摘要目的 探讨胰腺导管内管状乳头状肿瘤的临床病理学特征、诊断、鉴别诊断及分子生物学特点.方法 收集北京协和医院病理科2001年1月至2010年6月间6例胰腺导管内管状乳头状肿瘤病例,分析其临床特点,对标本进行病理形态学观察、免疫组织化学EnVision法和RT-PCR方法检测KRAS基因突变.结果 6例导管内管状乳头状肿瘤有男2例,女4例,平均年龄64岁.大体检查胰腺大导管内可见息肉样结节阻塞导管,1例扩张的导管周围可见质硬结节.镜下观察,导管内可见小管状腺体或小的腺泡样腺体背靠背密集排列,上皮细胞重度异型增生,核分裂象多见,细胞内几乎没有黏液,导管内的小灶坏死较常见.1例病变完全局限在导管内,4例局部可见微小浸润(＜0.5 cm),1例浸润深度＞1 cm;浸润成分为导管腺癌.免疫组织化学显示CK7和CK19均阳性,MUC5AC有3例阴性,3例局灶弱阳性；MUC2阴性；MUC1有2例局灶阳性；Ki-67阳性指数高.KRAS基因检测2/6阳性,突变位点分别为35G＞A及35G＞ T/34G＞A.6例随访12～ 112个月,平均随访时间为37个月,1例19个月后死于该肿瘤,1例胰尾手术83个月后胰头复发,余4例无复发及转移.结论 胰腺导管内管状乳头状肿瘤具有导管内腺管状和乳头状生长方式,上皮重度异型增生,细胞内外黏液分泌少等特点,在生长方式、黏液分泌及免疫组织化学表达等方面与导管内乳头状黏液性肿瘤有不同之处；与导管内乳头状黏液性肿瘤分开的意义尚需更多病例验证.

abstractsObjective To study the pathologic features,diagnosis,differential diagnosis and molecular characteristics of intraductal tubulopapillary neoplasm of the pancreas (ITPN).Methods The clinical findings,morphologic features,immunophenotype (by EnVision method) and KRAS gene alterations (by reverse transcriptase-polymerase chain reaction) of 6 cases of ITPN encountered during the period from January,2001 to June,2010 were analyzed.Results There were altogether 2 males and 4 females.The mean age of the patients was 64 years.Gross examination showed that the tumors were located in large pancreatic ducts and appeared as polypoid nodules with ductal obstruction.Solid tumor nodules associated with adjoining dilated ducts were identified in one case.Histologically,the tumors were characterized by tubulopapillary growth pattern without luminal mucin.The tumor cells showed high-grade nuclear atypia with scanty intracytoplasmic mucin.Intraductal necrotic foci were frequently observed.Immunohistochemical study showed that the tumor cells expressed CK7 and CK19.Focal positivity for MUC5AC was demonstrated.Two cases expressed MUC1.The staining for MUC2 was negative.KRAS gene mutations were identified in 2 cases,with a single-amino-acid substitution in codon 12 (35G ＞ A and 35G ＞ T/34G ＞ A).Conclusions ITPN is a newly described pancreatic intraductal neoplasm and different from intraductal papillary mucinous neoplasm.ITPN is characterized by intraductal tubulopapillary growth pattern,severe cytologic atypia and scanty mucin secretion.