北京大学学报(医学版) ›› 2023, Vol. 55 ›› Issue (2): 292-298. doi: 10.19723/j.issn.1671-167X.2023.02.013

• 论著 • 上一篇    下一篇

幽门螺杆菌阴性早期胃癌的临床病理特征

侯卫华1,宋书杰2,石中月3,金木兰3,*()   

  1. 1. 解放军联勤保障部队第九八九医院平顶山医疗区病理科,河南平顶山 467099
    2. 解放军联勤保障部队第九八九医院平顶山医疗区消化内科,河南平顶山 467099
    3. 首都医科大学附属北京朝阳医院病理科,北京 100020
  • 收稿日期:2022-09-13 出版日期:2023-04-18 发布日期:2023-04-12
  • 通讯作者: 金木兰 E-mail:kinmokuran@163.com

Clinicopathological features of Helicobacter pylori-negative early gastric cancer

Wei-hua HOU1,Shu-jie SONG2,Zhong-yue SHI3,Mu-lan JIN3,*()   

  1. 1. Department of Pathology, Pingdingshan Medical District, 989 Hospital of PLA Joint Logistics Support Force, Pingdingshan 467099, Henan, China
    2. Department of Gastroenterology, Pingdingshan Medical District, 989 Hospital of PLA Joint Logistics Support Force, Pingdingshan 467099, Henan, China
    3. Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
  • Received:2022-09-13 Online:2023-04-18 Published:2023-04-12
  • Contact: Mu-lan JIN E-mail:kinmokuran@163.com

摘要:

目的: 探讨幽门螺杆菌(Helicobacter pylori,Hp)阴性早期胃癌的临床病理特征。方法: 回顾性收集2009—2021年解放军联勤保障部队第九八九医院平顶山医疗区和首都医科大学附属北京朝阳医院共计30例Hp阴性早期胃癌的临床资料,观察其组织形态学特征和免疫表型,并结合文献进行探讨。结果: 30例患者的中位年龄58. 5岁(范围21~80岁),男性13例,女性17例;胃上部13例,胃中部9例,胃下部8例;肿瘤中位直径11 mm(范围1~30 mm);按巴黎分型0-Ⅱa型9例,0-Ⅱb型7例,0-Ⅱc型14例。内镜检查18例病变发红,12例病变呈退色调或发白,均可见微血管结构和微表面结构异常;所有病例胃体及胃角黏膜可见规律排列的集合小静脉。黏膜内高分化腺癌18例,肿瘤呈腺管样及乳头状结构,腺体密集,排列紊乱;细胞呈立方形或柱状,核染色质增多,核极性丢失,多表达胃型黏蛋白。印戒细胞癌7例,癌组织全部由印戒细胞构成,癌细胞主要分布在黏膜中表层内;胃泌酸腺瘤(局限于黏膜内的胃底腺型胃癌)2例、胃底腺型胃癌2例和胃底腺黏膜型胃癌1例。肿瘤组织由轻度大小不等的分枝管状腺构成,除1例黏膜表面上皮局部是肿瘤性外,其余4例黏膜表面上皮全为非肿瘤性;细胞单层排列,核靠近基底侧,细胞核仅有轻度的不典型性。5例胃底腺肿瘤免疫组织化学染色胃蛋白酶原Ⅰ和H+/K+ATPase阳性,其中1例黏膜表面和深处的小凹型肿瘤细胞MUC5AC阳性。所有的病例癌旁胃黏膜大致正常,无萎缩、肠上皮化生和Hp。结论: Hp阴性早期胃癌是一组异质性疾病群体,组织学类型多样,常见的有管状腺癌和印戒细胞癌。管状腺癌多发生于老年人和胃中上部,印戒细胞癌多发生于中青年人和胃下部,胃底腺型肿瘤相对罕见。

关键词: 胃肿瘤, 幽门螺杆菌阴性, 临床病理学, 内镜黏膜下剥离术

Abstract:

