Coexistence of multifocal gastric adenocarcinoma with signet-ring cell morphology and a gastrointestinal stromal tumour in a stomach with hp-associated gastritis

A 79-year-old man was admitted because of anemia during marcumar therapy with suspected bleeding in the gastrointestinal tract. Endoscopy revealed a large mutifocal poorly differentiated gastric signet ring cell adenocarcinoma. After staging by the usual oesophagogastroduodenoscopic method, a total D 2 gastrectomy was performed. In the pathological resection specimen of the stomach, a multifocal poorly differentiated signet ring cell adenocarcinoma, infiltrating the submucosa (so called early cancer of sm-type) and an incidental gastroinstinal stromal tumour, 0.8 cm in diameter, was diagnosed. This is the first case report of the synchronous occurrence of a multifocal poorly differentiated gastric adenocarcinoma with signet-ring cell morphology (diffuse type according to the Lauren classification) and a GIST incidentally within a stomach with Hp-associated gastritis.     

A case of gastric metastasis of breast carcinoma resembling early gastric cancer]

Many patients suffering from breast carcinoma have metastases at initial diagnosis. The common metastatic sites are skeleton, liver and lung. Metastases to stomach are rare and only three cases have been reported in Korea. The endoscopic features of gastric metastases from breast carcinoma can be divided into three main categories: diffuse infiltration, external compression, and localized tumor deposition with ulceration or with a polypoid mass. However, metastatic gastric lesions which resemble early gastric carcinoma are rare. Typically, gastric metastases are confined to submucosa and muscularis, so that mucosal biopsy specimens might be false-negative. We report a case of gastric metastasis from infiltrative lobular carcinoma of the breast in a 66-year-old woman who had undergone left mastectomy with postoperative radiotherapy 17 years earlier. Initial diagnosis was early gastric carcinoma, signet ring cell type on gastric biopsy findings. However, definitive diagnosis of metastatic breast cancer was confirmed after endoscopic mucosal resection of a presumed primary early gastric carcinoma.     

早期胃癌淋巴结转移规律及其影响因素分析

目的 探讨早期胃癌淋巴结转移规律及其影响因素,为选择合适的治疗方法提供依据.方法 对北京大学第三医院1988年3月-2009年3月于外科行胃癌根治术治疗的103例早期胃癌患者临床资料进行回顾性研究,对患者的年龄、性别,肿瘤的大小、部位、大体类型、分化程度及浸润深度与淋巴结转移的关系进行单因素及多因素分析.结果 早期胃癌的淋巴结转移率为17.5%(18/103),其中黏膜内癌的淋巴结转移率为4.1%(2/49),黏膜下层癌的淋巴结转移率为29.6%(16/54).logistic回归分析显示,浸润至黏膜下层(P=0.001)及肿瘤>2 cm(P=0.003)为早期胃癌淋巴结转移的独立危险因子.黏膜内癌发生淋巴结转移的2例均为直径>2 cm的印戒细胞癌;黏膜下层癌中,≤2 cm肿瘤的淋巴结转移率为16.1%(5/31),>2 cm肿瘤的淋巴结转移率高达47.8%(11/23)(P=0.012).高分化程度的早期胃癌的淋巴结转移率为0(0/13),中分化癌转移率为18.2%(4/22),低分化癌转移率为16.7%(5/30),印戒细胞癌转移率为23.7%(9/38),各组间差异无统计学意义(P=0.294).患者的年龄、性别、肿瘤部位(胃上部、中部、下部)和大体分型(隆起型、平坦型和凹陷型)与淋巴结转移无相关性.结论 肿瘤大小和浸润深度与早期胃癌淋巴结转移相关,决定早期胃癌治疗方案时,可参考上述因素判断淋巴结转移风险.     

