Gastric Carcinoids of Argyrophil ECL Cells

Histochemical and ultrastructural studies were carried out in four gastric carcinoids, two of which were associated with atrophic gastritis and pernicious anemia. All tumors showed intense argyrophilia and vesicular granules resembling those of endocrine enterochromaffinlike (ECL) cells in normal human gastric mucosa. Tumor cells were found to be unreactive to all the 18 available antiserums to gut hormones, including gastrin, somatostatin, glucagon, and pancreatic polypeptide. The tumors were interpreted as ECL cell argyrophil carcinoids with various degrees of differentiation and atypia.     

Smooth Muscle Cell Abnormalities Associated with Gastric ECL Cell Carcinoids

The histologic and immunohistochemical study of 45 ECL cell gastric carcinoids and of the extratumoral gastric mucosa revealed four variants of smooth muscle cell abnormalities: (1) hypertrophy of muscularis mucosae trapped within the tumors, a finding occurring in 76.5% of cases; (2) proliferation of stromal smooth muscle cells originating from the muscularis mucosae and mostly associated with tumor invasion of the submucosa (seen in 93.9% of cases with abundant stromal component of the tumors); (3) occurrence of frequent, prominent aggregates of smooth muscle cells in the lamina propria of the antral (but not of the fundic) mucosa of the stomach (found in 41.7% of cases); and (4) increased thickness of the extratumoral muscularis mucosae in the fundic (but not in the antral) mucosa of patients with gastric carcinoids. In addition, localized muscle cell proliferation was also associated with foci of micronodular hyperplasia of endocrine cells in the extratumoral mucosa. These findings were neither observed in control cases of gastric adenocarcinoma, gastric peptic ulcer, and duodenal peptic ulcer (10 unselected cases from each group) nor were they observed in 10 subjects with normal gastric mucosa collected at autopsy. With the possible exception of the increased thickness of the extratumoral fundic muscularis mucosae, which may be influenced by the mucosal inflammatory process, it is suggested that the present findings represent a proliferative response of smooth muscle cells to basic fibroblastic growth factor whose production by gastric carcinoids and their precursor lesions has recently been demonstrated.     

Ghrelin expression in hyperplastic and neoplastic proliferations of the enterochromaffin-like (ECL) cells

Ghrelin, a recently discovered peptide isolated from the gastric corpus mucosa, is believed to be important in the regulation of growth hormone secretion and has been shown to increase appetite and food intake as well. It may also have other gastrointestinal and cardiac functions. Because a cell of origin for ghrelin has not been convincingly identified in the gastric mucosa thus far, we studied the immunohistochemical expression of ghrelin in proliferative lesions of the enterochromaffin-like (ECL) cells—a cell that is not only exclusively confined to the gastric corpus mucosa but is its dominant endocrine cell type as well. Formalin-fixed, paraffin embedded tissues from three cases of gastric ECL cell hyperplasia and five ECL carcinoids (three with coexisting foci of diffuse, linear, and micronodular hyperplasia) were immunohistochemically stained for ghrelin, using a commercially available antibody. The Sevier-Munger stain for ECL cells and immunohistochemical stains for chromogranin, gastrin, serotonin, somatostatin, and vesicular monoamine transporter-2 (VMAT-2) were performed on parallel sections for correlation with the ghrelin staining results. All ECL cell carcinoids and hyperplastic lesions were positive for both the Sevier-Munger and the immunohistochemical stains for chromogranin and VMAT-2. Immunoreactivity for ghrelin was seen in 4/5 ECL carcinoids, all cases of ECL cell hyperplasia, as well as in all areas with linear and micronodular hyperplasia adjacent to the ECL cell carcinoids. In each instance, such staining was confined to the Sevier-Munger, and VMAT-2 positive cells only. Our findings indicate that the ECL cells are either the ghrelin-producing cells of the gastric mucosa or acquire the capability to synthesize ghrelin during proliferative states encompassing the entire hyperplasia to neoplasia spectrum. In view of the orexigenic and other known actions of ghrelin, the functional and/or biologic significance of ghrelin production in such ECL cell proliferations needs to be investigated further.     

