Histo-molecular oncogenesis of pancreatic cancer: From precancerous lesions to invasive ductal adenocarcinoma

Giulio Riva, Antonio Pea, Camilla Pilati, Giulia Fiadone, Rita Teresa Lawlor, Aldo Scarpa, Claudio Luchini, Giulio Riva, Antonio Pea, Camilla Pilati, Giulia Fiadone, Rita Teresa Lawlor, Aldo Scarpa, Claudio Luchini

Abstract

Pancreatic cancer is a lethal malignancy, whose precursor lesions are pancreatic intraepithelial neoplasm, intraductal papillary mucinous neoplasm, intraductal tubulopapillary neoplasm, and mucinous cystic neoplasm. To better understand the biology of pancreatic cancer, it is fundamental to know its precursors and to study the mechanisms of carcinogenesis. Each of these precursors displays peculiar histological features, as well as specific molecular alterations. Starting from such pre-invasive lesions, this review aims at summarizing the most important aspects of carcinogenesis of pancreatic cancer, with a specific focus on the recent advances and the future perspectives of the research on this lethal tumor type.

Keywords: Carcinogenesis; Intraductal papillary mucinous neoplasm; Intraductal tubulopapillary neoplasm; KRAS; Mucinous cystic neoplasm; Oncogenesis; Pancreatic cancer; Pancreatic ductal adenocarcinoma; Pancreatic intraepithelial neoplasm.

Conflict of interest statement

Conflict-of-interest statement: No potential conflict of interest.

Figures

Figure 1
Figure 1
Extensive involvement of the pancreas by an intraductal papillary mucinous neoplasm. This neoplasm involves almost all the pancreatic ductal tree. The asterisks indicate Wirsung's duct along its course.
Figure 2
Figure 2
Pancreatic intraepithelial neoplasm precursor lesions. A: High-grade pancreatic intraepithelial neoplasm (PanIN); B: Low-grade PanIN. Original magnification: × 10. Black arrows indicate ducts involved by PanINs.
Figure 3
Figure 3
The four different types of intraductal papillary mucinous neoplasm. A: Gastric; B: Pancreatobiliary; C: Intestinal; D: Oncocytic. Original magnification: A and C: × 10; B and D: × 20. Black arrowheads indicate the fibro-vascular axis of the papillary structures.
Figure 4
Figure 4
Colloid carcinoma with perineural invasion (A, black arrow) and nodal metastasis (B: low magnification; C: higher magnification of the same metastasis). Original magnification: A: × 10; B: × 4; C: × 20.
Figure 5
Figure 5
Mucinous cystic neoplasm precursor lesions. A: Low-grade mucinous cystic neoplasm (MCN); B: High-grade MCN. The black arrow indicates the ovarian-like stroma, a typical component of this type of lesion. Original magnification: × 10.
Figure 6
Figure 6
Intratubular papillary neoplasm precursor lesions. A: Low magnification showing an extensive intraductal growth; B: Higher magnification. Original magnification A: × 1; B: × 4.

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