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。     

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.     

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 type: Five cases treated with endoscopic resection

Recently,a new disease entity termed gastric adenocarcinoma of fundic gland type(GA-FG) was proposed.We treated five cases of GA-FG with endoscopic submucosal dissection.All tumors were small and located in the upper third of the stomach.Four tumors were macroscopically identified as 0-IIa and one was identified as 0-Ⅱb.Narrow-band imaging with magnifying endoscopy showed an irregular microvascular pattern in 2 cases and a regular microvascular pattern in the remainder.All tumors arose from the deep layer of the lamina propria mucosae and showed submucosal invasion.Lymphatic invasion was seen only in one case,while no venous invasion was recognized.All tumors were positive for pepsinogen-Ⅰ and MUC6 by immunohistochemistry.None showed p53 overexpression,and the labeling index of Ki-67 was low in all cases.All cases have been free from recurrence or metastasis.Herein,we discussed the clinicopathological features of GA-FG in comparison with past reports.     

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.     

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.     

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-type endocervical adenocarcinoma with mucoepithelial metaplasia combined with a serous borderline tumor: A case report

Rationale:Gastric-type endocervical adenocarcinoma (GAS) is a rare type of cervical adenocarcinoma that is a mucinous adenocarcinoma with a variety of gastral patterns. To date, there are no systematic clinical diagnosis and treatment guidelines.Patient concerns:In our case, a 49-year-old woman underwent pelvic magnetic resonance imaging (MRI) due to a pelvic mass, and cervical lesions were unexpectedly found. After receiving relevant surgical treatment, the pathological results showed the particularity of the tumor type—cervical gastric adenocarcinoma with a borderline serous tumor of both appendages and the right ovary.Diagnoses:Postoperative routine pathological examination showed mucoepithelial metaplasia accompanied by a borderline serous tumor.Interventions:After gynecological/urinary ultrasound, blood tests, MRI, cervical biopsy, and uterine curettage, “robot-assisted laparoscopic radical hysterectomy + bilateral salpingectomy-ovariectomy + pelvic lymph node dissection + pelvic adhesiolysis” were performed. After the surgery, the patient was treated with radiotherapy and concurrent chemotherapy.Outcomes:After the operation, radiotherapy, and chemotherapy, the patient had no tumor recurrence and is still in good condition.Lessons:The diagnosis of GAS is relatively difficult, its clinical manifestations lack specificity, and the pathogenesis has nothing to do with human papillomavirus infection. The patient was misdiagnosed with vaginitis at a local hospital. However, we found that MRI and pathological examination were helpful for the diagnosis of the disease. Although there are no relevant guidelines to explain the treatment principles of GAS, we believe that early surgery is conducive to the prognosis of the disease because GAS has a certain tolerance to radiotherapy and chemotherapy.     

Clinicopathological characteristics of primary peritoneal epithelioid mesothelioma of clear cell type: A case report

Rationale:Primary peritoneal epithelioid mesothelioma of clear cell type is an extremely rare entity composed of clear cytoplasm. It is challenging to diagnose because of the morphological resemblance to clear cell tumor.Patient''s concerns:A 69-year-old male patient had swollen lymph nodes in the right inguinal region for 7 months and was constipated for 1 month.Diagnosis:The patient was diagnosed as peritoneal epithelioid mesothelioma of clear cell type based on computed tomography scan, pathology, immunohistochemistry, special staining and whole-exome sequencing. This patient harbored VHL gene alteration in exon 1 and homologous recombination defect (with a score of 45). This finding indicated that this patient might be sensitive to platinum-based therapy and Poly ADP-ribose Polymerase (PARP) inhibitor. This patient carried no microsatellite instability, a low level of tumor mutation burden, and a high extent of intratumoral heterogeneity. Eighteen neoantigens were detected.Interventions:The patient received surgery-based multidisciplinary treatment by integrating cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). HIPEC was administered with docetaxel 120 mg plus cisplatin 120 mg, at 43°C, for 60 minutes. After operation, the patient received intravenous (IV) chemotherapy with docetaxel 60 mg, pemetrexed 750 mg and cisplatin 100 mg, and then intraperitoneal (IP) chemotherapy with docetaxel 40 mg. The patient received interventional therapy of hepatic artery embolization for 5 times.Outcomes:Regular follow-up was performed until Oct 14, 2020. The patient died 31.6 months later owing to incomplete intestinal obstruction.Lessons:Primary peritoneal epithelioid mesothelioma of clear cell type needs to be differentiated from a variety of clear cell tumors. This disease is characterized by specific genetic alteration. Whole-exome sequencing contributes to guide individualized therapy. CRS-HIPEC helps achieve long-term overall survival.     

