Hypothetical progression model of pancreatic cancer with origin in the centroacinar-acinar compartment

OBJECTIVES: Based mainly on animal models, 2 lesions have been suggested as possible precursors of pancreatic ductal adenocarcinoma (PDAC): pancreatic intraepithelial neoplasia (PanIN) and tubular complexes (TCs). The aim of the study was to find support for either of the 2 models through the analysis of a large panel of human pancreatic tissues. METHODS: Ninety-two PDAC, 45 chronic pancreatitis, and 27 serous cystadenoma cases were investigated using conventional morphology and immunohistochemistry. RESULTS: Most of the cases (78% of PDAC, 93% of chronic pancreatitis, and 67% of serous cystadenoma) exhibited putative precursor lesions, predominantly TC and low-grade PanIN lesions, often present in the same tissue area. High-grade lesions were exclusively observed in PDAC specimens. In 50% to 70% of the cases with TC and associated PanIN, a transitional zone of acinar-ductular transformation with mucinous differentiation of the ductular epithelium was identified. Expression of acinar and centroacinar markers was detected in TC, in the ductular structures of the transitional zones, as well as within the epithelium of mature PanINs. CONCLUSIONS: The results of the present study show that the coexistence of 2 different putative PDAC precursor lesions might not be a contradiction. A progression model that originates in the centroacinar-acinar compartment and ends with the development of PanIN lesions is suggested.