原发肛管杯状细胞腺癌伴肛周Paget病的组织学及分子病理学研究

Primary anal goblet cell adenocarcinoma with perianal Paget’s disease:a histological and molecular pathological study of two cases

目的探讨原发肛管杯状细胞腺癌(GCA)伴肛周Paget病的组织学及分子病理特征。方法选取2例原发肛管GCA伴肛周Paget病患者作为研究对象,对其临床资料进行回顾性分析,并采用HE染色、免疫组化、二代测序研究其原发病灶、肛周Paget病、淋巴结转移灶的组织学和分子病理特征。结果2例患者均为肛周肿物渐进性增大入院,显微镜下具有GCA的典型组织学和免疫组化特征。其中肛管原发GCA多呈条索状和实性片巢状排列,肿瘤细胞巢周围可见大量“黏液湖”样结构,似经典黏液癌;可见单纯或复杂腺管样结构,似经典结直肠管状腺癌;部分细胞核偏位、细胞浆富含黏液样物质的肿瘤细胞呈单个散在浸润性生长,似经典“印戒细胞癌”。肛管GCA继发肛周Paget病可见大量细胞核偏位、细胞浆富含黏液的“印戒样”细胞在复层鳞状上皮内原位浸润性生长伴局灶鳞状上皮乳头瘤样增生和Pinkus纤维上皮瘤样增生。淋巴结转移癌与肛管原发病灶组织学类型相似,组织形态相对单一,肿瘤细胞间异质性较低。病例1、2各部位肿瘤组织均检出ErbB3基因突变,未检出Kras、Nras、braf基因突变,未检出肿瘤组织微卫星不稳定现象(MSI)。结论肛管GCA在组织形态、免疫表型和分子病理等方面与阑尾多发的同类肿瘤相似,具有与经典管状腺癌、黏液癌、印戒细胞癌相似的组织学结构,同时伴有神经内分泌肿瘤的组织形态及免疫表型特征。

Objective To investigate the histological and molecular pathological features of primary anal goblet cell adenocarcinoma(GCA)with perianal Paget's disease.Methods The clinical data of two cases of primary anal GCA with perianal Paget's disease were retrospectively analyzed.HE staining,immunohistochemistry and next generation sequencing were used to study the histological and molecular pathological features of primary lesions,perianal Paget's disease and lymph node metastasis.Results Both patients were admitted to the hospital due to progressive enlargement of perianal masses,and under microscope,they had typical histological and immunohistochemical characteristics of GCA.The primary GCA of the anal canal showed a typical cord-like and solid sheet-like arrangement,and a large number of“mucoid lake”like structures were visible around the tumor cell nests,resembling classic mucinous carcinoma.Simple or complex glandular-like structures were visible,resembling classic colorectal tubular adenocarcinoma.Some tumor cells with nuclear deviation and cytoplasm rich in mucoid substances showed single scattered invasive growth,resembling classic“signet ring cell carcinoma”.Secondary perianal Paget's disease in anal canal GCA showed a large number of“signet ring cell”with nuclear deviation and cytoplasm rich in mucoid substances in situ invasive growth in stratified squamous epithelium with focal squamous epithelial papillomatous hyperplasia and Pinkus fibroepithelioma like changes.The histologic types of lymph node metastatic cancer and primary lesions of anal canal were similar,with relatively simple histomorphology and low heterogeneity among tumor cells.ErbB3 mutations were detected in all tumor tissues of cases 1 and 2,but Kras,Nras,braf mutations and microsatellite instability(MSI)were not detected.Conclusion GCA of the anal canal is similar to neoplasms of the appendix in morphology,immunophenotype and molecular pathology.It has similar histological features to classic tubular adenocarcinoma,mucinous carcinoma and signet ring cell carcinoma.