Gastric metastasis and transformation of primary lung adenocarcinoma to small cell cancer after acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors: A case report

Rationale:Transformation to small cell lung cancer (SCLC) is one of the mechanisms of resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, no standard treatment is available after the transformation. In addition, gastric metastasis of primary lung cancer is rarely observed; thus, little is known about its metastatic characteristics.Patient concerns:A 58-year-old male patient was treated with gefitinib (0.25 g /day) as the 1st line treatment due of recurrence after surgical resection for EGFR exon 19 mutation pulmonary adenocarcinoma. However, he experienced recurrence with positive T790 M, and osimertinib (80 mg/day) was administered as the 2nd line therapy.Diagnosis:One year and 6 months after osimertinib initiation, he complained of stomachache, and a diagnostic gastroscopy biopsy confirmed small cell lung cancer in the gastric body, indicating osimertinib-induced phenotypic transformation.Interventions and outcomes:The patient was treated with etoposide and platinum chemotherapy and maintenance therapy with osimertinib. Finally, the patient achieved a partial response after 4 cycles.Lessons:Timely second biopsies should be considered in the diagnosis of phenotypic transformation. After transformation, chemotherapeutic treatment with etoposide and platinum and maintenance therapy with osimertinib inhibited the progression of the disease.     

Expression of the human phosphatases of regenerating liver (PRLs) in colonic adenocarcinoma and its correlation with lymph node metastasis

Background Human phosphatases of regenerating liver (PRLs) can induce cell growth, differentiation, and malignant transformation. In this study, we used specific polyclonal antibodies against PRLs to investigate their expression in colonic adenocarcinomas and its correlation with patient gender, age, tumor differentiation, localization, invasion, and metastasis. Materials and methods The polyclonal antibodies against PRL-1, PRL-2, and PRL-3 were produced and purified. The expression of PRLs in human colorectal carcinoma cell lines (SW480 and SW620) was examined by Western blotting. We also examined their expression in normal and pathologic tissues from the human colon. The tissues included 49 primary colonic adenocarcinomas, 14 cases with lymph node metastases, 15 colonic adenomas, and 12 normal colon samples. Hematoxylin and eosin staining, immunohistochemistry, and semiquantitative morphological analysis were used to evaluate the sections. Results PRLs were widely expressed in SW480 and SW620. PRL-1, PRL-2, and PRL-3 were expressed, respectively, in 16, 10, and 16% of primary colonic adenocarcinomas. In contrast, PRLs were strongly expressed in all lymph node metastases. There were no significant correlations between the expression of PRLs and patient gender, age, tumor differentiation, depth of invasion, or localization of tumor within the different sections of the colon. PRLs were not expressed in normal colon tissues or in colonic adenomas. PRLs were mainly expressed in the cytoplasm and at the cytoplasmic membranes of the colonic adenocarcinoma cells as well as in the endothelial cells and the surrounding smooth muscle cells of larger vessels in the lymph node metastases. Conclusion Colonic adenocarcinoma cells have the ability to produce PRLs, which may relate to the lymph node metastasis of colonic adenocarcinoma. Y. Wang and Z.-F. Li contributed equally to this work.     

Successful treatment using immunotherapy in combination with chemotherapy for metastatic squamous cell carcinoma of unknown primary origin with bulky abdominal mass: A case report

Rationale:Cancer of unknown primary (CUP) means that the primary focus cannot be found after preliminary clinical evaluation. It accounts for 2.3% to 5% of newly diagnosed cancer cases. Due to the lack of standard treatment, CUP is usually associated with poor prognosis and is the third to fourth most common cause of cancer-related deaths.Patient concerns:We report the case of a 42-year-old female patient who was admitted to the hospital for intermittent right abdominal pain and abdominal distension. Abdominal computed tomography (CT) showed a large abdominal mass of unknown origin, which was difficult to resect due to its close relationship with surrounding tissues. Twenty days later, the patient had enlarged left supraclavicular lymph nodes, and percutaneous biopsy revealed squamous cell carcinoma. In addition, next-generation sequencing (NGS) of tissue and blood samples showed immune-related mutations and PD-L1 expression.Diagnoses:The patient was diagnosed with metastatic squamous cell carcinoma of unknown primary origin, with a bulky abdominal mass.Interventions:The patient was treated with carboplatin, albumin-binding paclitaxel, and immune checkpoint inhibitor (carilizumab). After 6 cycles, the patient was switched to maintenance treatment with carilizumab.Outcomes:The general condition of the patient improved, and the lesion was significantly reduced. The treatment efficacy was assessed as partial remission according to Response Evaluation Criteria in Solid Tumors. The patient benefited from immunotherapy combined with chemotherapy.Lessons:There is no recommended standard treatment for most CUPs, which leads to their poor prognoses. By performing NGS for patients and targeting immune-related positive predictors, immunotherapy combined with chemotherapy may prolong the overall survival of patients. This case report suggests that immunotherapy combined with chemotherapy is feasible and effective in patients with CUP.     