Mast Cell Interaction with Tumor Cells in Small Early Gastric Cancer: Ultrastructural Observations

The authors studied the mast cells by light and electron microscopy in four small intramucosal early gastric cancers (EGC). Mast cells were found in the tumor stroma and among neoplastic cells of adenocarcinoma glands. Stromal and ad-enocarcinoma-infiltrating mast cells were ultrastructurally identified as T mast cells, and exhibited anaphylactic or piecemeal degranulation. Tumor cells in intimate contact with mast cells showed no cytopathic changes. These data do not support a mast cell-mediated cancer lysis, such as that reported in some systems in vitro. The interepithelial localization of T mast cell in adenocarcinoma glands is similar to that observed in some disease states, including interstitial cystitis, fibrotic lung disorders, and mucosal allergic reaction. The findings suggest that T mast cells may be involved in the pathophysiology of the host reaction to small intramucosal EGC.     

An Unusual Case of Multiple Gastric Carcinoids Associated with Diffuse Endocrine Cell Hyperplasia and Parietal Cell Hypertrophy

We describe a case of multiple gastric carcinoid tumors in a 47-year-old Japanese man. The patient had markedly elevated serum gastrin levels (>800 pg/mL), which were suppressed by secretin-pancreozymin administration. In the partial gastrectomy specimen, a total of 19 carcinoids arose from diffuse linear and micronodular hyperplasia of the oxyntic mucosal endocrine cells. The carcinoid cells were chromogranin A-positive. Except for a very small number of serotonin-positive cells in several carcinoids, none of the 19 reacted with a battery of antibodies to other bioactive neuroendocrine substances. The most prominent findings in this case were peculiar fundic glands that were distended with a proteinaceous substance and lined with large hypertrophic parietal cells. At the ultrastructural level, these cells showed poorly developed intracytoplasmic canaliculi and vesicotubular profiles, yet their large cytoplasm had numerous mitochondria. On the basis of our histological and ultrastructural findings we suggest that an intrinsic HCl secretion abnormality of the parietal cells may be responsible for the patient's hypergastrinemia. Since there have been no reports on similar parietal cells changes, it is possible that our case may represent a pathological entity not previously described.     

Ultrastructural Descriptions of Heterotypic Aggregation between Eosinophils and Tumor Cells in Human Gastric Carcinomas

A histological variant of gastric adenocarcinoma, characterized by an intense tumor-associated tissue eosinophilia (TATE), has been occasionally reported in the literature. The purpose of this ultrastructural study was to determine the interactions between frequently occurring eosinophils and tumor cells in gastric carcinoma characterized by TATE. Fresh tumor tissue of 92 gastric carcinomas was processed for both light and electron microscopic examination. Intense TATE was found in 7 out of 92 (7.6%) gastric carcinomas (6 of intestinal-type and 1 of diffuse-type). Electron microscopy, selectively performed in 7 cases with intense TATE, revealed eosinophils, singly or in groups, in contact with damaged or necrotic tumor cells. Activated eosinophils showing piecemeal degranulation were also found in intimate contact with viable tumor cells, characterized by plasma membrane caveolar invaginations. The authors regard this close morphological relationship as in vivo evidence for possible cross-talk between eosinophil and viable tumor cell, a conclusion that has already been drawn from experimental studies, but until now inadequately supported by ultrastructural observations in a human tumor.     

