题提出建议,问题涉及食管癌的术前诊断、内镜切除适应证、内镜切除方案、可治愈性评估以及术后监测5个方面,旨在解决实际工作中的问题并提高临床实践质量,主要内容包括食管鳞癌和食管腺癌2个部分,本文主要就食管鳞癌部分的指南内容进行解读。