PEDUNCULATED GASTRIC SIGNET RING CELL CARCINOMA

Signet ring cell carcinoma (SRCC) is characterized by poor ductal formation and a diffuse progression pattern and generally presents as a depressed lesion in the majority of cases. We describe here an extremely rare case of gastric SRCC that presented as a pedunculated lesion. We hypothesize that the major factor responsible for the elevation of this lesion was proliferation of signet ring cells that did not lose their mutual connections. Among the two cases of early elevated‐type gastric SRCC that have been reported in the literature, this is the first case of pedunculated intramucosal SRCC. Pathological examination revealed no cancer cells in the basal part of the elevated lesion. The cellular morphology was consistent with SRCC, although the ductal structure was well preserved and more similar to well‐differentiated adenocarcinoma. Endoscopic examination showed a smooth‐surfaced lesion with no depressed region around the basal part of the elevated lesion. Because these findings differ significantly from previous reports of elevated SRCC, this report provides further insight into the nature of SRCC.     

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.     

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.     

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.     

A Small Gastric Cancer in Association with Menetrier Disease

Abstract: We studied a 57-year-old man who was diagnosed as having giant rugae at a mass-screening for gastric cancer. He was examined endoscopically for check-up purposes. In addition to giant rugal folds which occurred throughout the entire fundus and body of the stomach, a type IIc lesion was noted in the posterior lower wall of the gastric body. A biopsy revealed signet ring cell carcinoma. A total gastrectomy was performed. A resected specimen was serially sectioned and underwent histopathological examination; hypertrophy and cystic elongation of the gastric glands indicative of so-called giant hypertrophic gastritis was seen. The histological type of the type IIc lesion was undifferentiated adenocarcinoma with the signet ring cells being confined to the mucosal layer. This patient had a rare case of Menetrier's disease complicated by intramucosal carcinoma.     

SMALL EARLY GASTRIC CANCER OCCURRING IN A YOUNG WOMAN WITH NODULAR GASTRITIS

We found a small gastric cancer in a 25‐year‐old woman with nodular gastritis. Endoscopically, the cancer was identified as a whitish area in the gastric antrum. There was also a miliary pattern in the gastric antrum and corpus. In addition, serology and histology revealed the patient to have been infected by Helicobacter pylori. Histological examination of the resected stomach showed that the cancer was poorly differentiated adenocarcinoma with signet‐ring cell restricted to the mucosal layer. In the surrounding mucosa, there were chronic inflammatory cell infiltrates and enlarged lymphoid follicles with germinal centers. Our case suggests that nodular gastritis may be at a high risk for the development of gastric cancer of poorly differentiated type.     

Spontaneous antibody-secreting cells in the stomach of gastric cancer patients

The gastric mucosa has been regarded as an active site of humoral immunity since the discovery ofHelicobacter pylori. The present study was conducted to determine the in vivo activity of gastric B cells in 53 gastric cancer patients. B-cell activity was measured by protein-A plaque assay, in which IgA-, IgM-, and IgG-plaque-forming cells (PFC) were counted. The number of PFC was associated with the stage of cancer, but the response of lymphocytes in a non-tumorous area (NML) and tumor-infiltrating lymphocytes (TIL) differed. PFC in both sites were decreased compared to n0 cancer in n1 lymph node metastasis-positive cancer, while only NML showed raised PFC in n2+ (P<0.05, vs TIL). Cancer cells penetrating the submucosa caused the PFC of TIL (but not of NML) to decrease. Invasion of the intratumor capillary (V) or lymphatic (Ly) vessels also caused PFC to change, showing differences of Ig class; there was a decrease of PFC in V2 (IgG-and IgM-PFC) and in Ly2 (all Ig-PFC). IgA-PFC in Ly1 differed in TIL (decrease of PFC) and NML (increase). PFC also differed in TIL and NML in cancer cells, as follows: TIL<NML in tubular and poorly differentiated adenocarcinoma and TIL>NML in papillary and signet ring cell adenocarcinoma. Changes in lymph node (LNL) and blood lymphocytes were similar to those in gastric PFC whose IgA value was 10 times as much as that of LNL. The 5-year survival rate was significantly better in patients with lower rather than higher PFC such as 89% vs 68%. Gastric B cells thus appear to be active and to reflect gastric mucosal immunity.     