Gastric and intestinal mixed and solely intestinal types of intestinal metaplasia in the human stomach

To generate a novel understanding of Intestinal metaplasia (IM) on the basis of cellular differentiation status, a total of 132 gastric surgical specimens were studied using gastric and small intestinal cell markers by much histochemical and Immunohistochemical techniques. The cases were divided into two types: (i) gastric and intestinal (GI) mixed type; and (ii) solely intestinal (I) type, with the reference to the presence of gastric and/or intestinal cell markers. The GI mixed type was subdivided into six subtypes: (i) a subtype consisting of surface mucous (Su), pyloric gland (Py), Intestinal absorptive (Ab), and goblet (Go) cells, but lacking Paneth (Pa) cells, GI(Pa-); (ii) a GI(Pa-) subtype without Py cells, GI(Py-, Pa-); (iii) a GI(Pa-) subtype without Su cells, GI(Su-, Pa-); (iv) a GI(Su-, Pa-) subtype with Pa cells, GI(Su-, Pa+); (v) a Gi(Pa-) subtype with Pa cells, GI(Pa+); and (vi) a GI(Pa+) subtype without Py cells, GI(–, Pa+).The I type was subdivided Into: (I) a subtype consisting of cells with Ab and Go cells, I(Pa-); and (ii) a I(Pa-) subtype with Paneth cells, I(Pa+). The GI mixed subtypes, except for the GI(Py-, Pa-) and GI(Py-, Pa+), were characterized by Intestinalized gastric plts connected with underlying pyloric glands. Immunohistochemical staining of proliferating cell nuclear antigen (PCNA) revealed a common prolifemtive cell zone between the two. The GI mixed type, especially the GI(Pa-) subtype, predominated in the pyloric mucose, while the I type was most frequent In the fundle region, suggesting that the pathogenesis of IM differs between these two locations. The results of the study confirm that IM is an abnormal and unstable differentiation status between the stomach and small Intestine.     

人胃癌肿瘤浸润树突状细胞的形态学观察

目的　探讨人胃癌肿瘤浸润树突状细胞 (TIDC)的形态学特征。方法　应用免疫组织化学、光镜和电镜的方法观察人胃癌TIDC的分布和形态学变化。结果　TIDC主要分布癌周区 ,病变早期TIDC比病变晚期数量 (P <0 0 1)。电镜下 ,TIDC体积较大 ,形态不规则 ,表面有许多树突状突起 ,细胞核不规则 ,可见核仁 ,胞质内有丰富的线粒体、核糖体、高尔基复合体和内质网。TIDC与肿瘤浸润淋巴细胞 (TIL)和肿瘤接触方式和形式上呈多样性 ,一对一 ,一对多 ,或形成簇的接触方式 ,有紧密膜接触、指状膜接触和球状膜接触形式。结论　本实验提示TIDC数量多少与肿瘤的进展有关 ,TIDC与肿瘤浸润淋巴细胞和肿瘤细胞之间关系密切。     

Gastric hepatoid adenocarcinoma with autophagy-related necrosis-like tumor cell death: report of a case

A case of hepatoid adenocarcinoma of the stomach is presented. The characteristic features of the tumor are summarized on the basis of the authors' experience and the literature. Ultrastructural examination revealed patchy condensations of chromatin throughout the nucleus suggestive of necrosis-like programmed cell death (PCD). These nuclear alterations were associated with the occurrence of vacuoles and lipofuscins, conferring an autophagic phenotype to this PCD. Thus, the case reported here provides an example of autophagic-related necrosis-like PCD. Alternative PCDs are reviewed and their morphologic distinction is discussed.     

Gastric mucosal mast cells in atopic subjects

Intragastral allergen provocation under endoscopic control (IPEC) allows direct observation of gastric mucosa reactions after contact with inhalant allergens that reach the stomach. We selected patients with proved atopy to Parietaria but without clinical and endoscopic signs of gastric disease, and we tested them with the specific inhalant allergen during IPEC, recording gastric macroscopic reaction and mucosal mast-cell changes in biopsy specimens. All atopic patients showed visible changes in gastric mucosa quantified as IPEC score. Mast-cell numbers detected in atopic patients (135.4 ± 102.6/mm² of stromal area) were significantly higher than in nonatopic subjects (59.8 ± 25.4/mm²; P <0.03) and were positively correlated to atopic IPEC score ( P <0.01). In addition, 6/12 atopics who had both higher mast-cell counts and IPEC score showed an intraepithelial distribution of gastric mast cells which displayed ultrastructural features of partial degranulation. It is likely that changes observed in our patients with allergy to Parietaria reflect a subclinical activation of mast cells in the gastric mucosa.     

