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。

Clinicopathological features of very well-differentiated adenocarcinoma of the stomach

Objective To investigate the clinicopathological features of very well-differentiated adenocarcinoma(VWDA)of the stomach.Methods The clinicopathological data of 12 cases of VWDA of the stomach were collected retrospectively at the People′s Liberation Army Joint Logistics Support Force 989 Hospital(formerly 152 Hospital),Pingdingshan,China,from January 2013 to May 2021.The histological characteristics and immunophenotypes were observed and analyzed with review of current literature.Results There were 8 males and 4 females with a median age of 63 years(range 47 to 80 years).The tumor involved in the upper part of the stomach in 6 cases,the middle part in 2 cases,and the lower part in 4 cases.The median diameter of the tumors was 17 mm(range 5-65 mm).The tumor cells were similar to absorbent cells,Paneth cells,foveolar epithelial cells,and goblet cells.The cells were arranged in a single layer,and the nuclei were slightly enlarged and located at the base.The nuclei were fusiform to slightly irregular,with loss of nuclear polarity.Early tubular VWDA was found in 9 cases,and the tumor glands were similar to intestinal metaplasia.In two cases the tumors infiltrated into the submucosa.The lesions in the mucosa and submucosa showed the glands with cystic expansion,bending,branching,spiky and abortive growth pattern.One case of early papillary tubular VWDA was confined to the mucosal layer and composed of foveolar-type epithelial cells.There were two cases of advanced papillary tubular VWDA,which consisted of foveolar-type epithelial,pyloric glands,or mucinous neck cells and were associated with intra-lymphatic cancer embolus and lymph node metastases.Background mucosal atrophy and intestinal metaplasia were observed in all cases.Immunohistochemical staining showed intestinal type VWDA in 1 case,mixed gastrointestinal type VWDA in 9 cases,and gastric type VWDA in 2 cases.The Ki-67 proliferation index of 8 cases limited to the mucosa was 40%-70%,2 cases of infiltration into the submucosa and 2 cases of advanced carcinoma was 10%-25%.All the tumors showed a wild type of p53 protein expression pattern and negative HER2.Adenocarcinoma or high-grade dysplasia was diagnosed on preoperative biopsy in 5 cases,and chronic atrophic gastritis with intestinal metaplasia in 7 cases.The median follow-up time was 28 months(range 12-72 months).No recurrence was found in the 10 patients with early cancer.Of the two patients with advanced carcinoma,one patient had lung metastases and the other died.Conclusions Gastric VWDA is a rare low-grade malignancy with structural features of highly differentiated adenocarcinoma and extremely low cytological atypia.The diagnostic value of structural abnormality is significantly greater than cytological atypia.The invasive growth of irregular glands in the deep mucosa and submucosa is reliable evidence for diagnosis.The diagnosis of intramucosal VWDA is challenging and very difficult in some biopsy specimens.