Objective: To investigate the clinicopathological features of Helicobacter pylori (Hp)-negative early gastric cancer. Methods: The clinicopathological data of 30 cases of Hp-negative early gastric cancer were collected retrospectively at Pingdingshan Medical District, 989 Hospital of PLA Joint Logistics Support Force, and Beijing Chaoyang Hospital, Capital Medical University, from 2009 to 2021, and the histomorphological characteristics and immunophenotype were observed, and combined with the literature to explore. Results: The median age of 30 patients was 58.5 years (range: 21-80 years), including 13 males and 17 females. The upper part of the stomach was 13 cases, the middle part of the sto-mach was 9 cases, and the lower part of the stomach was 8 cases. The median diameter of the tumor was 11 mm (range: 1-30 mm). According to the Paris classification, 9 cases were 0-Ⅱa, 7 cases were 0-Ⅱb, and 14 cases were 0-Ⅱc. Endoscopic examination showed that 18 cases of lesions were red, 12 cases of lesions were faded or white, and microvascular structures and microsurface structures were abnormal. In all the cases, collecting venules were regularly arranged in the gastric body and corner mucosa. There were 18 cases of well differentiated adenocarcinoma in the mucosa. The tumor presented glandular tubular-like and papillary structure, with dense glands and disordered arrangement; the cells were cuboidal or columnar, with increased nuclear chromatin and loss of nuclear polarity, and most of them expressed gastric mucin. Signet-ring cell carcinoma was found in 7 cases, all the cancer tissues were composed of signet-ring cells, and the cancer cells were mainly distributed in the middle layer to the surface layer of mucosa. Gastric oxyntic gland adenoma (gastric adenocarcinoma of the fundic gland type confined to mucosa) in 2 cases, gastric adenocarcinoma of the fundic gland type in 2 cases, and gastric adenocarcinoma of fundic gland mucosa type in 1 case. The tumor tissue was composed of branching tubular glands, except 1 case of mucosal surface epithelium was partially neoplastic, the other 4 cases of mucosal surface epi-thelium were all non-neoplastic; the cells were arranged in a single layer, and the nucleus was close to the basal side, and the nucleus was only slightly atypical. Pepsinogen I and H+/K+ ATPase were positive in 5 cases of gastric fundus gland type tumors, and 1 case of foveolar-type tumor cells at the surface and depth of mucosa showed MUC5AC positive. The gastric mucosa adjacent to cancer was generally normal in all cases, without atrophy, intestinal metaplasia and Hp. Conclusion: Hp-negative early gastric cancer is a heterogeneous disease group with various histological types, and tubular adenocarcinoma and signet-ring cell carcinoma are common. Tubular adenocarcinoma mostly occurs in the elderly and the upper to middle part of the stomach, while signet-ring cell carcinoma mostly occurs in young and middle-aged people and the lower part of the stomach. Gastric neoplasm of the fundic gland type is relatively rare.

Key words: Stomach neoplasms, Helicobacter pylori-negative, Clinical pathology, Endoscopic submucosal dissection

中图分类号: 

  • R735.2

表1

幽门螺杆菌阴性早期胃癌不同类型患者的临床病理特征比较"

Parameter Well differentiated adenocarcinoma
(n=18)
Signet ring cell carcinomas
(n=7)
Gastric neoplasm of fundic gland type
(n=5)
Gender
   Male 8 2 3
   Female 10 5 2
Age
   <60 years 6 7 2
   ≥60 years 12 0 3
Location
   Upper part 9 1 3
   Middle part 7 1 1
   Lower part 2 5 1
Tumor diameter
   ≤20 mm 13 7 5
   >20 mm 5 0 0
Paris classification
   0-Ⅱa 5 0 4
   0-Ⅱb 4 3 0
   0-Ⅱc 9 4 1
Depth of invasion
   pT1a 18 7 2
   pT1b 0 0 3
Phenotypes
   Gastric 10 3 -
   Intestinal 0 2 -
   Gastrointestinal 8 2 -
Mutation expression of p53
   Yes 4 0 0
   No 14 7 5

图1

胃黏膜内高分化管状腺癌"

图2

胃黏膜内印戒细胞癌"

图3

胃底腺黏膜型胃癌"