胃癌中内分泌细胞与癌分化程度的关系

利用11例胃类癌和13例胃低、未分化癌的切除标本,探讨内分泌细胞出现的数量与胃癌类型和分化程度的关系。切片均作了嗜银、亲银组化染色,并用4种神经内分泌抗血清(胃泌素、生长抑素、胰多肽、血清素)PAP法免疫组化染色,4例作了电镜检查。结果胃类癌每例至少一项阳性,其中4例电镜证实有神经分泌颗粒;低、未分化癌组多数病例各项检查阴性,但4例不同阳性结果,其中2例阳性细胞数超过50%,可称内分泌细胞癌。表明肿瘤愈原始,愈多向分化。最后对胃癌中内分泌细胞与癌分化程度的关系,以及胃类癌和胃内分泌细胞癌的特征、名称和组织发生进行了讨论。     

腹腔镜联合胃镜行胃间质瘤切除术对胃间质瘤患者 术后康复及并发症的影响分析

目的 研究腹腔镜联合胃镜行胃间质瘤切除术对胃间质瘤患者术后康复及并发症的影响。方法 选取我院胃间质瘤患者52例,按手术方式不同分组,各26例。对照组给予开腹胃间质瘤切除术治疗,观察组给予腹腔镜联合胃镜行胃间质瘤切除术治疗,比较两组患者手术时长、失血量,术后排气时间、引流管拔除时间、住院天数及并发症发生情况。结果 观察组手术时长、失血量、排气时间、拔除引流管时间低于对照组,住院天数少于对照组,差异有统计学意义（P＜0.05）。观察组并发症发生率为3.85%,低于对照组的30.77%,差异有统计学意义（P＜0.05）。结论 腹腔镜联合胃镜行胃间质瘤切除术应用于胃间质瘤患者可减少术中失血量,缩短手术用时、排气时间、引流管拔除时间,减少住院天数,且并发症较少,值得应用推广。     

Polyvinylpyrrolidone Storage Disease: A Source of Error in the Diagnosis of Signet Ring Cell Gastric Adenocarcinoma

False-positive and false-negative diagnoses of cancer seldom occur during evaluation of gastric mucosal biopsy specimens obtained during flexible fiberoptic endoscopy of the stomach. When they do occur, false-negative diagnoses are usually the result of undersampling of the lesion, whereas false-positive diagnoses are the result of overinterpretation of benign histologic lesions. The diagnosis of diffuse signet ring cell adenocarcinoma is associated with both false-positive and false-negative diagnoses of cancer. The signet ring cell can be easily overlooked. Mucicarminophilic cells can be overinterpreted as diffuse signet ring cell adenocarcinoma. Polyvinylpyrrolidone is an unusual cause of this type of false-positive diagnosis of gastric adenocarcinoma. Judicious use of histochemical stains, immunohistochemistry, and electron microscopy plays a significant role in avoiding the false-positive diagnosis of diffuse signet ring cell adenocarcinoma.

The authors wish to acknowledge the diagnostic assistance provided by Dr Jan Kennedy, Department of Pathology, Grady Memorial Hospital; Dr Robert Pascal, Department of Pathology, Emory University; Dr Henry Appelman, Department of Pathology, University of Michigan Hospitals; Dr Frank B. Johnson, Chief, Chemical Pathology at the Armed Forces Institute of Pathology, Washington, DC, and Dr Leslie H. Sobin, Chief, Gastrointestinal Pathology at the Armed Forces Institute of Pathology, Washington, DC.     

