胃超高分化腺癌12例临床病理学特征分析

目的探讨胃超高分化腺癌(very well differentiated adenocarcinoma,VWDA)的临床病理学特征。方法收集2013年1月至2021年5月解放军联勤保障部队第九八九医院平顶山医疗区(原第一五二中心医院)诊断的胃VWDA 12例,收集患者的临床病理资料,观察其组织形态学特征和免疫表型,并结合文献进行分析。结果12例患者中男8例,女4例,中位年龄63岁(范围47~80岁)。胃上部6例,胃中部2例,胃下部4例。肿瘤中位直径17 mm(范围5~65 mm)。构成肿瘤的细胞类似吸收细胞、Paneth细胞、小凹上皮细胞和杯状细胞。细胞单层排列,核轻度增大位于基底侧,核呈纺锤形至轻度不规则形,核极向紊乱。早期胃管状VWDA 9例,肿瘤腺管类似肠上皮化生的腺管,其中2例浸润至黏膜下层,黏膜深部及黏膜下层的病变表现为腺管囊性扩张、弯曲、分支、尖角,以及流产型腺管。早期胃乳头状管状VWDA 1例,癌局限于黏膜层内,由小凹型上皮细胞构成。胃进展期乳头状管状VWDA 2例,由小凹型上皮、幽门腺或颈黏液细胞构成,且伴有淋巴管内癌栓和淋巴结转移。所有病例背景黏膜均见萎缩和肠上皮化生。免疫组织化学染色显示肠型1例,胃肠混合型9例,胃型2例。仅局限于黏膜内的8例胃VWDA Ki-67阳性指数40%~70%,2例浸润到黏膜下层的癌和2例进展期癌Ki-67阳性指数10%~25%。所有肿瘤均显示p53蛋白呈野生型表达模式、HER2阴性。在术前活检中被诊断为腺癌或高级别异型增生5例、慢性萎缩性胃炎伴肠上皮化生7例。术后中位随访时间28个月(范围12~72个月),10例早期癌未见复发;2例进展期癌中1例发生肺转移,另1例死亡。结论胃VWDA是罕见的低度恶性肿瘤,具有高分化腺癌的结构特征和极低度的细胞学异型性。结构异型性的诊断价值显著大于细胞学异型性,黏膜深部和黏膜下层的不规则腺管浸润性生长是诊断的可靠依据。黏膜内VWDA诊断具有挑战性,活检标本中的部分病例难以明确诊断。     

Ki-67在胃癌及癌旁组织中的表达

目的:探讨Ki-67在胃癌和癌旁黏膜上皮中的表达、分布特征及其在胃癌组织发生学上的意义。方法:采用免疫组化方法对36例胃癌及癌旁组织进行检测。结果:胃腺癌与癌旁伴异型增生慢性萎缩性胃炎Ki-67阳性率无显著性差异;胃腺癌与癌旁伴高、中增殖型肠上皮化生慢性萎缩性胃炎Ki-67阳性率无显著性差异(P>0.05)。结论:Ki-67是一种较好的癌前标志物,胃黏膜上皮异型增生和高、中增殖型肠上皮化生萎缩性胃炎与胃癌的发生密切相关。     

宫颈胃型腺癌伴肠母细胞样特征1例

宫颈胃型腺癌伴肠母细胞样特征目前文献报道较少。本文报道1例宫颈肿瘤, 细胞学查见胞质含透亮空泡的单个或小的三维立体状细胞, 以及含黏液空泡的拥挤的蜂窝状细胞团, 肿瘤细胞核中度异型, 染色质深染, 核膜不规则, 可见核仁。组织学显示肿瘤排列成实性巢状及腺管状, 巢状肿瘤细胞胞质含透明空泡, 表现为胚胎性肠上皮样形态;腺管状肿瘤胞质富含细小黏液空泡。实性巢状肿瘤细胞阳性表达SALL4、甲胎蛋白、Glypian3、CDX2, 阴性表达p16。腺管状肿瘤细胞阳性表达PAX8、MUC6, 阴性表达p16。     