Early-stage primary signet ring cell carcinoma of the colon

Primary signet ring cell carcinoma of the colorectum detected at an early stage is very rare; most cases are detected at an advanced stage. Therefore, its progno-sis is poorer than that of ordinary colorectal cancer. A 56-year-old Korean man was seen at this hospital for management of signet ring cell carcinoma of the co-lon. Colonoscopic examination revealed a Ⅱa-like, ill-defined and flatly elevated 9-mm residual tumor in the cecum. Endoscopic mucosal resection was preformed. Pathological examination of the resected specimen re-vealed signet ring cell carcinoma that had invaded the lamina propria without venous or perineural invasion. Abdominal computed tomography (CT) and positron CT showed no evidence of primary lesions or distant me-tastasis. An additional laparoscopic right-hemicolectomy was performed; no residual tumor or lymph node me-tastasis was found. We report a case of primary signet ring cell carcinoma of the colon detected at an early stage and provide a review of the literature.     

Endoscopic features of early-stage signet-ring-cell carcinoma of the stomach

AIM: To identify the features of early signet ring cell gastric carcinoma using magnification endoscopy with narrow band imaging (NBI).METHODS: A retrospective review was conducted of 12 cases of early signet ring cell gastric carcinoma who underwent treatment in a single institution between January 2009 and April 2013. All patients had magnification endoscopy with NBI and indigo carmine contrast to closely examine the mucosal architecture, including the microvasculature and arrangement of gastric pits. Histologic examination of the final endoscopic submucosal dissection or gastrectomy specimen was performed and compared with the endoscopic findings to identify patterns specific to signet ring cell carcinoma.RESULTS: Twelve patients with early signet ring cell gastric carcinoma were identified; 75% were male, and average age was 61 years. Most of the lesions were stage T1a (83%), while the remainder were T1b (17%). The mean lesion size was 1.4 cm². On standard endoscopy, all 12 patients had a pale, flat lesion without any evidence of mucosal abnormality such as ulceration, elevation, or depression. On magnification endoscopy with NBI, all of the patients had irregularities in the glands and microvasculature consistent with early gastric cancer. In addition, all 12 patients exhibited the “stretch sign”, an elongation or expansion of the architectural structure. Histologic examination of the resected specimens demonstrated an expanded and edematous mucosal layer infiltrated with tumor cells.CONCLUSION: The “stretch sign” appears to be specific for signet ring cell carcinoma and may aid in the early diagnosis and treatment of this aggressive pathology.     

Ultrastructural cytochemical study of enzymes expressed by signet ring cells in gastric cancer

AIM: To study the ultrastructural localization of five marker enzymes (ALPase, ACPase, G6Pase, TPPase and CCOase) in gastric cancer signet ring cells to demonstrate their biologic behaviors.METHODS: Five marker enzymes were examined in signet ring cells of seven gastric cancer patients by ultrastructural enzyme cytochemical techniques.RESULTS: The number of corresponding organelles and the activities of marker enzymes, especially ACPase and TPPase, increased, leading to stronger mucus synthesis, secretion and digestion in gastric cancer signet ring cells. There was a lack of collagenous fibers in the stroma around the cancer nests.CONCLUSION: Signet ring cell carcinoma is very invasive with metastasis rates due to the secretion of proteolytic enzymes.     

Multiple depressed‐type colonic cancer (IIC)‐like configurations: metastases from gastric cancer

We present a rare case of multiple colonic metastases from advanced gastric cancer presenting colon depressed‐type multiple early cancer (IIc)‐like configuration. The case was a 74‐year‐old man who presented with a symptom of abdominal fullness. Colonoscopy and barium enema study revealed multiple IIc‐like lesions, which were shown histologically to be metastatic deposits of signet ring cell carcinoma. He had synchronous gastric cancer, which histologically demonstrated moderate to poorly differentiated adenocarcinoma with signet ring cell differentiation. In addition, he had concomitant multiple small bowel metastatic lesions. This appears to be the first published report of multiple IIc‐like colonic metastatic lesions from a gastric cancer.     