胃癌细胞抗脱落凋亡的分子机制

目的探求胃癌细胞抗脱落凋亡的信号转导机制。方法用soft agar实验观察信号分子抑制剂对胃癌细胞非锚定生长的影响,流式细胞仪检测信号分子抑制剂对脱落培养胃癌细胞周期的影响及凋亡诱导作用,Western印迹检测胃癌细胞脱落培养后相关信号分子表达水平及活性的变化。结果信号分子抑制剂genistein、AG17和AG825完全抑制了胃癌细胞集落的形成、阻滞细胞于细胞周期的不同时期,而且诱导细胞脱落凋亡的作用比较明显;而LY、PD和SB作用细胞后,所形成的细胞集落与对照组相比略小、数目略少,亦阻滞细胞于细胞周期的不同时期,但是诱导细胞脱落凋亡的比例较低。Western印迹检测发现,胃癌细胞脱落培养24 h后,细胞的蛋白酪氨酸磷酸化水平明显增加,ERK的表达水平无显著差异,但是ERK-p水平显著升高。结论蛋白酪氨酸激酶、HER2激酶、ERK激酶和PDGFR激酶途径是胃癌细胞抗脱落凋亡的重要信号通路和信号分子。PI-3K途径和p38MAPK分子与胃癌细胞锚定非依赖性增殖密切相关,与胃癌细胞的锚定非依赖性存活无关。     

Comparative electron microscopic features of normal intermediate and metaplastic pyloric epithelium

The ultrastructural appearance of surface epithelial cells of normal and abnormal pyloric epithelium is presented. In addition to areas of complete intestinal metaplasia (IM) an incomplete metaplasia is described which contains poorly differentiated mucous cells, goblet cells, an occasional immature absorptive cell as well as the mature mucus-secreting surface epithelial cells of normal pyloric epithelium. This type of epithelium frequently appeared hyperplastic and showed alterations in the surface microvilli, terminal webs, plasma membranes and mucin granules. Apical vesicles, small electron-dense bodies and larger electron-dense multivesicular bodies were also found in the intermediate cells of incomplete IM and in the mature absorptive cells of complete IM. The intermediate cells described here may be synonymous with the sulphomucin-secreting cells found in adenocarcinomas of the stomach and oesophagus.     

ECL法检测前列腺特异抗原的临床价值

目的 :探讨前列腺特异性抗原 (PSA)浓度测定在前列腺疾病诊断中的应用价值。方法 :采用电化学发光免疫分析 (ECL)法检测 81例健康对照者、5 8例前列腺炎患者、1 2 1例良性前列腺增生 (BPH)患者和 6 9例前列腺癌 (PCa)患者血清中的PSA浓度 ,对检测结果进行统计分析。组间两两比较用t检验 ;良、恶性鉴别诊断界值的确定用ROC曲线。结果 :(1 )前列腺癌组患者血清PSA浓度明显高于其它各组 (p皆 <0 0 0 1 ) ;前列腺增生组部分病人血清PSA浓度升高 (与健康对照组和炎症组比较 p <0 0 0 1 ) ,但局限在一定范围 ,一般不超过 1 0ng/ml;前列腺炎组和健康对照组均在正常范围 (<4ng/ml)。 (2 )ROC曲线下面积为 0 98,当鉴别界值为4ng/ml时 ,灵敏度为 1 0 0 % ,特异度为 77 3% ;界值为 1 8ng/ml时 ,特异度 1 0 0 % ,灵敏度 6 8 1 % ;界值为 7 6ng/ml时 ,灵敏度为 95 7% ,特异度为 90 %。结论 :PSA是筛查前列腺癌的灵敏的肿瘤标志物 ,对良、恶性前列腺疾病有一定的鉴别诊断意义。     