141例胃癌临床病理分析(附30例超微结构观察)

本组病例男女之比为2.36:1,好发年龄为40～69岁;常发部位为幽门窦部;以溃疡型为多。光镜检查;管状腺癌占48.9%,其余依次为粘液腺癌,未分化癌、乳头状腺癌、印戒细胞癌、低分化腺癌、鳞状细胞癌、腺鳞癌。对30例各型胃癌新鲜活体组织进行电镜观察;胃癌细胞具有一般癌细胞超微结构特点。胃乳头状腺癌和管状腺癌管腔面有密集或较密集的微绒毛,胞浆内有丰富的线粒体和粗面内质网;粘液细胞型腺癌等癌细胞多呈单个游离状态,细胞间连接极少;肠型上皮癌细胞所含粘液颗粒电子     

胃底腺型胃癌2例临床病理观察

目的探讨胃底腺型胃癌(gastric adenocarcinoma of fundic gland type, GA-FG)的临床病理学特征、诊断及鉴别诊断。方法分析2例GA-FG的内镜、组织形态学和免疫表型特征。结果 2例患者分别为46岁女性和77岁男性,均伴有胃部胀满、嗳气,胃底腺息肉病史。内镜特征:2例均为表浅隆起型病变(0～Ⅱa),病变处黏膜颜色正常伴表面小血管充血,边界可见。镜下病变表面被覆无异型的胃小凹上皮,固有层腺体轻度异型增生,排列紊乱融合,由2种细胞构成:一种类似胃底腺主细胞,另一种类似壁细胞,以前者为主。病灶最大径分别为5 mm及2.5 mm,浸润黏膜下层(浸润深度分别为0.5 mm及0.4 mm),无间质反应及脉管侵犯。周围胃黏膜未见萎缩等异常,未查见幽门螺旋杆菌。免疫表型:异型腺体MUC6、pepsinogen-I弥漫(+),H~+/K~+-ATPase、p53散在(+),Ki-67增殖指数5%～10%,β-catenin胞膜/质(+)。结论 GA-FG是一种新的组织学类型胃癌,具有独特的临床病理特征,预后良好,但需要长期随访。     

肾脏原发黏液性囊性肿瘤3例临床病理分析

目的观察3例肾脏原发性黏液性肿瘤的临床病理特征。方法回顾性分析2 000余例肾脏肿瘤,其中3例肾脏原发性黏液性肿瘤,分析其临床病理特征并复习相关文献。结果 3例均呈囊性病变,囊壁均可见衬覆肠黏膜样腺上皮,细胞有明显异型性,肿瘤细胞内均可见黏液产生;3例腺上皮均形成乳头状结构。3例囊内均充满黏液,2例为多房囊样,2例囊内见实性肿瘤团块伴囊壁间质浸润性生长。临床有结石或其他导致尿路梗阻病史,常伴发血清CEA和CA199水平升高,术后降至正常。其中1例为马蹄肾同时发生黏液腺癌伴神经内分泌分化。AB/PAS、HID染色提示为不完全性小肠型肠上皮化生。结论肾脏黏液性肿瘤是一种罕见尿路上皮来源肿瘤,其发病与尿路梗阻所致尿路上皮肠上皮化生有关,术后检测CEA和CA199水平有利于了解肿瘤转移与复发。     

利用图象分析诊断胃良,恶性病变的可行性研究

目的：探讨胃的慢性炎症、肠上皮化生、异型增生、癌与ＤＮＡ指数（ＤＩ）及倍体分布的关系。方法：慢性胃炎３２例、肠上皮化生３１例、异型增生３４例、癌７３例，用多媒体彩色病理图文分析系统（ＭＰＩＡＳ－５００）测量各组病变细胞核ＤＩ值及倍体分布情况。结果：ＤＮＡ含量在各组病变胃粘膜中有显著差异（Ｐ＜０．００１）；倍体构成在慢性炎症、肠上皮化生、异型增生之间无显著差异（Ｐ＞０．０５），慢性炎症、肠上皮化生、异型增生与癌之间差异均有显著性（Ｐ＜０．０５）。结论：胃良、恶性病变细胞核ＤＮＡ含量及非整倍体细胞所占百分比不同。形态定量分析检测细胞核ＤＩ值及ＤＮＡ倍体分布，可作为胃良、恶性病变诊断和分类的辅助诊断，并有助于指导临床治疗和估计肿瘤的恶性潜能，以判断预后     

