High-grade Solid Pseudopapillary Neoplasms of the Pancreas
Shogo Honda, Hiroshi Yamaguchi, Eriko Aimono, Shigeo Hara, Sachiko Minamiguchi, Tomoko Norose, Nobuyuki Ohike, Toshiko Yamochi, Masanori Yasuda, Takuya Moriya, Yuki Shiko, Hiroshi Nishihara, Toshitaka Nagao
Abstract
Pancreatic solid pseudopapillary neoplasm (SPN) is a low-grade malignant neoplasm with a good prognosis. Clinically aggressive SPNs have rarely been reported but have not been analyzed in detail. In this study, we referred to this highly malignant type of SPN as high-grade SPN (HG-SPN) and compared its clinicopathological and genetic characteristics with conventional SPN (C-SPN) using immunohistochemistry and gene panel analyses. Five HG-SPNs and 15 C-SPNs were evaluated in this study. HG-SPNs share many pathologic characteristics: macroscopically, solid/cystic appearances, microscopically, pseudopapillary/pseudorosette pattern (100%), tumor cell loose cohesiveness (100%), thin/delicate vasculature (100%), tumor cell cytoplasmic vacuolization (100%), immunohistochemical positivity for β-catenin (nuclear expression) (100%), CD10 (80%), CD56 (80%), and vimentin (100%). Conversely, HG-SPNs showed distinct malignant features compared with C-SPNs: mean tumor size (11.7 vs. 2.9 cm, P <0.001); true necrosis (100% vs. 0%, P <0.001); high-grade nuclear atypia (100% vs. 0%, P <0.001); lymphatic and/or venous invasion (100% vs. 20%, P =0.004); mean mitotic count (4.38 vs. 0.05/high-power field, P <0.001); and mean Ki-67 labeling index (33.9% vs. 3.4%, P <0.001). All HG-SPN patients died of primary disease 3 to 36 months after surgery, while all C-SPN patients were alive without disease. Genetic studies have shown that all analyzed HG-SPNs have CTNNB1 mutations. Two HG-SPN cases showed RB1 mutations with altered immunohistochemical findings for RB1 and p16. Two HG-SPN cases had TP53 mutation and/or p53 overexpression. In conclusion, HG-SPNs show distinct malignant features and some genetic alterations that differ from C-SPNs, indicating the importance of differentiating between these 2 subtypes.