A sickle cell disease patient with dural venous sinus thrombosis: a case report and literature review

Abstract

Dural venous sinus thrombosis (DVST) is a rare disease associated with hypercoagulable states. Patients with sickle cell disease are known to be prothrombotic. We report a case of DVST presenting with anterior neck and facial pain in a 24-year-old female with sickle cell disease, found to have extensive thrombotic disease involving the internal jugular vein. A literature review of DVST in sickle cell disease consisting of 14 case reports was summarized. Headache was a presenting feature in two-thirds of patients. Nine cases were associated with vaso-occlusive crisis (VOC), transfusion, or acute respiratory illness. Most patients were treated with anticoagulation therapy. Over three-quarters either died or suffered from a serious neurological complication, including stroke, seizure, coma, or elevated intracranial pressure. Given its association with life-threatening complications, DVST should be considered when patients with sickle cell disease present with a VOC, especially in the context of headache or neurological deficits.     

Metachronous occurrence of main-duct intraductal papillary mucinous neoplasm (IPMN) and adenocarcinoma in a chronic pancreatitis patient: A case report

Rationale:Chronic pancreatitis (CP) is a risk factor for developing pancreatic ductal adenocarcinoma (PDAC). In addition, a patient with partial pancreatectomy for intraductal papillary mucinous neoplasm (IPMN) can also lead to PDAC. In contrast, IPMN is a distinct disease entity, independent of CP, and there have been few reports that CP is the cause of IPMN. To the best of our knowledge, this is the first clinical case report of the metachronous occurrence of main-duct IPMN and PDAC with a 9 and half-year interval in a patient with chronic alcoholic pancreatitis.Patient concerns:A 50-year-old man with a long medical history of recurrent alcoholic pancreatitis and hepatitis over a decade was diagnosed with another episode of acute pancreatitis based on laboratory findings and clinical symptoms. The patient underwent pylorus-preserving pancreaticoduodenectomy (PPPD) for a small nodular lesion in the main duct of the pancreatic head and was diagnosed with main-duct IPMN low-grade dysplasia and associated fibrosing CP. Nine and a half years later, a 59-year-old man lost 7 kg over 3 months and was diagnosed with new-onset diabetes mellitus.Diagnosis:The patient was diagnosed with metachronous, well-differentiated PDAC with concomitant CP.Interventions:The patient underwent radical antegrade modular pancreatosplenectomy (RAMPS) for a small nodular mass in the remnant pancreas.Outcomes:The patient was healthy for 44 months without evidence of tumor recurrence during clinical follow-up examinations including laboratory findings, tumor marker, and imaging studies.Lessons:Early diagnosis of metachronous pancreatic neoplasia in a patient with chronic pancreatitis could be made by correlating newly developed clinical symptoms and signs with careful radiological examinations.     

Characteristics of lymph node (No.5 and No.6) metastasis and significance of lymph node dissection in Siewert type II esophagogastric junction adenocarcinoma (AEG): No.5 and No.6 lymph node metastases of AEG and clearance

Background:To analyze the characteristics, related risk factors, and prognosis of lymph node metastasis (Number [No.] 5 and No.6) in the group of adenocarcinoma of esophagogastric junction (AEG).Methods:The patients with Siewert II AEG who underwent total gastrectomy and D2 lymph node dissection from September 2015 to December 2018 in Lanzhou University Second Hospital were enrolled in this study. The pathological features of the postoperative specimens were analyzed (sex, age, maximum diameter, location, depth of invasion, degree of differentiation, neurological and vascular invasion, etc), and the lymph node metastasis rate of No.5, No.6 groups were calculated. The analysis was performed by IBM SPSS statistical software. The risk factors associated with lymph node metastasis in No.5 and No.6 groups were analyzed. Survival analysis was performed by Kaplan-M method, and survival rate was estimated, Log-rank test was used for comparison, and the difference was statistically significant at P < .05.Results:There were 142 cases of Siewert type II AEG with the positive rate of No.5 lymph nodes being 10.81% (8/74), and the positive rate of No.6 lymph nodes was 8.33% (11/132). No.5 and No.6 lymph nodes metastasis were not associated with gender, age, tumor maximum diameter, location (cardiac left/cardiac right) (P > .05), and were associated with invasion depth, differentiation degree, nerve and vascular invasion (P < .05). In the No.5 lymph node-positive group, the 3-year Overall Survival (OS) was 25.0%, and the No.5 lymph node-negative group had a 5-year OS of 57.8%, which was statistically different (P < .05). The 3-year OS was 18.2% in No.6 node-positive group and 53.8% in No.6 node-negative group, and the difference was statistically significant (P < .05).Conclusion:For Siewert type II AEG, the lymph node metastasis rate was higher in No.5 and No.6 groups when the tumor invaded all layers of gastric wall and was poorly differentiated complicated with vascular nerve invasion, and the lymph node metastasis rate was lower at 3 years, which may be more appropriate for total gastrectomy +D2 lymph node dissection.