Mucinouscarcinoma of kidney: 3 cases report and literature review

目的 观察3例肾脏原发性黏液性肿瘤的临床病理特征.方法 回顾性分析2 000余例肾脏肿瘤,其中3例肾脏原发性黏液性肿瘤,分析其临床病理特征并复习相关文献.结果 3例均呈囊性病变,囊壁均可见衬覆肠黏膜样腺上皮,细胞有明显异型性,肿瘤细胞内均可见黏液产生;3例腺上皮均形成乳头状结构.3例囊内均充满黏液,2例为多房囊样,2例囊内见实性肿瘤团块伴囊壁间质浸润性生长.临床有结石或其他导致尿路梗阻病史,常伴发血清CEA和CA199水平升高,术后降至正常.其中1例为马蹄肾同时发生黏液腺癌伴神经内分泌分化.AB/PAS、HID染色提示为不完全性小肠型肠上皮化生.结论 肾脏黏液性肿瘤是一种罕见尿路上皮来源肿瘤,其发病与尿路梗阻所致尿路上皮肠上皮化生有关,术后检测CEA和CA199水平有利于了解肿瘤转移与复发.     

肾集合管癌的临床病理分析

目的 观察肾集合管癌的临床病理特点,探讨其病理诊断与鉴别诊断.方法 对2例肾集合管癌的临床特点、病理学检查进行观察,采用免疫组化EnVision法检查CK7、CK19、CK20、34βE12、vimentin、CD10、P504S、E-cadherin的表达.并选择9例Ⅱ型、核分级为Ⅲ级的乳头状肾细胞癌、6例伴广泛肾实质侵犯的肾盂高级别尿路上皮癌与肾集合管癌进行形态学与免疫表型的比较.结果 肾集合管癌占同期上皮性肿瘤的0.66%,血尿为主要临床表现,1例患者术后3月死于肺转移.肿瘤均位于肾髓质,以管状结构为主,伴有肉瘤样分化,广泛侵犯肾实质,间质纤维化及中性粒细胞反应,周围集合管可见异型增生;免疫组化CK19及vimentin( ,2/2)、CK7及34βE12( ,1/2),CK20、CD10、P504S、E-cadherin均阴性.Ⅱ型乳头状肾细胞癌、尿路上皮癌未见集合管上皮异型增生;乳头状肾细胞癌表达vimentin( ,8/9)、CD10及P504S( ,7/9)、CK7( ,3/9)、CK19( ,1/9),34βE12、E-cadherin、CK20均阴性;尿路上皮癌CK7、CK19、34βE12均( ,6/6),E-cadherin( ,5/6),CK20( ,4/6),CD10、p504s、vimentin均阴性.结论 集合管癌是一种少见、高度恶性的肾上皮性肿瘤,形态和免疫表型多样化.灰白色肿块位于髓质、周围集合管上皮异型增生,无肾盂尿路上皮异型增生及原位癌存在可与乳头状肾细胞癌、尿路上皮癌鉴别.CD10、CK19、34βE12、P504S 、E-cadherin的染色有助于鉴别诊断.     