1 Correa P , Piazuelo MB . The gastric precancerous cascade[J]. J Dig Dis, 2012, 13 (1): 2- 9.
doi: 10.1111/j.1751-2980.2011.00550.x
2 Rugge M , Genta RM , Di Mario F , et al. Gastric cancer as preventable disease[J]. Clin Gastroenterol Hepatol, 2017, 15 (12): 1833- 1843.
doi: 10.1016/j.cgh.2017.05.023
3 Yamamoto Y , Fujisaki J , Omae M , et al. Helicobacter pylori-negative gastric cancer: Characteristics and endoscopic findings[J]. Dig Endosc, 2015, 27 (5): 551- 561.
doi: 10.1111/den.12471
4 侯卫华, 王新钊, 石中月, 等. 幽门螺杆菌根除后早期胃癌的临床病理特征分析[J]. 中华病理学杂志, 2022, 51 (8): 10- 16.
5 Sato C , Hirasawa K , Tateishi Y , et al. Clinicopathological features of early gastric cancers arising in Helicobacter pylori uninfected patients[J]. World J Gastroenterol, 2020, 26 (20): 2618- 2631.
doi: 10.3748/wjg.v26.i20.2618
6 Japanese Gastric Cancer Association . Japanese classification of gastric carcinoma: 3rd English edition[J]. Gastric Cancer, 2011, 14 (2): 101- 112.
doi: 10.1007/s10120-011-0041-5
7 韩方海, 杨斌. 解读第15版日本胃癌处理规约[J]. 中华胃肠外科杂志, 2018, 21 (4): 409- 412.
doi: 10.3760/cma.j.issn.1671-0274.2018.04.010
8 九屿亮治. 胃癌病理分类: 日本国内实行的分类[M]//鹤田修. 胃与肠. 《胃与肠》翻译委员会, 译. 沈阳: 辽宁科学技术出版社, 2017: 15-26.
9 Yao T, Vieth M. Oxyntic gland adenoma[M]//WHO Classification of Tumours Editorial Board. WHO classification of tumours, digestive system tumours. 5th ed. Lyon: IARC Press, 2019: 83-84.
10 Yemelyanova A , Vang R , Kshirsagar M , et al. Immunohistoche-mical staining patterns of p53 can serve as a surrogate marker for TP53 mutations in ovarian carcinoma: An immunohistochemical and nucleotide sequencing analysis[J]. Mod Pathol, 2011, 24 (9): 1248- 1253.
doi: 10.1038/modpathol.2011.85
11 Yamada A , Kaise M , Inoshita N , et al. Characterization of Helicobacter pylori-naive early gastric cancers[J]. Digestion, 2018, 98 (2): 127- 134.
doi: 10.1159/000487795
12 Kakinoki R , Kushima R , Matsubara A , et al. Re-evaluation of histogenesis of gastric carcinomas: A comparative histopathological study between Helicobacter pylori-negative and H. pylori-positive cases[J]. Dig Dis Sci, 2009, 54 (3): 614- 620.
doi: 10.1007/s10620-008-0389-5
13 Yoon H , Kim N , Lee HS , et al. Helicobacter pylori-negative gastric cancer in South Korea: Incidence and clinicopathologic cha-racteristics[J]. Helicobacter, 2011, 16 (5): 382- 388.
doi: 10.1111/j.1523-5378.2011.00859.x
14 Kim HJ , Kim N , Yoon H , et al. Comparison between resectable Helicobacter pylori-negative and -positive gastric cancers[J]. Gut Liver, 2016, 10 (2): 212- 219.
doi: 10.5009/gnl14416
15 Mizutani T , Araki H , Saigo C , et al. Endoscopic and pathological characteristics of Helicobacter pylori infection-negative early gastric cancer[J]. Dig Dis, 2020, 38 (6): 474- 483.
