胰腺导管内管状乳头状肿瘤三例临床病理学特征

Clinicopathological analysis of 3 cases of intraductal tubulopapillary neoplasm of the pancreas and literature review

目的 分析胰腺导管内管状乳头状肿瘤（ITPN）的临床特征、病理形态学特征以及K-ras 基因突变状况,以提高对该病的认知度.方法 收集上海长海医院3例ITPN,并综合文献报道的16例资料,分析它们的临床表现、肿瘤的大体及病理组织学改变、免疫表型、K-ras基因突变状况,并与81例胰腺导管内黏液性乳头状肿瘤（IPMT）进行对比.结果 3例ITPN患者均为男性,中位年龄43岁,临床症状无特异性.2例肿瘤位于胰头部,1例位于胰体尾部;镜下表现为导管内实性团块,排列呈腺管样及筛孔状,细胞核中至重度异型,1例伴有浸润性导管腺癌成分并见胰周淋巴结转移;肿瘤细胞上皮标志物细胞角蛋白均阳性表达,部分肿瘤细胞p53阳性表达,神经内分泌标志物CHR、NSE及黏蛋白家族中的MUC2、MUC5AC均阴性表达,未检测到K-ras基因突变.IPMT的肿瘤细胞呈乳头状排列,可见筛孔结构;大部分细胞为黏液上皮或含较多杯状细胞（肠型）,少部分为嗜酸性上皮（嗜酸细胞型）和立方上皮（胰胆管型）;MUC2和MUC5AC表达阳性,K-ras基因突变发生率约50％.结论 ITPN是一种新的胰腺肿瘤类型,具有与IPMT不同的临床病理学特征.

Objective To analyze the clinical symptoms,pathological features and K-ras mutation alterations of intraductal tubulopapillary neoplasm （ITPN）,and to better understand ITPN.Methods We collected the clinical data of 3 cases of ITPNs of Changhai Hospital and 16 cases in literature,and analyzed the morphology,K-ras mutation,immunophenotype of tumor cells by routine H＆E staining,immonohistochemistry,and fluorescence PCR.Then it was compared with 81 cases of intraductal papillary mucinous tumor （IPMT）.Results All the 3 patients of ITPN were male,with a median age of 43 years.Two lesions were located in pancreatic head and 1 case in pancreatic body and tail.ITPNs presented as intraductal solid masses,and consisted of cells with uniformly median-to-high grade nuclear atypia,and tumor cells were arranged as glandular and cribriform.One case was accompanied with invasive ductal adenocarcinoma and peripancreatic lymph node metastasis.All tumor cells of epithelial marker cytokeratin was positively expressed,and p53 was positively expressed in some tumor cells.However,CHR,NSE,MUC2 and MUC5AC were negatively expressed,and K-ras mutation was not detected.The tumor cells of IPMT were presented as papillary pattern and cribriform structure was observed.The majority of cells were mucous epithelium,or goblet cells （intestinal type）,a few were eosinophilic epithelium （eosinophilic cells type） and cuboidal epithelium （pancreatic,biliary duct type）,MUC2 and MUC5AC was positively expressed,and K-ras mutation rate was 50％.Conclusions As a new tumor entity of pancreas,ITPNs show distinctive features with IPMTs.