十二指肠腺增生性病变18例临床病理分析

目的探讨十二指肠腺增生性病变的临床病理学特点、免疫表型、诊断及鉴别诊断。方法回顾性分析18例十二指肠腺增生性病变的临床资料、病理学特征、免疫表型,并复习相关文献。结果患者发病年龄35～71岁,男、女性各9例。18例患者中十二指肠腺增生、十二指肠腺错构瘤各9例,两者的形态及病变大小无明显差异。十二指肠腺错构瘤的镜下表现比十二指肠腺增生多样,且其腺体可伴上皮内瘤变,免疫组化标记p53、Ki-67及Muc5AC可以辅助诊断。大部分十二指肠腺增生性病变的表面黏膜均有Muc5AC不同程度的表达,提示表面黏膜有不同程度的胃小凹化生,部分表面黏膜还可见糜烂及溃疡形成。结论十二指肠腺增生性病变临床罕见,包括十二指肠腺增生和十二指肠腺错构瘤,两者主要通过镜下形态特点进行鉴别。采用免疫组化检测可鉴别十二指肠腺的上皮内瘤变或原位癌变与硬化性改变;表面黏膜的胃小凹化生、糜烂及溃疡形成提示病变可能的发生、发展机制。     

Marked epithelial hyperplasia of the rat glandular stomach induced by long-term administration of iodoacetamide

Iodoacetamide (IAA), an ulcerogenic compound, was continuously given to male Wistar rats for up to 74 weeks. No carcinomas developed but marked glandular hyperplasias were frequently observed accompanied by chronic ulcer or erosion in the fundic region. They showed pseudo-invasive growth into the submucosa, the granulomatous tissue and even into the muscle layer, but no cellular and nuclear atypia was observed in their glands. Characteristically the mucosal damage caused by chronic IAA treatment was restricted to the fundic mucosa along the limiting ridge. Abnormally regenerated mucosa in the damaged area showed pyloric gland type metaplasia, demonstrated histochemically by paradoxical concanavalin A-staining and high-iron diamine-Alcian blue staining for mucin. No intestinal metaplasia was observed in these mucosa.     

MARKED EPITHELIAL HYPERPLASIA OF THE RAT GLANDULAR STOMACH INDUCED BY LONG-TERM ADMINISTRATION OF IODOACETAMIDE

Iodoacetamide (IAA), an ulcerogenic compound, was continuously given to male Wistar rats for up to 74 weeks. No carcinomas developed but marked glandular hyperplasias were frequently observed accompanied by chronic ulcer or erosion in the fundic region. They showed pseudo-invasive growth into the submucosa, the granulomatous tissue and even into the muscle layer, but no cellular and nuclear atypia was observed in their glands. Characteristically the mucosal damage caused by chronic IAA treatment was restricted to the fundic mucosa along the limiting ridge. Abnormally regenerated mucosa in the damaged area showed pyloric gland type metaplasia, demonstrated histo-chemically by paradoxical concanavalin A-staining and high-iron diamine-Alcian blue staining for mucin. No intestinal metaplasia was observed in these mucosa.     

Intestinal metaplasia of the stomach--the significance of single-layer and double-layer metaplasia

Resected early gastric carcinomas (1,690 cases) and atypical epithelial proliferations (adenomatous lesions, 310 cases) were investigated by the 5 mm-wide step sections. There were two types of intestinal metaplasia; double-layer type, where intestinal metaplasia was in the superficial area with the remaining pyloric or pseudopyloric glands in the deep region of the propria mucosae, and single-layer type, where intestinal metaplasia was usually present in a single layer without remaining deep non-metaplastic glands. These two types of intestinal metaplasia were usually found in the same specimen, however, most of the atypical epithelial proliferations (adenomatous lesions) arose from the area of intestinal metaplasia showing a double-layer type. The mitotic activity was usually found in the transitional zone showing these double-layer intestinal metaplasia. Atypical epithelial cells arose in the transitional zone of the double-layer intestinal metaplasia and spread into the luminal side by budding or replacement of existing epithelial cells. However, the author suspected that the cells in the under area of the transitional zone reproduce non-atypical cells to supplement the cells in the existing pyloric or pseudopyloric glands. On the other hand, atypical epithelial proliferations of single-layer type were rarely found showing a concaved appearance. Some of them may arise from the intestinal metaplasia of single-layer type, where the mitotic region moved towards the lower 1/3 of the glands. It seemed likely that most of the well-differentiated adenocarcinomas arise with intimate relation to these two types of intestinal metaplasia, where the incidence of malignant change of each type has been unknown.     