doi: 10.1159/000506120
16 苏惠, 金鹏, 杨浪, 等. 幽门螺杆菌阴性早期胃癌的内镜及组织学特点分析[J]. 中华消化内镜杂志, 2021, 38 (7): 551- 555.
doi: 10.3760/cma.j.cn321463-20201031-00270
17 Takita M , Ohata K , Inamoto R , et al. Endoscopic and histological features of Helicobacter pylori-negative differentiated gastric adenocarcinoma arising in the antrum[J]. JGH Open, 2021, 5 (4): 470- 477.
doi: 10.1002/jgh3.12518
18 Nikaido M , Kakiuchi N , Miyamoto S , et al. Indolent feature of Helicobacter pylori-uninfected intramucosal signet ring cell carcinomas with CDH1 mutations[J]. Gastric Cancer, 2021, 24 (5): 1102- 1114.
doi: 10.1007/s10120-021-01191-8
19 Yorita N , Ito M , Boda T , et al. Potential of Helicobacter pylori-uninfected signet ring cell carcinoma to invade the submucosal layer[J]. J Gastroenterol Hepatol, 2019, 34 (11): 1955- 1962.
doi: 10.1111/jgh.14706
20 Tanaka M , Hoteya S , Kikuchi D , et al. Effect of Helicobacter pylori infection on malignancy of undifferentiated-type gastric cancer[J]. BMC Gastroenterol, 2022, 22 (1): 7.
doi: 10.1186/s12876-021-02034-7
21 Ushiku T , Kunita A , Kuroda R , et al. Oxyntic gland neoplasm of the stomach: Expanding the spectrum and proposal of terminology[J]. Mod Pathol, 2020, 33 (2): 206- 216.
doi: 10.1038/s41379-019-0338-1
22 Benedict MA , Lauwers GY , Jain D . Gastric adenocarcinoma of the fundic gland type: Update and literature review[J]. Am J Clin Pathol, 2018, 149 (6): 461- 473.
doi: 10.1093/ajcp/aqy019
23 Sato Y , Sato T , Matsushima J , et al. Histopathologic change of a case of gastric oxyntic neoplasm (gastric adenocarcinoma of fundic gland mucosa type) through 5 years with concurrent other oxyntic gland lesions[J]. Int J Surg Pathol, 2021, 29 (5): 557- 564.
doi: 10.1177/1066896920962574
24 Ueyama H , Yao T , Akazawa Y , et al. Gastric epithelial neoplasm of fundic-gland mucosa lineage: Proposal for a new classification in association with gastric adenocarcinoma of fundic-gland type[J]. J Gastroenterol, 2021, 56 (9): 814- 828.
doi: 10.1007/s00535-021-01813-z
25 Hou W , Li C , Shen M , et al. Endoscopic and clinicopathological features of gastric adenocarcinoma of fundic gland mucosa type: A case report and literature review[J]. Int J Clin Exp Med, 2019, 12 (12): 13993- 14000.
26 Iwamuro M , Kusumoto C , Nakagawa M , et al. Endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type differ between patients with and without Helicobacter pylori infection: A retrospective observational study[J]. BMC Gastroenterol, 2022, 22 (1): 294.
doi: 10.1186/s12876-022-02368-w
27 Takatsuna M , Azumi R , Mizusawa T , et al. A case of Helicobacter pylori-negative early gastric adenocarcinoma with gastrointestinal phenotype[J]. Endosc Int Open, 2021, 9 (6): E863- E866.