Gastric adenocarcinoma inducing portal hypertension： A rare presentation

Advanced gastric cancer usually presents with symptoms due to direct extension into adjacent viscera, distant metastases from lymphatic or hematogenic dissemination and peritoneal seeding. However, portal hypertension as a presentation of metastatic gastric cancer is rare and usually seen in association with other malignancies, e.g. hepatocellular and pancreatic carcinoma. We report a case of signet ring adenocarcinoma of the stomach that presented with esophageal and duodenal varices and bleeding due to portal hypertensive gastropathy. Pagetoid spread of cancer cells likely caused early metastasis and the unusual presentation. We also discussed the pathophysiology of development of portal hypertension in association with malignancies.     

Small gastrointestinal stromal tumor concomitant with early gastric cancer： A case report

The term gastrointestinal stromal tumors (GISTs)is defined diagnostically as the main group of mesenchymal tumors with spindle or epithelioid cells arising from the wall of the gastrointestinal tract with immunohistochemical reactivity for CD117 antibody.Previous studies revealed that cells in GISTs express a growth factor receptor with tyrosine kinase activity (termed c-kit), which is the product of the c-kit protooncogene. The most specific and practical diagnostic criteria for GISTs are: immunohistochemically determined c-kit (CD117) expression; mitotic score; and tumor size.A small GIST concomitant with early gastric cancer is rarely encountered clinically. Herein we have reported a case of a 1.1-cm GIST detected by esophagogastroduo denoscopy concomitant with a Ⅱc type of early gastric cancer (signet ring cell type). It was detected during a routine physical health examination. To our knowledge,this is the first report of a small GIST concomitant with a signet ring cell type of early gastric cancer.     

Minute signet ring cell carcinoma occurring in gastric hyperplastic polyp

We describe a 45-year-old woman with minute signet ring cell carcinoma occurring in a gastric hyperplastic polyp. A biopsy specimen obtained from the gastric hyperplastic polyp revealed signet ring cell carcinoma. Endoscopic mucosal resection （EMR） was performed to confirm the diagnosis. Histological examination of the EMR specimen revealed focal signet ring cell carcinoma in the hyperplastic polyp. There are few cases of gastric hyperplastic polyp associated with signet ring cell carcinoma.     

A case of early gastric cancer with bone metastases: are bone marrow micrometastases significant?

Gastric adenocarcinoma is currently the 14th cause of death worldwide. Early gastric cancer, defined as cancer not penetrating deeper than the submucosa, is considered to carry an excellent prognosis with 5-year survival rates reaching more than 90%. Cases of bone metastases due to intramucosal gastric cancer are very rarely described. A case of a 70-year old male presenting with confirmed bone metastases 7 years after a curative resection for a mucosal gastric carcinoma is discussed. The patient was investigated with bone marrow biopsy and bone scan and showed no other signs of disease. The clinicopathologic features included poor differentiation, signet ring cells presence, no lymph node involvement and a negative second laparotomy two years after the initial surgery. Studies concerning the presence of residual disease in the form of bone marrow micrometastases are briefly reviewed emphasizing that intramucosal gastric cancer still carries the p sibility for metastasis, many years after a curative resection, mandating long term alertness from the attending physician.     

Multiple early gastric cancer with gastritis cystica profunda showing various histological types

We report a case of multiple early gastric cancer showing varied histological types associated with gastritis cystica profunda (GCP). A 61-year-old man who had early gastric cancer associated with GCP underwent a distal gastrectomy with lymphadenectomy. Histological examination showed various histological types of cancer -well differentiated, moderately differentiated, poorly differentiated adenocarcinoma, mucinous adenocarcinoma and signet ring cell carcinoma- that had developed independently in the mucosal and submucosal layers of the resected specimen. Furthermore, multiple cysts with a single layer of columnar epithelium were present in the submucosa around the cancerous lesions. However, no neoplastic changes were found in those epithelial cells. Helicobacter pylori was detected in the residual stomach 3 months after surgery. Although the mechanism of the relationship between gastric carcinoma and GCPs is obscure, we speculate that repeated erosion and regeneration induced by chronic inflammation causes multicentric carcinogenesis as well as an aberration of the gastric glands. GCPs may be a risk factor for multiple gastric cancer.     