Modifications of gastric mucosa in diffuse and intestinal cancer

The study was made of 29 intestinal type gastric carcinomas, 37 diffuse type gastric carcinomas and stomach mucosa (SM). Both carcinomas slightly differed by frequency of the fundal glands atrophy. Intestinal type was characterized by a higher frequency of antral glands atrophy, intestinal metaplasia, particularly of colon type. Intestinal cell differentiation was about the same in both types. Hyperplasia of lining and endocrine cells in the fundal part of the mucosa was more frequent and neuroendocrine differentiation was more pronounced in diffuse stomach carcinoma. It is suggested that environmental impacts including helicobacter pylori result in proliferation of the epithelium, intestinal metaplasia, dysplasia and carcinoma of the intestinal type. Diffuse carcinoma is associated with proliferation of glandular epithelium (parietal, endocrine, cervical) due to genetic factors, hypergastrinemia caused by fundal gland atrophy, alkalization of the mucosa due to Helicobacter pylori infection.     

Immune aspects of intestinal metaplasia of the stomach: An immunohistochemical study

Summary Immune characteristics of intestinal metaplasia of the stomach were analyzed by the immunoperoxidase technique in frozen and paraffin-embedded specimens. In fetal and minimally inflamed adult gastric mucosa, secretory component (SC) was absent from epithelial cells. Non-intestinalized gastric mucosa with evident inflammatory changes showed weak SC immunoreactivity at the generative cell zone. Enhanced immunoreactivity of SC with evidence of transepithelial transport of IgA and IgM, but not of IgG, was demonstrated in intestinalized glands of either the complete or incomplete type. The number of inflammatory cells and lymphoid follicles was decreased in intestinalized mucosa when compared with that in non-intestinalized gastritic mucosa; J chain-negative IgG plasma cells and T cells, both of which were fairly abundant in the latter mucosa, were remarkably decreased in the former mucosa, whereas the decrease of J chain-positive IgA or IgM plasma cells was slight or equivocal. In either mucosa, IgA was the most popular immunoglobulin class in plasma cells. IgD plasma cells were very rare. In the germinal centers of lymphoid follicles which were preferentially distributed in non-intestinalized gastritic mucosa, IgM or IgG germinocytes predominated over IgA germinocytes, and a few T cells and NK cells also were present. Intraepithelial lymphoid cells with a T-suppressor phenotype were detected in intestinalized glands. The possibility that intestinal metaplasia is an adaptation to long-standing chronic gastritis is discussed.     

Tritiated thymidine autoradiographic study on histogenesis and spreading of intestinal metaplasia in human stomach.

The non-diseased portions of the antral mucosa of patients suffering from gastric cancer or ulcer were biopsied. The biopsy specimens were then labelled with 3H-thymidine in vitro, and distribution of the labelled epithelial cells in the normal pyloric and in the intestinalized mucosa was studied with autoradiography, and modes of histogenesis and spreading of the intestinal metaplasia were studied, and kinetic characteristics of the intestinalized mucosa were discussed. In the normal pyloric mucosa, the labelled cells were confined to the isthmus region (the middle one-third level of the mucosa), indicating that the surface epithelial and the pyloric glandular cells are normally replaced from the isthmus region. On the other hand, a zone of the labelled cells was found at the lower one-third level in the intestinalized mucosa. The absorptive and the goblet cells in the intestinalized mucosa appear to be renewed by about 70 hours in a fashion similar to that of the small intestine. Microscopic and autoradiographic analysis of the antral mucosa in the course of intestinalization indicates that the intestinal metaplasia begins in the isthmus region of the pyloric glandular tubules of an intact mucosa unaffected by gross injury through transformation of the generative cells from a pyloric to an intestinal pattern. This permits the pyloric lining cells to be replaced with intestinal villous cells and also permits the generative cell zone of the intestinal tubules to shift from the isthmus to the base of the gland until the process is complete. The downward shift of the intestinal tubules occurs in a framework of one of the branched pyloric glands and other glands disappear, resulting in a change of mucosal architectures of the antrum from a branched to a simple tubular gland. The intestinal metaplasia spreads in the mucosa through multi-focal (and sporadical) transformation of the neck generative cells in individual glandular tubules.     