doi: 10.1055/a-1396-3854
28 Sun QH , Zhang J , Shi YY , et al. Microbiome changes in the gastric mucosa and gastric juice in different histological stages of Helicobacter pylori-negative gastric cancers[J]. World J Gastroenterol, 2022, 28 (3): 365- 380.
doi: 10.3748/wjg.v28.i3.365
[1] 沈棋,刘亿骁,何群. 肾黏液样小管状和梭形细胞癌的临床病理特点及预后[J]. 北京大学学报(医学版), 2023, 55(2): 276-282.
[2] 刘菊梅,梁丽,张继新,戎龙,张梓怡,吴悠,赵旭东,李挺. 411例早期胃癌及癌前病变内镜黏膜下剥离术标本的病理学评估[J]. 北京大学学报(医学版), 2023, 55(2): 299-307.
[3] 农琳,王微,梁丽,李东,李鑫,李挺. 母细胞性浆样树突细胞肿瘤13例临床病理学特征[J]. 北京大学学报(医学版), 2023, 55(2): 308-314.
[4] 哈雪梅,姚永正,孙莉华,辛春杨,熊焰. 实性肺胎盘样变形1例及文献复习[J]. 北京大学学报(医学版), 2023, 55(2): 357-361.
[5] 宁博涵,张青霞,杨慧,董颖. 伴间质细胞增生、玻璃样变性及索状结构的子宫内膜样腺癌1例[J]. 北京大学学报(医学版), 2023, 55(2): 366-369.
[6] 博尔术,洪鹏,张宇,邓绍晖,葛力源,陆敏,李楠,马潞林,张树栋. 乳头状肾细胞癌的临床病理特征和预后分析[J]. 北京大学学报(医学版), 2022, 54(4): 615-620.
[7] 武颖超,蔡云龙,戎龙,张继新,刘金,汪欣. 早期胃癌淋巴结转移规律及内镜黏膜下剥离术治疗早期胃癌的疗效评价[J]. 北京大学学报(医学版), 2020, 52(6): 1093-1097.
[8] 杨阳,刘毅强,王晓红,季科,李忠武,白健,杨爱蓉,胡颖,韩海勃,李子禹,步召德,吴晓江,张连海,季加孚. 单中心大样本Epstein-Barr病毒相关性胃癌亚型的临床病理及分子特征分析[J]. 北京大学学报(医学版), 2019, 51(3): 451-458.
[9] 黄子雄,杜依青,张晓鹏,刘士军,徐涛. 肾细胞癌骨转移的临床与病理分析[J]. 北京大学学报(医学版), 2018, 50(5): 811-815.
[10] 高翔,陈香梅,张婷,张静,陈茉,郭正阳,石岩岩,鲁凤民,丁士刚. 巨噬细胞加帽蛋白与胃癌细胞增殖及迁移能力的关系[J]. 北京大学学报(医学版), 2017, 49(3): 489-494.
[11] 张贺军,刘琳娜,张超,石岩岩,丁士刚. 硫氧还蛋白-1高表达的幽门螺杆菌慢性感染蒙古沙土鼠模型的建立与评价[J]. 北京大学学报(医学版), 2016, 48(5): 766-770.
[12] 李士杰,王警,李子禹,步召德,苏向前,李忠武,吴齐. 内镜黏膜下剥离术在早期胃癌治疗中的应用[J]. 北京大学学报(医学版), 2015, 47(6): 945-951.
[13] 黄昊, 韩勇, 吴健, 田志华, 曲立科, 寿成超. 胃癌细胞MGC-803耐药细胞株的建立及分泌蛋白差异分析[J]. 北京大学学报(医学版), 2014, 46(2): 183-189.
[14] 龚继芳,陆明,李洁,李燕,周军,鲁智豪,王晰程,李健,张小田,沈琳. 注射用紫杉醇(白蛋白结合型)治疗进展期胃癌[J]. 北京大学学报(医学版), 2014, 46(1): 144-148.
[15] 刘琳娜, 张静, 丁士刚, 钟丽君, 李广川, 石岩岩, 王晔. 胃癌高、低发区胃癌与慢性胃炎患者幽门螺杆菌差异蛋白质的比较[J]. 北京大学学报(医学版), 2011, 43(6): 827-832.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 王军, 肖水芳, 秦永, 王全桂, 陈丽. 以面神经麻痹为首诊表现的Wegener肉芽肿病一例[J]. 北京大学学报(医学版), 2007, 39(4): 434 -436 .
[2] 柳晓辉, 那加, 刘玲玲, 罗斌. 头颈部血管肉瘤3例[J]. 北京大学学报(医学版), 2001, 33(3): 288 -289 .
[3] 张震康. 口腔医学科学研究的重要进展和方向[J]. 北京大学学报(医学版), 2002, 34(2): 97 -98 .
[4] 梁成, 王兴, 伊彪, 李自力, 王晓霞. 骨性颞下颌关节强直伴小颌畸形及阻塞性睡眠呼吸暂停综合征的牵引成骨治疗[J]. 北京大学学报(医学版), 2002, 34(2): 112 -116 .
[5] 张勇, 栾庆先. 牙周维护治疗在保持牙周长期疗效中的作用[J]. 北京大学学报(医学版), 2011, 43(1): 29 -33 .
[6] 夏永华, 刘冬, 张彩凤, 付丹丹, 李敏, 李占国, 田中伟. NF-κB信号通路的阻断对皮肤鳞癌SCL-1细胞凋亡的影响[J]. 北京大学学报(医学版), 2011, 43(2): 179 -182 .
[7] 孙宇, 刘毅强, 冯国双, 李吉友. 转化生长因子β1在萎缩性胃炎发生中的作用[J]. 北京大学学报(医学版), 2009, 41(6): 635 -639 .
[8] 张少衡, 贾竹青, 郭静萱, 张萍, 马康涛, 王淑玲, 刘永刚, 李凌松, 周春燕. 骨髓细胞移植上调血管内皮生长因子及其受体的表达并改善缺血心脏功能[J]. 北京大学学报(医学版), 2003, 35(4): 429 -433 .
[9] 李文海, 张建中. 二期梅毒皮疹中梅毒螺旋体基因检测和浸润细胞研究[J]. 北京大学学报(医学版), 2003, 35(5): 485 -487 .
[10] 李海霞, 屈晨雪, 徐国宾, 闫存玲, 张国华, 李传保, 王建中, 夏铁安. 检验科SARS标本检测安全管理介绍[J]. 北京大学学报(医学版), 2003, 35(z1): 92 -94 .