Nerve invasion as an independent predictor of poor prognosis in gastric cancer after curative resection

The study aims to reveal the clinical significance of perineural invasion (PNI) for gastric cancer prognosis and determine the risk factors of PNI in gastric cancer. This study retrospectively analyzed 350 patients who were diagnosed with GC and underwent curative surgical resection. Variables used to analyze survival included gender, age, degree of differentiation, T classification, lymph node metastasis, lymphovascular invasion, nerve invasion, mucinous adenocarcinoma component, and signet ring cell carcinoma component. The tumors of all patients were surgically resected. All resected specimens were stained with hematoxylin-eosin and immunohistochemical. The data for the patient’s lymphovascular invasion and PNI came from the collected pathological reports. The results of the survival analysis showed that T staging (P < .001), lymph node metastasis (P < .001), lymphovascular invasion (P = .013), PNI (P = .001), and signet ring cell carcinoma components (P = .046) affect the survival time and have a statistically significant difference. Multivariate analysis indicated that the positivity of PNI was an independent prognostic factor (P = .014). T staging (P = .006) and lymph node metastasis (P = .013) were independent prognostic parameters too. Using the Spearman correlation analysis, the following clinicopathological indicators were associated with PNI positivity, such as tumor differentiation, T staging, lymph node metastasis, vascular invasion, and signet ring cell carcinoma components (P < .05). PNI is an independent marker of poor prognosis in patients with gastric cancer.     

青年人与老年人胃癌临床病理及预后对比分析

目的探讨青年与老年胃癌的临床、内镜、术后病理特点及预后。方法回顾性总结我院2003年12月～2012年12月经胃镜检查,手术确诊的青年人(≤35岁)胃癌51例及老年人(≥65岁)胃癌284例,进行临床表现、内镜表现、术后病理分型及预后等对比分析。结果近年来,胃癌患病总人数下降,同期内老年人胃癌总人数多于青年人;青年组胃癌以女性多,老年组以男性多;青年组多在胃下1/3,老年组多在胃上1/3;内镜下青年组多表现为Borrmann Ⅲ、Borrmann Ⅳ,术后病理以低分化腺癌、黏液腺癌、印戒细胞癌为主;老年组以Borrmann Ⅰ、Borrmann Ⅲ为主,术后以高-中分化腺癌居多;两组胃癌手术方式无差异性;老年组1年、3年生存率高于青年组。结论青年人胃癌临床症状隐匿,病理分化差,预后差。早期胃镜检查、定期复查、幽门螺杆菌根除、手术是青年人胃癌治疗的关键。     

Risk of lymph node metastasis in mixed-type early gastric cancer determined by the extent of the poorly differentiated component

AIM: To predict the rate of lymph node (LN) metastasis in diffuse- and mixed-type early gastric cancers (EGC) for guidelines of the treatment.METHODS: We reviewed 550 cases of EGC with diffuse- and mixed-type histology. We investigated the clinicopathological factors and histopathological components that influence the probability of LN metastasis, including sex, age, site, gross type, presence of ulceration, tumour size, depth of invasion, perineural invasion, lymphovascular invasion, and LN metastasis status. We reviewed all slides and estimated the proportions of each tumour component; pure diffuse type, mixed-predominantly diffuse type (diffuse > intestinal type), mixed-predominantly intestinal type (intestinal > diffuse type), and mixed diffuse = intestinal type. We calculated the extents of the respective components.RESULTS: LN metastasis was observed in 12.9% (71/550) of early gastric cancers cases [15/288 mucosal EGCs (5.2%) and 56/262 submucosal EGCs (21.4%)]. Of 550 cases, 302 were diffuse-type and 248 were mixed-type EGCs. Of 248 mixed-type EGCs, 163 were mixed-predominantly diffuse type, 82 were mixed-predominantly intestinal type, and 3 were mixed diffuse = intestinal type. Mixed-type cases with predominantly diffuse type histology showed a higher frequency of LN metastasis (20.2%) than cases of pure diffuse type (9.3%) and predominantly intestinal type (12.2%) histology. We measured the dimensions of each component (intestinal and diffuse type) to determine the association of the extent of each component with LN metastasis in mixed-type gastric carcinoma. The total tumour size and the extent of poorly differentiated components was associated with LN metastasis, while that of signet ring cell components was not.CONCLUSION: We recommend careful identification and quantitative evaluation of mixed-type early gastric cancer components after endoscopic resection to determine the intensity of the treatment.     