EARLY GASTRIC CANCER WITH WIDESPREAD DUODENAL INVASION WITHIN THE MUCOSA

We report a rare case of early gastric cancer confined to the mucosal layer with extensive duodenal invasion, curatively removed with distal gastrectomy. An 84‐year‐old Japanese woman was referred to our hospital with gastric cancer. A barium meal examination and esophagogastroduodenoscopy revealed an irregular nodulated lesion measuring 6.5 x 5.5 cm in the gastric antrum and an aggregation of small nodules in the duodenal bulb. A biopsy specimen showed well‐differentiated adenocarcinoma. The patient underwent distal gastrectomy with partial resection of the duodenal region containing the tumor and regional lymph node dissection, with no complication. Histological examination of the resected tissue confirmed well‐differentiated adenocarcinoma limited to the mucosal layer and without lymph node metastasis. The cancer extended into the duodenum as far as 38 mm distant from the pyloric ring, and the resected margins were free of cancer cells. Gastric cancer located adjacent to the pyloric ring thus has the potential for duodenal invasion, even when tumor invasion is confined to the mucosal layer. In such cases, care should be taken during examinations to detect duodenal invasion, and the distal surgical margin must be negative given sufficient duodenal resection.     

Gastric cancer with metastasis to the gingiva

The present case report describes a gastric cancer which showed unusual metastasis in the oral region. A 56-year-old male patient underwent total gastrectomy and splenectomy due to advanced gastric cancer in the upper third of the stomach. Fifteen months later, he presented with anorexia and gingival swelling of durations of approximately 3 and 1 month, respectively. The gastric tumor was histologically a signet ring cell and a poorly differentiated cancer with a moderate degree of vascular invasion. Biopsy specimens from the gingival tumor revealed a signet ring cell cancer. Other metastatic sites were the brain, limb bones and abdominal lymph nodes. A bone scintigram revealed an abnormal uptake in the limb bones, while it did not exhibit any abnormality in the oral region. Correlation between the histology of the gingival tumor with that of the gastric cancer, as well as the absence of a gingival tumor at the time of prior gastrectomy, led to a diagnosis that the gingival tumor was a metastasis from gastric cancer. Gastric cancer metastasizing to the oral region, either the osseus or the oral soft tissue, is very rare. Although it cannot be proved without an autopsy, negative findings in the mandible by bone scanning in the present case suggest that direct gingival metastasis can be considered, rather than mandibular metastasis involving the gingiva. Hematogenous spread could be a mechanism of metastasis for this unusual tumor.     

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.     

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.     

APUD cells in gastric cancer

Endocrine cells (APUD cells) of digestive mucosa can be source of neoplasias, usually called "carcinoids". Nevertheless, there are some reports in literature about the presence of APUD cells in carcinomas as a tumor component. However, these tumors seem to have not the biological and clinical behavior of carcinoids. These types of neoplasias have been reported mainly in stomach and colon. In the present work, the frequency of APUD cells was studied in 42 gastric carcinomas. Argyrophil cells were observed in six cases (14.3%) and argentaffin cells in one (2.3%); their histopathological pattern were well differentiated adenocarcinoma (5) and "signet ring cell carcinoma" (1). The APUD cell distribution and number in these neoplasias were quite irregular in each case examined and in different areas of the same case.     

Metastatic signet ring gastric adenocarcinoma presenting with microangiopathic hemolytic anemia.

Metastatic adenocarcinoma presenting as microangiopathic hemolytic anemia (MAHA) and leukoerythroblastic blood picture is rare. We report three patients who presented with MAHA as the initial symptom of metastatic signet ring cell gastric adenocarcinoma. One patient had past history of gastric ulcer. In all these patients the initial diagnosis was based on peripheral blood smear followed by bone marrow biopsy; upper GI endoscopy showed presence of gastric ulcers with focally scattered neo-plastic signet ring cells on histopathology. All patients died within a week of diagnosis.     

Cathepsins D and E in normal, metaplastic, dysplastic, and carcinomatous gastric tissue: an immunohistochemical study.