Ultrastructural Studies of Glioma Stem Cells/Progenitor Cells

Although the ultrastructural features of several brain tumor cells have been studied in details, the ultrastructure of glioma stem cells/progenitors cells (GSPC) has rarely been reported. In this paper, the authors describe the ultrastructural features of GSPCs isolated from both a glioma tissue and the human glioma cell SHG-44 cell line. The ultrastructural features of the two kinds of GSPCs were similar, with relatively developed mitochondria, Golgi apparatuses, ribosomes, undeveloped rough endoplasmic reticula, seldom lysosomes and no typical autophagosomes, and high nuclear–cytoplasmic ratio. Their nuclei, frequently containing huge amounts of euchromatin and a small quantity of heterochromatin, were mostly globular; and the majority of the nuclei had only one nucleole. Typical apoptotic cells could hardly be found in tumor spheres, and between adjacent cells there were cell junctions, which probably were incompletely developed desmosomes or intermediate junctions. In conclusion, their ultrastructural features showed that GSPCs were at the primary stage of differentiation, and could even partially reveal the underlying reasons for the malignant proliferation and differential inhibition of GSPCs.     

Ultrastructural and histochemical identification of sclerosing liposarcoma

A paratesticular tumour by light microscopy showed large amounts of partly hyalinized collagenous stroma, spindle shaped fibroblast-like cells, pleomorphic cells with foamy cytoplasm, multinucleated tumour type giant cells and lipid inclusions. By light microscopy, there was a problem as to whether the tumour should be classified with the liposarcomas or with the fibrous histiocytic group. Ultrastructurally, spindle shaped cells resembled fibroblasts and, in a few cells, intracellular collagen fibres were seen. Histochemical studies revealed the presence of mannose-rich glycoprotein which is characteristic for collagen producing cells, but frequently these cells also showed numerous lipid inclusions. The foamy cytoplasmic areas of pleomorphic cells were shown to consist of dilated ergastoplasmic sacs and large vacuoles lined by smooth endoplasmic reticulum negating the possibility that these cells were of histiocytic origin. This is supported further by the dearth of lysosomes and absence of lysozyme (muramidase) in the tumour cells. The presence of numerous lipid inclusions in many of the tumour cells, which are otherwise ultrastructurally similar to fibroblasts, suggests that these cells represent precursors of lipoblasts. The above findings taken together allowed the tumour to be categorized as a sclerosing liposarcoma.     

Human bone marrow mast cells in systemic mast cell disease

In a case of systemic mast cell disease with moderate bone marrow involvement, we studied the sensitivity of mast cell cationic dye-binding to formaldehyde fixation, as well as the mast cell ultrastructure, so as to determine whether these cells possess characteristics of mucosal mast cells. This histochemical method has proved to be one of the few which reveal heterogeneity of the mast cells in human intestine. Even though rat bone marrow mast cells have been shown to belong to the mucosal mast cell compartment, we have found no difference in mast cell counts in samples fixed either in formaldehyde or Carnoy's fixative. The ultrastructure did not show major differences with cutaneous mast cells. A few cells presented two nuclei, suggesting mitotic division of mature mast cells in bone marrow.     

Histochemical and ultrastructural studies of inclusion bodies found in tissues from three siblings with 1-cell disease

Tissues from three siblings with inclusion-cell (l-cell) disease (a 16 month old boy and two fetuses aborted at 20 and 18 weeks) were investigated histologically, histochemically and ultrastructurally. The lymphocytes, fibroblasts, endothelial cells, epithelial cells and histiocytes of various organs were affected. The cells had many intracytoplasmic vacuoles, which showed positive staining with colloidal iron, periodic acid-Schiff (PAS), alcian blue, and Sudan III and IV. Ultrastructurally, the cells contained various inclusion bodies, showing vesicles, granules, flocculent material, amorphous electron-dense globules and myelin structures. The amounts and ultrastructural features of the inclusion bodies differed among the various kinds of cells.