早期胃癌淋巴结转移规律及内镜切除指征的探讨

目的探讨不同组织学类型早期胃癌的淋巴结转移情况及内镜下治疗的可行性。方法回顾性分析524例行胃癌根治术治疗并经病理确诊的早期胃癌患者的病例资料,比较不同组织学类型早期胃癌的临床病理特征并对其与淋巴结转移的相关性进行单因素及多因素分析。结果印戒细胞癌与分化型腺癌、低分化腺癌相比,在肿瘤大小（P值分别为0．048和0．023）和浸润深度（P值均为0．000）方面差异均有统计学意义,其淋巴结转移率（9．7％,11／113）明显低于低分化型腺癌（22．2％,20／90）,差异有统计学意义（P=0．018）,但与分化型腺癌（13．t％,42／321）比较差异无统计学意义（P=0．406）。单因素分析显示肿瘤大小（P=0．007）、浸润深度（P=0．000）、组织学类型（P=0．030）、淋巴管肿瘤浸润（P=0．000）和有无溃疡（P=0．002）与淋巴结转移显著相关;多因素分析结果显示浸润深度（P=0．007）、肿瘤大小（P=0．010）、组织学分型（P=0．000）和淋巴管肿瘤浸润（P=0．000）为淋巴结转移的独立危险因素。联合上述4个独立危险因素分析显示肿瘤直径小于2cm且无淋巴管肿瘤浸润的印戒细胞型黏膜内癌未见淋巴结转移。结论印戒细胞型早期胃癌的临床病理特征与分化型和低分化型早期腺癌存在差异,直径小于2cm且无淋巴管肿瘤浸润的印戒细胞型黏膜内癌患者可行内镜切除术。     

Expression transformation of claudin-1 in the process of gastric adenocarcinoma invasion

AIM： To investigate the relation of expression transformation of claudin-1 with invasiveness and metastasis of gastric carcinoma. METHODS： By using immunohistochemistry, expression of claudin-1 in mucosa and invasive front of 136 gastric adenocarcinoma cases and proliferative index （Ki-67） were detected and analyzed. RESULTS： In mucosa, the claudin-1 over-expression rate of mucinous adenocarcinomas （including signetring cell carcinomas） was the highest. It was negatively related with the differentiation but positively related with the invasiveness and metastasis of gastric cancer. In invasive front, the claudin-1 over-expression rate was positively related with the differentiation, invasiveness and metastasis of gastric carcinoma. The expression transformation of claudin-1 was found in gastric carcinoma. The expression of claudin-1 in invasive front was transformed in 28/136 gastric carcinoma cases. The transformation rate in highly differentiated tubular adenocarcinomas was the highest （51.5%, 17/33）. The deeper was the invasiveness, the higher was the transformation rate. The claudin-1 expression transformation rate in serosa and omenta was significantly higher （92.9%） than in tunica muscularis of invasive gastric cancer cases, as well as in patients with lymph node metastasis than in those without lymph node metastasis. CONCLUSION： Up-regulation of claudin-1 expression and its transformation in invasive and metastatic gastric carcinoma suggest that claudin-1 participates in the transformation of biological behaviors in neo- plasms. Further study is needed to elucidate the precise mechanism and the relation of claudin-1 expression with the neoplasm progress.     