Immunohistochemical distributions of cathepsins D and E were determined in normal mucosa, metaplastic, dysplastic, and cancerous lesions of the human stomach. Cathepsins D and E were localised in the foveolar epithelium and parietal cells of the normal gastric mucosa, but their intracytoplasmic distributions were different - cathepsin E distribution was even and diffuse in the cytoplasm while cathepsin D was found in coarse intracytoplasmic granules. Chronic inflammation and ulcer did not influence the distribution of these enzymes. No positive staining was obtained in the incomplete type of intestinal metaplasia, dysplasia, and well differentiated adenocarcinoma. Tumour cells of signet ring cell carcinoma and poorly differentiated adenocarcinoma cells, however, gave strong and diffuse stainings for cathepsins D and E in the cytoplasm. The results suggest that the distribution of cathepsins D and E is related to each specialised function of the foveolar epithelium and the parietal cells, and that their disappearance is associated with development of well differentiated adenocarcinoma from intestinal metaplasia.     

Dedifferentiation of adenocarcinomas by activation of phosphatidylinositol 3-kinase

Signet ring cell carcinoma is a malignant type of poorly differentiated adenocarcinomas in stomach, which is characterized by the occasional presence of signet ring-like cancer cells. We found that expression of constitutively active phosphatidylinositol 3-kinase (PI 3-kinase) in well differentiated adenocarcinoma cell lines induced the loss of cell-cell contact and some of the cells changed their shapes to signet ring cell-like, characterized by appearance of mucus droplets in the cytoplasm with well developed endplasmic reticulum and Golgi complexes. The active PI 3-kinase-expressing cells formed poorly differentiated tumors in nude mice, which were clearly different from those of the original cell lines. The PI 3-kinase activities detected in anti-phosphotyrosine immunoprecipitates were higher in several signet ring cell carcinoma-derived cell lines than in other adenocarcinoma cell lines. In addition, PI 3-kinase was found to be associated with a 200-kDa protein phosphorylated in tyrosine in 4 of 6 signet ring cells but not in other cell lines, suggesting that PI 3-kinase is possibly activated in these cells by binding to the 200-kDa protein. The 200-kDa protein-PI 3-kinase complex was exclusively fractionated in the membrane fractions. The specific activity of the PI 3-kinase immunoprecipitated with anti-phosphotyrosine antibody was approximately 3-fold higher than that with anti-PI 3-kinase antibody. These results suggest that PI 3-kinase in signet ring cell carcinoma is recruited to the membrane and activated by the binding to the 200-kDa protein.     

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。     

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.     

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。     

Characterization of a newly established cell line (JR-St) derived from human gastric signet ring cell cancer, producing tumor markers.

Despite the importance of in vitro study of gastric cancer, there are very few established cell lines derived from human gastric carcinoma. We have recently established a new cell line derived from human gastric cancer which has the ability to produce tumor markers. This cell line has been designated JR-St. This cell line was derived from the cerebrospinal fluid of a 37-yr-old female patient who had metastatic brain tumor of signet ring cell gastric adenocarcinoma. This cell line has been maintained for more than 24 months through 80 passages with stable growth. PAS staining showed intracellular mucin granules. Transmission and scanning electron microscopy revealed cells with numerous microvilli and fine projections as well as intracellular granules, indicating mucin. This cell line had the ability to produce high concentrations of tumor markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9. Thus Thus this cell line should provide a very useful tool for the investigation of gastric cancer such as analysis of tumor markers as well as effects of anti-cancer drugs or growth factors.     

Case of early gastric cancer with nodular gastritis

A case of depressed early gastric cancer with nodular gastritis is described. A 47‐year‐old Japanese man was referred to our hospital and admitted for surgical treatment of gastric cancer. Barium upper gastrointestinal study and endoscopy examination showed a 4.5 × 3.0 cm depressed lesion with a deep central ulceration in the anterior wall of the lower corpus. An unusual miliary pattern resembling ‘goose flesh’ was observed endoscopically in the antrum. Biopsy specimens from the tumor showed poorly differentiated adenocarcinoma, and specimens from the antrum showed many lymphoid follicles with a germinal center. Immunoglobulin G antibody and histological tests (Giemsa stain) for Helicobacter pylori were both positive. Early gastric cancer with nodular gastritis was diagnosed and a subtotal gastrectomy was performed. Histological examination of the resected specimen showed a stage I tumor infiltrating a poorly differentiated adenocarcinoma with a depressed lesion in the corpus (type 0 IIc + III) and nodular gastritis in the antrum. The patient is doing well 1 year after surgery.