An unusual heterotopia of pyloric glands of the stomach with inverted downgrowth

A rarely reported, large heterotopia of gastric glands in the submucosal layer of the stomach is observed in a 79 year old Japanese man with early gastric cancer. Histologically, it consists of marked hyperplasia of benign foveolar-type epithelia and tubular glands which instead of growing upwards grow downwards into the submucosa. Immunohistochemically, many gastrin-positive G cells are observed within it, indicating the existence of independent pyloric-type glands from the surrounding mucosa with intestinal metaplasia. Muscle actin-positive fascicles, derived from the muscularis mucosae, are demonstrated to branch into it and to encapsulate it. This result suggests that the present lesion may not represent a truly submucosal ectopic location, but an inverted downgrowth of the mucosa into the submucosa, thus resembling an inverted polyp of the colon. An awareness of this unique lesion is important in order that it not be mistaken for a submucosal extension of the primary adenocarcinoma.     

A HISTOPATHOLOGICAL STUDY OF DIFFUSE HYPERPLASIA OF GASTRIC ARGYROPHIL CELLS

The present study includes a histopathological and immunohistochemical study of 4 cases of diffuse hyperplasia of gastric argyrophil cells. The mode of proliferation of these cells and the production of hormone by these cells have been documented. The distribution of microacinar nests composed of argyrophil cells was thought to be related to chronic gastritis in which there are atrophy of mucosa and intestinal metaplasia. In the case in which these nests were found only in the corpus ventriculi, there was intestinal metaplasia throughout the stomach. On the other hand, in the case in which these nests appeared only in the pyloric area, atrophy of the mucosa with mild intestinal metaplasia was observed only in the pyloric area. The microacinar nests composed of argyrophil cells were distributed in the deep mucosa at the basal portion of the glands in the area with intestinal metaplasia. Serial sections revealed a sprout composed of argyrophil cells budding from the gland with intestinal metaplastic changes. The sprout buds out from the growth zone of glands with Intestinal metaplasia and then becomes isolated and gives rise to reactive hyperplasia. The peptide hormone contained in these cells differs according to the mucosal environments. Cells containing gastrin were observed in the pyloric area, but not in the corpus ventriculi where there was marked intestinal metaplasia. The cells in this area were assumed to contain other hormones.     

A proposal for a new validated histological definition of the gastroesophageal junction

Present definitions of the gastroesophageal junction (GEJ) are the point of flaring of the tubular esophagus and the proximal limit of the gastric rugal folds. Neither of these has been validated as the true GEJ. This study aims to validate the location of the true GEJ using the criterion of esophageal submucosal glands. Ten esophagogastrectomy specimens, in which there was a well-defined point of flaring of the tubular esophagus that coincided with the proximal limit of gastric rugal folds, were examined by complete histological mapping to evaluate the distribution of esophageal submucosal glands and surface epithelial types. Oxyntocardiac and cardiac mucosa with or without intestinal metaplasia were present under rugal folds distal to the end of tubular esophagus in all patients to a length of 0.31 to 2.05 cm. Submucosal glands were present in the tubular esophagus and in the proximal pouch distal to the tubular esophagus in a distribution that closely coincided with squamous epithelium, oxyntocardiac, cardiac, and intestinal epithelia. Submucosal glands were never found under oxyntic mucosa. We conclude that a variable part of the saccular region distal to the tubular esophagus contains esophageal submucosal glands, therefore representing reflux-damaged distal esophagus. This results in an error, where up to 2.05 cm of distal reflux-damaged dilated esophagus can be mistaken as proximal stomach when presently accepted definitions for the GEJ are used. The true GEJ is the proximal limit of gastric oxyntic mucosa defined by histology.