Invasive ductal carcinoma (IDC) of the pancreas arises in the ductal epithelium and extends into the pancreatic tissue via stromal invasion. Carcinoma in situ (CIS) is believed to be a precursor lesion to invasive carcinoma. IDC is composed of intraductal components and infiltrating components. The intraductal components of IDC are considered to represent both CIS/colonization of ducts and the intraductal invasion/cancerization of ducts. Colonization of ducts is defined as intraductal carcinoma in another location to which CIS has spread. A tubular pattern of intraductal components indicates intraductal invasion, while a low papillary pattern indicates CIS/colonization of ducts. Intraductal components of IDC can be identified by visualizing mural ductal system elastic fibers on elastica van Gieson (EVG)-stained sections. Each carcinoma component shows different biological behavior. IDC is a highly invasive neoplasm that also spreads noninvasively through the pancreatic ductal tree. Intraductal spread is a characteristic feature of well-differentiated IDC and the number of intraductal carcinoma foci is correlated with the grade of tumor differentiation. The large branch ducts are the main routes of intraductal spread, which suggests IDC might be derived from the epithelium of large branch ducts. IDC can also spread through the ducts beyond the tumor mass. Intraductal spread is confined to the vicinity of the tumor mass (within 2.0 cm), and it can involve the pancreatic resection margin. It is emphasized that the pancreatic margin of resection should be at least 2.0 cm from the macroscopical tumor mass. The prolifera-tive activity is lower in the intraductal components than in the corresponding infiltrating ones. The presence or absence of intraductal components is not correlated with age, sex, tumor location, tumor size, or stage. IDC with intraductal components tends to be associated with longer survival compared with IDC without intraductal components.

Copyright © 2007 S. Karger AG, Basel

IDC of the pancreas is believed to originate from the ductal system [1]. Pancreatic duct cell changes may occur in the normal pancreas or in association with IDC [2]. Major duct epithelium changes are distinguished in squamous metaplasia, mucinous cell hypertrophy, papillary hyperplasia, atypical hyperplasia and CIS. The prevalence of squamous metaplasia and mucinous cell hypertrophy is not significantly different between cases with and without IDC [3-5]. Papillary hyperplasia is more prevalent in the vicinity of the IDC and the larger ducts [6]. Papillary hyperplasia can be secondary to the IDC duct occlusion or it might be due to a primary neoplastic change [3]. In surgically resected IDC specimens, atypical hyperplasia or intraductal carcinoma foci are observed in and around the tumor mass [1-8]. These intraductal carcinoma foci associated with IDC have also been described as CIS. Because of these facts, CIS and atypical hyperplasia are considered to be precursor lesions for IDCs [9].

Recent molecular studies on intraductal lesions and associated infiltrating components of IDC indicate that accumulation of specific genetic alterations underlies the multistage processes of tumorigenesis and progression in IDC [10]. The oncogene K-ras mutation is an early event in the pathogenesis of IDC. A number of tumor suppressor genes have been found to play a critical role in the progression of pancreatic carcinogenesis [5]. Yamano et al. described genetic divergence, as well as genetic progression, in the clonal evolution of pancreatic cancer by studying allelic loss of intraductal lesions and infiltrating components of IDC [11]. Along these lines, pancreatic intraepithelial neoplasia (or PanIN), which is a new nomenclature and classification system for pancreatic duct lesions, has been proposed [12].

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