Extensive bone marrow necrosis associated with carcinomatosis 7 years after operation for gastric cancer

A case of extensive bone marrow necrosis due to cancer metastasis is reported. A 55-year-old female, who had a history of subtotal gastrectomy for signet ring cell carcinoma of the stomach 7 years ago, was admitted to our hospital with a complaint of lumbago on October 25, 1987. Red blood cell count was 92 X 10(4)/microliters, hemoglobin 2.7 g/dl, hematocrit 8.0%, platelet 6.4 X 10(4)/microliters, and white blood cell count 13,400/microliters with leukoerythroblastosis. Bone marrow aspiration of the sternum, left iliac crest, and bilateral posterior superior iliac supine showed extensive bone marrow necrosis. Serum ALP was increased to 7410IU/l, dominated isozyme of bone type. Hemostatic findings suggested a complication of consumption coagulopathy. Skull, vertebrae, iliac and pelvic bone X-ray showed multiple osteolytic lesions, and irregular isotope uptake was recognized on the bone scintigraphy using 99mTc. Sixth bone marrow examination at the right iliac crest revealed signet ring cell carcinoma metastasis. In spite of detailed examinations, there was no evidence of primary carcinoma, including the remnant of stomach. We speculated that the signet ring cells were originated from the respected gastric cancer. The patient has received anti-cancer chemotherapy with UFT and OK432, and is still alive 9 months after diagnosis.     

Phenotypic classification of gastric signet ring cell carcinoma and its relationship with clinicopathologic parameters and prognosis

AIM: To distinguish subtypes of gastric signet ring cell (SRC) carcinoma by investigating the expression of gastric and intestinal phenotypic markers, and to study the significance of phenotypic classification in predicting tumor progression and outcome. METHODS: Immunohistochemistry was performed in 66 cases of SRC carcinoma with MUC2, VILLIN, CDX2, Li-cadherin antibodies as intestinal phenotype markers and MUC5AC, HGM, MUC6 antibodies as gastric phenotype markers, and the relationship was analyzed between the phenotypic expression pattern and clinicopathologic parameters, as well as the 3-year survival rate. RESULTS: Expression of intestinal phenotypic markers was positively associated with tumor size, wall invasion, vascular invasion, lymph node metastasis and tumor-node-metastasis (TNM) stage. Cases expressing one or more intestinal markers had a significant lower survival rate than cases expressing none of the intestinal markers. CONCLUSION: The SRC carcinomas expressing intestinal phenotype markers exhibited a high pro-liferative potential, bad biological behaviors and poor prognosis. Examination of phenotype expression may be useful in distinguishing histological type and in predicting the prognosis of gastric SRC carcinoma.     

Prophylactic lymph node dissection for early gastric cancer invading submucosa

BACKGROUND/AIMS: Prophylactic lymph node dissection for gastric cancer patients was considered to prolong survival time and D2 lymph node dissection was a standard treatment for early gastric cancer invading submucosa without lymph node metastasis. We investigated the possibility of minimizing the extent of prophylactic lymph node dissection for early gastric cancer invading submucosa if there was no evidence of lymph node metastasis. METHODOLOGY: We analyzed data on 404 patients with early gastric cancer invading the submucosa who underwent gastrectomy from 1979 to 1998 in the National Kyushu Medical Center, Fukuoka, Japan. The postoperative survival rate of patients with standard D2 dissection was compared with cases of those with limited D2 dissection which was defined as confined as D2 dissection dissections No.7 (lymph nodes were those along the left gastric artery), No.8 (lymph nodes along the anterosuperior common hepatic artery) and No.9 (lymph nodes along the celiac artery). RESULTS: Of the 404 patients, 52 and 17 had lymph node metastasis in group 1 and group 2 nodes, respectively. Of 17 patients with lymph node metastasis in group 2, 14 (82.4%) had metastasis confined to No.7, 8 and 9 of group 2 nodes. The 5-year survival rate of patients with submucosal cancer without lymph node metastasis was 94.4% after limited D2 dissection and 97.3% after standard D2 dissection, respectively. CONCLUSIONS: The appropriate prophylactic lymph node dissection for early gastric cancer invading the submucosa without lymph node metastasis was considered to be minimized to limited D2 dissection.